Endocrinology

For 3 years, Ajala Efem’s type 2 diabetes was so poorly controlled that her blood sugar often soared northward of 500 mg/dL despite insulin shots three to five times a day. She would experience dizziness, vomiting, severe headaches, and the neuropathy in her feet made walking painful. She was also — literally — frothing at the mouth. The 47-year-old single mother of two adult children with mental disabilities feared that she would die.

Ms. Efem lives in the South Bronx, which is among the poorest areas of New York City, where the combined rate of prediabetes and diabetes is close to 30%, the highest rate of any borough in the city.

She had to wait 8 months for an appointment with an endocrinologist, but that visit proved to be life-changing. She lost 28 pounds and got off 15 medications in a single month. She did not join a gym or count calories; she simply changed the food she ate and adopted a low-carb diet.

“I went from being sick to feeling so great,” she told her endocrinologist recently: “My feet aren’t hurting; I’m not in pain; I’m eating as much as I want, and I really enjoy my food so much.” 

Ms. Efem’s life-changing visit was with Mariela Glandt, MD, at the offices of Essen Health Care. One month earlier, Dr. Glandt’s company, OwnaHealth, was contracted by Essen to conduct a 100-person pilot program for endocrinology patients. Essen is the largest Medicaid provider in New York City, and “they were desperate for an endocrinologist,” said Dr. Glandt, who trained at Columbia University in New York. So she came — all the way from Madrid, Spain. She commutes monthly, staying for a week each visit.

Dr. Glandt keeps up this punishing schedule because, as she explains, “it’s such a high for me to see these incredible transformations.” Her mostly Black and Hispanic patients are poor and lack resources, yet they lose significant amounts of weight, and their health issues resolve.

“Food is medicine” is an idea very much in vogue. The concept was central to the landmark White House Conference on Hunger, Nutrition, and Health in 2022 and is now the focus of a number of a wide range of government programs. Recently, the Senate held a hearing aimed at further expanding food as medicine programs.

Still, only a single randomized controlled clinical trial has been conducted on this nutritional approach, with unexpectedly disappointing results. In the mid-Atlantic region, 456 food-insecure adults with type 2 diabetes were randomly assigned to usual care or the provision of weekly groceries for their entire families for about 1 year. Provisions for a Mediterranean-style diet included whole grains, fruits and vegetables, lean protein, low-fat dairy products, cereal, brown rice, and bread. In addition, participants received dietary consultations. Yet, those who got free food and coaching did not see improvements in their average blood sugar (the study’s primary outcome), and their low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels appeared to have worsened. 

“To be honest, I was surprised,” the study’s lead author, Joseph Doyle, PhD, professor at the Sloan School of Management at MIT in Cambridge, Massachusetts, told me. “I was hoping we would show improved outcomes, but the way to make progress is to do well-randomized trials to find out what works.”

I was not surprised by these results because a recent rigorous systematic review and meta-analysis in The BMJ did not show a Mediterranean-style diet to be the most effective for glycemic control. And Ms. Efem was not in fact following a Mediterranean-style diet.

Ms. Efem’s low-carb success story is anecdotal, but Dr. Glandt has an established track record from her 9 years’ experience as the medical director of the eponymous diabetes center she founded in Tel Aviv. A recent audit of 344 patients from the center found that after 6 months of following a very low–carbohydrate diet, 96.3% of those with diabetes saw their A1c fall from a median 7.6% to 6.3%. Weight loss was significant, with a median drop of 6.5 kg (14 pounds) for patients with diabetes and 5.7 kg for those with prediabetes. The diet comprises 5%-10% of calories from carbs, but Dr. Glandt does not use numeric targets with her patients.

Blood pressure, triglycerides, and liver enzymes also improved. And though LDL cholesterol went up by 8%, this result may have been offset by an accompanying 13% rise in HDL cholesterol. Of the 78 patients initially on insulin, 62 were able to stop this medication entirely.

Although these results aren’t from a clinical trial, they’re still highly meaningful because the current dietary standard of care for type 2 diabetes can only slow the progression of the disease, not cause remission. Indeed, the idea that type 2 diabetes could be put into remission was not seriously considered by the American Diabetes Association (ADA) until 2009. By 2019, an ADA report concluded that “[r]educing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia.” In other words, the best way to improve the key factor in diabetes is to reduce total carbohydrates. Yet, the ADA still advocates filling one quarter of one’s plate with carbohydrate-based foods, an amount that will prevent remission. Given that the ADA’s vision statement is “a life free of diabetes,” it seems negligent not to tell people with a deadly condition that they can reverse this diagnosis. 

A 2023 meta-analysis of 42 controlled clinical trials on 4809 patients showed that a very low–carbohydrate ketogenic diet (keto) was “superior” to alternatives for glycemic control. A more recent review of 11 clinical trials found that this diet was equal but not superior to other nutritional approaches in terms of blood sugar control, but this review also concluded that keto led to greater increases in HDL cholesterol and lower triglycerides. 

Dr. Glandt’s patients in the Bronx might not seem like obvious low-carb candidates. The diet is considered expensive and difficult to sustain. My interviews with a half dozen patients revealed some of these difficulties, but even for a woman living in a homeless shelter, the obstacles are not insurmountable.

Jerrilyn, who preferred that I use only her first name, lives in a shelter in Queens. While we strolled through a nearby park, she told me about her desire to lose weight and recover from polycystic ovary syndrome, which terrified her because it had caused dramatic hair loss. When she landed in Dr. Glandt’s office at age 28, she weighed 180 pounds. 

Less than 5 months later, Jerrilyn had lost 25 pounds, and her period had returned with some regularity. She said she used “food stamps,” known as the Supplemental Nutrition Assistance Program (SNAP), to buy most of her food at local delis because the meals served at the shelter were too heavy in starches. She starts her day with eggs, turkey bacon, and avocado. 

“It was hard to give up carbohydrates because in my culture [Latina], we have nothing but carbs: rice, potatoes, yuca,” Jerrilyn shared. She noticed that carbs make her hungrier, but after 3 days of going low-carb, her cravings diminished. “It was like getting over an addiction,” she said.

Jerrilyn told me she’d seen many doctors but none as involved as Dr. Glandt. “It feels awesome to know that I have a lot of really useful information coming from her all the time.” The OwnaHealth app tracks weight, blood pressure, blood sugar, ketones, meals, mood, and cravings. Patients wear continuous glucose monitors and enter other information manually. Ketone bodies are used to measure dietary adherence and are obtained through finger pricks and test strips provided by OwnaHealth. Dr. Glandt gives patients her own food plan, along with free visual guides to low-carbohydrate foods by dietdoctor.com. 

Dr. Glandt also sends her patients for regular blood work. She says she does not frequently see a rise in LDL cholesterol, which can sometimes occur on a low-carbohydrate diet. This effect is most common among people who are lean and fit. She says she doesn’t discontinue statins unless cholesterol levels improve significantly.

Samuel Gonzalez, age 56, weighed 275 pounds when he walked into Dr. Glandt’s office this past November. His A1c was 9.2%, but none of his previous doctors had diagnosed him with diabetes. “I was like a walking bag of sugar!” he joked. 

A low-carbohydrate diet seemed absurd to a Puerto Rican like himself: “Having coffee without sugar? That’s like sacrilegious in my culture!” exclaimed Mr. Gonzalez. Still, he managed, with SNAP, to cook eggs and bacon for breakfast and some kind of protein for dinner. He keeps lunch light, “like tuna fish,” and finds checking in with the OwnaHealth app to be very helpful. “Every day, I’m on it,” he said. In the past 7 months, he’s lost 50 pounds, normalized his cholesterol and blood pressure levels, and lowered his A1c to 5.5%.

Mr. Gonzalez gets disability payments due to a back injury, and Ms. Efem receives government payments because her husband died serving in the military. Ms. Efem says her new diet challenges her budget, but Mr. Gonzalez says he manages easily.

Mélissa Cruz, a 28-year-old studying to be a nail technician while also doing back office work at a physical therapy practice, says she’s stretched thin. “I end up sad because I can’t put energy into looking up recipes and cooking for me and my boyfriend,” she told me. She’ll often cook rice and plantains for him and meat for herself, but “it’s frustrating when I’m low on funds and can’t figure out what to eat.” 

Low-carbohydrate diets have a reputation for being expensive because people often start eating pricier foods, like meat and cheese, to replace cheaper starchy foods such as pasta and rice. Eggs and ground beef are less expensive low-carb meal options, and meat, unlike fruits and vegetables, is easy to freeze and doesn’t spoil quickly. These advantages can add up.

A 2019 cost analysis published in Nutrition & Dietetics compared a low-carbohydrate dietary pattern with the New Zealand government’s recommended guidelines (which are almost identical to those in the United States) and found that it cost only an extra $1.27 in US dollars per person per day. One explanation is that protein and fat are more satiating than carbohydrates, so people who mostly consume these macronutrients often cut back on snacks like packaged chips, crackers, and even fruits. Also, those on a ketogenic diet usually cut down on medications, so the additional $1.27 daily is likely offset by reduced spending at the pharmacy.

It’s not just Bronx residents with low socioeconomic status (SES) who adapt well to low-carbohydrate diets. Among Alabama state employees with diabetes enrolled in a low-carbohydrate dietary program provided by a company called Virta, the low SES population had the best outcomes. Virta also published survey data in 2023 showing that participants in a program with the Veteran’s Administration did not find additional costs to be an obstacle to dietary adherence. In fact, some participants saw cost reductions due to decreased spending on processed snacks and fast foods.

Ms. Cruz told me she struggles financially, yet she’s still lost nearly 30 pounds in 5 months, and her A1c went from 7.1% down to 5.9%, putting her diabetes into remission. Equally motivating for her are the improvements she’s seen in other hormonal issues. Since childhood, she’s had acanthosis, a condition that causes the skin to darken in velvety patches, and more recently, she developed severe hirsutism to the point of growing sideburns. “I had tried going vegan and fasting, but these just weren’t sustainable for me, and I was so overwhelmed with counting calories all the time.” Now, on a low-carbohydrate diet, which doesn’t require calorie counting, she’s finally seeing both these conditions improve significantly.

When I last checked in with Ms. Cruz, she said she had “kind of ghosted” Dr. Glandt due to her work and school constraints, but she hadn’t abandoned the diet. She appreciated, too, that Dr. Glandt had not given up on her and kept calling and messaging. “She’s not at all like a typical doctor who would just tell me to lose weight and shake their head at me,” Ms. Cruz said. 

Because Dr. Glandt’s approach is time-intensive and high-touch, it might seem impractical to scale up, but Dr. Glandt’s app uses artificial intelligence to help with communications thus allowing her, with help from part-time health coaches, to care for patients. 

This early success in one of the United States’ poorest and sickest neighborhoods should give us hope that type 2 diabetes need not to be a progressive irreversible disease, even among the disadvantaged. 

OwnaHealth’s track record, along with that of Virta and other similar low-carbohydrate medical practices also give hope to the food-is-medicine idea. Diabetes can go into remission, and people can be healed, provided that health practitioners prescribe the right foods. And in truth, it’s not a diet. It’s a way of eating that must be maintained. The sustainability of low-carbohydrate diets has been a point of contention, but the Virta trial, with 38% of patients sustaining remission at 2 years, showed that it’s possible. (OwnaHealth, for its part, offers long-term maintenance plans to help patients stay very low-carb permanently.) 

Given the tremendous costs and health burden of diabetes, this approach should no doubt be the first line of treatment for doctors and the ADA. The past two decades of clinical trial research have demonstrated that remission of type 2 diabetes is possible through diet alone. It turns out that for metabolic diseases, only certain foods are truly medicine. 
 

Tools and Tips for Clinicians: 

• Free two-page keto starter’s guide by OwnaHealth; Dr. Glandt uses this guide with her patients.
• Illustrated low-carb guides by dietdoctor.com
• Free low-carbohydrate starter guide by the Michigan Collaborative for Type 2 Diabetes
• Low-Carb for Any Budget, a free digital booklet by Mark Cucuzzella, MD, and Kristie Sullivan, PhD
• Recipe and meal ideas from Ruled.me, Keto-Mojo.com, and 

Dr. Teicholz is the founder of Nutrition Coalition, an independent nonprofit dedicated to ensuring that US dietary guidelines align with current science. She disclosed receiving book royalties from The Big Fat Surprise, and received honorarium not exceeding $2000 for speeches from various sources.

A version of this article appeared on Medscape.com.

For 3 years, Ajala Efem’s type 2 diabetes was so poorly controlled that her blood sugar often soared northward of 500 mg/dL despite insulin shots three to five times a day. She would experience dizziness, vomiting, severe headaches, and the neuropathy in her feet made walking painful. She was also — literally — frothing at the mouth. The 47-year-old single mother of two adult children with mental disabilities feared that she would die.

Ms. Efem lives in the South Bronx, which is among the poorest areas of New York City, where the combined rate of prediabetes and diabetes is close to 30%, the highest rate of any borough in the city.

She had to wait 8 months for an appointment with an endocrinologist, but that visit proved to be life-changing. She lost 28 pounds and got off 15 medications in a single month. She did not join a gym or count calories; she simply changed the food she ate and adopted a low-carb diet.

“I went from being sick to feeling so great,” she told her endocrinologist recently: “My feet aren’t hurting; I’m not in pain; I’m eating as much as I want, and I really enjoy my food so much.” 

Ms. Efem’s life-changing visit was with Mariela Glandt, MD, at the offices of Essen Health Care. One month earlier, Dr. Glandt’s company, OwnaHealth, was contracted by Essen to conduct a 100-person pilot program for endocrinology patients. Essen is the largest Medicaid provider in New York City, and “they were desperate for an endocrinologist,” said Dr. Glandt, who trained at Columbia University in New York. So she came — all the way from Madrid, Spain. She commutes monthly, staying for a week each visit.

Dr. Glandt keeps up this punishing schedule because, as she explains, “it’s such a high for me to see these incredible transformations.” Her mostly Black and Hispanic patients are poor and lack resources, yet they lose significant amounts of weight, and their health issues resolve.

“Food is medicine” is an idea very much in vogue. The concept was central to the landmark White House Conference on Hunger, Nutrition, and Health in 2022 and is now the focus of a number of a wide range of government programs. Recently, the Senate held a hearing aimed at further expanding food as medicine programs.

Still, only a single randomized controlled clinical trial has been conducted on this nutritional approach, with unexpectedly disappointing results. In the mid-Atlantic region, 456 food-insecure adults with type 2 diabetes were randomly assigned to usual care or the provision of weekly groceries for their entire families for about 1 year. Provisions for a Mediterranean-style diet included whole grains, fruits and vegetables, lean protein, low-fat dairy products, cereal, brown rice, and bread. In addition, participants received dietary consultations. Yet, those who got free food and coaching did not see improvements in their average blood sugar (the study’s primary outcome), and their low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels appeared to have worsened. 

“To be honest, I was surprised,” the study’s lead author, Joseph Doyle, PhD, professor at the Sloan School of Management at MIT in Cambridge, Massachusetts, told me. “I was hoping we would show improved outcomes, but the way to make progress is to do well-randomized trials to find out what works.”

I was not surprised by these results because a recent rigorous systematic review and meta-analysis in The BMJ did not show a Mediterranean-style diet to be the most effective for glycemic control. And Ms. Efem was not in fact following a Mediterranean-style diet.

Ms. Efem’s low-carb success story is anecdotal, but Dr. Glandt has an established track record from her 9 years’ experience as the medical director of the eponymous diabetes center she founded in Tel Aviv. A recent audit of 344 patients from the center found that after 6 months of following a very low–carbohydrate diet, 96.3% of those with diabetes saw their A1c fall from a median 7.6% to 6.3%. Weight loss was significant, with a median drop of 6.5 kg (14 pounds) for patients with diabetes and 5.7 kg for those with prediabetes. The diet comprises 5%-10% of calories from carbs, but Dr. Glandt does not use numeric targets with her patients.

Blood pressure, triglycerides, and liver enzymes also improved. And though LDL cholesterol went up by 8%, this result may have been offset by an accompanying 13% rise in HDL cholesterol. Of the 78 patients initially on insulin, 62 were able to stop this medication entirely.

Although these results aren’t from a clinical trial, they’re still highly meaningful because the current dietary standard of care for type 2 diabetes can only slow the progression of the disease, not cause remission. Indeed, the idea that type 2 diabetes could be put into remission was not seriously considered by the American Diabetes Association (ADA) until 2009. By 2019, an ADA report concluded that “[r]educing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia.” In other words, the best way to improve the key factor in diabetes is to reduce total carbohydrates. Yet, the ADA still advocates filling one quarter of one’s plate with carbohydrate-based foods, an amount that will prevent remission. Given that the ADA’s vision statement is “a life free of diabetes,” it seems negligent not to tell people with a deadly condition that they can reverse this diagnosis. 

A 2023 meta-analysis of 42 controlled clinical trials on 4809 patients showed that a very low–carbohydrate ketogenic diet (keto) was “superior” to alternatives for glycemic control. A more recent review of 11 clinical trials found that this diet was equal but not superior to other nutritional approaches in terms of blood sugar control, but this review also concluded that keto led to greater increases in HDL cholesterol and lower triglycerides. 

Dr. Glandt’s patients in the Bronx might not seem like obvious low-carb candidates. The diet is considered expensive and difficult to sustain. My interviews with a half dozen patients revealed some of these difficulties, but even for a woman living in a homeless shelter, the obstacles are not insurmountable.

Jerrilyn, who preferred that I use only her first name, lives in a shelter in Queens. While we strolled through a nearby park, she told me about her desire to lose weight and recover from polycystic ovary syndrome, which terrified her because it had caused dramatic hair loss. When she landed in Dr. Glandt’s office at age 28, she weighed 180 pounds. 

Less than 5 months later, Jerrilyn had lost 25 pounds, and her period had returned with some regularity. She said she used “food stamps,” known as the Supplemental Nutrition Assistance Program (SNAP), to buy most of her food at local delis because the meals served at the shelter were too heavy in starches. She starts her day with eggs, turkey bacon, and avocado. 

“It was hard to give up carbohydrates because in my culture [Latina], we have nothing but carbs: rice, potatoes, yuca,” Jerrilyn shared. She noticed that carbs make her hungrier, but after 3 days of going low-carb, her cravings diminished. “It was like getting over an addiction,” she said.

Jerrilyn told me she’d seen many doctors but none as involved as Dr. Glandt. “It feels awesome to know that I have a lot of really useful information coming from her all the time.” The OwnaHealth app tracks weight, blood pressure, blood sugar, ketones, meals, mood, and cravings. Patients wear continuous glucose monitors and enter other information manually. Ketone bodies are used to measure dietary adherence and are obtained through finger pricks and test strips provided by OwnaHealth. Dr. Glandt gives patients her own food plan, along with free visual guides to low-carbohydrate foods by dietdoctor.com. 

Dr. Glandt also sends her patients for regular blood work. She says she does not frequently see a rise in LDL cholesterol, which can sometimes occur on a low-carbohydrate diet. This effect is most common among people who are lean and fit. She says she doesn’t discontinue statins unless cholesterol levels improve significantly.

Samuel Gonzalez, age 56, weighed 275 pounds when he walked into Dr. Glandt’s office this past November. His A1c was 9.2%, but none of his previous doctors had diagnosed him with diabetes. “I was like a walking bag of sugar!” he joked. 

A low-carbohydrate diet seemed absurd to a Puerto Rican like himself: “Having coffee without sugar? That’s like sacrilegious in my culture!” exclaimed Mr. Gonzalez. Still, he managed, with SNAP, to cook eggs and bacon for breakfast and some kind of protein for dinner. He keeps lunch light, “like tuna fish,” and finds checking in with the OwnaHealth app to be very helpful. “Every day, I’m on it,” he said. In the past 7 months, he’s lost 50 pounds, normalized his cholesterol and blood pressure levels, and lowered his A1c to 5.5%.

Mr. Gonzalez gets disability payments due to a back injury, and Ms. Efem receives government payments because her husband died serving in the military. Ms. Efem says her new diet challenges her budget, but Mr. Gonzalez says he manages easily.

Mélissa Cruz, a 28-year-old studying to be a nail technician while also doing back office work at a physical therapy practice, says she’s stretched thin. “I end up sad because I can’t put energy into looking up recipes and cooking for me and my boyfriend,” she told me. She’ll often cook rice and plantains for him and meat for herself, but “it’s frustrating when I’m low on funds and can’t figure out what to eat.” 

Low-carbohydrate diets have a reputation for being expensive because people often start eating pricier foods, like meat and cheese, to replace cheaper starchy foods such as pasta and rice. Eggs and ground beef are less expensive low-carb meal options, and meat, unlike fruits and vegetables, is easy to freeze and doesn’t spoil quickly. These advantages can add up.

A 2019 cost analysis published in Nutrition & Dietetics compared a low-carbohydrate dietary pattern with the New Zealand government’s recommended guidelines (which are almost identical to those in the United States) and found that it cost only an extra $1.27 in US dollars per person per day. One explanation is that protein and fat are more satiating than carbohydrates, so people who mostly consume these macronutrients often cut back on snacks like packaged chips, crackers, and even fruits. Also, those on a ketogenic diet usually cut down on medications, so the additional $1.27 daily is likely offset by reduced spending at the pharmacy.

It’s not just Bronx residents with low socioeconomic status (SES) who adapt well to low-carbohydrate diets. Among Alabama state employees with diabetes enrolled in a low-carbohydrate dietary program provided by a company called Virta, the low SES population had the best outcomes. Virta also published survey data in 2023 showing that participants in a program with the Veteran’s Administration did not find additional costs to be an obstacle to dietary adherence. In fact, some participants saw cost reductions due to decreased spending on processed snacks and fast foods.

Ms. Cruz told me she struggles financially, yet she’s still lost nearly 30 pounds in 5 months, and her A1c went from 7.1% down to 5.9%, putting her diabetes into remission. Equally motivating for her are the improvements she’s seen in other hormonal issues. Since childhood, she’s had acanthosis, a condition that causes the skin to darken in velvety patches, and more recently, she developed severe hirsutism to the point of growing sideburns. “I had tried going vegan and fasting, but these just weren’t sustainable for me, and I was so overwhelmed with counting calories all the time.” Now, on a low-carbohydrate diet, which doesn’t require calorie counting, she’s finally seeing both these conditions improve significantly.

When I last checked in with Ms. Cruz, she said she had “kind of ghosted” Dr. Glandt due to her work and school constraints, but she hadn’t abandoned the diet. She appreciated, too, that Dr. Glandt had not given up on her and kept calling and messaging. “She’s not at all like a typical doctor who would just tell me to lose weight and shake their head at me,” Ms. Cruz said. 

Because Dr. Glandt’s approach is time-intensive and high-touch, it might seem impractical to scale up, but Dr. Glandt’s app uses artificial intelligence to help with communications thus allowing her, with help from part-time health coaches, to care for patients. 

This early success in one of the United States’ poorest and sickest neighborhoods should give us hope that type 2 diabetes need not to be a progressive irreversible disease, even among the disadvantaged. 

OwnaHealth’s track record, along with that of Virta and other similar low-carbohydrate medical practices also give hope to the food-is-medicine idea. Diabetes can go into remission, and people can be healed, provided that health practitioners prescribe the right foods. And in truth, it’s not a diet. It’s a way of eating that must be maintained. The sustainability of low-carbohydrate diets has been a point of contention, but the Virta trial, with 38% of patients sustaining remission at 2 years, showed that it’s possible. (OwnaHealth, for its part, offers long-term maintenance plans to help patients stay very low-carb permanently.) 

Given the tremendous costs and health burden of diabetes, this approach should no doubt be the first line of treatment for doctors and the ADA. The past two decades of clinical trial research have demonstrated that remission of type 2 diabetes is possible through diet alone. It turns out that for metabolic diseases, only certain foods are truly medicine. 
 

Tools and Tips for Clinicians: 

• Free two-page keto starter’s guide by OwnaHealth; Dr. Glandt uses this guide with her patients.
• Illustrated low-carb guides by dietdoctor.com
• Free low-carbohydrate starter guide by the Michigan Collaborative for Type 2 Diabetes
• Low-Carb for Any Budget, a free digital booklet by Mark Cucuzzella, MD, and Kristie Sullivan, PhD
• Recipe and meal ideas from Ruled.me, Keto-Mojo.com, and 

Dr. Teicholz is the founder of Nutrition Coalition, an independent nonprofit dedicated to ensuring that US dietary guidelines align with current science. She disclosed receiving book royalties from The Big Fat Surprise, and received honorarium not exceeding $2000 for speeches from various sources.

A version of this article appeared on Medscape.com.

For 3 years, Ajala Efem’s type 2 diabetes was so poorly controlled that her blood sugar often soared northward of 500 mg/dL despite insulin shots three to five times a day. She would experience dizziness, vomiting, severe headaches, and the neuropathy in her feet made walking painful. She was also — literally — frothing at the mouth. The 47-year-old single mother of two adult children with mental disabilities feared that she would die.

Ms. Efem lives in the South Bronx, which is among the poorest areas of New York City, where the combined rate of prediabetes and diabetes is close to 30%, the highest rate of any borough in the city.

She had to wait 8 months for an appointment with an endocrinologist, but that visit proved to be life-changing. She lost 28 pounds and got off 15 medications in a single month. She did not join a gym or count calories; she simply changed the food she ate and adopted a low-carb diet.

“I went from being sick to feeling so great,” she told her endocrinologist recently: “My feet aren’t hurting; I’m not in pain; I’m eating as much as I want, and I really enjoy my food so much.” 

Ms. Efem’s life-changing visit was with Mariela Glandt, MD, at the offices of Essen Health Care. One month earlier, Dr. Glandt’s company, OwnaHealth, was contracted by Essen to conduct a 100-person pilot program for endocrinology patients. Essen is the largest Medicaid provider in New York City, and “they were desperate for an endocrinologist,” said Dr. Glandt, who trained at Columbia University in New York. So she came — all the way from Madrid, Spain. She commutes monthly, staying for a week each visit.

Dr. Glandt keeps up this punishing schedule because, as she explains, “it’s such a high for me to see these incredible transformations.” Her mostly Black and Hispanic patients are poor and lack resources, yet they lose significant amounts of weight, and their health issues resolve.

“Food is medicine” is an idea very much in vogue. The concept was central to the landmark White House Conference on Hunger, Nutrition, and Health in 2022 and is now the focus of a number of a wide range of government programs. Recently, the Senate held a hearing aimed at further expanding food as medicine programs.

Still, only a single randomized controlled clinical trial has been conducted on this nutritional approach, with unexpectedly disappointing results. In the mid-Atlantic region, 456 food-insecure adults with type 2 diabetes were randomly assigned to usual care or the provision of weekly groceries for their entire families for about 1 year. Provisions for a Mediterranean-style diet included whole grains, fruits and vegetables, lean protein, low-fat dairy products, cereal, brown rice, and bread. In addition, participants received dietary consultations. Yet, those who got free food and coaching did not see improvements in their average blood sugar (the study’s primary outcome), and their low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels appeared to have worsened. 

“To be honest, I was surprised,” the study’s lead author, Joseph Doyle, PhD, professor at the Sloan School of Management at MIT in Cambridge, Massachusetts, told me. “I was hoping we would show improved outcomes, but the way to make progress is to do well-randomized trials to find out what works.”

I was not surprised by these results because a recent rigorous systematic review and meta-analysis in The BMJ did not show a Mediterranean-style diet to be the most effective for glycemic control. And Ms. Efem was not in fact following a Mediterranean-style diet.

Ms. Efem’s low-carb success story is anecdotal, but Dr. Glandt has an established track record from her 9 years’ experience as the medical director of the eponymous diabetes center she founded in Tel Aviv. A recent audit of 344 patients from the center found that after 6 months of following a very low–carbohydrate diet, 96.3% of those with diabetes saw their A1c fall from a median 7.6% to 6.3%. Weight loss was significant, with a median drop of 6.5 kg (14 pounds) for patients with diabetes and 5.7 kg for those with prediabetes. The diet comprises 5%-10% of calories from carbs, but Dr. Glandt does not use numeric targets with her patients.

Blood pressure, triglycerides, and liver enzymes also improved. And though LDL cholesterol went up by 8%, this result may have been offset by an accompanying 13% rise in HDL cholesterol. Of the 78 patients initially on insulin, 62 were able to stop this medication entirely.

Although these results aren’t from a clinical trial, they’re still highly meaningful because the current dietary standard of care for type 2 diabetes can only slow the progression of the disease, not cause remission. Indeed, the idea that type 2 diabetes could be put into remission was not seriously considered by the American Diabetes Association (ADA) until 2009. By 2019, an ADA report concluded that “[r]educing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia.” In other words, the best way to improve the key factor in diabetes is to reduce total carbohydrates. Yet, the ADA still advocates filling one quarter of one’s plate with carbohydrate-based foods, an amount that will prevent remission. Given that the ADA’s vision statement is “a life free of diabetes,” it seems negligent not to tell people with a deadly condition that they can reverse this diagnosis. 

A 2023 meta-analysis of 42 controlled clinical trials on 4809 patients showed that a very low–carbohydrate ketogenic diet (keto) was “superior” to alternatives for glycemic control. A more recent review of 11 clinical trials found that this diet was equal but not superior to other nutritional approaches in terms of blood sugar control, but this review also concluded that keto led to greater increases in HDL cholesterol and lower triglycerides. 

Dr. Glandt’s patients in the Bronx might not seem like obvious low-carb candidates. The diet is considered expensive and difficult to sustain. My interviews with a half dozen patients revealed some of these difficulties, but even for a woman living in a homeless shelter, the obstacles are not insurmountable.

Jerrilyn, who preferred that I use only her first name, lives in a shelter in Queens. While we strolled through a nearby park, she told me about her desire to lose weight and recover from polycystic ovary syndrome, which terrified her because it had caused dramatic hair loss. When she landed in Dr. Glandt’s office at age 28, she weighed 180 pounds. 

Less than 5 months later, Jerrilyn had lost 25 pounds, and her period had returned with some regularity. She said she used “food stamps,” known as the Supplemental Nutrition Assistance Program (SNAP), to buy most of her food at local delis because the meals served at the shelter were too heavy in starches. She starts her day with eggs, turkey bacon, and avocado. 

“It was hard to give up carbohydrates because in my culture [Latina], we have nothing but carbs: rice, potatoes, yuca,” Jerrilyn shared. She noticed that carbs make her hungrier, but after 3 days of going low-carb, her cravings diminished. “It was like getting over an addiction,” she said.

Jerrilyn told me she’d seen many doctors but none as involved as Dr. Glandt. “It feels awesome to know that I have a lot of really useful information coming from her all the time.” The OwnaHealth app tracks weight, blood pressure, blood sugar, ketones, meals, mood, and cravings. Patients wear continuous glucose monitors and enter other information manually. Ketone bodies are used to measure dietary adherence and are obtained through finger pricks and test strips provided by OwnaHealth. Dr. Glandt gives patients her own food plan, along with free visual guides to low-carbohydrate foods by dietdoctor.com. 

Dr. Glandt also sends her patients for regular blood work. She says she does not frequently see a rise in LDL cholesterol, which can sometimes occur on a low-carbohydrate diet. This effect is most common among people who are lean and fit. She says she doesn’t discontinue statins unless cholesterol levels improve significantly.

Samuel Gonzalez, age 56, weighed 275 pounds when he walked into Dr. Glandt’s office this past November. His A1c was 9.2%, but none of his previous doctors had diagnosed him with diabetes. “I was like a walking bag of sugar!” he joked. 

A low-carbohydrate diet seemed absurd to a Puerto Rican like himself: “Having coffee without sugar? That’s like sacrilegious in my culture!” exclaimed Mr. Gonzalez. Still, he managed, with SNAP, to cook eggs and bacon for breakfast and some kind of protein for dinner. He keeps lunch light, “like tuna fish,” and finds checking in with the OwnaHealth app to be very helpful. “Every day, I’m on it,” he said. In the past 7 months, he’s lost 50 pounds, normalized his cholesterol and blood pressure levels, and lowered his A1c to 5.5%.

Mr. Gonzalez gets disability payments due to a back injury, and Ms. Efem receives government payments because her husband died serving in the military. Ms. Efem says her new diet challenges her budget, but Mr. Gonzalez says he manages easily.

Mélissa Cruz, a 28-year-old studying to be a nail technician while also doing back office work at a physical therapy practice, says she’s stretched thin. “I end up sad because I can’t put energy into looking up recipes and cooking for me and my boyfriend,” she told me. She’ll often cook rice and plantains for him and meat for herself, but “it’s frustrating when I’m low on funds and can’t figure out what to eat.” 

Low-carbohydrate diets have a reputation for being expensive because people often start eating pricier foods, like meat and cheese, to replace cheaper starchy foods such as pasta and rice. Eggs and ground beef are less expensive low-carb meal options, and meat, unlike fruits and vegetables, is easy to freeze and doesn’t spoil quickly. These advantages can add up.

A 2019 cost analysis published in Nutrition & Dietetics compared a low-carbohydrate dietary pattern with the New Zealand government’s recommended guidelines (which are almost identical to those in the United States) and found that it cost only an extra $1.27 in US dollars per person per day. One explanation is that protein and fat are more satiating than carbohydrates, so people who mostly consume these macronutrients often cut back on snacks like packaged chips, crackers, and even fruits. Also, those on a ketogenic diet usually cut down on medications, so the additional $1.27 daily is likely offset by reduced spending at the pharmacy.

It’s not just Bronx residents with low socioeconomic status (SES) who adapt well to low-carbohydrate diets. Among Alabama state employees with diabetes enrolled in a low-carbohydrate dietary program provided by a company called Virta, the low SES population had the best outcomes. Virta also published survey data in 2023 showing that participants in a program with the Veteran’s Administration did not find additional costs to be an obstacle to dietary adherence. In fact, some participants saw cost reductions due to decreased spending on processed snacks and fast foods.

Ms. Cruz told me she struggles financially, yet she’s still lost nearly 30 pounds in 5 months, and her A1c went from 7.1% down to 5.9%, putting her diabetes into remission. Equally motivating for her are the improvements she’s seen in other hormonal issues. Since childhood, she’s had acanthosis, a condition that causes the skin to darken in velvety patches, and more recently, she developed severe hirsutism to the point of growing sideburns. “I had tried going vegan and fasting, but these just weren’t sustainable for me, and I was so overwhelmed with counting calories all the time.” Now, on a low-carbohydrate diet, which doesn’t require calorie counting, she’s finally seeing both these conditions improve significantly.

When I last checked in with Ms. Cruz, she said she had “kind of ghosted” Dr. Glandt due to her work and school constraints, but she hadn’t abandoned the diet. She appreciated, too, that Dr. Glandt had not given up on her and kept calling and messaging. “She’s not at all like a typical doctor who would just tell me to lose weight and shake their head at me,” Ms. Cruz said. 

Because Dr. Glandt’s approach is time-intensive and high-touch, it might seem impractical to scale up, but Dr. Glandt’s app uses artificial intelligence to help with communications thus allowing her, with help from part-time health coaches, to care for patients. 

This early success in one of the United States’ poorest and sickest neighborhoods should give us hope that type 2 diabetes need not to be a progressive irreversible disease, even among the disadvantaged. 

OwnaHealth’s track record, along with that of Virta and other similar low-carbohydrate medical practices also give hope to the food-is-medicine idea. Diabetes can go into remission, and people can be healed, provided that health practitioners prescribe the right foods. And in truth, it’s not a diet. It’s a way of eating that must be maintained. The sustainability of low-carbohydrate diets has been a point of contention, but the Virta trial, with 38% of patients sustaining remission at 2 years, showed that it’s possible. (OwnaHealth, for its part, offers long-term maintenance plans to help patients stay very low-carb permanently.) 

Given the tremendous costs and health burden of diabetes, this approach should no doubt be the first line of treatment for doctors and the ADA. The past two decades of clinical trial research have demonstrated that remission of type 2 diabetes is possible through diet alone. It turns out that for metabolic diseases, only certain foods are truly medicine. 
 

Tools and Tips for Clinicians: 

• Free two-page keto starter’s guide by OwnaHealth; Dr. Glandt uses this guide with her patients.
• Illustrated low-carb guides by dietdoctor.com
• Free low-carbohydrate starter guide by the Michigan Collaborative for Type 2 Diabetes
• Low-Carb for Any Budget, a free digital booklet by Mark Cucuzzella, MD, and Kristie Sullivan, PhD
• Recipe and meal ideas from Ruled.me, Keto-Mojo.com, and 

Dr. Teicholz is the founder of Nutrition Coalition, an independent nonprofit dedicated to ensuring that US dietary guidelines align with current science. She disclosed receiving book royalties from The Big Fat Surprise, and received honorarium not exceeding $2000 for speeches from various sources.

A version of this article appeared on Medscape.com.

A recent report by this news organization of a vitamin D clinical practice guideline released by the Endocrine Society in June triggered an outpouring of objections in the comments section from doctors and other readers.

A society press release listed the key new recommendations on the use of vitamin D supplementation and screening to reduce disease risks in individuals without established indications for such treatment or testing:

• For healthy adults younger than 75, no supplementation at doses above the recommended dietary intakes.
• Populations that may benefit from higher doses include: children and adolescents 18 and younger to prevent rickets and to reduce risk for respiratory infection, individuals 75 and older to possibly lower mortality risk, “pregnant people” to potentially reduce various risks, and people with prediabetes to potentially reduce risk of progression.
• No routine testing for 25-hydroxyvitamin D levels because outcome-specific benefits based on those levels have not been identified (including screening in people with dark complexion or obesity).
• Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.

This news organization covered the guideline release and simultaneous presentation at the Endocrine Society annual meeting. In response to the coverage, more than 200 doctors and other readers expressed concerns about the guideline, and some said outright that they would not follow it (readers quoted below are identified by the usernames they registered with on the website).

One reader who posted as Dr. Joseph Destefano went so far as to call the guideline “dangerous” and “almost ... evil.” Ironically, some readers attacked this news organization, thinking that the coverage implied an endorsement, rather than a news report.
 

Ignores Potential Benefits

Although the guideline is said to be for people who are “otherwise healthy” (other than the exceptions noted above), many readers were concerned that the recommendations ignore the potential benefits of supplementation for other health conditions relevant to patients and other populations.

“They address issues dealing only with endocrinology and bone health for the most part,” Dr. Emilio Gonzalez wrote. “However, vitamin D insufficiency and deficiency are not rare, and they impact the treatment of autoimmune disorders, chronic pain control, immunosuppression, cancer prevention, cardiovascular health, etc. There is plenty of literature in this regard.”

“They make these claims as if quality studies contradicting their guidelines have not been out there for years,” Dr. Brian Batcheldor said. “What about the huge demographic with diseases that impact intestinal absorption, eg, Crohn’s and celiac disease, cystic fibrosis, and ulcerative colitis? What about the one in nine that now have autoimmune diseases still awaiting diagnosis? What about night workers or anyone with more restricted access to sun exposure? How about those whose cultural or religious dress code limit skin exposure?”

The latter group was also mentioned in a post from Dr. Eve Finkelstein who said, “They don’t take into account women who are totally covered for religious reasons. They have no skin other than part of their face exposed. It does not make sense not to supplement them. Ignoring women’s health needs seems to be the norm.”

“I don’t think they considered the oral health effects of vitamin D deficiency,” pointed out commenter Corie Lewis. “Excess dental calculus (tartar) from excess calcium/phosphate in saliva significantly increases an individual’s periodontal disease risks (gum disease), and low saliva calcium/phosphate increases dental caries (cavities) risks, which generally indicates an imbalance of the oral microbiome. Vitamin D can help create balance and reduce those oral health risks.”

Noted Kimberley Morris-Windisch, “Having worked in rheumatology and pain for most of my career, I have seen too many people benefit from correcting deficiency of vitamin D. To ignore this is to miss opportunities to improve patient health.” Furthermore, “I find it unlikely that it would only improve mortality after age 75. That makes no sense.”

“Also,” she added, “what is the number [needed] to harm? In my 25 years, I have seen vitamin D toxicity once and an excessively high level without symptoms one other time.”

“WHY? Just WHY?” lamented Anne Kinchen. “Low levels in pregnant women have long-term effects on the developing fetus — higher and earlier rates of osteopenia in female children, weaker immune systems overall. There are just SO many reasons to test. These guidelines for no testing are absurd!”
 

No Screening, No Need for Decision-Making?

Several readers questioned the society’s rationale for not screening, as expressed by session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine.

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it,” Dr. Rosen said. “That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen. ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life. ... Screening is probably not worthwhile in any age group.”

Among the reader comments in this regard:

“So misguided. Don’t look because we don’t know what do to with data. That’s the message this article exposes. The recommendation is do nothing. But, doing nothing IS an action — not a default.” (Lisa Tracy)

“So now, you will not screen for vitamin D because you do not know what to do next? See a naturopathic doctor — we know what to do next!” (Dr. Joyce Roberson)

“Gee, how do we treat it? ... What to do? Sounds incompetent at minimum. I suspect it’s vital, easy, and inexpensive ... so hide it.” (Holly Kohley)

“Just because we do not know is not a rationale for not testing. The opposite should be done.” (Dr. JJ Gold)
 

Caters to Industry?

Many commentators intimated that pharma and/or insurance company considerations played a role in the recommendations. Their comments included the following:

“I have been under the impression people do routine checkups to verify there are no hidden problems. If only some testing is done, the probability of not finding a problem is huge. ... Preventive healthcare should be looking for something to prevent instead of waiting until they can cure it. Of course, it might come back to ‘follow the money.’ It is much more profitable to diagnose and treat than it is to prevent.” (Grace Kyser)

“The current irrational ‘recommendation’ gives insurance companies an excuse to deny ALL tests of vitamin D — even if the proper code is supplied. The result is — people suffer. This recommendation does harm!” (Dr JJ Gold)

“Essentially, they are saying let’s not screen ‘healthy’ individuals and ignore it altogether. Better to wait till they’re old, pregnant, or already sick and diagnosed with a disease. This is the problem with the healthcare in this country.” (Brittney Lesher)

“Until allopathic medicine stops waiting for severe symptoms to develop before even screening for potential health problems, the most expensive healthcare (aka, sick care) system in the world will continue to be content to focus on medical emergencies and ignore prevention. ...” (Dean Raffelock)

“Don’t test? Are you kidding me? Especially when people are supplementing? That is akin to taking a blood pressure medication without measuring blood pressures! ... Don’t test? Don’t supplement? ... I have only one explanation for such nonsense: Pharma lives off sick people, not healthy ones.” (Georg Schlomka)

On a somewhat conciliatory and pointed note, Dr Francesca Luna-Rudin commented, “I would like to remind all of my fellow physicians that recommendations should be regarded as just that, a ‘recommendation.’ As doctors, we can use guidelines and recommendations in our practice, but if a new one is presented that does not make sense or would lead to harm based on our education and training, then we are not bound to follow it!”

A version of this article first appeared on Medscape.com.

A recent report by this news organization of a vitamin D clinical practice guideline released by the Endocrine Society in June triggered an outpouring of objections in the comments section from doctors and other readers.

A society press release listed the key new recommendations on the use of vitamin D supplementation and screening to reduce disease risks in individuals without established indications for such treatment or testing:

• For healthy adults younger than 75, no supplementation at doses above the recommended dietary intakes.
• Populations that may benefit from higher doses include: children and adolescents 18 and younger to prevent rickets and to reduce risk for respiratory infection, individuals 75 and older to possibly lower mortality risk, “pregnant people” to potentially reduce various risks, and people with prediabetes to potentially reduce risk of progression.
• No routine testing for 25-hydroxyvitamin D levels because outcome-specific benefits based on those levels have not been identified (including screening in people with dark complexion or obesity).
• Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.

This news organization covered the guideline release and simultaneous presentation at the Endocrine Society annual meeting. In response to the coverage, more than 200 doctors and other readers expressed concerns about the guideline, and some said outright that they would not follow it (readers quoted below are identified by the usernames they registered with on the website).

One reader who posted as Dr. Joseph Destefano went so far as to call the guideline “dangerous” and “almost ... evil.” Ironically, some readers attacked this news organization, thinking that the coverage implied an endorsement, rather than a news report.
 

Ignores Potential Benefits

Although the guideline is said to be for people who are “otherwise healthy” (other than the exceptions noted above), many readers were concerned that the recommendations ignore the potential benefits of supplementation for other health conditions relevant to patients and other populations.

“They address issues dealing only with endocrinology and bone health for the most part,” Dr. Emilio Gonzalez wrote. “However, vitamin D insufficiency and deficiency are not rare, and they impact the treatment of autoimmune disorders, chronic pain control, immunosuppression, cancer prevention, cardiovascular health, etc. There is plenty of literature in this regard.”

“They make these claims as if quality studies contradicting their guidelines have not been out there for years,” Dr. Brian Batcheldor said. “What about the huge demographic with diseases that impact intestinal absorption, eg, Crohn’s and celiac disease, cystic fibrosis, and ulcerative colitis? What about the one in nine that now have autoimmune diseases still awaiting diagnosis? What about night workers or anyone with more restricted access to sun exposure? How about those whose cultural or religious dress code limit skin exposure?”

The latter group was also mentioned in a post from Dr. Eve Finkelstein who said, “They don’t take into account women who are totally covered for religious reasons. They have no skin other than part of their face exposed. It does not make sense not to supplement them. Ignoring women’s health needs seems to be the norm.”

“I don’t think they considered the oral health effects of vitamin D deficiency,” pointed out commenter Corie Lewis. “Excess dental calculus (tartar) from excess calcium/phosphate in saliva significantly increases an individual’s periodontal disease risks (gum disease), and low saliva calcium/phosphate increases dental caries (cavities) risks, which generally indicates an imbalance of the oral microbiome. Vitamin D can help create balance and reduce those oral health risks.”

Noted Kimberley Morris-Windisch, “Having worked in rheumatology and pain for most of my career, I have seen too many people benefit from correcting deficiency of vitamin D. To ignore this is to miss opportunities to improve patient health.” Furthermore, “I find it unlikely that it would only improve mortality after age 75. That makes no sense.”

“Also,” she added, “what is the number [needed] to harm? In my 25 years, I have seen vitamin D toxicity once and an excessively high level without symptoms one other time.”

“WHY? Just WHY?” lamented Anne Kinchen. “Low levels in pregnant women have long-term effects on the developing fetus — higher and earlier rates of osteopenia in female children, weaker immune systems overall. There are just SO many reasons to test. These guidelines for no testing are absurd!”
 

No Screening, No Need for Decision-Making?

Several readers questioned the society’s rationale for not screening, as expressed by session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine.

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it,” Dr. Rosen said. “That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen. ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life. ... Screening is probably not worthwhile in any age group.”

Among the reader comments in this regard:

“So misguided. Don’t look because we don’t know what do to with data. That’s the message this article exposes. The recommendation is do nothing. But, doing nothing IS an action — not a default.” (Lisa Tracy)

“So now, you will not screen for vitamin D because you do not know what to do next? See a naturopathic doctor — we know what to do next!” (Dr. Joyce Roberson)

“Gee, how do we treat it? ... What to do? Sounds incompetent at minimum. I suspect it’s vital, easy, and inexpensive ... so hide it.” (Holly Kohley)

“Just because we do not know is not a rationale for not testing. The opposite should be done.” (Dr. JJ Gold)
 

Caters to Industry?

Many commentators intimated that pharma and/or insurance company considerations played a role in the recommendations. Their comments included the following:

“I have been under the impression people do routine checkups to verify there are no hidden problems. If only some testing is done, the probability of not finding a problem is huge. ... Preventive healthcare should be looking for something to prevent instead of waiting until they can cure it. Of course, it might come back to ‘follow the money.’ It is much more profitable to diagnose and treat than it is to prevent.” (Grace Kyser)

“The current irrational ‘recommendation’ gives insurance companies an excuse to deny ALL tests of vitamin D — even if the proper code is supplied. The result is — people suffer. This recommendation does harm!” (Dr JJ Gold)

“Essentially, they are saying let’s not screen ‘healthy’ individuals and ignore it altogether. Better to wait till they’re old, pregnant, or already sick and diagnosed with a disease. This is the problem with the healthcare in this country.” (Brittney Lesher)

“Until allopathic medicine stops waiting for severe symptoms to develop before even screening for potential health problems, the most expensive healthcare (aka, sick care) system in the world will continue to be content to focus on medical emergencies and ignore prevention. ...” (Dean Raffelock)

“Don’t test? Are you kidding me? Especially when people are supplementing? That is akin to taking a blood pressure medication without measuring blood pressures! ... Don’t test? Don’t supplement? ... I have only one explanation for such nonsense: Pharma lives off sick people, not healthy ones.” (Georg Schlomka)

On a somewhat conciliatory and pointed note, Dr Francesca Luna-Rudin commented, “I would like to remind all of my fellow physicians that recommendations should be regarded as just that, a ‘recommendation.’ As doctors, we can use guidelines and recommendations in our practice, but if a new one is presented that does not make sense or would lead to harm based on our education and training, then we are not bound to follow it!”

A version of this article first appeared on Medscape.com.

A recent report by this news organization of a vitamin D clinical practice guideline released by the Endocrine Society in June triggered an outpouring of objections in the comments section from doctors and other readers.

A society press release listed the key new recommendations on the use of vitamin D supplementation and screening to reduce disease risks in individuals without established indications for such treatment or testing:

• For healthy adults younger than 75, no supplementation at doses above the recommended dietary intakes.
• Populations that may benefit from higher doses include: children and adolescents 18 and younger to prevent rickets and to reduce risk for respiratory infection, individuals 75 and older to possibly lower mortality risk, “pregnant people” to potentially reduce various risks, and people with prediabetes to potentially reduce risk of progression.
• No routine testing for 25-hydroxyvitamin D levels because outcome-specific benefits based on those levels have not been identified (including screening in people with dark complexion or obesity).
• Based on insufficient evidence, the panel could not determine specific blood-level thresholds for 25-hydroxyvitamin D for adequacy or for target levels for disease prevention.

This news organization covered the guideline release and simultaneous presentation at the Endocrine Society annual meeting. In response to the coverage, more than 200 doctors and other readers expressed concerns about the guideline, and some said outright that they would not follow it (readers quoted below are identified by the usernames they registered with on the website).

One reader who posted as Dr. Joseph Destefano went so far as to call the guideline “dangerous” and “almost ... evil.” Ironically, some readers attacked this news organization, thinking that the coverage implied an endorsement, rather than a news report.
 

Ignores Potential Benefits

Although the guideline is said to be for people who are “otherwise healthy” (other than the exceptions noted above), many readers were concerned that the recommendations ignore the potential benefits of supplementation for other health conditions relevant to patients and other populations.

“They address issues dealing only with endocrinology and bone health for the most part,” Dr. Emilio Gonzalez wrote. “However, vitamin D insufficiency and deficiency are not rare, and they impact the treatment of autoimmune disorders, chronic pain control, immunosuppression, cancer prevention, cardiovascular health, etc. There is plenty of literature in this regard.”

“They make these claims as if quality studies contradicting their guidelines have not been out there for years,” Dr. Brian Batcheldor said. “What about the huge demographic with diseases that impact intestinal absorption, eg, Crohn’s and celiac disease, cystic fibrosis, and ulcerative colitis? What about the one in nine that now have autoimmune diseases still awaiting diagnosis? What about night workers or anyone with more restricted access to sun exposure? How about those whose cultural or religious dress code limit skin exposure?”

The latter group was also mentioned in a post from Dr. Eve Finkelstein who said, “They don’t take into account women who are totally covered for religious reasons. They have no skin other than part of their face exposed. It does not make sense not to supplement them. Ignoring women’s health needs seems to be the norm.”

“I don’t think they considered the oral health effects of vitamin D deficiency,” pointed out commenter Corie Lewis. “Excess dental calculus (tartar) from excess calcium/phosphate in saliva significantly increases an individual’s periodontal disease risks (gum disease), and low saliva calcium/phosphate increases dental caries (cavities) risks, which generally indicates an imbalance of the oral microbiome. Vitamin D can help create balance and reduce those oral health risks.”

Noted Kimberley Morris-Windisch, “Having worked in rheumatology and pain for most of my career, I have seen too many people benefit from correcting deficiency of vitamin D. To ignore this is to miss opportunities to improve patient health.” Furthermore, “I find it unlikely that it would only improve mortality after age 75. That makes no sense.”

“Also,” she added, “what is the number [needed] to harm? In my 25 years, I have seen vitamin D toxicity once and an excessively high level without symptoms one other time.”

“WHY? Just WHY?” lamented Anne Kinchen. “Low levels in pregnant women have long-term effects on the developing fetus — higher and earlier rates of osteopenia in female children, weaker immune systems overall. There are just SO many reasons to test. These guidelines for no testing are absurd!”
 

No Screening, No Need for Decision-Making?

Several readers questioned the society’s rationale for not screening, as expressed by session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine.

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it,” Dr. Rosen said. “That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen. ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life. ... Screening is probably not worthwhile in any age group.”

Among the reader comments in this regard:

“So misguided. Don’t look because we don’t know what do to with data. That’s the message this article exposes. The recommendation is do nothing. But, doing nothing IS an action — not a default.” (Lisa Tracy)

“So now, you will not screen for vitamin D because you do not know what to do next? See a naturopathic doctor — we know what to do next!” (Dr. Joyce Roberson)

“Gee, how do we treat it? ... What to do? Sounds incompetent at minimum. I suspect it’s vital, easy, and inexpensive ... so hide it.” (Holly Kohley)

“Just because we do not know is not a rationale for not testing. The opposite should be done.” (Dr. JJ Gold)
 

Caters to Industry?

Many commentators intimated that pharma and/or insurance company considerations played a role in the recommendations. Their comments included the following:

“I have been under the impression people do routine checkups to verify there are no hidden problems. If only some testing is done, the probability of not finding a problem is huge. ... Preventive healthcare should be looking for something to prevent instead of waiting until they can cure it. Of course, it might come back to ‘follow the money.’ It is much more profitable to diagnose and treat than it is to prevent.” (Grace Kyser)

“The current irrational ‘recommendation’ gives insurance companies an excuse to deny ALL tests of vitamin D — even if the proper code is supplied. The result is — people suffer. This recommendation does harm!” (Dr JJ Gold)

“Essentially, they are saying let’s not screen ‘healthy’ individuals and ignore it altogether. Better to wait till they’re old, pregnant, or already sick and diagnosed with a disease. This is the problem with the healthcare in this country.” (Brittney Lesher)

“Until allopathic medicine stops waiting for severe symptoms to develop before even screening for potential health problems, the most expensive healthcare (aka, sick care) system in the world will continue to be content to focus on medical emergencies and ignore prevention. ...” (Dean Raffelock)

“Don’t test? Are you kidding me? Especially when people are supplementing? That is akin to taking a blood pressure medication without measuring blood pressures! ... Don’t test? Don’t supplement? ... I have only one explanation for such nonsense: Pharma lives off sick people, not healthy ones.” (Georg Schlomka)

On a somewhat conciliatory and pointed note, Dr Francesca Luna-Rudin commented, “I would like to remind all of my fellow physicians that recommendations should be regarded as just that, a ‘recommendation.’ As doctors, we can use guidelines and recommendations in our practice, but if a new one is presented that does not make sense or would lead to harm based on our education and training, then we are not bound to follow it!”

A version of this article first appeared on Medscape.com.

Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

Recent research on popular weight loss drugs has uncovered surprising benefits beyond their intended use, like lowering the risk of fatal heart attacks. And now there may be another unforeseen advantage: People with type 2 diabetes who took these drugs had a lower risk of having 10 out of 13 obesity-related cancers, compared to those who used insulin therapy.

That’s according to a study published July 5 in JAMA Network Open where researchers studied glucagon-like peptide receptor agonists (known as GLP-1RAs), a class of drugs used to treat diabetes and obesity. Ozempic, Wegovy, Mounjaro, and Zepbound, which have become well-known recently because they are linked to rapid weight loss, contain GLP-1RAs.

For the study, they looked at electronic health records of 1.7 million patients who had type 2 diabetes, no prior diagnosis of obesity-related cancers, and had been prescribed GLP-1RAs, insulins, or metformin from March 2005 to November 2018.

The scientists found that compared to patients who took insulin, people who took GLP-1RAs had a “significant risk reduction” in 10 of 13 obesity-related cancers. Those 10 cancers were esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma.

Compared with patients taking insulin, patients taking GLP-1RAs showed no statistically significant reduction in stomach cancer and no reduced risk of breast and thyroid cancers, the study said.

But the study found no decrease in cancer risk with GLP-1RAs compared with metformin.

While the study results suggest that these drugs may reduce the risk of certain obesity-related cancers better than insulins, more research is needed, they said.

A version of this article appeared on WebMD.com.

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.

Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.

The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,

In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.

Metformin in Fathers

Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.

The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.

“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

A version of this article first appeared on Medscape.com.

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

A version of this article first appeared on Medscape.com.

BOSTON — Men who stop using performance-enhancing anabolic-androgenic steroids (AAS) experience significant depression, anxiety, and diminished sexual function within the first year after quitting, new research found.

The data suggest that monitoring these men and, pending clinical trial evidence, intervening to minimize these effects could help prevent recidivism, Bonnie Grant, MBBS, a clinical research fellow at Imperial College London, London, England, told this news organization.

“Nothing has actually been studied in proper randomized controlled trials … but I think there’s going to be a role for medicine alongside psychological treatment … Clinicians often see men who have stopped [taking steroids] who report feeling low in mood … a lot of these men will just restart taking them again,” she said.

Anabolic steroids taken exogenously suppress the hypothalamic-pituitary-gonadal system, thereby suppressing endogenous testosterone secretion. While AAS do enhance muscle-building, they can also lead to enlarged hearts, hypertension, and infertility. Most of these are reversible if the man stops taking the AAS.

However, after stopping, the testosterone levels can take up to a year to return to normal. During that time, the man can experience symptoms including low libido, erectile dysfunction, low mood, and fatigue. This leads to a dependence syndrome in about 30%. About 65% of men who stop taking anabolic steroids will restart taking them within the first year, Dr. Grant said in presenting her findings at the annual meeting of the Endocrine Society.

Asked to comment, session moderator Frances Hayes, MBBCh, associate clinical chief of the Division of Reproductive Endocrinology at Massachusetts General Hospital, Boston, said, “One question is, if you intervene with an antidepressant, will that prevent the people from relapsing and going back to using? I think that’s certainly something that would need to be explored and tested.”

Dr. Hayes also noted that fertility problems may lead some men to decide to stop using the steroids. “That can be a strong motivator. If you have a motivated patient, then you add in an antidepressant or anxiolytic or link the patients with mental health services. I think that would definitely be beneficial and definitely something we need to address and see if it is worthwhile doing.”

Dr. Grant presented data from her group’s cross-sectional, observational study. Of a total 245 men, 116 were current AAS users, 84 were previous AAS users who had quit within the past year, and 45 had never used them. All completed extensive questionnaires about their substance use, mood, sexual function, and anxiety. They had morning blood tests, and urine samples were taken for toxicology testing.

The three groups didn’t differ by age (most were in their mid-30s) or ethnicity (most were White). However, the proportion who self-reported psychiatric diagnoses (mostly depression or anxiety) was significantly higher among both the current (29%) and past (25%) AAS users than among the never users (6.6%), with P = .0094.

Dr. Hayes commented, “One of the drawbacks of this study was they didn’t have baseline data. But it would make sense, I think, that the incidence of depression and anxiety was higher in the people who went on to use anabolic steroids.”

Use of other illicit drugs — mostly cocaine and cannabis — was also higher among the past (40.5%) and current (47.4%) AAS users than among the nonusers (17.7%), P = .0025.

Not surprisingly, total testosterone levels were much higher in current AAS users (62.8 nmol/L) than in past users (20.1 nmol/L) and nonusers (20.0 nmol/L), P < .001. Levels of luteinizing hormone (LH), follicle-stimulating hormone, and sex hormone-binding globulin were significantly lower in the current AAS users than in the other two groups, while estradiol levels were significantly higher (all P < .001).

There were no differences in total testosterone between the never users and previous users. However, about 25% of the men who stopped continued to have lower-than-normal testosterone levels, Dr. Grant noted.

Depression scores, as assessed by the Beck Depression Inventory-II, were highest in men who stopped using AAS, and lowest in the never users. Moderate to severe depression was present in 20% of the men who stopped using AAS, 6% of current users, and none of the nonusers.

In multivariable analysis, having a prior psychiatric diagnosis increased the risk for current depression on the Beck inventory by twofold in the current AAS users (P = .001) and threefold in the past users (P < .001). “Interestingly, testosterone levels were not associated with depression,” she noted.

Sexual function, as measured by the International Index of Erectile Function (IIEF) 15, was significantly worse among those who had stopped using AAS compared with current users and nonusers (P = .023). At the same time, total testosterone levels were only weakly correlated with IIEF scores.

In multivariate analysis, higher LH levels were associated with worse sexual function (P = .01).

Anxiety, as measured by the General Anxiety Disorder-7 assessment, was higher in previous users than in never users. Overall, 12% of the previous users had moderate or severe anxiety vs just 2% of nonusers.

The next step in the research will be to examine the urine toxicology for AAS and other illicit substances, Dr. Grant said.

“We’re hoping this information will allow for future studies to be developed to design treatments, which will help millions of men worldwide to stop and stay off anabolic steroids,” she concluded.

Dr. Grant and Dr. Hayes had no disclosures.

A version of this article first appeared on Medscape.com.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

USPSTF

University of Chicago Medicine

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

USPSTF

University of Chicago Medicine

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

USPSTF

University of Chicago Medicine

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest. 

In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.

“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization. 

There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.

 

Are Milder Cases the Ones Being Missed?

Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”

She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.” 

She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.” 

However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
 

Is Wisconsin Representative of Cushing Everywhere?

Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%. 

The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded. 

A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said. 

However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said. 

Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders. 

On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted. 

Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded. 

Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures. 
 

A version of this article appeared on Medscape.com.

BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest. 

In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.

“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization. 

There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.

 

Are Milder Cases the Ones Being Missed?

Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”

She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.” 

She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.” 

However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
 

Is Wisconsin Representative of Cushing Everywhere?

Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%. 

The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded. 

A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said. 

However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said. 

Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders. 

On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted. 

Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded. 

Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures. 
 

A version of this article appeared on Medscape.com.

BOSTON — The prevalence of Cushing syndrome (CS) in the United States may be considerably higher than currently appreciated, new data from a single US institution suggest. 

In contrast to estimates of 1 to 3 cases per million patient-years from population-based European studies, researchers at the University of Wisconsin, Milwaukee, estimated that the incidence of CS in Wisconsin is a minimum of 7.2 cases per million patient-years. What’s more, contrary to all previous studies, they found that adrenal Cushing syndrome was more common than pituitary adrenocorticotropic hormone (ACTH)–secreting tumors (Cushing disease), and that fewer than half of individuals with adrenal Cushing syndrome had classic physical features of hypercortisolism, such as weight gain, round face, excessive hair growth, and stretch marks.

“Cases are absolutely being missed. ... Clinicians should realize that cortisol excess is not rare. It may not be common, but it needs to be considered in patients with any constellation of features that are seen in cortisol excess,” study investigator Ty B. Carroll, MD, associate professor of medicine, endocrinology and molecular medicine, and the endocrine fellowship program director at Medical College of Wisconsin in Milwaukee, told this news organization. 

There are several contributing factors, he noted, “including the obesity and diabetes epidemics which make some clinical features of cortisol excess more common and less notable. Providers get used to seeing patients with some features of cortisol excess and don’t think to screen. The consequence of this is more difficult-to-control diabetes and hypertension, more advance metabolic bone disease, and likely more advanced cardiovascular disease, all resulting from extended exposure to cortisol excess,” he said.

 

Are Milder Cases the Ones Being Missed?

Asked to comment, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University College of Physicians and Surgeons, New York City, said, “When we talk about Cushing [syndrome], we usually think of pituitary ACTH as more [common], followed by adrenal adenomas, and then ectopic. But they’re seeing more adrenal adenoma ... we are probably diagnosing this a little more now.”

She also suggested that the Wisconsin group may have a lower threshold for diagnosing the milder cortisol elevation seen with adrenal Cushing syndrome. “If you screen for Cushing with a dexamethasone suppression test … [i]f you have autonomous secretion by the adrenal, you don’t suppress as much. ... When you measure 24-hour urinary cortisol, it may be normal. So you’re in this in-between [state]. ... Maybe in Wisconsin they’re diagnosing it more. Or, maybe it’s just being underdiagnosed in other places.” 

She also pointed out that “you can’t diagnose it unless you think of it. I’m not so sure that with these mild cases it’s so much that it’s more common, but maybe it’s like thyroid nodules, where we didn’t know about it until everybody started getting all of these CT scans. We’re now seeing all these incidental thyroid nodules ... I don’t think we’re missing florid Cushing.” 

However, Dr. Wardlaw said, it’s probably worthwhile to detect even milder hypercortisolism because it could still have long-term damaging effects, including osteoporosis, muscle weakness, glucose intolerance, and frailty. “You could do something about it and normalize it if you found it. I think that would be the reason to do it.”
 

Is Wisconsin Representative of Cushing Everywhere?

Dr. Carroll presented the findings at the annual meeting of the Endocrine Society. He began by noting that most of the previous CS incidence studies, with estimates of 1.2-3.2 cases per million per year, come from European data published from 1994 to 2019 and collected as far back as 1955. The method of acquisition of patients and the definitions of confirmed cases varied widely in those studies, which reported CS etiologies of ACTH-secreting neoplasms (pituitary or ectopic) in 75%-85% and adrenal-dependent cortisol excess in 15%-20%. 

The current study included data from clinic records between May 1, 2017, and December 31, 2022, of Wisconsin residents newly diagnosed with and treated for CS. The CS diagnosis was established with standard guideline-supported biochemical testing and appropriate imaging. Patients with exogenous and non-neoplastic hypercortisolism and those who did not receive therapy for CS were excluded. 

A total of 185 patients (73% female, 27% male) were identified from 27 of the total 72 counties in Wisconsin, representing a population of 4.5 million. On the basis of the total 5.9 million population of Wisconsin, the incidence of CS in the state works out to 7.2 cases per million population per year, Dr. Carroll said. 

However, data from the Wisconsin Hospital Association show that the University of Wisconsin’s Milwaukee facility treated just about half of patients in the state who are discharged from the hospital with a diagnosis of CS during 2019-2023. “So ... that means that an actual or approximate incidence of 14-15 cases per million per year rather than the 7.2 cases that we produce,” he said. 

Etiologies were 60% adrenal (111 patients), 36.8% pituitary (68 patients), and 3.2% ectopic (6 patients). Those proportions were similar between genders. 

On biochemical testing, values for late-night salivary cortisol, dexamethasone suppression, and urinary free cortisol were highest for the ectopic group (3.189 µg/dL, 42.5 µg/dL, and 1514.2 µg/24 h, respectively) and lowest for the adrenal group (0.236 µg/dL, 6.5 µg/dL, and 64.2 µg/24 h, respectively). All differences between groups were highly statistically significant, at P < .0001, Dr. Carroll noted. 

Classic physical features of CS were present in 91% of people with pituitary CS and 100% of those ectopic CS but just 44% of individuals with adrenal CS. “We found that adrenal-dependent disease was the most common form of Cushing syndrome. It frequently presented without classic physical features that may be due to the milder biochemical presentation,” he concluded. 

Dr. Carroll reported consulting and investigator fees from Corcept Therapeutics. Dr. Wardlaw has no disclosures. 
 

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

BOSTON — Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrenal insufficiency (AI). 

Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.

The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.

The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.

“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.

And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.

In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”

But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”

The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”

Twelve Patients Seen During 2022-2023

The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.

Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.

Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).

Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.

Dr. Wei and Dr. Wardlaw had no disclosures.

A version of this article appeared on Medscape.com.

BOSTON — Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrenal insufficiency (AI). 

Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.

The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.

The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.

“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.

And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.

In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”

But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”

The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”

Twelve Patients Seen During 2022-2023

The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.

Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.

Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).

Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.

Dr. Wei and Dr. Wardlaw had no disclosures.

A version of this article appeared on Medscape.com.

BOSTON — Use of over-the-counter arthritis supplements containing undisclosed glucocorticoids can lead to iatrogenic adrenal dysfunction, Cushing syndrome, and/or adrenal insufficiency (AI). 

Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.

The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.

The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.

“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.

And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.

In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”

But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”

The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”

Twelve Patients Seen During 2022-2023

The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.

Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.

Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).

Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.

Dr. Wei and Dr. Wardlaw had no disclosures.

A version of this article appeared on Medscape.com.