Miriam E. Tucker

WASHINGTON — Elderly adults with subclinical hypothyroidism and a thyroid-stimulating hormone level at or above 7 mIU/L are at increased risk for heart failure, Nicolas Rodondi, M.D., reported at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

However, adults aged 70–79 with subclinical hypothyroidism with thyroid-stimulating hormone values below 7 mIU/L are not at increased risk for heart failure. Subclinical hypothyroidism does not appear to be associated with other cardiovascular events in that age group, regardless of thyroid-stimulating hormone level, said Dr. Rodondi of the University of California, San Francisco.

Previous studies have shown that subclinical hypothyroidism—in which T₄ is normal but thyroid-stimulating hormone is elevated (4.5 mIU/L or above)—is associated with elevated total cholesterol, LDL cholesterol, and C-reactive protein. But data on cardiovascular outcomes are conflicting, he noted at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The current study included 2,740 men and women aged 70–79 years who were participating in the Health, Aging, and Body Composition Study, funded by the National Institute on Aging. Subjects with abnormal T₄ levels or thyroid-stimulating hormone levels at or below 0.1 mIU/L had been previously excluded.

The 339 individuals who had subclinical hypothyroidism at baseline were less likely than the 2,401 euthyroid subjects to be black (25.4% vs. 41.8%), but did not differ significantly by age or gender. At baseline, total cholesterol was significantly higher among those with subclinical hypothyroidism (211.5 vs. 204.5 mg/dL). About 30% of both groups had prevalent cardiovascular disease at baseline, while 8.3% of the subclinical hypothyroid and 6.2% of the euthyroid groups had preexisting heart failure.

The cardiovascular events that occurred during the 4 years of follow-up included 336 coronary heart disease cases (including 98 myocardial infarctions), 154 strokes, 83 peripheral arterial disease cases, and 183 instances of congestive heart failure.

Rates of heart failure were 16.9 per 1,000 person-years in the euthyroid group, compared with 21.9/1,000 person-years in the subclinical hypothyroid group.

Among subjects who had thyroid-stimulating hormone levels of 10 mIU/L or greater, the mean rate of heart failure was 36.9/1,000 person-years, with a hazard ratio of 3.10 after adjustment for demographics, socioeconomic characteristics, thyroid hormone use, cardiovascular risk factors, and prevalent cardiovascular disease.

For those with thyroid-stimulating hormone of 7–9.9 mIU/L, the rate was 37.4/1,000 person-years and the adjusted hazard ratio 2.88.

The heart failure rate among subjects with thyroid-stimulating hormone levels of 4.5–6.9 mIU/L was 14.8/1,000 person-years, not significantly different from the euthyroid group, and none of the subclinical hypothyroid group had significantly elevated rates of coronary heart disease, stroke, peripheral artery disease, or mortality.

Among the 2,558 subjects without heart failure at baseline, the hazard ratio for developing heart failure during the 4-year follow-up among those with thyroid-stimulating hormone at or above 7 mIU/L was 2.49, compared with those who were euthyroid.

Among the 182 who already had heart failure at baseline, the risk for recurrent heart failure was even greater, with a hazard ratio of 7.62.

It remains to be determined whether subclinical hypothyroidism causes or worsens preexisting heart failure. Since the association was stronger for recurrent heart failure events, further investigation that incorporates echocardiography is warranted, Dr. Rodondi told this newspaper.

WASHINGTON — Elderly adults with subclinical hypothyroidism and a thyroid-stimulating hormone level at or above 7 mIU/L are at increased risk for heart failure, Nicolas Rodondi, M.D., reported at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

However, adults aged 70–79 with subclinical hypothyroidism with thyroid-stimulating hormone values below 7 mIU/L are not at increased risk for heart failure. Subclinical hypothyroidism does not appear to be associated with other cardiovascular events in that age group, regardless of thyroid-stimulating hormone level, said Dr. Rodondi of the University of California, San Francisco.

Previous studies have shown that subclinical hypothyroidism—in which T₄ is normal but thyroid-stimulating hormone is elevated (4.5 mIU/L or above)—is associated with elevated total cholesterol, LDL cholesterol, and C-reactive protein. But data on cardiovascular outcomes are conflicting, he noted at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The current study included 2,740 men and women aged 70–79 years who were participating in the Health, Aging, and Body Composition Study, funded by the National Institute on Aging. Subjects with abnormal T₄ levels or thyroid-stimulating hormone levels at or below 0.1 mIU/L had been previously excluded.

The 339 individuals who had subclinical hypothyroidism at baseline were less likely than the 2,401 euthyroid subjects to be black (25.4% vs. 41.8%), but did not differ significantly by age or gender. At baseline, total cholesterol was significantly higher among those with subclinical hypothyroidism (211.5 vs. 204.5 mg/dL). About 30% of both groups had prevalent cardiovascular disease at baseline, while 8.3% of the subclinical hypothyroid and 6.2% of the euthyroid groups had preexisting heart failure.

The cardiovascular events that occurred during the 4 years of follow-up included 336 coronary heart disease cases (including 98 myocardial infarctions), 154 strokes, 83 peripheral arterial disease cases, and 183 instances of congestive heart failure.

Rates of heart failure were 16.9 per 1,000 person-years in the euthyroid group, compared with 21.9/1,000 person-years in the subclinical hypothyroid group.

Among subjects who had thyroid-stimulating hormone levels of 10 mIU/L or greater, the mean rate of heart failure was 36.9/1,000 person-years, with a hazard ratio of 3.10 after adjustment for demographics, socioeconomic characteristics, thyroid hormone use, cardiovascular risk factors, and prevalent cardiovascular disease.

For those with thyroid-stimulating hormone of 7–9.9 mIU/L, the rate was 37.4/1,000 person-years and the adjusted hazard ratio 2.88.

The heart failure rate among subjects with thyroid-stimulating hormone levels of 4.5–6.9 mIU/L was 14.8/1,000 person-years, not significantly different from the euthyroid group, and none of the subclinical hypothyroid group had significantly elevated rates of coronary heart disease, stroke, peripheral artery disease, or mortality.

Among the 2,558 subjects without heart failure at baseline, the hazard ratio for developing heart failure during the 4-year follow-up among those with thyroid-stimulating hormone at or above 7 mIU/L was 2.49, compared with those who were euthyroid.

Among the 182 who already had heart failure at baseline, the risk for recurrent heart failure was even greater, with a hazard ratio of 7.62.

It remains to be determined whether subclinical hypothyroidism causes or worsens preexisting heart failure. Since the association was stronger for recurrent heart failure events, further investigation that incorporates echocardiography is warranted, Dr. Rodondi told this newspaper.

WASHINGTON — Elderly adults with subclinical hypothyroidism and a thyroid-stimulating hormone level at or above 7 mIU/L are at increased risk for heart failure, Nicolas Rodondi, M.D., reported at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

However, adults aged 70–79 with subclinical hypothyroidism with thyroid-stimulating hormone values below 7 mIU/L are not at increased risk for heart failure. Subclinical hypothyroidism does not appear to be associated with other cardiovascular events in that age group, regardless of thyroid-stimulating hormone level, said Dr. Rodondi of the University of California, San Francisco.

Previous studies have shown that subclinical hypothyroidism—in which T₄ is normal but thyroid-stimulating hormone is elevated (4.5 mIU/L or above)—is associated with elevated total cholesterol, LDL cholesterol, and C-reactive protein. But data on cardiovascular outcomes are conflicting, he noted at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The current study included 2,740 men and women aged 70–79 years who were participating in the Health, Aging, and Body Composition Study, funded by the National Institute on Aging. Subjects with abnormal T₄ levels or thyroid-stimulating hormone levels at or below 0.1 mIU/L had been previously excluded.

The 339 individuals who had subclinical hypothyroidism at baseline were less likely than the 2,401 euthyroid subjects to be black (25.4% vs. 41.8%), but did not differ significantly by age or gender. At baseline, total cholesterol was significantly higher among those with subclinical hypothyroidism (211.5 vs. 204.5 mg/dL). About 30% of both groups had prevalent cardiovascular disease at baseline, while 8.3% of the subclinical hypothyroid and 6.2% of the euthyroid groups had preexisting heart failure.

The cardiovascular events that occurred during the 4 years of follow-up included 336 coronary heart disease cases (including 98 myocardial infarctions), 154 strokes, 83 peripheral arterial disease cases, and 183 instances of congestive heart failure.

Rates of heart failure were 16.9 per 1,000 person-years in the euthyroid group, compared with 21.9/1,000 person-years in the subclinical hypothyroid group.

Among subjects who had thyroid-stimulating hormone levels of 10 mIU/L or greater, the mean rate of heart failure was 36.9/1,000 person-years, with a hazard ratio of 3.10 after adjustment for demographics, socioeconomic characteristics, thyroid hormone use, cardiovascular risk factors, and prevalent cardiovascular disease.

For those with thyroid-stimulating hormone of 7–9.9 mIU/L, the rate was 37.4/1,000 person-years and the adjusted hazard ratio 2.88.

The heart failure rate among subjects with thyroid-stimulating hormone levels of 4.5–6.9 mIU/L was 14.8/1,000 person-years, not significantly different from the euthyroid group, and none of the subclinical hypothyroid group had significantly elevated rates of coronary heart disease, stroke, peripheral artery disease, or mortality.

Among the 2,558 subjects without heart failure at baseline, the hazard ratio for developing heart failure during the 4-year follow-up among those with thyroid-stimulating hormone at or above 7 mIU/L was 2.49, compared with those who were euthyroid.

Among the 182 who already had heart failure at baseline, the risk for recurrent heart failure was even greater, with a hazard ratio of 7.62.

It remains to be determined whether subclinical hypothyroidism causes or worsens preexisting heart failure. Since the association was stronger for recurrent heart failure events, further investigation that incorporates echocardiography is warranted, Dr. Rodondi told this newspaper.

WASHINGTON — Patients' adherence to warfarin therapy should be monitored on a regular basis and not just at the beginning of therapy, Stephen E. Kimmel, M.D., reported in a poster at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Previous data suggest that about 50% of patient time on warfarin is spent either under- or overcoagulated. Physicians often attribute this to nonadherence, although this has never been rigorously investigated, Dr. Kimmel said at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The prospective cohort study by Dr. Kimmel and his associates at the University of Pennsylvania, Philadelphia, was conducted at three centers (a university hospital, a veteran's hospital, and an anticoagulation clinic). Electronic monitoring devices (microelectrical mechanical systems, or EMS caps) were used to measure the exact time and date each time a pill bottle was opened. Of 145 patients aged 25–85 years who were newly prescribed warfarin, 70% were male, 55% were African American, and 39% were white.

Over 12 months, patients took the correct dose on 78% of the days, took no pills on 19% of days, and took an extra pill on 3% (it was assumed that one pill was taken per bottle opening). There were no significant differences in adherence behavior by age, race, or clinic site. However, men were more likely than women to be overadherent, they reported.

Patient adherence waned over the first 6 months, from 83% in month 1 to 76% in month 3 to 73% in month 6. After that, however, adherence rebounded up to 78% at month 9 and 82% by 1 year. This may be due to a dropout effect, differential adherence by indication, or perhaps differential clinician patterns of patient counseling, the investigators speculated.

Interestingly, the clinicians' ability to discern whether a patient was adherent was only slightly statistically better than chance. Among the patients who took the correct dose on less than 50% of days, 14% had been labeled “adherent” by the clinician.

On the flip side, they labeled as “nonadherent” 81% of patients who took the correct dose on more than 50% of days, and 59% of those who got it right on more than 70% of days.

WASHINGTON — Patients' adherence to warfarin therapy should be monitored on a regular basis and not just at the beginning of therapy, Stephen E. Kimmel, M.D., reported in a poster at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Previous data suggest that about 50% of patient time on warfarin is spent either under- or overcoagulated. Physicians often attribute this to nonadherence, although this has never been rigorously investigated, Dr. Kimmel said at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The prospective cohort study by Dr. Kimmel and his associates at the University of Pennsylvania, Philadelphia, was conducted at three centers (a university hospital, a veteran's hospital, and an anticoagulation clinic). Electronic monitoring devices (microelectrical mechanical systems, or EMS caps) were used to measure the exact time and date each time a pill bottle was opened. Of 145 patients aged 25–85 years who were newly prescribed warfarin, 70% were male, 55% were African American, and 39% were white.

Over 12 months, patients took the correct dose on 78% of the days, took no pills on 19% of days, and took an extra pill on 3% (it was assumed that one pill was taken per bottle opening). There were no significant differences in adherence behavior by age, race, or clinic site. However, men were more likely than women to be overadherent, they reported.

Patient adherence waned over the first 6 months, from 83% in month 1 to 76% in month 3 to 73% in month 6. After that, however, adherence rebounded up to 78% at month 9 and 82% by 1 year. This may be due to a dropout effect, differential adherence by indication, or perhaps differential clinician patterns of patient counseling, the investigators speculated.

Interestingly, the clinicians' ability to discern whether a patient was adherent was only slightly statistically better than chance. Among the patients who took the correct dose on less than 50% of days, 14% had been labeled “adherent” by the clinician.

On the flip side, they labeled as “nonadherent” 81% of patients who took the correct dose on more than 50% of days, and 59% of those who got it right on more than 70% of days.

WASHINGTON — Patients' adherence to warfarin therapy should be monitored on a regular basis and not just at the beginning of therapy, Stephen E. Kimmel, M.D., reported in a poster at a conference on cardiovascular disease epidemiology and prevention sponsored by the American Heart Association.

Previous data suggest that about 50% of patient time on warfarin is spent either under- or overcoagulated. Physicians often attribute this to nonadherence, although this has never been rigorously investigated, Dr. Kimmel said at the conference, also sponsored by the National Heart, Lung, and Blood Institute.

The prospective cohort study by Dr. Kimmel and his associates at the University of Pennsylvania, Philadelphia, was conducted at three centers (a university hospital, a veteran's hospital, and an anticoagulation clinic). Electronic monitoring devices (microelectrical mechanical systems, or EMS caps) were used to measure the exact time and date each time a pill bottle was opened. Of 145 patients aged 25–85 years who were newly prescribed warfarin, 70% were male, 55% were African American, and 39% were white.

Over 12 months, patients took the correct dose on 78% of the days, took no pills on 19% of days, and took an extra pill on 3% (it was assumed that one pill was taken per bottle opening). There were no significant differences in adherence behavior by age, race, or clinic site. However, men were more likely than women to be overadherent, they reported.

Patient adherence waned over the first 6 months, from 83% in month 1 to 76% in month 3 to 73% in month 6. After that, however, adherence rebounded up to 78% at month 9 and 82% by 1 year. This may be due to a dropout effect, differential adherence by indication, or perhaps differential clinician patterns of patient counseling, the investigators speculated.

Interestingly, the clinicians' ability to discern whether a patient was adherent was only slightly statistically better than chance. Among the patients who took the correct dose on less than 50% of days, 14% had been labeled “adherent” by the clinician.

On the flip side, they labeled as “nonadherent” 81% of patients who took the correct dose on more than 50% of days, and 59% of those who got it right on more than 70% of days.

Treatment of gestational diabetes reduces serious perinatal morbidity, Caroline A. Crowther, M.D., of the University of Adelaide (Australia) and her associates reported.

Although the risks associated with gestational diabetes mellitus (GDM) are well recognized, it has been uncertain whether screening and treatment to reduce maternal glucose levels reduces these risks. Given this uncertainty, professional groups disagree on which patients should be screened, the investigators said (N. Engl. J. Med. 2005;352:2477–86).

Now, new investigation findings in favor of screening come from the 18-center Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) in which serious perinatal complications occurred in just 1% of the infants of 490 women with GDM who were randomized to intensive glucose management, compared with 4% of 510 women who received routine care.

In an accompanying editorial, Michael F. Greene, M.D., and Caren G. Solomon, M.D., wrote that “this study provides critical evidence that identifying and treating [GDM] can substantially reduce the risk of adverse perinatal outcomes without, at least in this trial, increasing the rate of cesarean delivery.”

However, Dr. Greene and Dr. Solomon, both on the editorial board of the New England Journal of Medicine, noted that the study leaves unanswered the question of what level of blood glucose warrants routine intervention (N. Engl. J. Med. 2005;352:2544–6).

The study included women with a singleton or twin pregnancy between 16 and 30 weeks' gestation who had at least one risk factor for GDM on selective screening or a positive 50-g oral glucose challenge test, with a 1-hour postchallenge glucose level of at least 140 mg/dL followed by a 75-g oral glucose tolerance test at 24–34 weeks' gestation in which venous plasma glucose was less than 140 mg/dL after an overnight fast and 140–198 mg/dL at 2 hours.

When the study began, these women had been classified as having glucose intolerance of pregnancy by the World Health Organization, but during the course of the study (in 1998) WHO began classifying any glucose level above normal as being GDM. Women whose glucose values exceeded these cutoffs were not included in the study.

The women randomized to intensive intervention were informed of their diagnosis. They received dietary counseling and were taught how to perform self-blood glucose monitoring, with targets of no more than 99 mg/dL premeal and 126 mg/dL 2 hours after eating. Twenty percent received insulin therapy. The women randomized to routine care were told they did not have GDM, according to Dr. Crowther and her associates.

Serious perinatal outcomes, including death, shoulder dystocia, bone fracture, and nerve palsy, occurred in 1% of the intervention group vs. 4% of the routine care group after adjustment for maternal age, race/ethnicity, and parity. Thus, 34 mothers would need to be treated to prevent one serious outcome in an infant, they said.

Women in the intervention group were significantly more likely to have induction of labor (39% vs. 29%), but the rates of cesarean delivery were similar (31% vs. 32%), as were the reasons for it. Infants in the intervention group also had fewer admissions to the neonatal nursery (71% vs. 61%). At 3 months' post partum, fewer women in the intervention group had a score on the Edinburgh Postnatal Depression Scale suggestive of depression (8% vs. 17%); anxiety scores were similar.

Among the secondary outcomes, there were no perinatal deaths among the infants from the intervention group, but three stillbirths and two neonatal deaths occurred among infants in the routine care group. There were no differences in the rates of shoulder dystocia between the two groups. No bone fractures or nerve palsies occurred in the intervention group; the routine care group had one of the former and three of the latter.

Birth weights were significantly lower among the infants born to women in the intervention group (3,335 g vs. 3,482 g), and they were also born at an earlier gestational age, which makes sense given their higher rate of induction of labor. Significantly fewer infants in the intervention group were large for gestational age (13% vs. 22%), and fewer had macrosomia, defined by a birth weight of 4 kg or greater (10% vs. 21%).

Women in the intervention group made fewer prenatal clinic visits after enrollment than did the routine care group, but they made more visits to the physician. Weight gain was less in the intervention group, and fewer women were diagnosed with preeclampsia. The rates of prenatal hospital admissions were similar.

Dr. Greene and Dr. Solomon agreed with the authors' justification for having randomized one group of women to no treatment—that before this study there were no conclusive data regarding the effects of treating GDM, even after the WHO definition was revised.

Treatment of gestational diabetes reduces serious perinatal morbidity, Caroline A. Crowther, M.D., of the University of Adelaide (Australia) and her associates reported.

Although the risks associated with gestational diabetes mellitus (GDM) are well recognized, it has been uncertain whether screening and treatment to reduce maternal glucose levels reduces these risks. Given this uncertainty, professional groups disagree on which patients should be screened, the investigators said (N. Engl. J. Med. 2005;352:2477–86).

Now, new investigation findings in favor of screening come from the 18-center Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) in which serious perinatal complications occurred in just 1% of the infants of 490 women with GDM who were randomized to intensive glucose management, compared with 4% of 510 women who received routine care.

In an accompanying editorial, Michael F. Greene, M.D., and Caren G. Solomon, M.D., wrote that “this study provides critical evidence that identifying and treating [GDM] can substantially reduce the risk of adverse perinatal outcomes without, at least in this trial, increasing the rate of cesarean delivery.”

However, Dr. Greene and Dr. Solomon, both on the editorial board of the New England Journal of Medicine, noted that the study leaves unanswered the question of what level of blood glucose warrants routine intervention (N. Engl. J. Med. 2005;352:2544–6).

The study included women with a singleton or twin pregnancy between 16 and 30 weeks' gestation who had at least one risk factor for GDM on selective screening or a positive 50-g oral glucose challenge test, with a 1-hour postchallenge glucose level of at least 140 mg/dL followed by a 75-g oral glucose tolerance test at 24–34 weeks' gestation in which venous plasma glucose was less than 140 mg/dL after an overnight fast and 140–198 mg/dL at 2 hours.

When the study began, these women had been classified as having glucose intolerance of pregnancy by the World Health Organization, but during the course of the study (in 1998) WHO began classifying any glucose level above normal as being GDM. Women whose glucose values exceeded these cutoffs were not included in the study.

The women randomized to intensive intervention were informed of their diagnosis. They received dietary counseling and were taught how to perform self-blood glucose monitoring, with targets of no more than 99 mg/dL premeal and 126 mg/dL 2 hours after eating. Twenty percent received insulin therapy. The women randomized to routine care were told they did not have GDM, according to Dr. Crowther and her associates.

Serious perinatal outcomes, including death, shoulder dystocia, bone fracture, and nerve palsy, occurred in 1% of the intervention group vs. 4% of the routine care group after adjustment for maternal age, race/ethnicity, and parity. Thus, 34 mothers would need to be treated to prevent one serious outcome in an infant, they said.

Women in the intervention group were significantly more likely to have induction of labor (39% vs. 29%), but the rates of cesarean delivery were similar (31% vs. 32%), as were the reasons for it. Infants in the intervention group also had fewer admissions to the neonatal nursery (71% vs. 61%). At 3 months' post partum, fewer women in the intervention group had a score on the Edinburgh Postnatal Depression Scale suggestive of depression (8% vs. 17%); anxiety scores were similar.

Among the secondary outcomes, there were no perinatal deaths among the infants from the intervention group, but three stillbirths and two neonatal deaths occurred among infants in the routine care group. There were no differences in the rates of shoulder dystocia between the two groups. No bone fractures or nerve palsies occurred in the intervention group; the routine care group had one of the former and three of the latter.

Birth weights were significantly lower among the infants born to women in the intervention group (3,335 g vs. 3,482 g), and they were also born at an earlier gestational age, which makes sense given their higher rate of induction of labor. Significantly fewer infants in the intervention group were large for gestational age (13% vs. 22%), and fewer had macrosomia, defined by a birth weight of 4 kg or greater (10% vs. 21%).

Women in the intervention group made fewer prenatal clinic visits after enrollment than did the routine care group, but they made more visits to the physician. Weight gain was less in the intervention group, and fewer women were diagnosed with preeclampsia. The rates of prenatal hospital admissions were similar.

Dr. Greene and Dr. Solomon agreed with the authors' justification for having randomized one group of women to no treatment—that before this study there were no conclusive data regarding the effects of treating GDM, even after the WHO definition was revised.

Treatment of gestational diabetes reduces serious perinatal morbidity, Caroline A. Crowther, M.D., of the University of Adelaide (Australia) and her associates reported.

Although the risks associated with gestational diabetes mellitus (GDM) are well recognized, it has been uncertain whether screening and treatment to reduce maternal glucose levels reduces these risks. Given this uncertainty, professional groups disagree on which patients should be screened, the investigators said (N. Engl. J. Med. 2005;352:2477–86).

Now, new investigation findings in favor of screening come from the 18-center Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) in which serious perinatal complications occurred in just 1% of the infants of 490 women with GDM who were randomized to intensive glucose management, compared with 4% of 510 women who received routine care.

In an accompanying editorial, Michael F. Greene, M.D., and Caren G. Solomon, M.D., wrote that “this study provides critical evidence that identifying and treating [GDM] can substantially reduce the risk of adverse perinatal outcomes without, at least in this trial, increasing the rate of cesarean delivery.”

However, Dr. Greene and Dr. Solomon, both on the editorial board of the New England Journal of Medicine, noted that the study leaves unanswered the question of what level of blood glucose warrants routine intervention (N. Engl. J. Med. 2005;352:2544–6).

The study included women with a singleton or twin pregnancy between 16 and 30 weeks' gestation who had at least one risk factor for GDM on selective screening or a positive 50-g oral glucose challenge test, with a 1-hour postchallenge glucose level of at least 140 mg/dL followed by a 75-g oral glucose tolerance test at 24–34 weeks' gestation in which venous plasma glucose was less than 140 mg/dL after an overnight fast and 140–198 mg/dL at 2 hours.

When the study began, these women had been classified as having glucose intolerance of pregnancy by the World Health Organization, but during the course of the study (in 1998) WHO began classifying any glucose level above normal as being GDM. Women whose glucose values exceeded these cutoffs were not included in the study.

The women randomized to intensive intervention were informed of their diagnosis. They received dietary counseling and were taught how to perform self-blood glucose monitoring, with targets of no more than 99 mg/dL premeal and 126 mg/dL 2 hours after eating. Twenty percent received insulin therapy. The women randomized to routine care were told they did not have GDM, according to Dr. Crowther and her associates.

Serious perinatal outcomes, including death, shoulder dystocia, bone fracture, and nerve palsy, occurred in 1% of the intervention group vs. 4% of the routine care group after adjustment for maternal age, race/ethnicity, and parity. Thus, 34 mothers would need to be treated to prevent one serious outcome in an infant, they said.

Women in the intervention group were significantly more likely to have induction of labor (39% vs. 29%), but the rates of cesarean delivery were similar (31% vs. 32%), as were the reasons for it. Infants in the intervention group also had fewer admissions to the neonatal nursery (71% vs. 61%). At 3 months' post partum, fewer women in the intervention group had a score on the Edinburgh Postnatal Depression Scale suggestive of depression (8% vs. 17%); anxiety scores were similar.

Among the secondary outcomes, there were no perinatal deaths among the infants from the intervention group, but three stillbirths and two neonatal deaths occurred among infants in the routine care group. There were no differences in the rates of shoulder dystocia between the two groups. No bone fractures or nerve palsies occurred in the intervention group; the routine care group had one of the former and three of the latter.

Birth weights were significantly lower among the infants born to women in the intervention group (3,335 g vs. 3,482 g), and they were also born at an earlier gestational age, which makes sense given their higher rate of induction of labor. Significantly fewer infants in the intervention group were large for gestational age (13% vs. 22%), and fewer had macrosomia, defined by a birth weight of 4 kg or greater (10% vs. 21%).

Women in the intervention group made fewer prenatal clinic visits after enrollment than did the routine care group, but they made more visits to the physician. Weight gain was less in the intervention group, and fewer women were diagnosed with preeclampsia. The rates of prenatal hospital admissions were similar.

Dr. Greene and Dr. Solomon agreed with the authors' justification for having randomized one group of women to no treatment—that before this study there were no conclusive data regarding the effects of treating GDM, even after the WHO definition was revised.

SAN DIEGO — Weight gain in the 5 years before pregnancy is associated with an increased risk for gestational diabetes, Monique Hedderson reported in a poster at the annual scientific sessions of the American Diabetes Association.

In a nested case-control study including 114 women with gestational diabetes mellitus (GDM) and 95 controls who were members of Kaiser Permanente of Northern California, those who had gained between 1 kg and 10 kg in the 5 years before their last menstrual period were nearly twice as likely (crude odds ratio 1.98) to have developed GDM during pregnancy than were those whose weight remained within 1 kg of baseline. Those who had lost 1.1–8.3 kg had an insignificantly lower unadjusted risk for GDM (0.79), said Ms. Hedderson, of Kaiser Permanente, Oakland, Calif., and her associates.

The women who developed GDM were older, more likely to be from an ethnic minority group, more likely to be overweight at baseline, and more likely to be primiparous or to have had at least two prior live births. After adjustment for these factors, the relationship between prepregnancy weight gain and GDM was even stronger, with an odds ratio of 2.58. The relationship with weight loss was again insignificant (OR 0.9).

SAN DIEGO — Weight gain in the 5 years before pregnancy is associated with an increased risk for gestational diabetes, Monique Hedderson reported in a poster at the annual scientific sessions of the American Diabetes Association.

In a nested case-control study including 114 women with gestational diabetes mellitus (GDM) and 95 controls who were members of Kaiser Permanente of Northern California, those who had gained between 1 kg and 10 kg in the 5 years before their last menstrual period were nearly twice as likely (crude odds ratio 1.98) to have developed GDM during pregnancy than were those whose weight remained within 1 kg of baseline. Those who had lost 1.1–8.3 kg had an insignificantly lower unadjusted risk for GDM (0.79), said Ms. Hedderson, of Kaiser Permanente, Oakland, Calif., and her associates.

The women who developed GDM were older, more likely to be from an ethnic minority group, more likely to be overweight at baseline, and more likely to be primiparous or to have had at least two prior live births. After adjustment for these factors, the relationship between prepregnancy weight gain and GDM was even stronger, with an odds ratio of 2.58. The relationship with weight loss was again insignificant (OR 0.9).

SAN DIEGO — Weight gain in the 5 years before pregnancy is associated with an increased risk for gestational diabetes, Monique Hedderson reported in a poster at the annual scientific sessions of the American Diabetes Association.

In a nested case-control study including 114 women with gestational diabetes mellitus (GDM) and 95 controls who were members of Kaiser Permanente of Northern California, those who had gained between 1 kg and 10 kg in the 5 years before their last menstrual period were nearly twice as likely (crude odds ratio 1.98) to have developed GDM during pregnancy than were those whose weight remained within 1 kg of baseline. Those who had lost 1.1–8.3 kg had an insignificantly lower unadjusted risk for GDM (0.79), said Ms. Hedderson, of Kaiser Permanente, Oakland, Calif., and her associates.

The women who developed GDM were older, more likely to be from an ethnic minority group, more likely to be overweight at baseline, and more likely to be primiparous or to have had at least two prior live births. After adjustment for these factors, the relationship between prepregnancy weight gain and GDM was even stronger, with an odds ratio of 2.58. The relationship with weight loss was again insignificant (OR 0.9).

WASHINGTON — Two-thirds of Americans with type 2 diabetes are not meeting the American Association of Clinical Endocrinologists' target hemoglobin A_1c level of 6.5% or less, according to a report issued by the association at its annual meeting.

The AACE's “State of Diabetes in America” report is based in part on data from more than 157,000 individuals with type 2 diabetes from 39 states and the District of Columbia who were tracked by Surveillance Data Inc. (SDI) during 2003–2004. The study was funded by GlaxoSmithKline Inc.

Overall, 67% of patients had HbA_1c levels above 6.5%. The 10 worst states were Mississippi (73%); Illinois (73%); Utah (72%); Ohio (72%); Alabama, Louisiana, New York, and Pennsylvania (all approximately 71%); Arkansas and West Virginia (both approximately 70%); and Georgia (69%). Even in the best state, Montana, 55% did not meet the AACE target.

In 11 additional states in which SDI data were not available, the National Committee for Quality Assurance's Health Employer Data and Information Set (HEDIS) were used instead, showing the proportion of patients with HbA_1c levels above 9%. Of those, California was the worst, with 35% of patients having HbA_1c values that high. The next four were Hawaii (33%), and North Dakota, Rhode Island, and Massachusetts (all approximately 30%). New Hampshire scored the “best,” at 20%.

The AACE has launched a public awareness campaign encouraging patients to take an “oath” to better control their blood sugar levels. To take the oath and order items such as a diabetes-friendly cookbook, patients can go to www.stateofdiabetes.com

WASHINGTON — Two-thirds of Americans with type 2 diabetes are not meeting the American Association of Clinical Endocrinologists' target hemoglobin A_1c level of 6.5% or less, according to a report issued by the association at its annual meeting.

The AACE's “State of Diabetes in America” report is based in part on data from more than 157,000 individuals with type 2 diabetes from 39 states and the District of Columbia who were tracked by Surveillance Data Inc. (SDI) during 2003–2004. The study was funded by GlaxoSmithKline Inc.

Overall, 67% of patients had HbA_1c levels above 6.5%. The 10 worst states were Mississippi (73%); Illinois (73%); Utah (72%); Ohio (72%); Alabama, Louisiana, New York, and Pennsylvania (all approximately 71%); Arkansas and West Virginia (both approximately 70%); and Georgia (69%). Even in the best state, Montana, 55% did not meet the AACE target.

In 11 additional states in which SDI data were not available, the National Committee for Quality Assurance's Health Employer Data and Information Set (HEDIS) were used instead, showing the proportion of patients with HbA_1c levels above 9%. Of those, California was the worst, with 35% of patients having HbA_1c values that high. The next four were Hawaii (33%), and North Dakota, Rhode Island, and Massachusetts (all approximately 30%). New Hampshire scored the “best,” at 20%.

The AACE has launched a public awareness campaign encouraging patients to take an “oath” to better control their blood sugar levels. To take the oath and order items such as a diabetes-friendly cookbook, patients can go to www.stateofdiabetes.com

WASHINGTON — Two-thirds of Americans with type 2 diabetes are not meeting the American Association of Clinical Endocrinologists' target hemoglobin A_1c level of 6.5% or less, according to a report issued by the association at its annual meeting.

The AACE's “State of Diabetes in America” report is based in part on data from more than 157,000 individuals with type 2 diabetes from 39 states and the District of Columbia who were tracked by Surveillance Data Inc. (SDI) during 2003–2004. The study was funded by GlaxoSmithKline Inc.

Overall, 67% of patients had HbA_1c levels above 6.5%. The 10 worst states were Mississippi (73%); Illinois (73%); Utah (72%); Ohio (72%); Alabama, Louisiana, New York, and Pennsylvania (all approximately 71%); Arkansas and West Virginia (both approximately 70%); and Georgia (69%). Even in the best state, Montana, 55% did not meet the AACE target.

In 11 additional states in which SDI data were not available, the National Committee for Quality Assurance's Health Employer Data and Information Set (HEDIS) were used instead, showing the proportion of patients with HbA_1c levels above 9%. Of those, California was the worst, with 35% of patients having HbA_1c values that high. The next four were Hawaii (33%), and North Dakota, Rhode Island, and Massachusetts (all approximately 30%). New Hampshire scored the “best,” at 20%.

The AACE has launched a public awareness campaign encouraging patients to take an “oath” to better control their blood sugar levels. To take the oath and order items such as a diabetes-friendly cookbook, patients can go to www.stateofdiabetes.com

WASHINGTON — Even in a private subspecialty endocrinology practice, most patients with type 2 diabetes still aren't meeting American Diabetes Association goals for hemoglobin A_1c, blood pressure, and lipids, Pardis Dana, M.D., reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

“Clearly, a need exists for more aggressive, detail-oriented [diabetes] management with use of far more resources and improved patient compliance, along with more efficacious and better-tolerated pharmacologic considerations,” according to Dr. Dana of the Endocrine and Diabetes Center, Vienna and Woodbridge, Va.

In a report published last year that included data from the 1999–2000 National Health and Nutrition Examination Survey (NHANES), only 7% of 441 study participants with type 2 diabetes met all three goals: hemoglobin A_1c below 7%, blood pressure below 130/80 mm Hg, and total cholesterol below 200 mg/dL (JAMA 2004;291:335–42).

Dr. Dana and his associates retrospectively compared outcomes for 334 of their own type 2 diabetic patients with those of the NHANES study, as well as with the American Diabetes Association's guidelines of HbA_1c below 7%, BP below 130/80 mm Hg, LDL cholesterol below 100 mg/dL, HDL cholesterol of at least 40 mg/dL, and triglycerides below 150 mg/dL.

The 185 men and 149 women had all made at least three visits per year from January 2000 to December 2003. Statistically significant changes that occurred with subspecialty management included reductions of 1.87 percentage points in HbA_1c, 2.56 mm Hg in systolic blood pressure, 29.32 mg/dL total cholesterol, 17.87 mg/dL in LDL cholesterol, and 113.03 mg/dL in triglycerides. Changes in diastolic blood pressure, HDL cholesterol, and BMI were not significant, they reported.

But despite the improvements, only 2% of the patients had achieved all three target goals of the NHANES study at the time of their most recent office visit. For the ADA guidelines, 9% reached all five, 28% reached four, 28% reached three, 22% reached two, 10% reached one, and 3% reached none.

Lack of medication was not the reason: Of the 334 patients, 59% were taking metformin, 40% insulin, 38% thiazolidinediones, 36% sulfonylureas, and 16% nonsulfonylurea secretagogues (8% repaglinide and 8% nateglinide). Of these, monotherapy was used in 25%, two glucose-lowering drugs in 41%, three in 22%, a three-drug regimen plus insulin in 6%, and lifestyle modification in 5%.

As for antihypertensive drugs, 53% were receiving angiotensin-converting enzyme inhibitors, 28% diuretics, 17% angiotensin II receptor blockers, 14% β-adrenergic blocking agents, 12% calcium channel blockers, and 1% α-adrenergic blocking agents. Of these patients, 42% were taking one, 23% two, 8% three, and 3% more than three, while 24% were not taking any antihypertensive drugs.

In the lipid-lowering category, statins were taken by 61%, fibrates by 10%, ezetimibe by 9%, and niacin by 1%. Most (63%) were on monotherapy, while 9% were taking two drugs and 28% weren't taking any, they reported.

WASHINGTON — Even in a private subspecialty endocrinology practice, most patients with type 2 diabetes still aren't meeting American Diabetes Association goals for hemoglobin A_1c, blood pressure, and lipids, Pardis Dana, M.D., reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

“Clearly, a need exists for more aggressive, detail-oriented [diabetes] management with use of far more resources and improved patient compliance, along with more efficacious and better-tolerated pharmacologic considerations,” according to Dr. Dana of the Endocrine and Diabetes Center, Vienna and Woodbridge, Va.

In a report published last year that included data from the 1999–2000 National Health and Nutrition Examination Survey (NHANES), only 7% of 441 study participants with type 2 diabetes met all three goals: hemoglobin A_1c below 7%, blood pressure below 130/80 mm Hg, and total cholesterol below 200 mg/dL (JAMA 2004;291:335–42).

Dr. Dana and his associates retrospectively compared outcomes for 334 of their own type 2 diabetic patients with those of the NHANES study, as well as with the American Diabetes Association's guidelines of HbA_1c below 7%, BP below 130/80 mm Hg, LDL cholesterol below 100 mg/dL, HDL cholesterol of at least 40 mg/dL, and triglycerides below 150 mg/dL.

The 185 men and 149 women had all made at least three visits per year from January 2000 to December 2003. Statistically significant changes that occurred with subspecialty management included reductions of 1.87 percentage points in HbA_1c, 2.56 mm Hg in systolic blood pressure, 29.32 mg/dL total cholesterol, 17.87 mg/dL in LDL cholesterol, and 113.03 mg/dL in triglycerides. Changes in diastolic blood pressure, HDL cholesterol, and BMI were not significant, they reported.

But despite the improvements, only 2% of the patients had achieved all three target goals of the NHANES study at the time of their most recent office visit. For the ADA guidelines, 9% reached all five, 28% reached four, 28% reached three, 22% reached two, 10% reached one, and 3% reached none.

Lack of medication was not the reason: Of the 334 patients, 59% were taking metformin, 40% insulin, 38% thiazolidinediones, 36% sulfonylureas, and 16% nonsulfonylurea secretagogues (8% repaglinide and 8% nateglinide). Of these, monotherapy was used in 25%, two glucose-lowering drugs in 41%, three in 22%, a three-drug regimen plus insulin in 6%, and lifestyle modification in 5%.

As for antihypertensive drugs, 53% were receiving angiotensin-converting enzyme inhibitors, 28% diuretics, 17% angiotensin II receptor blockers, 14% β-adrenergic blocking agents, 12% calcium channel blockers, and 1% α-adrenergic blocking agents. Of these patients, 42% were taking one, 23% two, 8% three, and 3% more than three, while 24% were not taking any antihypertensive drugs.

In the lipid-lowering category, statins were taken by 61%, fibrates by 10%, ezetimibe by 9%, and niacin by 1%. Most (63%) were on monotherapy, while 9% were taking two drugs and 28% weren't taking any, they reported.

WASHINGTON — Even in a private subspecialty endocrinology practice, most patients with type 2 diabetes still aren't meeting American Diabetes Association goals for hemoglobin A_1c, blood pressure, and lipids, Pardis Dana, M.D., reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

“Clearly, a need exists for more aggressive, detail-oriented [diabetes] management with use of far more resources and improved patient compliance, along with more efficacious and better-tolerated pharmacologic considerations,” according to Dr. Dana of the Endocrine and Diabetes Center, Vienna and Woodbridge, Va.

In a report published last year that included data from the 1999–2000 National Health and Nutrition Examination Survey (NHANES), only 7% of 441 study participants with type 2 diabetes met all three goals: hemoglobin A_1c below 7%, blood pressure below 130/80 mm Hg, and total cholesterol below 200 mg/dL (JAMA 2004;291:335–42).

Dr. Dana and his associates retrospectively compared outcomes for 334 of their own type 2 diabetic patients with those of the NHANES study, as well as with the American Diabetes Association's guidelines of HbA_1c below 7%, BP below 130/80 mm Hg, LDL cholesterol below 100 mg/dL, HDL cholesterol of at least 40 mg/dL, and triglycerides below 150 mg/dL.

The 185 men and 149 women had all made at least three visits per year from January 2000 to December 2003. Statistically significant changes that occurred with subspecialty management included reductions of 1.87 percentage points in HbA_1c, 2.56 mm Hg in systolic blood pressure, 29.32 mg/dL total cholesterol, 17.87 mg/dL in LDL cholesterol, and 113.03 mg/dL in triglycerides. Changes in diastolic blood pressure, HDL cholesterol, and BMI were not significant, they reported.

But despite the improvements, only 2% of the patients had achieved all three target goals of the NHANES study at the time of their most recent office visit. For the ADA guidelines, 9% reached all five, 28% reached four, 28% reached three, 22% reached two, 10% reached one, and 3% reached none.

Lack of medication was not the reason: Of the 334 patients, 59% were taking metformin, 40% insulin, 38% thiazolidinediones, 36% sulfonylureas, and 16% nonsulfonylurea secretagogues (8% repaglinide and 8% nateglinide). Of these, monotherapy was used in 25%, two glucose-lowering drugs in 41%, three in 22%, a three-drug regimen plus insulin in 6%, and lifestyle modification in 5%.

As for antihypertensive drugs, 53% were receiving angiotensin-converting enzyme inhibitors, 28% diuretics, 17% angiotensin II receptor blockers, 14% β-adrenergic blocking agents, 12% calcium channel blockers, and 1% α-adrenergic blocking agents. Of these patients, 42% were taking one, 23% two, 8% three, and 3% more than three, while 24% were not taking any antihypertensive drugs.

In the lipid-lowering category, statins were taken by 61%, fibrates by 10%, ezetimibe by 9%, and niacin by 1%. Most (63%) were on monotherapy, while 9% were taking two drugs and 28% weren't taking any, they reported.

SAN DIEGO — Intensive lipid lowering is linked to fewer cardiovascular events in diabetic patients with established cardiovascular disease—and, as in nondiabetics, “lower is better.”

That was the message from a subanalysis of 1,501 patients with diabetes who were among the 10,001 participants in Pfizer's Treating to New Targets (TNT) study, reported by James Shepherd, M.D., at the annual scientific sessions of the American Diabetes Association.

“The results suggest to me that we really should be quite aggressive with our intervention in our diabetic patients, not only with their glucose control, but also with their cardiovascular risk control,” said Dr. Shepherd, professor of pathological biochemistry at the University of Glasgow, Scotland.

In the original study, first reported in March at the American College of Cardiology meeting, 10,001 patients with stable, established coronary heart disease (CHD) and a starting LDL cholesterol level of 130 mg/dL or less were randomized to receive either 10 mg or 80 mg of atorvastatin per day and were followed for a mean of 4.9 years, lowering mean LDL levels to 101 mg/dL and 77 mg/dL, respectively.

The high-dose regimen not only resulted in a 22% relative reduction in risk of major cardiovascular events, but also significantly reduced the relative risk of stroke by 35% and of heart failure by 26% (N. Engl. J. Med. 2005;352;1425–35).

In the TNT study, 753 diabetics were randomized to 10-mg atorvastatin, while the other 748 received 80 mg. At baseline, the two groups were well matched, with an average age of 63 years.

Compared with the overall study cohort, the diabetics were heavier and had a higher proportion of women.

They also were more likely to have hypertension, peripheral vascular disease, and a history of previous cerebrovascular accidents. However, their diabetes was relatively well controlled, with a hemoglobin A_1c of 7.4%, as was their mean blood pressure, at 135/77 mm Hg, Dr. Shepherd said.

At baseline, their mean LDL cholesterol level was about 150 mg/dL. After an 8-week open-label run-in period of 10-mg atorvastatin, that level was reduced to just under 100 mg/dL.

The 753 who remained on 10-mg atorvastatin for the rest of the study had a final LDL cholesterol level of 98.6 mg/dL, compared with 76.7 mg/dL in the 748 randomized to 80 mg.

During the trial, the average triglyceride level was 177.9 in the 10-mg group, compared with 145.1 mg/dL in those on 80 mg/day. Levels of HDL cholesterol were not appreciably different between the two groups.

Differences in the rates of major cardiovascular events between the high- and low-dose atorvastatin appeared soon after randomization and remained significant the entire 4.9 years, with a relative risk reduction of 25%. Overall, 17.9% of the 10-mg group had a major event, compared with 13.8% of those taking 80 mg.

Although the numbers for each individual end point were too small to reach statistical significance, most showed the same trend: 4.1% vs. 3.1% died of coronary heart disease, 8.1% vs. 6.6% had a nonfatal, nonprocedure-related MI, and 5.7% vs. 3.7% experienced a fatal or nonfatal stroke, Dr. Shepherd reported.

Cerebrovascular events were reduced by 31% overall, occurring in 10% and 7% of the 10-mg and 80-mg groups, respectively. Reductions were seen in both fatal and nonfatal stroke (5.8% vs. 4.3%) and in transient ischemic attacks (4.1% vs. 2.7%).

Although overall event rates were higher among the diabetics, the pattern of benefit with aggressive lipid lowering was similar to that of the entire TNT cohort, in whom overall major cardiovascular event rates were 10.9% with 80 mg and 8.7% with 10 mg, 2.5% vs. 2% for CHD deaths, 6.2% vs. 4.9% for nonfatal, nonprocedure-related MI, and 3.1% vs. 2.3% for fatal or nonfatal stroke.

In the diabetic participants, similar patterns were also seen for secondary event rates and clearly illustrated that having diabetes increases vascular disease risks across the board: The proportions experiencing any cardiovascular event, for example, were 44.1% of the diabetics with 10-mg atorvastatin and 39.8% of those taking 80 mg, compared with 33.5% and 28.1%, respectively, for the nondiabetics.

Peripheral arterial disease occurred in 8.9% vs. 9.1% of the diabetics, compared with 5.6% and 5.5% of the nondiabetics.

Current guidelines from the National Cholesterol Education Program, which consider diabetes a coronary risk equivalent, advise an LDL cholesterol level below 100 mg/dL for all diabetic patients.

An NCEP update published last year suggested that in patients at very high risk, including those with “multiple major risk factors (especially diabetes),” an LDL target of less than 70 mg/dL might be considered as a therapeutic option (Circulation 2004;110:227–39).

There were no differences in treatment-related side effects between the 10-mg and 80-mg diabetic groups.

Treatment-related myalgia occurred in 3.6% of the 10-mg group and 2.4% of those taking 80 mg, while persistent liver-enzyme elevations three times the upper limit of normal occurred in 0.4% vs. 0.8%, respectively. No cases of rhabdomyolysis occurred in any patient throughout the 5 study years.

SAN DIEGO — Intensive lipid lowering is linked to fewer cardiovascular events in diabetic patients with established cardiovascular disease—and, as in nondiabetics, “lower is better.”

That was the message from a subanalysis of 1,501 patients with diabetes who were among the 10,001 participants in Pfizer's Treating to New Targets (TNT) study, reported by James Shepherd, M.D., at the annual scientific sessions of the American Diabetes Association.

“The results suggest to me that we really should be quite aggressive with our intervention in our diabetic patients, not only with their glucose control, but also with their cardiovascular risk control,” said Dr. Shepherd, professor of pathological biochemistry at the University of Glasgow, Scotland.

In the original study, first reported in March at the American College of Cardiology meeting, 10,001 patients with stable, established coronary heart disease (CHD) and a starting LDL cholesterol level of 130 mg/dL or less were randomized to receive either 10 mg or 80 mg of atorvastatin per day and were followed for a mean of 4.9 years, lowering mean LDL levels to 101 mg/dL and 77 mg/dL, respectively.

The high-dose regimen not only resulted in a 22% relative reduction in risk of major cardiovascular events, but also significantly reduced the relative risk of stroke by 35% and of heart failure by 26% (N. Engl. J. Med. 2005;352;1425–35).

In the TNT study, 753 diabetics were randomized to 10-mg atorvastatin, while the other 748 received 80 mg. At baseline, the two groups were well matched, with an average age of 63 years.

Compared with the overall study cohort, the diabetics were heavier and had a higher proportion of women.

They also were more likely to have hypertension, peripheral vascular disease, and a history of previous cerebrovascular accidents. However, their diabetes was relatively well controlled, with a hemoglobin A_1c of 7.4%, as was their mean blood pressure, at 135/77 mm Hg, Dr. Shepherd said.

At baseline, their mean LDL cholesterol level was about 150 mg/dL. After an 8-week open-label run-in period of 10-mg atorvastatin, that level was reduced to just under 100 mg/dL.

The 753 who remained on 10-mg atorvastatin for the rest of the study had a final LDL cholesterol level of 98.6 mg/dL, compared with 76.7 mg/dL in the 748 randomized to 80 mg.

During the trial, the average triglyceride level was 177.9 in the 10-mg group, compared with 145.1 mg/dL in those on 80 mg/day. Levels of HDL cholesterol were not appreciably different between the two groups.

Differences in the rates of major cardiovascular events between the high- and low-dose atorvastatin appeared soon after randomization and remained significant the entire 4.9 years, with a relative risk reduction of 25%. Overall, 17.9% of the 10-mg group had a major event, compared with 13.8% of those taking 80 mg.

Although the numbers for each individual end point were too small to reach statistical significance, most showed the same trend: 4.1% vs. 3.1% died of coronary heart disease, 8.1% vs. 6.6% had a nonfatal, nonprocedure-related MI, and 5.7% vs. 3.7% experienced a fatal or nonfatal stroke, Dr. Shepherd reported.

Cerebrovascular events were reduced by 31% overall, occurring in 10% and 7% of the 10-mg and 80-mg groups, respectively. Reductions were seen in both fatal and nonfatal stroke (5.8% vs. 4.3%) and in transient ischemic attacks (4.1% vs. 2.7%).

Although overall event rates were higher among the diabetics, the pattern of benefit with aggressive lipid lowering was similar to that of the entire TNT cohort, in whom overall major cardiovascular event rates were 10.9% with 80 mg and 8.7% with 10 mg, 2.5% vs. 2% for CHD deaths, 6.2% vs. 4.9% for nonfatal, nonprocedure-related MI, and 3.1% vs. 2.3% for fatal or nonfatal stroke.

In the diabetic participants, similar patterns were also seen for secondary event rates and clearly illustrated that having diabetes increases vascular disease risks across the board: The proportions experiencing any cardiovascular event, for example, were 44.1% of the diabetics with 10-mg atorvastatin and 39.8% of those taking 80 mg, compared with 33.5% and 28.1%, respectively, for the nondiabetics.

Peripheral arterial disease occurred in 8.9% vs. 9.1% of the diabetics, compared with 5.6% and 5.5% of the nondiabetics.

Current guidelines from the National Cholesterol Education Program, which consider diabetes a coronary risk equivalent, advise an LDL cholesterol level below 100 mg/dL for all diabetic patients.

An NCEP update published last year suggested that in patients at very high risk, including those with “multiple major risk factors (especially diabetes),” an LDL target of less than 70 mg/dL might be considered as a therapeutic option (Circulation 2004;110:227–39).

There were no differences in treatment-related side effects between the 10-mg and 80-mg diabetic groups.

Treatment-related myalgia occurred in 3.6% of the 10-mg group and 2.4% of those taking 80 mg, while persistent liver-enzyme elevations three times the upper limit of normal occurred in 0.4% vs. 0.8%, respectively. No cases of rhabdomyolysis occurred in any patient throughout the 5 study years.

SAN DIEGO — Intensive lipid lowering is linked to fewer cardiovascular events in diabetic patients with established cardiovascular disease—and, as in nondiabetics, “lower is better.”

That was the message from a subanalysis of 1,501 patients with diabetes who were among the 10,001 participants in Pfizer's Treating to New Targets (TNT) study, reported by James Shepherd, M.D., at the annual scientific sessions of the American Diabetes Association.

“The results suggest to me that we really should be quite aggressive with our intervention in our diabetic patients, not only with their glucose control, but also with their cardiovascular risk control,” said Dr. Shepherd, professor of pathological biochemistry at the University of Glasgow, Scotland.

In the original study, first reported in March at the American College of Cardiology meeting, 10,001 patients with stable, established coronary heart disease (CHD) and a starting LDL cholesterol level of 130 mg/dL or less were randomized to receive either 10 mg or 80 mg of atorvastatin per day and were followed for a mean of 4.9 years, lowering mean LDL levels to 101 mg/dL and 77 mg/dL, respectively.

The high-dose regimen not only resulted in a 22% relative reduction in risk of major cardiovascular events, but also significantly reduced the relative risk of stroke by 35% and of heart failure by 26% (N. Engl. J. Med. 2005;352;1425–35).

In the TNT study, 753 diabetics were randomized to 10-mg atorvastatin, while the other 748 received 80 mg. At baseline, the two groups were well matched, with an average age of 63 years.

Compared with the overall study cohort, the diabetics were heavier and had a higher proportion of women.

They also were more likely to have hypertension, peripheral vascular disease, and a history of previous cerebrovascular accidents. However, their diabetes was relatively well controlled, with a hemoglobin A_1c of 7.4%, as was their mean blood pressure, at 135/77 mm Hg, Dr. Shepherd said.

At baseline, their mean LDL cholesterol level was about 150 mg/dL. After an 8-week open-label run-in period of 10-mg atorvastatin, that level was reduced to just under 100 mg/dL.

The 753 who remained on 10-mg atorvastatin for the rest of the study had a final LDL cholesterol level of 98.6 mg/dL, compared with 76.7 mg/dL in the 748 randomized to 80 mg.

During the trial, the average triglyceride level was 177.9 in the 10-mg group, compared with 145.1 mg/dL in those on 80 mg/day. Levels of HDL cholesterol were not appreciably different between the two groups.

Differences in the rates of major cardiovascular events between the high- and low-dose atorvastatin appeared soon after randomization and remained significant the entire 4.9 years, with a relative risk reduction of 25%. Overall, 17.9% of the 10-mg group had a major event, compared with 13.8% of those taking 80 mg.

Although the numbers for each individual end point were too small to reach statistical significance, most showed the same trend: 4.1% vs. 3.1% died of coronary heart disease, 8.1% vs. 6.6% had a nonfatal, nonprocedure-related MI, and 5.7% vs. 3.7% experienced a fatal or nonfatal stroke, Dr. Shepherd reported.

Cerebrovascular events were reduced by 31% overall, occurring in 10% and 7% of the 10-mg and 80-mg groups, respectively. Reductions were seen in both fatal and nonfatal stroke (5.8% vs. 4.3%) and in transient ischemic attacks (4.1% vs. 2.7%).

Although overall event rates were higher among the diabetics, the pattern of benefit with aggressive lipid lowering was similar to that of the entire TNT cohort, in whom overall major cardiovascular event rates were 10.9% with 80 mg and 8.7% with 10 mg, 2.5% vs. 2% for CHD deaths, 6.2% vs. 4.9% for nonfatal, nonprocedure-related MI, and 3.1% vs. 2.3% for fatal or nonfatal stroke.

In the diabetic participants, similar patterns were also seen for secondary event rates and clearly illustrated that having diabetes increases vascular disease risks across the board: The proportions experiencing any cardiovascular event, for example, were 44.1% of the diabetics with 10-mg atorvastatin and 39.8% of those taking 80 mg, compared with 33.5% and 28.1%, respectively, for the nondiabetics.

Peripheral arterial disease occurred in 8.9% vs. 9.1% of the diabetics, compared with 5.6% and 5.5% of the nondiabetics.

Current guidelines from the National Cholesterol Education Program, which consider diabetes a coronary risk equivalent, advise an LDL cholesterol level below 100 mg/dL for all diabetic patients.

An NCEP update published last year suggested that in patients at very high risk, including those with “multiple major risk factors (especially diabetes),” an LDL target of less than 70 mg/dL might be considered as a therapeutic option (Circulation 2004;110:227–39).

There were no differences in treatment-related side effects between the 10-mg and 80-mg diabetic groups.

Treatment-related myalgia occurred in 3.6% of the 10-mg group and 2.4% of those taking 80 mg, while persistent liver-enzyme elevations three times the upper limit of normal occurred in 0.4% vs. 0.8%, respectively. No cases of rhabdomyolysis occurred in any patient throughout the 5 study years.

A new national active surveillance system designed to detect adverse drug events is good at picking up true cases, but not particularly sensitive—especially in detecting hypoglycemia caused by diabetes medications and bleeding associated with anticoagulants, the Centers for Disease Control and Prevention reported.

In 2003, the CDC worked with the Consumer Product Safety Commission and the Food and Drug Administration to develop the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project.

Adverse drug events (ADEs) are often more difficult to identify than other injuries, so the CDC conducted an independent chart review in a sample of six NEISS-CADES hospitals (0.2%–1.7% of emergency department visits).

Of 4,561 charts reviewed, 68 ADE cases were identified. Of the 29 ADE cases that had been reported to NEISS-CADES prior to the chart review, 25 were among the 68 cases detected by the reviewers. The remaining four were false positives in which an injury attributed to a drug in the chief complaint section of the chart was not confirmed elsewhere in the chart (MMWR 2005;54:380–3).

The estimated sensitivity of the NEISS-CADES for ascertaining ADEs was 0.33, while the estimated positive predictive value of a reported ADE was 0.92. The relatively low sensitivity was attributed to the difficulty in detecting hypoglycemia associated with diabetes agents (just 3 of 16 were detected), and of bleeding associated with anticoagulants such as warfarin and heparin (1 of 9 were detected). When those two types of cases were excluded, sensitivity of the NEISS-CADES increased to 0.45. That figure compares favorably with the FDA's Adverse Event Reporting System, a passive surveillance system.

A new national active surveillance system designed to detect adverse drug events is good at picking up true cases, but not particularly sensitive—especially in detecting hypoglycemia caused by diabetes medications and bleeding associated with anticoagulants, the Centers for Disease Control and Prevention reported.

In 2003, the CDC worked with the Consumer Product Safety Commission and the Food and Drug Administration to develop the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project.

Adverse drug events (ADEs) are often more difficult to identify than other injuries, so the CDC conducted an independent chart review in a sample of six NEISS-CADES hospitals (0.2%–1.7% of emergency department visits).

Of 4,561 charts reviewed, 68 ADE cases were identified. Of the 29 ADE cases that had been reported to NEISS-CADES prior to the chart review, 25 were among the 68 cases detected by the reviewers. The remaining four were false positives in which an injury attributed to a drug in the chief complaint section of the chart was not confirmed elsewhere in the chart (MMWR 2005;54:380–3).

The estimated sensitivity of the NEISS-CADES for ascertaining ADEs was 0.33, while the estimated positive predictive value of a reported ADE was 0.92. The relatively low sensitivity was attributed to the difficulty in detecting hypoglycemia associated with diabetes agents (just 3 of 16 were detected), and of bleeding associated with anticoagulants such as warfarin and heparin (1 of 9 were detected). When those two types of cases were excluded, sensitivity of the NEISS-CADES increased to 0.45. That figure compares favorably with the FDA's Adverse Event Reporting System, a passive surveillance system.

A new national active surveillance system designed to detect adverse drug events is good at picking up true cases, but not particularly sensitive—especially in detecting hypoglycemia caused by diabetes medications and bleeding associated with anticoagulants, the Centers for Disease Control and Prevention reported.

In 2003, the CDC worked with the Consumer Product Safety Commission and the Food and Drug Administration to develop the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project.

Adverse drug events (ADEs) are often more difficult to identify than other injuries, so the CDC conducted an independent chart review in a sample of six NEISS-CADES hospitals (0.2%–1.7% of emergency department visits).

Of 4,561 charts reviewed, 68 ADE cases were identified. Of the 29 ADE cases that had been reported to NEISS-CADES prior to the chart review, 25 were among the 68 cases detected by the reviewers. The remaining four were false positives in which an injury attributed to a drug in the chief complaint section of the chart was not confirmed elsewhere in the chart (MMWR 2005;54:380–3).

The estimated sensitivity of the NEISS-CADES for ascertaining ADEs was 0.33, while the estimated positive predictive value of a reported ADE was 0.92. The relatively low sensitivity was attributed to the difficulty in detecting hypoglycemia associated with diabetes agents (just 3 of 16 were detected), and of bleeding associated with anticoagulants such as warfarin and heparin (1 of 9 were detected). When those two types of cases were excluded, sensitivity of the NEISS-CADES increased to 0.45. That figure compares favorably with the FDA's Adverse Event Reporting System, a passive surveillance system.

WASHINGTON — Obese patients with coronary disease don't always see their excess weight as being part of the problem, Francisco Lopez-Jimenez, M.D., and his associates reported in a conference on cardiovascular disease epidemiology and prevention, sponsored by the American Heart Association.

A prospective survey of 229 patients who had recently been hospitalized for a coronary syndrome or revascularization revealed that, despite being aware of their excess weight, few actually perceived that it was related to their heart problems.

“Don't assume your patients understand this. You must make them aware of the implications of obesity with regard to heart disease, because how people perceive themselves drives their behavior,” Dr. Lopez-Jimenez, of the Mayo Clinic and Mayo Foundation, Rochester, Minn., said in an interview with this newspaper.

The patients had a mean age of 66 years and a mean body mass index of 30.5 kg/m

The investigators looked for factors that were correlated with self-perception of risk for heart disease. After adjustment for sex, comorbidities, socioeconomic status, and other potential confounders, only four factors—age, history of diabetes, and levels of readiness to change for weight loss and exercise—were significantly correlated with the patient's perceived risk for heart disease.

There was no such correlation with self-perception of obesity, despite the fact that 67% of the patients had endorsed the general concept that obesity is a risk factor for myocardial infarction.

“It is complicated … . In general, we tend to recognize risky habits, but fail to recognize ourselves at risk,” he said, adding that studies in patients who smoke, have AIDS, and engage in other risky behaviors have shown similar tendencies.

At the 6-month follow-up, the belief that obesity is a risk factor for heart disease was the strongest predictor of weight loss. History of diabetes and self-perceived excess weight were also significantly correlated with weight loss, but self-perceived risk for heart disease was not.

Although these data suggest some denial on the part of patients, a previous study by Dr. Lopez-Jimenez and his associates indicated that underappreciation of obesity as a cardiovascular disease risk factor extends to clinicians as well. In a randomly selected sample of 627 patients discharged after an MI during 2001–2002 from five U.S. teaching hospitals, BMI had been documented in the charts of only 14% and waist circumference in none, despite the fact that 83% were overweight, including 55% who were obese and 8% who were morbidly obese (Int. J. Obes. Relat. Metab. Disord. 2005;29:137–41).

In only 20% of patients with a BMI at or above 30 was the diagnosis of obesity documented as a current medical problem, part of the past medical history, or as a final diagnosis. The proportion that received dietary counseling (61%) was identical for those with a BMI at or above 25 and those with a BMI below 25.

Weight loss was described as part of the treatment or among the goals at discharge for just 7% of overweight and 9% of obese patients. There was no change in either the recognition of obesity or the proportion of obese patients for whom weight loss was described as part of the treatment plan or among the goals at discharge between the 301 patients seen before the Surgeon General's Call to Action on obesity in December 2001 and the 326 seen after.

“Physicians also need to recognize obesity as a major health problem and to follow the awareness with some action. This should be particularly relevant for patients who already suffer the consequences of obesity like [those] with heart disease or diabetes,” Dr. Lopez-Jimenez said.

WASHINGTON — Obese patients with coronary disease don't always see their excess weight as being part of the problem, Francisco Lopez-Jimenez, M.D., and his associates reported in a conference on cardiovascular disease epidemiology and prevention, sponsored by the American Heart Association.

A prospective survey of 229 patients who had recently been hospitalized for a coronary syndrome or revascularization revealed that, despite being aware of their excess weight, few actually perceived that it was related to their heart problems.

“Don't assume your patients understand this. You must make them aware of the implications of obesity with regard to heart disease, because how people perceive themselves drives their behavior,” Dr. Lopez-Jimenez, of the Mayo Clinic and Mayo Foundation, Rochester, Minn., said in an interview with this newspaper.

The patients had a mean age of 66 years and a mean body mass index of 30.5 kg/m

The investigators looked for factors that were correlated with self-perception of risk for heart disease. After adjustment for sex, comorbidities, socioeconomic status, and other potential confounders, only four factors—age, history of diabetes, and levels of readiness to change for weight loss and exercise—were significantly correlated with the patient's perceived risk for heart disease.

There was no such correlation with self-perception of obesity, despite the fact that 67% of the patients had endorsed the general concept that obesity is a risk factor for myocardial infarction.

“It is complicated … . In general, we tend to recognize risky habits, but fail to recognize ourselves at risk,” he said, adding that studies in patients who smoke, have AIDS, and engage in other risky behaviors have shown similar tendencies.

At the 6-month follow-up, the belief that obesity is a risk factor for heart disease was the strongest predictor of weight loss. History of diabetes and self-perceived excess weight were also significantly correlated with weight loss, but self-perceived risk for heart disease was not.

Although these data suggest some denial on the part of patients, a previous study by Dr. Lopez-Jimenez and his associates indicated that underappreciation of obesity as a cardiovascular disease risk factor extends to clinicians as well. In a randomly selected sample of 627 patients discharged after an MI during 2001–2002 from five U.S. teaching hospitals, BMI had been documented in the charts of only 14% and waist circumference in none, despite the fact that 83% were overweight, including 55% who were obese and 8% who were morbidly obese (Int. J. Obes. Relat. Metab. Disord. 2005;29:137–41).

In only 20% of patients with a BMI at or above 30 was the diagnosis of obesity documented as a current medical problem, part of the past medical history, or as a final diagnosis. The proportion that received dietary counseling (61%) was identical for those with a BMI at or above 25 and those with a BMI below 25.

Weight loss was described as part of the treatment or among the goals at discharge for just 7% of overweight and 9% of obese patients. There was no change in either the recognition of obesity or the proportion of obese patients for whom weight loss was described as part of the treatment plan or among the goals at discharge between the 301 patients seen before the Surgeon General's Call to Action on obesity in December 2001 and the 326 seen after.

“Physicians also need to recognize obesity as a major health problem and to follow the awareness with some action. This should be particularly relevant for patients who already suffer the consequences of obesity like [those] with heart disease or diabetes,” Dr. Lopez-Jimenez said.

WASHINGTON — Obese patients with coronary disease don't always see their excess weight as being part of the problem, Francisco Lopez-Jimenez, M.D., and his associates reported in a conference on cardiovascular disease epidemiology and prevention, sponsored by the American Heart Association.

A prospective survey of 229 patients who had recently been hospitalized for a coronary syndrome or revascularization revealed that, despite being aware of their excess weight, few actually perceived that it was related to their heart problems.

“Don't assume your patients understand this. You must make them aware of the implications of obesity with regard to heart disease, because how people perceive themselves drives their behavior,” Dr. Lopez-Jimenez, of the Mayo Clinic and Mayo Foundation, Rochester, Minn., said in an interview with this newspaper.

The patients had a mean age of 66 years and a mean body mass index of 30.5 kg/m

The investigators looked for factors that were correlated with self-perception of risk for heart disease. After adjustment for sex, comorbidities, socioeconomic status, and other potential confounders, only four factors—age, history of diabetes, and levels of readiness to change for weight loss and exercise—were significantly correlated with the patient's perceived risk for heart disease.

There was no such correlation with self-perception of obesity, despite the fact that 67% of the patients had endorsed the general concept that obesity is a risk factor for myocardial infarction.

“It is complicated … . In general, we tend to recognize risky habits, but fail to recognize ourselves at risk,” he said, adding that studies in patients who smoke, have AIDS, and engage in other risky behaviors have shown similar tendencies.

At the 6-month follow-up, the belief that obesity is a risk factor for heart disease was the strongest predictor of weight loss. History of diabetes and self-perceived excess weight were also significantly correlated with weight loss, but self-perceived risk for heart disease was not.

Although these data suggest some denial on the part of patients, a previous study by Dr. Lopez-Jimenez and his associates indicated that underappreciation of obesity as a cardiovascular disease risk factor extends to clinicians as well. In a randomly selected sample of 627 patients discharged after an MI during 2001–2002 from five U.S. teaching hospitals, BMI had been documented in the charts of only 14% and waist circumference in none, despite the fact that 83% were overweight, including 55% who were obese and 8% who were morbidly obese (Int. J. Obes. Relat. Metab. Disord. 2005;29:137–41).

In only 20% of patients with a BMI at or above 30 was the diagnosis of obesity documented as a current medical problem, part of the past medical history, or as a final diagnosis. The proportion that received dietary counseling (61%) was identical for those with a BMI at or above 25 and those with a BMI below 25.

Weight loss was described as part of the treatment or among the goals at discharge for just 7% of overweight and 9% of obese patients. There was no change in either the recognition of obesity or the proportion of obese patients for whom weight loss was described as part of the treatment plan or among the goals at discharge between the 301 patients seen before the Surgeon General's Call to Action on obesity in December 2001 and the 326 seen after.

“Physicians also need to recognize obesity as a major health problem and to follow the awareness with some action. This should be particularly relevant for patients who already suffer the consequences of obesity like [those] with heart disease or diabetes,” Dr. Lopez-Jimenez said.

WASHINGTON — The hypoandrogenic effects of oral contraceptives may not be completely reversible after discontinuation of their use, Claudia Panzer, M.D., reported at the annual meeting of the American Association of Clinical Endocrinologists.

OCs are known to decrease serum testosterone levels by decreasing ovarian production of testosterone and increasing production of sex hormone-binding globulin (SHBG) by the liver. Higher SHBG levels lower the amount of free testosterone that reaches the tissues. Such changes have been associated with decreases in sexual interest, arousal, vaginal lubrication, and frequency of sexual intercourse.

It has long been assumed that these changes are reversible after discontinuation of OC use, but findings from a retrospective review of 124 premenopausal women with female sexual dysfunction suggest otherwise, said Dr. Panzer, an endocrinologist at Boston University.

Among the subjects were 62 current OC users, 39 former users, and 23 who had never used OCs. None of the subjects had used OCs for reasons other than birth control. The “never users” were older than the current users (36 vs. 32 years), and had a longer duration of sexual dysfunction than current and former OC users (9 years vs. 6 years in both OC groups).

Those who had never used OCs also scored higher on the Female Sexual Function Index, indicating better function (21 points, vs. 15 points for the current OC users and 10 points for the former users). Women on OCs had lower scores in the domain of sexual desire, compared with those who had never used them, and also complained more about sexual pain.

Of the 101 users, 39 said the knowledge that the pill might cause sexual dysfunction would convince them to stop taking it.

Baseline SHBG levels were four times higher in the current OC users (157 nmol/L) and the former users (161 nmol/L) than in the never-users (41 nmol/L). Although SHBG levels did decrease after discontinuation of OC use, they remained elevated after 49–120 days (62 nmol/L) and again at more than 120 days (63 nmol/L), compared with the never-users, for whom SHBG measured after 120 days was 35 nmol/L, she said.

The fact that the SHBG value after 120 days in the group that had discontinued OCs had fallen into the normal reference range despite being twice as high as for the never-users suggests that the currently used SHBG reference range may be too wide. A narrower range might better reflect hormonal changes seen in women who use OCs, Dr. Panzer commented.

Testosterone levels at baseline did not differ between the three groups, but the never-users had higher free androgen indexes than did the current and former OC users (3.7 vs. 0.8 for both OC groups), calculated free testosterone levels (6.2 pg/mL vs. 2 pg/mL for both OC groups), and calculated bioavailable testosterone (146.5 pg/mL vs. 47.8 pg/mL for former users and 46.7 pg/mL for current users).

These data suggest that total testosterone is a poor test to evaluate androgen status in OC users and that assessments of free or bioavailable testosterone are superior, Dr. Panzer said.

WASHINGTON — The hypoandrogenic effects of oral contraceptives may not be completely reversible after discontinuation of their use, Claudia Panzer, M.D., reported at the annual meeting of the American Association of Clinical Endocrinologists.

OCs are known to decrease serum testosterone levels by decreasing ovarian production of testosterone and increasing production of sex hormone-binding globulin (SHBG) by the liver. Higher SHBG levels lower the amount of free testosterone that reaches the tissues. Such changes have been associated with decreases in sexual interest, arousal, vaginal lubrication, and frequency of sexual intercourse.

It has long been assumed that these changes are reversible after discontinuation of OC use, but findings from a retrospective review of 124 premenopausal women with female sexual dysfunction suggest otherwise, said Dr. Panzer, an endocrinologist at Boston University.

Among the subjects were 62 current OC users, 39 former users, and 23 who had never used OCs. None of the subjects had used OCs for reasons other than birth control. The “never users” were older than the current users (36 vs. 32 years), and had a longer duration of sexual dysfunction than current and former OC users (9 years vs. 6 years in both OC groups).

Those who had never used OCs also scored higher on the Female Sexual Function Index, indicating better function (21 points, vs. 15 points for the current OC users and 10 points for the former users). Women on OCs had lower scores in the domain of sexual desire, compared with those who had never used them, and also complained more about sexual pain.

Of the 101 users, 39 said the knowledge that the pill might cause sexual dysfunction would convince them to stop taking it.

Baseline SHBG levels were four times higher in the current OC users (157 nmol/L) and the former users (161 nmol/L) than in the never-users (41 nmol/L). Although SHBG levels did decrease after discontinuation of OC use, they remained elevated after 49–120 days (62 nmol/L) and again at more than 120 days (63 nmol/L), compared with the never-users, for whom SHBG measured after 120 days was 35 nmol/L, she said.

The fact that the SHBG value after 120 days in the group that had discontinued OCs had fallen into the normal reference range despite being twice as high as for the never-users suggests that the currently used SHBG reference range may be too wide. A narrower range might better reflect hormonal changes seen in women who use OCs, Dr. Panzer commented.

Testosterone levels at baseline did not differ between the three groups, but the never-users had higher free androgen indexes than did the current and former OC users (3.7 vs. 0.8 for both OC groups), calculated free testosterone levels (6.2 pg/mL vs. 2 pg/mL for both OC groups), and calculated bioavailable testosterone (146.5 pg/mL vs. 47.8 pg/mL for former users and 46.7 pg/mL for current users).

These data suggest that total testosterone is a poor test to evaluate androgen status in OC users and that assessments of free or bioavailable testosterone are superior, Dr. Panzer said.

WASHINGTON — The hypoandrogenic effects of oral contraceptives may not be completely reversible after discontinuation of their use, Claudia Panzer, M.D., reported at the annual meeting of the American Association of Clinical Endocrinologists.

OCs are known to decrease serum testosterone levels by decreasing ovarian production of testosterone and increasing production of sex hormone-binding globulin (SHBG) by the liver. Higher SHBG levels lower the amount of free testosterone that reaches the tissues. Such changes have been associated with decreases in sexual interest, arousal, vaginal lubrication, and frequency of sexual intercourse.

It has long been assumed that these changes are reversible after discontinuation of OC use, but findings from a retrospective review of 124 premenopausal women with female sexual dysfunction suggest otherwise, said Dr. Panzer, an endocrinologist at Boston University.

Among the subjects were 62 current OC users, 39 former users, and 23 who had never used OCs. None of the subjects had used OCs for reasons other than birth control. The “never users” were older than the current users (36 vs. 32 years), and had a longer duration of sexual dysfunction than current and former OC users (9 years vs. 6 years in both OC groups).

Those who had never used OCs also scored higher on the Female Sexual Function Index, indicating better function (21 points, vs. 15 points for the current OC users and 10 points for the former users). Women on OCs had lower scores in the domain of sexual desire, compared with those who had never used them, and also complained more about sexual pain.

Of the 101 users, 39 said the knowledge that the pill might cause sexual dysfunction would convince them to stop taking it.

Baseline SHBG levels were four times higher in the current OC users (157 nmol/L) and the former users (161 nmol/L) than in the never-users (41 nmol/L). Although SHBG levels did decrease after discontinuation of OC use, they remained elevated after 49–120 days (62 nmol/L) and again at more than 120 days (63 nmol/L), compared with the never-users, for whom SHBG measured after 120 days was 35 nmol/L, she said.

The fact that the SHBG value after 120 days in the group that had discontinued OCs had fallen into the normal reference range despite being twice as high as for the never-users suggests that the currently used SHBG reference range may be too wide. A narrower range might better reflect hormonal changes seen in women who use OCs, Dr. Panzer commented.

Testosterone levels at baseline did not differ between the three groups, but the never-users had higher free androgen indexes than did the current and former OC users (3.7 vs. 0.8 for both OC groups), calculated free testosterone levels (6.2 pg/mL vs. 2 pg/mL for both OC groups), and calculated bioavailable testosterone (146.5 pg/mL vs. 47.8 pg/mL for former users and 46.7 pg/mL for current users).

These data suggest that total testosterone is a poor test to evaluate androgen status in OC users and that assessments of free or bioavailable testosterone are superior, Dr. Panzer said.