Lila O'Connor, Editor

Ideally, chemicals that are toxic to human health are identified and removed from use. Many such chemicals, known as persistent organic pollutants (POPs), have been studied individually for their ill effects in humans. DDT, for instance, once a widely used insecticide, is now classified as a probable human carcinogen and has not been used in the United States since the early 1970s.¹ Other insecticides have similarly been banned but have long half-lives and can persist in the environment for decades. Humans are exposed to POPs mainly through diet, say Ouidir and colleagues, with exposure “nearly ubiquitous.”²



The association between POP exposure during pregnancy and birth weight has not been established, as results from previous studies have been inconsistent, according to researchers.² In addition, birth weight does not distinguish growth-restricted fetuses from those that are constitutionally small. Therefore, Ouidir and colleagues analyzed maternal plasma levels of POPs and measures of fetal growth. Their research was published in JAMA Pediatrics.²



The investigators examined chemical class mixtures of organochlorine pesticides (OCPs), dioxin-like polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), among other groups of POPs, as well as individual chemicals, in 2,284 nonobese low-risk pregnant women before 14 weeks of gestation. They measured 14 fetal growth biometrics using ultrasonography throughout the women’s pregnancies, with researchers focusing their main findings on head and abdominal circumference and femur length measurements.



The researchers found that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% confidence interval [CI], -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. In addition, exposure to the PCB and PBDE mixtures were associated with reduced abdominal circumference.



OCPs have been associated with adverse effects on the endocrine system, lipid metabolism, and embryonic development. They also can result in hematologic and hepatic alterations.³



The JAMA Pediatrics study authors point out that their findings may not take into account the risk pregnant women with occupational exposure to POPs, or other higher exposure situations, may have, as the POP concentrations in their sample were low compared with levels in a nationally representative sample of pregnant women. They say that their findings provide insight into the “implications of POPs for fetal growth when exposures are low and suggest that, even if exposures could be successfully minimized, these associations may persist.”²
 

Ideally, chemicals that are toxic to human health are identified and removed from use. Many such chemicals, known as persistent organic pollutants (POPs), have been studied individually for their ill effects in humans. DDT, for instance, once a widely used insecticide, is now classified as a probable human carcinogen and has not been used in the United States since the early 1970s.¹ Other insecticides have similarly been banned but have long half-lives and can persist in the environment for decades. Humans are exposed to POPs mainly through diet, say Ouidir and colleagues, with exposure “nearly ubiquitous.”²



The association between POP exposure during pregnancy and birth weight has not been established, as results from previous studies have been inconsistent, according to researchers.² In addition, birth weight does not distinguish growth-restricted fetuses from those that are constitutionally small. Therefore, Ouidir and colleagues analyzed maternal plasma levels of POPs and measures of fetal growth. Their research was published in JAMA Pediatrics.²



The investigators examined chemical class mixtures of organochlorine pesticides (OCPs), dioxin-like polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), among other groups of POPs, as well as individual chemicals, in 2,284 nonobese low-risk pregnant women before 14 weeks of gestation. They measured 14 fetal growth biometrics using ultrasonography throughout the women’s pregnancies, with researchers focusing their main findings on head and abdominal circumference and femur length measurements.



The researchers found that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% confidence interval [CI], -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. In addition, exposure to the PCB and PBDE mixtures were associated with reduced abdominal circumference.



OCPs have been associated with adverse effects on the endocrine system, lipid metabolism, and embryonic development. They also can result in hematologic and hepatic alterations.³



The JAMA Pediatrics study authors point out that their findings may not take into account the risk pregnant women with occupational exposure to POPs, or other higher exposure situations, may have, as the POP concentrations in their sample were low compared with levels in a nationally representative sample of pregnant women. They say that their findings provide insight into the “implications of POPs for fetal growth when exposures are low and suggest that, even if exposures could be successfully minimized, these associations may persist.”²
 

Ideally, chemicals that are toxic to human health are identified and removed from use. Many such chemicals, known as persistent organic pollutants (POPs), have been studied individually for their ill effects in humans. DDT, for instance, once a widely used insecticide, is now classified as a probable human carcinogen and has not been used in the United States since the early 1970s.¹ Other insecticides have similarly been banned but have long half-lives and can persist in the environment for decades. Humans are exposed to POPs mainly through diet, say Ouidir and colleagues, with exposure “nearly ubiquitous.”²



The association between POP exposure during pregnancy and birth weight has not been established, as results from previous studies have been inconsistent, according to researchers.² In addition, birth weight does not distinguish growth-restricted fetuses from those that are constitutionally small. Therefore, Ouidir and colleagues analyzed maternal plasma levels of POPs and measures of fetal growth. Their research was published in JAMA Pediatrics.²



The investigators examined chemical class mixtures of organochlorine pesticides (OCPs), dioxin-like polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), among other groups of POPs, as well as individual chemicals, in 2,284 nonobese low-risk pregnant women before 14 weeks of gestation. They measured 14 fetal growth biometrics using ultrasonography throughout the women’s pregnancies, with researchers focusing their main findings on head and abdominal circumference and femur length measurements.



The researchers found that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% confidence interval [CI], -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. In addition, exposure to the PCB and PBDE mixtures were associated with reduced abdominal circumference.



OCPs have been associated with adverse effects on the endocrine system, lipid metabolism, and embryonic development. They also can result in hematologic and hepatic alterations.³



The JAMA Pediatrics study authors point out that their findings may not take into account the risk pregnant women with occupational exposure to POPs, or other higher exposure situations, may have, as the POP concentrations in their sample were low compared with levels in a nationally representative sample of pregnant women. They say that their findings provide insight into the “implications of POPs for fetal growth when exposures are low and suggest that, even if exposures could be successfully minimized, these associations may persist.”²
 

Whether or not women experience symptoms from uterine fibroid(s) can be dependent on a fibroid’s size and location. Heavy menstrual bleeding (HMB) is the most common symptom resulting from fibroids, and it occurs in up to one-third of women with fibroids. For fibroids that are large (>10 cm), “bulk” symptoms may occur, including pelvic pressure, urinary urgency or frequency, incontinence, constipation, abdominal protrusion, etc.¹

Elagolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was US Food and Drug Administration–approved in 2018 to treat moderate to severe pain caused by endometriosis. ² Elagolix is being evaluated in 2 phase 3 randomized, double-blind trials for the additional treatment of HMB associated with uterine fibroids. The results of these studies were presented at the 2019 AAGL meeting on November 12, in Vancouver, Canada.
 

Phase 3 study details

Premenopausal women aged 18 to 51 years were included in the Elaris UF-1 and UF-2 studies if they had HMB (defined using the alkaline hematin methodology as menstrual blood loss [MBL] >80 mL/cycle) and uterine fibroids as confirmed through ultrasound. Because elagolix suppresses estrogen and progesterone, treatment results in dose- and duration-dependent decreases in bone mineral density (BMD),² and add-back therapy can lessen these adverse effects. Subsequently, participants were randomly assigned 1:1:2 to placebo, elagolix 300 mg twice daily, or elagolix 300 mg twice daily with add-back therapy (1 mg estradiol/0.5 mg norethidrone acetate [E2/NETA]) once daily. Uterine volume and size and location of uterine fibroid(s) were assessed by ultrasound. Subgroups were defined by baseline FIGO categories, grouped FIGO 0-3, FIGO 4, or FIGO 5-8.³

Over the 6-month studies, 72.2% (95% confidence interval [CI], 67.65–76.73) of the 395 women who received elagolix plus E2/NETA achieved < 80 mL MBL during the final month and ≥ 50% MBL reduction from baseline to the final month. When stratified by FIGO classification, the results were similar for all subgroups: FIGO 0-3, 77.7% (95% CI, 67.21–80.85). Similar results were seen in women with a primary fibroid volume of either greater or less than 36.2 cm³ (median).³



The most frequently reported adverse events among women taking elagolix plus E2/NETA were hot flushes, night sweats, nausea, and headache. Changes in BMD among these women were not significant compared with women taking placebo.³

The Elaris UF-1 and UF-2 studies are funded by AbbVie Inc.

Whether or not women experience symptoms from uterine fibroid(s) can be dependent on a fibroid’s size and location. Heavy menstrual bleeding (HMB) is the most common symptom resulting from fibroids, and it occurs in up to one-third of women with fibroids. For fibroids that are large (>10 cm), “bulk” symptoms may occur, including pelvic pressure, urinary urgency or frequency, incontinence, constipation, abdominal protrusion, etc.¹

Elagolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was US Food and Drug Administration–approved in 2018 to treat moderate to severe pain caused by endometriosis. ² Elagolix is being evaluated in 2 phase 3 randomized, double-blind trials for the additional treatment of HMB associated with uterine fibroids. The results of these studies were presented at the 2019 AAGL meeting on November 12, in Vancouver, Canada.
 

Phase 3 study details

Premenopausal women aged 18 to 51 years were included in the Elaris UF-1 and UF-2 studies if they had HMB (defined using the alkaline hematin methodology as menstrual blood loss [MBL] >80 mL/cycle) and uterine fibroids as confirmed through ultrasound. Because elagolix suppresses estrogen and progesterone, treatment results in dose- and duration-dependent decreases in bone mineral density (BMD),² and add-back therapy can lessen these adverse effects. Subsequently, participants were randomly assigned 1:1:2 to placebo, elagolix 300 mg twice daily, or elagolix 300 mg twice daily with add-back therapy (1 mg estradiol/0.5 mg norethidrone acetate [E2/NETA]) once daily. Uterine volume and size and location of uterine fibroid(s) were assessed by ultrasound. Subgroups were defined by baseline FIGO categories, grouped FIGO 0-3, FIGO 4, or FIGO 5-8.³

Over the 6-month studies, 72.2% (95% confidence interval [CI], 67.65–76.73) of the 395 women who received elagolix plus E2/NETA achieved < 80 mL MBL during the final month and ≥ 50% MBL reduction from baseline to the final month. When stratified by FIGO classification, the results were similar for all subgroups: FIGO 0-3, 77.7% (95% CI, 67.21–80.85). Similar results were seen in women with a primary fibroid volume of either greater or less than 36.2 cm³ (median).³



The most frequently reported adverse events among women taking elagolix plus E2/NETA were hot flushes, night sweats, nausea, and headache. Changes in BMD among these women were not significant compared with women taking placebo.³

The Elaris UF-1 and UF-2 studies are funded by AbbVie Inc.

Whether or not women experience symptoms from uterine fibroid(s) can be dependent on a fibroid’s size and location. Heavy menstrual bleeding (HMB) is the most common symptom resulting from fibroids, and it occurs in up to one-third of women with fibroids. For fibroids that are large (>10 cm), “bulk” symptoms may occur, including pelvic pressure, urinary urgency or frequency, incontinence, constipation, abdominal protrusion, etc.¹

Elagolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was US Food and Drug Administration–approved in 2018 to treat moderate to severe pain caused by endometriosis. ² Elagolix is being evaluated in 2 phase 3 randomized, double-blind trials for the additional treatment of HMB associated with uterine fibroids. The results of these studies were presented at the 2019 AAGL meeting on November 12, in Vancouver, Canada.
 

Phase 3 study details

Premenopausal women aged 18 to 51 years were included in the Elaris UF-1 and UF-2 studies if they had HMB (defined using the alkaline hematin methodology as menstrual blood loss [MBL] >80 mL/cycle) and uterine fibroids as confirmed through ultrasound. Because elagolix suppresses estrogen and progesterone, treatment results in dose- and duration-dependent decreases in bone mineral density (BMD),² and add-back therapy can lessen these adverse effects. Subsequently, participants were randomly assigned 1:1:2 to placebo, elagolix 300 mg twice daily, or elagolix 300 mg twice daily with add-back therapy (1 mg estradiol/0.5 mg norethidrone acetate [E2/NETA]) once daily. Uterine volume and size and location of uterine fibroid(s) were assessed by ultrasound. Subgroups were defined by baseline FIGO categories, grouped FIGO 0-3, FIGO 4, or FIGO 5-8.³

Over the 6-month studies, 72.2% (95% confidence interval [CI], 67.65–76.73) of the 395 women who received elagolix plus E2/NETA achieved < 80 mL MBL during the final month and ≥ 50% MBL reduction from baseline to the final month. When stratified by FIGO classification, the results were similar for all subgroups: FIGO 0-3, 77.7% (95% CI, 67.21–80.85). Similar results were seen in women with a primary fibroid volume of either greater or less than 36.2 cm³ (median).³



The most frequently reported adverse events among women taking elagolix plus E2/NETA were hot flushes, night sweats, nausea, and headache. Changes in BMD among these women were not significant compared with women taking placebo.³

The Elaris UF-1 and UF-2 studies are funded by AbbVie Inc.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

The REPLENISH trial evaluated the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4) approved by the US Food and Drug Administration in October 2018 as Bijuva (TherapeuticsMD) for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause. In separate subanalyses presented at the annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019), researchers examined E2/P4’s ability to address VMS according to age and body mass index (BMI), ability to address sleep, and appropriate dosing in smokers versus nonsmokers.

REPLENISH

The REPLENISH trial was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of VMS in 1,835 postmenopausal women aged 40 to 65 years with a uterus. Women with moderate to severe VMS (≥7/day or ≥50/week) were randomly assigned to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo.¹

E2/P4 and VMS according to age and BMI

Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 versus placebo were analyzed by age (<55 and ≥55 years) and BMI in the study participants.¹ The BMI subgroups had similar baseline VMS, but women in the younger age group had higher baseline frequency of moderate to severe VMS than women in the older age group.

Age. The percent changes in VMS frequency from baseline for women treated with E2/P4 were similar at weeks 4 and 12 between age groups. While subgroup analyses were not powered for statistical significance, significant differences were observed between E2/P4 dosages and placebo at week 12. For VMS severity, the percent changes from baseline for women treated with E2/P4 ranged from 16% to 22% at week 4 and 24% to 51% for either age group at week 12.

BMI. When analyzed by BMI, larger percent reductions from baseline in VMS frequency and severity were observed with E2/P4 dosaging versus placebo, with some groups meeting statistical significance at both weeks 4 and 12.

The authors concluded that their subgroup analyses show a consistency of efficacy for VMS frequency and severity among the different age group and BMI populations of women treated with E2/P4.

E2/P4 and sleep outcomes

Participants in the REPLENISH trial took 2 surveys related to sleep—the Medical Outcomes Study (MOS)-Sleep, a 12-item questionnaire measuring 6 sleep dimensions, and the Menopause-specific Quality of Life (MENQOL), which included a “difficulty sleeping” item.² Except for women treated with E2/P4 0.25/50 at week 12, women receiving E2/P4 reported significantly better change in the MOS-Sleep total, as well as better ratings on sleep problems and disturbance subscales, than women treated with placebo at week 12 and months 6 and 12. The incidence of somnolence was low with E2/P4 treatment. In addition, sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly through improvements in VMS. The study authors concluded that women taking E2/P4 for moderate to severe VMS may experience improved sleep.

Smoking and E2/P4 dosage

Among postmenopausal women, smoking has been shown to reduce the efficacy of hormone therapy.³ Researchers found that nonsmokers (never or past smokers) may benefit more from a lower E2/P4 dosage than current smokers (<15 cigarettes per day).⁴ (Women smoking ≥15 cigarettes per day or any e-cigarettes were excluded from REPLENISH). Compared with nonsmokers taking placebo, nonsmokers taking any dosage of E2/P4 had a significant and clinically meaningful reduction in VMS frequency and severity beginning at week 4 and maintained through week 12 (except for the E2/P4 dosage of 0.5/50 at week 4 for severity). By contrast, current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo, and proportions of smokers who did measure some response to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. In addition, current smokers had significantly lower median levels of systemic estradiol and estrone concentrations with all E2/P4 treatment groups than did nonsmokers, despite both groups having similar estradiol and estrone concentrations at baseline.

Researchers from Kaiser Permanente Northwest and Oregon Health & Science University, both in Portland, performed a secondary analysis of a survey of postmenopausal women conducted to assess the impact of a health system intervention on genitourinary syndrome of menopause (GSM). They presented their results at the recent annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019). The intervention included clinician education and computer support tools and was assessed in a clinic-based, cluster-randomized trial in which primary care and gynecology clinics either received the intervention or did not. Women received follow-up 2 weeks after a well-woman visit with a survey that elicited vulvovaginal, sexual, and urinary symptoms with bother.

About 45% of those responding to the survey (N = 1,533) reported 1 or more vulvovaginal atrophy (VVA) symptoms—on average described as somewhat or moderately bothersome—but less than half of those women (39%) discussed their symptom(s) at their well-woman visit. Typically it was the woman, rather than the clinician, who initiated the discussion of the VVA symptom(s) (59% vs 22%, respectively). About 16% of women reported that both parties brought up the symptom(s). Most women (83%) were satisfied with the VVA symptom discussion. Of the women not having such a discussion, 18% wished that one had occurred. A VVA symptom discussion was positively associated with clinicians providing written materials, suggesting lubricants or vaginal estrogen, and providing a referral. Therefore, there is a greater role for clinician-initiated screening for GSM, the study authors concluded.
 

Researchers from Kaiser Permanente Northwest and Oregon Health & Science University, both in Portland, performed a secondary analysis of a survey of postmenopausal women conducted to assess the impact of a health system intervention on genitourinary syndrome of menopause (GSM). They presented their results at the recent annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019). The intervention included clinician education and computer support tools and was assessed in a clinic-based, cluster-randomized trial in which primary care and gynecology clinics either received the intervention or did not. Women received follow-up 2 weeks after a well-woman visit with a survey that elicited vulvovaginal, sexual, and urinary symptoms with bother.

About 45% of those responding to the survey (N = 1,533) reported 1 or more vulvovaginal atrophy (VVA) symptoms—on average described as somewhat or moderately bothersome—but less than half of those women (39%) discussed their symptom(s) at their well-woman visit. Typically it was the woman, rather than the clinician, who initiated the discussion of the VVA symptom(s) (59% vs 22%, respectively). About 16% of women reported that both parties brought up the symptom(s). Most women (83%) were satisfied with the VVA symptom discussion. Of the women not having such a discussion, 18% wished that one had occurred. A VVA symptom discussion was positively associated with clinicians providing written materials, suggesting lubricants or vaginal estrogen, and providing a referral. Therefore, there is a greater role for clinician-initiated screening for GSM, the study authors concluded.
 

Researchers from Kaiser Permanente Northwest and Oregon Health & Science University, both in Portland, performed a secondary analysis of a survey of postmenopausal women conducted to assess the impact of a health system intervention on genitourinary syndrome of menopause (GSM). They presented their results at the recent annual Scientific Meeting of the North American Menopause Society in Chicago, Illinois (September 25-28, 2019). The intervention included clinician education and computer support tools and was assessed in a clinic-based, cluster-randomized trial in which primary care and gynecology clinics either received the intervention or did not. Women received follow-up 2 weeks after a well-woman visit with a survey that elicited vulvovaginal, sexual, and urinary symptoms with bother.

About 45% of those responding to the survey (N = 1,533) reported 1 or more vulvovaginal atrophy (VVA) symptoms—on average described as somewhat or moderately bothersome—but less than half of those women (39%) discussed their symptom(s) at their well-woman visit. Typically it was the woman, rather than the clinician, who initiated the discussion of the VVA symptom(s) (59% vs 22%, respectively). About 16% of women reported that both parties brought up the symptom(s). Most women (83%) were satisfied with the VVA symptom discussion. Of the women not having such a discussion, 18% wished that one had occurred. A VVA symptom discussion was positively associated with clinicians providing written materials, suggesting lubricants or vaginal estrogen, and providing a referral. Therefore, there is a greater role for clinician-initiated screening for GSM, the study authors concluded.
 

To determine if a nationwide implementation of robotic minimally invasive surgery (MIS) influenced the risk of severe complications and survival among women with early-stage endometrial cancer, a group of researchers from the University of Southern Denmark studied the Danish Gynecological Cancer Database, a nationwide, mandatory prospective registration of new cases of women with endometrial cancer who received their surgical treatment in a public hospital.¹ Siv Joergensen, MD, reported results at the 47th AAGL Global Congress on Minimally Invasive Gynecology annual meeting on November 13, 2018, in Las Vegas, Nevada.

The transition to robotic MIS was undertaken in Denmark from 2008 to 2013, with the centralization of endometrial cancer treatment in 2012. Over the span of 10 years, the surgical approach to treatment changed from 97% open access surgery to 95% MIS.

For the prospective cohort study, more than 7,000 women with endometrial cancer who received a hysterectomy from January 2005 to June 2015 were grouped by those receiving surgical care before (group 1) and after (group 2) robotic MIS implementation in Denmark. A total of 5,654 women with FIGO Stage I–II endometrial cancer were included in the final study.

Severe complications were 7.3% in group 1 and 6.2% in group 2 (odds ratio, 1.38; 95% confidence interval [CI], 1.10–1.73). Five-year survival rates were significantly lower before robotic MIS was implemented (hazard ratio, 1.22; 95% CI, 1.05–1.41), and no difference was found between laparoscopic and robotic MIS.

The authors concluded that nationwide implementation of robotic MIS enabled a shift toward all types of MIS (with a 73% reduction in hysterectomies performed by laparotomy) and translated into reduced risk of severe complications and increased survival.

How do these results compare with those in the United States?

According to Erica Dun, MD, MPH, who provided commentary for Dr. Joergensen’s study, the United States adopted robotic MIS in the early 2000s. Around 2008, 14% of hysterectomies performed for early-stage endometrial cancer were done through a MIS approach.² In 2014, after a study in which Walker and colleagues found that laparoscopy was safe and feasible compared with laparotomy,³ the American College of Obstetricians and Gynecologists, jointly with the Society of Gynecologic Oncologists, stated that “MIS should be embraced as the standard surgical approach for comprehensive surgical staging in women with endometrial cancer.”⁴

Dr. Dun pointed out that Casarin and colleagues found in 2018 that 71.4% of surgeries performed in the United States for endometrial cancer were performed through MIS.⁵ That number rose to 86.5% MIS (72.5% robot-assisted) for centers of the National Comprehensive Cancer Network.⁶

Dr. Dun concluded that nationwide implementation of robotic MIS is feasible for gynecologic oncologists, and it is beneficial for patients.

To determine if a nationwide implementation of robotic minimally invasive surgery (MIS) influenced the risk of severe complications and survival among women with early-stage endometrial cancer, a group of researchers from the University of Southern Denmark studied the Danish Gynecological Cancer Database, a nationwide, mandatory prospective registration of new cases of women with endometrial cancer who received their surgical treatment in a public hospital.¹ Siv Joergensen, MD, reported results at the 47th AAGL Global Congress on Minimally Invasive Gynecology annual meeting on November 13, 2018, in Las Vegas, Nevada.

The transition to robotic MIS was undertaken in Denmark from 2008 to 2013, with the centralization of endometrial cancer treatment in 2012. Over the span of 10 years, the surgical approach to treatment changed from 97% open access surgery to 95% MIS.

For the prospective cohort study, more than 7,000 women with endometrial cancer who received a hysterectomy from January 2005 to June 2015 were grouped by those receiving surgical care before (group 1) and after (group 2) robotic MIS implementation in Denmark. A total of 5,654 women with FIGO Stage I–II endometrial cancer were included in the final study.

Severe complications were 7.3% in group 1 and 6.2% in group 2 (odds ratio, 1.38; 95% confidence interval [CI], 1.10–1.73). Five-year survival rates were significantly lower before robotic MIS was implemented (hazard ratio, 1.22; 95% CI, 1.05–1.41), and no difference was found between laparoscopic and robotic MIS.

The authors concluded that nationwide implementation of robotic MIS enabled a shift toward all types of MIS (with a 73% reduction in hysterectomies performed by laparotomy) and translated into reduced risk of severe complications and increased survival.

How do these results compare with those in the United States?

According to Erica Dun, MD, MPH, who provided commentary for Dr. Joergensen’s study, the United States adopted robotic MIS in the early 2000s. Around 2008, 14% of hysterectomies performed for early-stage endometrial cancer were done through a MIS approach.² In 2014, after a study in which Walker and colleagues found that laparoscopy was safe and feasible compared with laparotomy,³ the American College of Obstetricians and Gynecologists, jointly with the Society of Gynecologic Oncologists, stated that “MIS should be embraced as the standard surgical approach for comprehensive surgical staging in women with endometrial cancer.”⁴

Dr. Dun pointed out that Casarin and colleagues found in 2018 that 71.4% of surgeries performed in the United States for endometrial cancer were performed through MIS.⁵ That number rose to 86.5% MIS (72.5% robot-assisted) for centers of the National Comprehensive Cancer Network.⁶

Dr. Dun concluded that nationwide implementation of robotic MIS is feasible for gynecologic oncologists, and it is beneficial for patients.

To determine if a nationwide implementation of robotic minimally invasive surgery (MIS) influenced the risk of severe complications and survival among women with early-stage endometrial cancer, a group of researchers from the University of Southern Denmark studied the Danish Gynecological Cancer Database, a nationwide, mandatory prospective registration of new cases of women with endometrial cancer who received their surgical treatment in a public hospital.¹ Siv Joergensen, MD, reported results at the 47th AAGL Global Congress on Minimally Invasive Gynecology annual meeting on November 13, 2018, in Las Vegas, Nevada.

The transition to robotic MIS was undertaken in Denmark from 2008 to 2013, with the centralization of endometrial cancer treatment in 2012. Over the span of 10 years, the surgical approach to treatment changed from 97% open access surgery to 95% MIS.

For the prospective cohort study, more than 7,000 women with endometrial cancer who received a hysterectomy from January 2005 to June 2015 were grouped by those receiving surgical care before (group 1) and after (group 2) robotic MIS implementation in Denmark. A total of 5,654 women with FIGO Stage I–II endometrial cancer were included in the final study.

Severe complications were 7.3% in group 1 and 6.2% in group 2 (odds ratio, 1.38; 95% confidence interval [CI], 1.10–1.73). Five-year survival rates were significantly lower before robotic MIS was implemented (hazard ratio, 1.22; 95% CI, 1.05–1.41), and no difference was found between laparoscopic and robotic MIS.

The authors concluded that nationwide implementation of robotic MIS enabled a shift toward all types of MIS (with a 73% reduction in hysterectomies performed by laparotomy) and translated into reduced risk of severe complications and increased survival.

How do these results compare with those in the United States?

According to Erica Dun, MD, MPH, who provided commentary for Dr. Joergensen’s study, the United States adopted robotic MIS in the early 2000s. Around 2008, 14% of hysterectomies performed for early-stage endometrial cancer were done through a MIS approach.² In 2014, after a study in which Walker and colleagues found that laparoscopy was safe and feasible compared with laparotomy,³ the American College of Obstetricians and Gynecologists, jointly with the Society of Gynecologic Oncologists, stated that “MIS should be embraced as the standard surgical approach for comprehensive surgical staging in women with endometrial cancer.”⁴

Dr. Dun pointed out that Casarin and colleagues found in 2018 that 71.4% of surgeries performed in the United States for endometrial cancer were performed through MIS.⁵ That number rose to 86.5% MIS (72.5% robot-assisted) for centers of the National Comprehensive Cancer Network.⁶

Dr. Dun concluded that nationwide implementation of robotic MIS is feasible for gynecologic oncologists, and it is beneficial for patients.

In order to identify the prevalence of concerns among postpartum women and the factors associated with them, the University of California–San Francisco (UCSF) began calling all of its obstetric patients through an automated phone call within 72 hours after hospital discharge.

Study details

All postpartum women from March to June 2017 were contacted after discharge via an automated call. Calls were considered successful if the woman engaged with the automated system; those who reported concerns were contacted by a nurse. UCSF researchers compared call success and presence of concerns by mode of delivery, insurance type (public or private), parity, pregnancy complication (diabetes, hypertension, hemorrhage), and neonatal intensive care (ICN) admission using univariate analyses and multivariable logistic regression.

A total of 881 women were called, and 730 (83%) were successfully contacted (meaning they engaged with the automated system through to the end of the call). About one-third of women (224 / 29%) reported a concern. Women with operative vaginal delivery were more likely to report an issue than spontaneous vaginal and cesarean delivery (42% vs 28%; P = .04). Nulliparous women also were more likely to report an issue (32% vs 25%; P = .05). They also were more likely to answer the call (86% vs 79%; P = .004). Women with public insurance were less likely to be successfully contacted (68% vs 84%; P = .003), but the frequency of concerns were equivalent (28% vs 29%). Women with neonates in the ICN were less likely to be successfully contacted. When controlling for confounders, nulliparity (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1–2.2) and private insurance (OR, 1.9; 95% CI, 1.1–3.8) both were independently associated with successful contact.

What do the results mean for practice?

Nulliparous women and women with operative vaginal deliveries may benefit from additional discharge support, concluded the researchers. “For most patients we can’t predict in advance if they will have an operative vaginal delivery but I do think that we could do more counseling in the antepartum period about different options or mode of delivery and include operative vaginal deliveries in that bucket, especially as we are doing more of them,” said Dr. Molly Siegel, Resident at UCSF. “In the postpartum period we probably should be thinking more about our instructions to those patients because we have cesarean delivery and vaginal delivery discharge instructions, and I think there needs to be something specific for operative vaginal delivery. Ultimately the goal is to improve our counseling of patients so that they don’t have as many questions after they leave the hospital.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

In order to identify the prevalence of concerns among postpartum women and the factors associated with them, the University of California–San Francisco (UCSF) began calling all of its obstetric patients through an automated phone call within 72 hours after hospital discharge.

Study details

All postpartum women from March to June 2017 were contacted after discharge via an automated call. Calls were considered successful if the woman engaged with the automated system; those who reported concerns were contacted by a nurse. UCSF researchers compared call success and presence of concerns by mode of delivery, insurance type (public or private), parity, pregnancy complication (diabetes, hypertension, hemorrhage), and neonatal intensive care (ICN) admission using univariate analyses and multivariable logistic regression.

A total of 881 women were called, and 730 (83%) were successfully contacted (meaning they engaged with the automated system through to the end of the call). About one-third of women (224 / 29%) reported a concern. Women with operative vaginal delivery were more likely to report an issue than spontaneous vaginal and cesarean delivery (42% vs 28%; P = .04). Nulliparous women also were more likely to report an issue (32% vs 25%; P = .05). They also were more likely to answer the call (86% vs 79%; P = .004). Women with public insurance were less likely to be successfully contacted (68% vs 84%; P = .003), but the frequency of concerns were equivalent (28% vs 29%). Women with neonates in the ICN were less likely to be successfully contacted. When controlling for confounders, nulliparity (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1–2.2) and private insurance (OR, 1.9; 95% CI, 1.1–3.8) both were independently associated with successful contact.

What do the results mean for practice?

Nulliparous women and women with operative vaginal deliveries may benefit from additional discharge support, concluded the researchers. “For most patients we can’t predict in advance if they will have an operative vaginal delivery but I do think that we could do more counseling in the antepartum period about different options or mode of delivery and include operative vaginal deliveries in that bucket, especially as we are doing more of them,” said Dr. Molly Siegel, Resident at UCSF. “In the postpartum period we probably should be thinking more about our instructions to those patients because we have cesarean delivery and vaginal delivery discharge instructions, and I think there needs to be something specific for operative vaginal delivery. Ultimately the goal is to improve our counseling of patients so that they don’t have as many questions after they leave the hospital.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

In order to identify the prevalence of concerns among postpartum women and the factors associated with them, the University of California–San Francisco (UCSF) began calling all of its obstetric patients through an automated phone call within 72 hours after hospital discharge.

Study details

All postpartum women from March to June 2017 were contacted after discharge via an automated call. Calls were considered successful if the woman engaged with the automated system; those who reported concerns were contacted by a nurse. UCSF researchers compared call success and presence of concerns by mode of delivery, insurance type (public or private), parity, pregnancy complication (diabetes, hypertension, hemorrhage), and neonatal intensive care (ICN) admission using univariate analyses and multivariable logistic regression.

A total of 881 women were called, and 730 (83%) were successfully contacted (meaning they engaged with the automated system through to the end of the call). About one-third of women (224 / 29%) reported a concern. Women with operative vaginal delivery were more likely to report an issue than spontaneous vaginal and cesarean delivery (42% vs 28%; P = .04). Nulliparous women also were more likely to report an issue (32% vs 25%; P = .05). They also were more likely to answer the call (86% vs 79%; P = .004). Women with public insurance were less likely to be successfully contacted (68% vs 84%; P = .003), but the frequency of concerns were equivalent (28% vs 29%). Women with neonates in the ICN were less likely to be successfully contacted. When controlling for confounders, nulliparity (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1–2.2) and private insurance (OR, 1.9; 95% CI, 1.1–3.8) both were independently associated with successful contact.

What do the results mean for practice?

Nulliparous women and women with operative vaginal deliveries may benefit from additional discharge support, concluded the researchers. “For most patients we can’t predict in advance if they will have an operative vaginal delivery but I do think that we could do more counseling in the antepartum period about different options or mode of delivery and include operative vaginal deliveries in that bucket, especially as we are doing more of them,” said Dr. Molly Siegel, Resident at UCSF. “In the postpartum period we probably should be thinking more about our instructions to those patients because we have cesarean delivery and vaginal delivery discharge instructions, and I think there needs to be something specific for operative vaginal delivery. Ultimately the goal is to improve our counseling of patients so that they don’t have as many questions after they leave the hospital.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

Access ACOG/SMFM algorithm for treatment of pregnant women with flu-like illness

Access ACOG/SMFM algorithm for treatment of pregnant women with flu-like illness

Access ACOG/SMFM algorithm for treatment of pregnant women with flu-like illness

Drug overdose is the leading cause of death for Americans under age 50. And the number of men and women dying from drug overdose shows no abating, with a sharp 17% increase in 2016 over 2015.¹ The rate of fatal overdoses rose to nearly 20 people per 100,000 in 2016, according to the Centers for Disease Control and Prevention. The highest death rates are reported in West Virginia, New Hampshire, Kentucky, Ohio, and Rhode Island.²

Dr. Andrew Kolodny, director of opioid policy research at Brandeis University, told The New York Times that there are “roughly two groups of Americans that are getting addicted. We have an older group that is overdosing on pain medicine, and we have a younger group that is overdosing on black market opioids.”¹

Are ObGyns contributing to the over-prescription of opioid pain medications? Investigators from Florida Hospital, the University of Florida, and Orlando VA Medical Center are researching the question, and preliminary findings indicate that, yes, in fact “gynecologists are overprescribing postoperative prescription opioids in all levels of gynecologic surgery,” including after laparotomies and major and minor minimally invasive surgeries. Their work thus far, a prospective cohort study involving 113 patients enrolled to date, was presented November 15, 2017, in Washington, DC, as part of the 46th AAGL Global Congress on MIGS. They found that, on average, patients were prescribed 29.6 (SD, 9.3) opioid tablets, and they had 19.1 (SD, 12.6) tablets left over after surgery. Not surprisingly, patients undergoing major minimally invasive surgery and laparotomy were prescribed larger amounts of opioids than those undergoing minor minimally invasive surgery, but the amount of pain medication left over was similar regardless of surgery type.

The researchers also asked patients if they were told how to dispose of their leftover opioids; only 3 patients reported being told what to do if they had leftover medication.

Too many pills prescribed

In separate research presented at the meeting, investigators from Tufts Medical Center and Lahey Hospital and Medical Center in Boston, Massachusetts, sought to determine opioid prescription practices and patient opioid use after benign hysterectomy. Using retrospective online physician and telephone patient surveys, they found that 51 gynecologists prescribed a median of 30 tabs of oxycodone or hydromorphone after abdominal hysterectomy and a median of 20 tabs after laparoscopic or vaginal hysterectomy. Nearly 65% (36/56) of women used less than half of the opioids they were prescribed, and 16.1% (9/56) used zero tabs. Opioid use was not found to be significantly different for women undergoing abdominal versus minimally invasive hysterectomy.

Managing pain expectations

It takes only 3 days of opioid use for a patient to be at risk for continued use (1 to 3 years) of opioids, said Georgine Lamvu, MD, MPH, CPE, in the educational session “Perioperative Management of the Chronic Pain Patient” at the AAGL meeting. And long-term opioid use is associated with addiction, misuse, and mortality.³ It is therefore crucial to understand how to prescribe pain medications and how to educate women on expectations of pain relief.

Dr. Lamvu and fellow presenters described a 4-step process to pain management: 1) assess—including taking a history and physical exam and providing a risk assessment; 2) check—for other medications that a patient may be taking and possible interactions, as well make sure that the patient is not obtaining opioids or benzodiazepines from other providers; 3) discuss—what pain expectations you have for the patient following surgery; and 4) observe—for clinical improvement, overuse, and misuse, and go slow with dose increases and consult support pain management teams when needed.

Overall, they recommended that surgeons perform a risk assessment (determine the risks and benefits of available therapies); educate themselves and their patients on the risks and benefits; and document the risk assessment, the final recommendations to the patient, and the education provided to the patient.

“We need to do a lot better job at educating ourselves and our patients about pain medications and pain management strategies,” said Dr. Lamvu. The presenters provided these key points for patient and family education:

• Opioids are not first-line or routine therapy for chronic pain, and for acute pain they are used only for severe pain and in short-duration amounts.
• Analgesia will not make you pain free. It only helps to alleviate some pain, and most pain medications take 1 to 2 hours to take effect.
• A 30% improvement in pain and function can be expected for most therapies.
• Recovery from surgical or acute traumatic injury is not immediate; it is expected to take 2 to 4 weeks.
• Do not take extra medication doses beyond what is prescribed, and tell all of your providers what medications you are taking.
• Do not stop taking opioids suddenly, instead taper the dose slowly as instructed by your provider.
• Dispose of excess drugs appropriately—by taking unused pills back to your provider or crushing the pills, placing them in a small amount of liquid, and putting them in the trash.

“The reality is that the majority of patients are not using as many pills as we give them,” said Dr. Lamvu. “Adequate pain control does not supersede patient safety or the responsibility that we have as providers to our society.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Drug overdose is the leading cause of death for Americans under age 50. And the number of men and women dying from drug overdose shows no abating, with a sharp 17% increase in 2016 over 2015.¹ The rate of fatal overdoses rose to nearly 20 people per 100,000 in 2016, according to the Centers for Disease Control and Prevention. The highest death rates are reported in West Virginia, New Hampshire, Kentucky, Ohio, and Rhode Island.²

Dr. Andrew Kolodny, director of opioid policy research at Brandeis University, told The New York Times that there are “roughly two groups of Americans that are getting addicted. We have an older group that is overdosing on pain medicine, and we have a younger group that is overdosing on black market opioids.”¹

Are ObGyns contributing to the over-prescription of opioid pain medications? Investigators from Florida Hospital, the University of Florida, and Orlando VA Medical Center are researching the question, and preliminary findings indicate that, yes, in fact “gynecologists are overprescribing postoperative prescription opioids in all levels of gynecologic surgery,” including after laparotomies and major and minor minimally invasive surgeries. Their work thus far, a prospective cohort study involving 113 patients enrolled to date, was presented November 15, 2017, in Washington, DC, as part of the 46th AAGL Global Congress on MIGS. They found that, on average, patients were prescribed 29.6 (SD, 9.3) opioid tablets, and they had 19.1 (SD, 12.6) tablets left over after surgery. Not surprisingly, patients undergoing major minimally invasive surgery and laparotomy were prescribed larger amounts of opioids than those undergoing minor minimally invasive surgery, but the amount of pain medication left over was similar regardless of surgery type.

The researchers also asked patients if they were told how to dispose of their leftover opioids; only 3 patients reported being told what to do if they had leftover medication.

Too many pills prescribed

In separate research presented at the meeting, investigators from Tufts Medical Center and Lahey Hospital and Medical Center in Boston, Massachusetts, sought to determine opioid prescription practices and patient opioid use after benign hysterectomy. Using retrospective online physician and telephone patient surveys, they found that 51 gynecologists prescribed a median of 30 tabs of oxycodone or hydromorphone after abdominal hysterectomy and a median of 20 tabs after laparoscopic or vaginal hysterectomy. Nearly 65% (36/56) of women used less than half of the opioids they were prescribed, and 16.1% (9/56) used zero tabs. Opioid use was not found to be significantly different for women undergoing abdominal versus minimally invasive hysterectomy.

Managing pain expectations

It takes only 3 days of opioid use for a patient to be at risk for continued use (1 to 3 years) of opioids, said Georgine Lamvu, MD, MPH, CPE, in the educational session “Perioperative Management of the Chronic Pain Patient” at the AAGL meeting. And long-term opioid use is associated with addiction, misuse, and mortality.³ It is therefore crucial to understand how to prescribe pain medications and how to educate women on expectations of pain relief.

Dr. Lamvu and fellow presenters described a 4-step process to pain management: 1) assess—including taking a history and physical exam and providing a risk assessment; 2) check—for other medications that a patient may be taking and possible interactions, as well make sure that the patient is not obtaining opioids or benzodiazepines from other providers; 3) discuss—what pain expectations you have for the patient following surgery; and 4) observe—for clinical improvement, overuse, and misuse, and go slow with dose increases and consult support pain management teams when needed.

Overall, they recommended that surgeons perform a risk assessment (determine the risks and benefits of available therapies); educate themselves and their patients on the risks and benefits; and document the risk assessment, the final recommendations to the patient, and the education provided to the patient.

“We need to do a lot better job at educating ourselves and our patients about pain medications and pain management strategies,” said Dr. Lamvu. The presenters provided these key points for patient and family education:

• Opioids are not first-line or routine therapy for chronic pain, and for acute pain they are used only for severe pain and in short-duration amounts.
• Analgesia will not make you pain free. It only helps to alleviate some pain, and most pain medications take 1 to 2 hours to take effect.
• A 30% improvement in pain and function can be expected for most therapies.
• Recovery from surgical or acute traumatic injury is not immediate; it is expected to take 2 to 4 weeks.
• Do not take extra medication doses beyond what is prescribed, and tell all of your providers what medications you are taking.
• Do not stop taking opioids suddenly, instead taper the dose slowly as instructed by your provider.
• Dispose of excess drugs appropriately—by taking unused pills back to your provider or crushing the pills, placing them in a small amount of liquid, and putting them in the trash.

“The reality is that the majority of patients are not using as many pills as we give them,” said Dr. Lamvu. “Adequate pain control does not supersede patient safety or the responsibility that we have as providers to our society.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Drug overdose is the leading cause of death for Americans under age 50. And the number of men and women dying from drug overdose shows no abating, with a sharp 17% increase in 2016 over 2015.¹ The rate of fatal overdoses rose to nearly 20 people per 100,000 in 2016, according to the Centers for Disease Control and Prevention. The highest death rates are reported in West Virginia, New Hampshire, Kentucky, Ohio, and Rhode Island.²

Dr. Andrew Kolodny, director of opioid policy research at Brandeis University, told The New York Times that there are “roughly two groups of Americans that are getting addicted. We have an older group that is overdosing on pain medicine, and we have a younger group that is overdosing on black market opioids.”¹

Are ObGyns contributing to the over-prescription of opioid pain medications? Investigators from Florida Hospital, the University of Florida, and Orlando VA Medical Center are researching the question, and preliminary findings indicate that, yes, in fact “gynecologists are overprescribing postoperative prescription opioids in all levels of gynecologic surgery,” including after laparotomies and major and minor minimally invasive surgeries. Their work thus far, a prospective cohort study involving 113 patients enrolled to date, was presented November 15, 2017, in Washington, DC, as part of the 46th AAGL Global Congress on MIGS. They found that, on average, patients were prescribed 29.6 (SD, 9.3) opioid tablets, and they had 19.1 (SD, 12.6) tablets left over after surgery. Not surprisingly, patients undergoing major minimally invasive surgery and laparotomy were prescribed larger amounts of opioids than those undergoing minor minimally invasive surgery, but the amount of pain medication left over was similar regardless of surgery type.

The researchers also asked patients if they were told how to dispose of their leftover opioids; only 3 patients reported being told what to do if they had leftover medication.

Too many pills prescribed

In separate research presented at the meeting, investigators from Tufts Medical Center and Lahey Hospital and Medical Center in Boston, Massachusetts, sought to determine opioid prescription practices and patient opioid use after benign hysterectomy. Using retrospective online physician and telephone patient surveys, they found that 51 gynecologists prescribed a median of 30 tabs of oxycodone or hydromorphone after abdominal hysterectomy and a median of 20 tabs after laparoscopic or vaginal hysterectomy. Nearly 65% (36/56) of women used less than half of the opioids they were prescribed, and 16.1% (9/56) used zero tabs. Opioid use was not found to be significantly different for women undergoing abdominal versus minimally invasive hysterectomy.

Managing pain expectations

It takes only 3 days of opioid use for a patient to be at risk for continued use (1 to 3 years) of opioids, said Georgine Lamvu, MD, MPH, CPE, in the educational session “Perioperative Management of the Chronic Pain Patient” at the AAGL meeting. And long-term opioid use is associated with addiction, misuse, and mortality.³ It is therefore crucial to understand how to prescribe pain medications and how to educate women on expectations of pain relief.

Dr. Lamvu and fellow presenters described a 4-step process to pain management: 1) assess—including taking a history and physical exam and providing a risk assessment; 2) check—for other medications that a patient may be taking and possible interactions, as well make sure that the patient is not obtaining opioids or benzodiazepines from other providers; 3) discuss—what pain expectations you have for the patient following surgery; and 4) observe—for clinical improvement, overuse, and misuse, and go slow with dose increases and consult support pain management teams when needed.

Overall, they recommended that surgeons perform a risk assessment (determine the risks and benefits of available therapies); educate themselves and their patients on the risks and benefits; and document the risk assessment, the final recommendations to the patient, and the education provided to the patient.

“We need to do a lot better job at educating ourselves and our patients about pain medications and pain management strategies,” said Dr. Lamvu. The presenters provided these key points for patient and family education:

• Opioids are not first-line or routine therapy for chronic pain, and for acute pain they are used only for severe pain and in short-duration amounts.
• Analgesia will not make you pain free. It only helps to alleviate some pain, and most pain medications take 1 to 2 hours to take effect.
• A 30% improvement in pain and function can be expected for most therapies.
• Recovery from surgical or acute traumatic injury is not immediate; it is expected to take 2 to 4 weeks.
• Do not take extra medication doses beyond what is prescribed, and tell all of your providers what medications you are taking.
• Do not stop taking opioids suddenly, instead taper the dose slowly as instructed by your provider.
• Dispose of excess drugs appropriately—by taking unused pills back to your provider or crushing the pills, placing them in a small amount of liquid, and putting them in the trash.

“The reality is that the majority of patients are not using as many pills as we give them,” said Dr. Lamvu. “Adequate pain control does not supersede patient safety or the responsibility that we have as providers to our society.”

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Up to 80% of women who are of reproductive age have uterine fibroids that cause heavy and prolonged bleeding.¹ Additional concerns include infertility and pain, says James Simon, MD, Clinical Professor at George Washington University in Washington, DC. Black women are more likely than white women to undergo hysterectomy for uterine fibroids. They also are more likely to experience severe or very severe symptoms from fibroids and report that these symptoms interfere with physical activities, relationships, and work.²

Current medical treatments include on- and off-label use of oral contraceptives, gonadotropin-releasing hormone (GnRH) receptor agonists, and progestins. Data on investigational oral GnRH antagonists and oral selective progesterone-receptor modulators (SPRMs) were presented at the 2017 Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists.

Details of VENUS I

In the phase 3, randomized, controlled VENUS I trial, investigators assessed the efficacy and safety of ulipristal acetate (UPA), an SPRM, by race and body mass index (BMI) in premenopausal women (aged 18 to 50) with symptomatic uterine fibroids.¹

Simon and colleagues randomly assigned participants to UPA 5 mg, UPA 10 mg, or placebo once daily for 12 weeks, followed by a 12-week treatment-free follow-up period. UPA, at 5 and 10 mg, was significantly more efficacious than placebo in rate of and time to amenorrhea (P<.0001). The superiority was observed regardless of race and BMI. In addition, women taking UPA versus placebo reported significantly less impact on activities due to uterine fibroids. The study authors concluded that “UPA treatment provides effective control of bleeding and improvement in physical and social activities for women with symptomatic uterine fibroids, regardless of race and BMI.”¹

Establishing the ideal treatment period for UPA to avoid progesterone-associated endometrial changes (in this study it was 12 weeks of once-daily therapy) is a current goal, said Simon.

Details of elagolix phase 2b study

Simon also presented data on another investigational drug, elagolix, an orally administered GnRH antagonist, which has an inhibiting effect on luteinizing hormone and follicle-stimulating hormone secretion. This in turn reduces production of estradiol and progesterone. Elagolix also is being studied for the treatment of endometriosis.³

In the uterine fibroids study, a 24-week, multicenter, double-blind, randomized controlled, parallel group trial, 567 premenopausal women aged 18 to 51 with heavy menstrual bleeding of >80 mL of blood loss were assigned to placebo or elagolix 300 mg twice per day or 600 mg once per day alone or in combination with add-back therapy (with estradiol/norethindrone acetate) to prevent bone loss and menopausal symptoms.⁴

Compared with placebo, women treated with elagolix with or without add-back therapy had significant reductions from baseline in mean menstrual blood loss. Women treated with elagolix also had significant increases in hemoglobin concentration from baseline to month 6 compared with placebo.⁴

Adverse effects were similar to menopause symptoms: bone loss, hot flashes, night sweats, headaches, and disturbed sleep, said Simon. With the add-back treatments, adverse effects were mitigated in a dose-dependent fashion, he pointed out, and were most likely tolerable compared with the heavy bleeding experienced by women at the start of the study.

Up to 80% of women who are of reproductive age have uterine fibroids that cause heavy and prolonged bleeding.¹ Additional concerns include infertility and pain, says James Simon, MD, Clinical Professor at George Washington University in Washington, DC. Black women are more likely than white women to undergo hysterectomy for uterine fibroids. They also are more likely to experience severe or very severe symptoms from fibroids and report that these symptoms interfere with physical activities, relationships, and work.²

Current medical treatments include on- and off-label use of oral contraceptives, gonadotropin-releasing hormone (GnRH) receptor agonists, and progestins. Data on investigational oral GnRH antagonists and oral selective progesterone-receptor modulators (SPRMs) were presented at the 2017 Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists.

Details of VENUS I

In the phase 3, randomized, controlled VENUS I trial, investigators assessed the efficacy and safety of ulipristal acetate (UPA), an SPRM, by race and body mass index (BMI) in premenopausal women (aged 18 to 50) with symptomatic uterine fibroids.¹

Simon and colleagues randomly assigned participants to UPA 5 mg, UPA 10 mg, or placebo once daily for 12 weeks, followed by a 12-week treatment-free follow-up period. UPA, at 5 and 10 mg, was significantly more efficacious than placebo in rate of and time to amenorrhea (P<.0001). The superiority was observed regardless of race and BMI. In addition, women taking UPA versus placebo reported significantly less impact on activities due to uterine fibroids. The study authors concluded that “UPA treatment provides effective control of bleeding and improvement in physical and social activities for women with symptomatic uterine fibroids, regardless of race and BMI.”¹

Establishing the ideal treatment period for UPA to avoid progesterone-associated endometrial changes (in this study it was 12 weeks of once-daily therapy) is a current goal, said Simon.

Details of elagolix phase 2b study

Simon also presented data on another investigational drug, elagolix, an orally administered GnRH antagonist, which has an inhibiting effect on luteinizing hormone and follicle-stimulating hormone secretion. This in turn reduces production of estradiol and progesterone. Elagolix also is being studied for the treatment of endometriosis.³

In the uterine fibroids study, a 24-week, multicenter, double-blind, randomized controlled, parallel group trial, 567 premenopausal women aged 18 to 51 with heavy menstrual bleeding of >80 mL of blood loss were assigned to placebo or elagolix 300 mg twice per day or 600 mg once per day alone or in combination with add-back therapy (with estradiol/norethindrone acetate) to prevent bone loss and menopausal symptoms.⁴

Compared with placebo, women treated with elagolix with or without add-back therapy had significant reductions from baseline in mean menstrual blood loss. Women treated with elagolix also had significant increases in hemoglobin concentration from baseline to month 6 compared with placebo.⁴

Adverse effects were similar to menopause symptoms: bone loss, hot flashes, night sweats, headaches, and disturbed sleep, said Simon. With the add-back treatments, adverse effects were mitigated in a dose-dependent fashion, he pointed out, and were most likely tolerable compared with the heavy bleeding experienced by women at the start of the study.

Up to 80% of women who are of reproductive age have uterine fibroids that cause heavy and prolonged bleeding.¹ Additional concerns include infertility and pain, says James Simon, MD, Clinical Professor at George Washington University in Washington, DC. Black women are more likely than white women to undergo hysterectomy for uterine fibroids. They also are more likely to experience severe or very severe symptoms from fibroids and report that these symptoms interfere with physical activities, relationships, and work.²

Current medical treatments include on- and off-label use of oral contraceptives, gonadotropin-releasing hormone (GnRH) receptor agonists, and progestins. Data on investigational oral GnRH antagonists and oral selective progesterone-receptor modulators (SPRMs) were presented at the 2017 Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists.

Details of VENUS I

In the phase 3, randomized, controlled VENUS I trial, investigators assessed the efficacy and safety of ulipristal acetate (UPA), an SPRM, by race and body mass index (BMI) in premenopausal women (aged 18 to 50) with symptomatic uterine fibroids.¹

Simon and colleagues randomly assigned participants to UPA 5 mg, UPA 10 mg, or placebo once daily for 12 weeks, followed by a 12-week treatment-free follow-up period. UPA, at 5 and 10 mg, was significantly more efficacious than placebo in rate of and time to amenorrhea (P<.0001). The superiority was observed regardless of race and BMI. In addition, women taking UPA versus placebo reported significantly less impact on activities due to uterine fibroids. The study authors concluded that “UPA treatment provides effective control of bleeding and improvement in physical and social activities for women with symptomatic uterine fibroids, regardless of race and BMI.”¹

Establishing the ideal treatment period for UPA to avoid progesterone-associated endometrial changes (in this study it was 12 weeks of once-daily therapy) is a current goal, said Simon.

Details of elagolix phase 2b study

Simon also presented data on another investigational drug, elagolix, an orally administered GnRH antagonist, which has an inhibiting effect on luteinizing hormone and follicle-stimulating hormone secretion. This in turn reduces production of estradiol and progesterone. Elagolix also is being studied for the treatment of endometriosis.³

In the uterine fibroids study, a 24-week, multicenter, double-blind, randomized controlled, parallel group trial, 567 premenopausal women aged 18 to 51 with heavy menstrual bleeding of >80 mL of blood loss were assigned to placebo or elagolix 300 mg twice per day or 600 mg once per day alone or in combination with add-back therapy (with estradiol/norethindrone acetate) to prevent bone loss and menopausal symptoms.⁴

Compared with placebo, women treated with elagolix with or without add-back therapy had significant reductions from baseline in mean menstrual blood loss. Women treated with elagolix also had significant increases in hemoglobin concentration from baseline to month 6 compared with placebo.⁴

Adverse effects were similar to menopause symptoms: bone loss, hot flashes, night sweats, headaches, and disturbed sleep, said Simon. With the add-back treatments, adverse effects were mitigated in a dose-dependent fashion, he pointed out, and were most likely tolerable compared with the heavy bleeding experienced by women at the start of the study.

JoAnn Pinkerton, MD, Professor of Obstetrics and Gynecology at the University of Virginia, Executive Director of the North American Menopause Society (NAMS), and OBG Management Board of Editors Member, revealed the 2016 NAMS position statement on hormone therapy (HT) in Orlando, Florida, on Thursday, October 6, at the NAMS 2016 Annual Scientific Meeting.

The process of consensus among the more than 20 menopause experts who authored the 2016 statement was at times a challenge, indicated Pinkerton, given the variance in views on the significance of published clinical trial findings since the Society’s 2012¹ HT position statement. Over a 9-month period, the experts developed guidelines for clinicians, using levels of evidence to identify strength of the recommendations.

The clearest benefit for HT to treat hot flashes and prevent bone loss was found for women aged younger than 60 years and within 10 years of menopause onset.

According to the 2016 statement presented at NAMS:

Level I US Food and Drug Administration (FDA)-approved indications for HT include:

• as first-line therapy for women with vasomotor symptoms (VMS) of menopause without contraindications
• possible first-line therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk for fracture (primarily for women aged younger than 60 years and within 10 years of menopause onset)
• low-dose vaginal estrogen as first-line treatment for women with isolated genitourinary symptoms caused by menopause (genitourinary syndrome of menopause [GSM]/vulvovaginal atrophy).

Level II FDA-approved indications for HT include:

• at least until age 52 (the median age of menopause onset) for women with early onset menopause (women with hypogonadism, primary ovarian insufficiency, or premature surgical menopause) and no HT contraindications.

Other level II indications, with observational data indicating benefit over risk, for HT include:

• at least until the median age of menopause for women with early onset menopause
• consideration among women with a family history of breast cancer, although family history is one risk among many for breast cancer that should be assessed
• benefit/risk consideration for women with a BRCA gene mutation who have undergone risk-reducing oophorectomy
• consideration of systemic use until the median age of menopause—after appropriate counseling and in the absence of HT contraindications, with longer duration of HT use individualized.

Level III indications for HT include:

• individualized decisions on use after the age of 60. (The position statement authors did not find that the current Beers criteria recommendation to routinely discontinue HT at age 65 was supported by data.)

The 2016 bottom line on HT

Overall, HT has clear benefits for the treatment of VMS and bone loss prevention, according to the presented position statement. These benefits are most favorable among women aged younger than 60 years who are within 10 years of menopause onset and have no contraindications to HT use. Women older than age 60 who initiate HT beyond 10 years of menopause onset appear to have a less favorable benefit-risk ratio because of elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

The risks of HT vary among women depending on the HT type, duration of use, administration route, timing of treatment initiation, and whether a progestogen is needed. (With longer HT use, estrogen therapy is more favorable than estrogen-progestin therapy.) Therefore, HT should be individualized and reevaluated periodically to maximize the benefits as well as minimize the risks of use, according to the position statement.

Nonhormonal therapies for menopausal symptoms

The Society released its position on nonhormonal management of menopause-associated VMS in 2015.² Based on examination of 340 original research articles and 105 systematic reviews, clinical and research experts categorized therapies as recommended, recommended with caution, and not recommended at this time.

Recommended non-HT to reduce VMS include:

• cognitive-behavioral therapy
• clinical hypnosis
• low-dose salt of paroxetine (FDA approved for menopausal VMS management)
• other SSRIs/SNRIs
• gabapentinoids
• clonidine.

Recommended-with-caution non-HT for VMS include:

• weight loss
• stress reduction (mindfulness based)
• S-equol derivatives of soy isoflavones
• stellate ganglion block.

Not recommended non-HT for VMS due to negative, insufficient, or inconclusive data include:

• cooling techniques
• avoidance of triggers
• exercise
• yoga
• paced respiration
• relaxation
• over-the-counter supplements and herbs
• acupuncture
• calibration of neural oscillations
• chiropractic interventions.

Note that the NAMS 2016 Hormone Therapy Position Statement was presented at the 2016 Annual Scientific Meeting of the North American Menopause Society, but the statement is not yet published.

JoAnn Pinkerton, MD, Professor of Obstetrics and Gynecology at the University of Virginia, Executive Director of the North American Menopause Society (NAMS), and OBG Management Board of Editors Member, revealed the 2016 NAMS position statement on hormone therapy (HT) in Orlando, Florida, on Thursday, October 6, at the NAMS 2016 Annual Scientific Meeting.

The process of consensus among the more than 20 menopause experts who authored the 2016 statement was at times a challenge, indicated Pinkerton, given the variance in views on the significance of published clinical trial findings since the Society’s 2012¹ HT position statement. Over a 9-month period, the experts developed guidelines for clinicians, using levels of evidence to identify strength of the recommendations.

The clearest benefit for HT to treat hot flashes and prevent bone loss was found for women aged younger than 60 years and within 10 years of menopause onset.

According to the 2016 statement presented at NAMS:

Level I US Food and Drug Administration (FDA)-approved indications for HT include:

• as first-line therapy for women with vasomotor symptoms (VMS) of menopause without contraindications
• possible first-line therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk for fracture (primarily for women aged younger than 60 years and within 10 years of menopause onset)
• low-dose vaginal estrogen as first-line treatment for women with isolated genitourinary symptoms caused by menopause (genitourinary syndrome of menopause [GSM]/vulvovaginal atrophy).

Level II FDA-approved indications for HT include:

• at least until age 52 (the median age of menopause onset) for women with early onset menopause (women with hypogonadism, primary ovarian insufficiency, or premature surgical menopause) and no HT contraindications.

Other level II indications, with observational data indicating benefit over risk, for HT include:

• at least until the median age of menopause for women with early onset menopause
• consideration among women with a family history of breast cancer, although family history is one risk among many for breast cancer that should be assessed
• benefit/risk consideration for women with a BRCA gene mutation who have undergone risk-reducing oophorectomy
• consideration of systemic use until the median age of menopause—after appropriate counseling and in the absence of HT contraindications, with longer duration of HT use individualized.

Level III indications for HT include:

• individualized decisions on use after the age of 60. (The position statement authors did not find that the current Beers criteria recommendation to routinely discontinue HT at age 65 was supported by data.)

The 2016 bottom line on HT

Overall, HT has clear benefits for the treatment of VMS and bone loss prevention, according to the presented position statement. These benefits are most favorable among women aged younger than 60 years who are within 10 years of menopause onset and have no contraindications to HT use. Women older than age 60 who initiate HT beyond 10 years of menopause onset appear to have a less favorable benefit-risk ratio because of elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

The risks of HT vary among women depending on the HT type, duration of use, administration route, timing of treatment initiation, and whether a progestogen is needed. (With longer HT use, estrogen therapy is more favorable than estrogen-progestin therapy.) Therefore, HT should be individualized and reevaluated periodically to maximize the benefits as well as minimize the risks of use, according to the position statement.

Nonhormonal therapies for menopausal symptoms

The Society released its position on nonhormonal management of menopause-associated VMS in 2015.² Based on examination of 340 original research articles and 105 systematic reviews, clinical and research experts categorized therapies as recommended, recommended with caution, and not recommended at this time.

Recommended non-HT to reduce VMS include:

• cognitive-behavioral therapy
• clinical hypnosis
• low-dose salt of paroxetine (FDA approved for menopausal VMS management)
• other SSRIs/SNRIs
• gabapentinoids
• clonidine.

Recommended-with-caution non-HT for VMS include:

• weight loss
• stress reduction (mindfulness based)
• S-equol derivatives of soy isoflavones
• stellate ganglion block.

Not recommended non-HT for VMS due to negative, insufficient, or inconclusive data include:

• cooling techniques
• avoidance of triggers
• exercise
• yoga
• paced respiration
• relaxation
• over-the-counter supplements and herbs
• acupuncture
• calibration of neural oscillations
• chiropractic interventions.

Note that the NAMS 2016 Hormone Therapy Position Statement was presented at the 2016 Annual Scientific Meeting of the North American Menopause Society, but the statement is not yet published.

JoAnn Pinkerton, MD, Professor of Obstetrics and Gynecology at the University of Virginia, Executive Director of the North American Menopause Society (NAMS), and OBG Management Board of Editors Member, revealed the 2016 NAMS position statement on hormone therapy (HT) in Orlando, Florida, on Thursday, October 6, at the NAMS 2016 Annual Scientific Meeting.

The process of consensus among the more than 20 menopause experts who authored the 2016 statement was at times a challenge, indicated Pinkerton, given the variance in views on the significance of published clinical trial findings since the Society’s 2012¹ HT position statement. Over a 9-month period, the experts developed guidelines for clinicians, using levels of evidence to identify strength of the recommendations.

The clearest benefit for HT to treat hot flashes and prevent bone loss was found for women aged younger than 60 years and within 10 years of menopause onset.

According to the 2016 statement presented at NAMS:

Level I US Food and Drug Administration (FDA)-approved indications for HT include:

• as first-line therapy for women with vasomotor symptoms (VMS) of menopause without contraindications
• possible first-line therapy for prevention of bone loss and fracture in postmenopausal women at elevated risk for fracture (primarily for women aged younger than 60 years and within 10 years of menopause onset)
• low-dose vaginal estrogen as first-line treatment for women with isolated genitourinary symptoms caused by menopause (genitourinary syndrome of menopause [GSM]/vulvovaginal atrophy).

Level II FDA-approved indications for HT include:

• at least until age 52 (the median age of menopause onset) for women with early onset menopause (women with hypogonadism, primary ovarian insufficiency, or premature surgical menopause) and no HT contraindications.

Other level II indications, with observational data indicating benefit over risk, for HT include:

• at least until the median age of menopause for women with early onset menopause
• consideration among women with a family history of breast cancer, although family history is one risk among many for breast cancer that should be assessed
• benefit/risk consideration for women with a BRCA gene mutation who have undergone risk-reducing oophorectomy
• consideration of systemic use until the median age of menopause—after appropriate counseling and in the absence of HT contraindications, with longer duration of HT use individualized.

Level III indications for HT include:

• individualized decisions on use after the age of 60. (The position statement authors did not find that the current Beers criteria recommendation to routinely discontinue HT at age 65 was supported by data.)

The 2016 bottom line on HT

Overall, HT has clear benefits for the treatment of VMS and bone loss prevention, according to the presented position statement. These benefits are most favorable among women aged younger than 60 years who are within 10 years of menopause onset and have no contraindications to HT use. Women older than age 60 who initiate HT beyond 10 years of menopause onset appear to have a less favorable benefit-risk ratio because of elevated risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

The risks of HT vary among women depending on the HT type, duration of use, administration route, timing of treatment initiation, and whether a progestogen is needed. (With longer HT use, estrogen therapy is more favorable than estrogen-progestin therapy.) Therefore, HT should be individualized and reevaluated periodically to maximize the benefits as well as minimize the risks of use, according to the position statement.

Nonhormonal therapies for menopausal symptoms

The Society released its position on nonhormonal management of menopause-associated VMS in 2015.² Based on examination of 340 original research articles and 105 systematic reviews, clinical and research experts categorized therapies as recommended, recommended with caution, and not recommended at this time.

Recommended non-HT to reduce VMS include:

• cognitive-behavioral therapy
• clinical hypnosis
• low-dose salt of paroxetine (FDA approved for menopausal VMS management)
• other SSRIs/SNRIs
• gabapentinoids
• clonidine.

Recommended-with-caution non-HT for VMS include:

• weight loss
• stress reduction (mindfulness based)
• S-equol derivatives of soy isoflavones
• stellate ganglion block.

Not recommended non-HT for VMS due to negative, insufficient, or inconclusive data include:

• cooling techniques
• avoidance of triggers
• exercise
• yoga
• paced respiration
• relaxation
• over-the-counter supplements and herbs
• acupuncture
• calibration of neural oscillations
• chiropractic interventions.

Note that the NAMS 2016 Hormone Therapy Position Statement was presented at the 2016 Annual Scientific Meeting of the North American Menopause Society, but the statement is not yet published.