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USPSTF discourages postmenopausal hormone therapy for prevention
Hormone therapy, in the form of estrogen combined with progestin, is not recommended to prevent chronic conditions such as heart disease and diabetes in postmenopausal women, according to updated draft recommendations from the U.S. Preventive Services Task Force. They also recommended against the use of estrogen alone in postmenopausal women who have had a hysterectomy.
The updated recommendations were published online May 16 on the U.S. Preventive Services Task Force website.
After considering new evidence in the last several years, the recommendations are essentially unchanged from the final recommendations published in 2012, according to a Task Force statement published with the recommendations. “The benefits of using menopausal hormone therapy to prevent chronic conditions like heart disease and diabetes do not outweigh the harms in women who have gone through menopause,” Maureen G. Phipps, MD, MPH, a task force member, said in the statement.
The draft recommendations were based on a review of 17 randomized clinical trials published through Aug. 1, 2016, that included data from the Women’s Health Initiative.
Women taking estrogen/progestin reported a significantly lower risk (per 10,000 women approximately 5 years) of colorectal cancer, diabetes, and fractures, compared with women on a placebo, wrote Gerald Gartlehner, MD, and his colleagues at the RTI International–University of North Carolina Evidence-Based Practice Center in Research Triangle Park, NC, in the evidence report accompanying the draft recommendations.
However, the risks for several other conditions were significantly higher among women on hormone therapy, compared with placebo, including invasive breast cancer (52 more cases), coronary heart disease (41 more cases) probable dementia (88 more cases), gallbladder disease (259 more cases), stroke (53 more cases), and venous thromboembolism (120 more cases). Additionally, urinary incontinence rates were higher after a 1-year follow up among women on hormone therapy (876 more cases/10,000 women).
Some evidence suggests that women who began hormone therapy closer to menopause might have a lower risk for developing cardiovascular complications, but the evidence is insufficient for firm conclusions, the researchers wrote.
The recommendations against hormone therapy do not apply to women younger than 50 years who have undergone oophorectomies or premature menopause, or to those considering hormone therapy to manage menopausal symptoms, according to the Task Force.
Public comments on the draft recommendations may be submitted on the Task Force website until June 12. The researchers had no financial conflicts to disclose.
View the recommendations online at uspreventiveservicestaskforce.org.
Hormone therapy, in the form of estrogen combined with progestin, is not recommended to prevent chronic conditions such as heart disease and diabetes in postmenopausal women, according to updated draft recommendations from the U.S. Preventive Services Task Force. They also recommended against the use of estrogen alone in postmenopausal women who have had a hysterectomy.
The updated recommendations were published online May 16 on the U.S. Preventive Services Task Force website.
After considering new evidence in the last several years, the recommendations are essentially unchanged from the final recommendations published in 2012, according to a Task Force statement published with the recommendations. “The benefits of using menopausal hormone therapy to prevent chronic conditions like heart disease and diabetes do not outweigh the harms in women who have gone through menopause,” Maureen G. Phipps, MD, MPH, a task force member, said in the statement.
The draft recommendations were based on a review of 17 randomized clinical trials published through Aug. 1, 2016, that included data from the Women’s Health Initiative.
Women taking estrogen/progestin reported a significantly lower risk (per 10,000 women approximately 5 years) of colorectal cancer, diabetes, and fractures, compared with women on a placebo, wrote Gerald Gartlehner, MD, and his colleagues at the RTI International–University of North Carolina Evidence-Based Practice Center in Research Triangle Park, NC, in the evidence report accompanying the draft recommendations.
However, the risks for several other conditions were significantly higher among women on hormone therapy, compared with placebo, including invasive breast cancer (52 more cases), coronary heart disease (41 more cases) probable dementia (88 more cases), gallbladder disease (259 more cases), stroke (53 more cases), and venous thromboembolism (120 more cases). Additionally, urinary incontinence rates were higher after a 1-year follow up among women on hormone therapy (876 more cases/10,000 women).
Some evidence suggests that women who began hormone therapy closer to menopause might have a lower risk for developing cardiovascular complications, but the evidence is insufficient for firm conclusions, the researchers wrote.
The recommendations against hormone therapy do not apply to women younger than 50 years who have undergone oophorectomies or premature menopause, or to those considering hormone therapy to manage menopausal symptoms, according to the Task Force.
Public comments on the draft recommendations may be submitted on the Task Force website until June 12. The researchers had no financial conflicts to disclose.
View the recommendations online at uspreventiveservicestaskforce.org.
Hormone therapy, in the form of estrogen combined with progestin, is not recommended to prevent chronic conditions such as heart disease and diabetes in postmenopausal women, according to updated draft recommendations from the U.S. Preventive Services Task Force. They also recommended against the use of estrogen alone in postmenopausal women who have had a hysterectomy.
The updated recommendations were published online May 16 on the U.S. Preventive Services Task Force website.
After considering new evidence in the last several years, the recommendations are essentially unchanged from the final recommendations published in 2012, according to a Task Force statement published with the recommendations. “The benefits of using menopausal hormone therapy to prevent chronic conditions like heart disease and diabetes do not outweigh the harms in women who have gone through menopause,” Maureen G. Phipps, MD, MPH, a task force member, said in the statement.
The draft recommendations were based on a review of 17 randomized clinical trials published through Aug. 1, 2016, that included data from the Women’s Health Initiative.
Women taking estrogen/progestin reported a significantly lower risk (per 10,000 women approximately 5 years) of colorectal cancer, diabetes, and fractures, compared with women on a placebo, wrote Gerald Gartlehner, MD, and his colleagues at the RTI International–University of North Carolina Evidence-Based Practice Center in Research Triangle Park, NC, in the evidence report accompanying the draft recommendations.
However, the risks for several other conditions were significantly higher among women on hormone therapy, compared with placebo, including invasive breast cancer (52 more cases), coronary heart disease (41 more cases) probable dementia (88 more cases), gallbladder disease (259 more cases), stroke (53 more cases), and venous thromboembolism (120 more cases). Additionally, urinary incontinence rates were higher after a 1-year follow up among women on hormone therapy (876 more cases/10,000 women).
Some evidence suggests that women who began hormone therapy closer to menopause might have a lower risk for developing cardiovascular complications, but the evidence is insufficient for firm conclusions, the researchers wrote.
The recommendations against hormone therapy do not apply to women younger than 50 years who have undergone oophorectomies or premature menopause, or to those considering hormone therapy to manage menopausal symptoms, according to the Task Force.
Public comments on the draft recommendations may be submitted on the Task Force website until June 12. The researchers had no financial conflicts to disclose.
View the recommendations online at uspreventiveservicestaskforce.org.
Endometrial cancer rates increased following WHI
SAN DIEGO – Endometrial cancer (EC) rates increased after 2002, coinciding with the release of results from the Women’s Health Initiative and including a 10% spike between 2006 and 2014, according to a large analysis of national data.
“Be aware of an increase of endometrial cancer and, whenever possible, look to minimize possible inciting causes,” Ginger Constantine, MD, lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Be certain that the hormonal products that patients are taking are delivering adequate progesterone to the endometrium in those patients at an increased risk of endometrial cancer, such as those with unopposed estrogen.”
“We sought to look at possible causes for the increase of the known risk factors for EC,” she said. “What has changed in the years leading up to 2006?” To find out, she and her associates obtained EC incidence from the Surveillance, Epidemiology, and End Result Program database from 1975 through 2014. They evaluated the incidence of risk factors thought to be associated with EC, including age, obesity, race, number of menstrual cycles, gravidity and parity, metabolic syndromes, diet and exercise, and medications, including various types of hormone therapy, tamoxifen, and hormonal contraceptives.
Shelli Graham, PhD, vice president of medical affairs for Boca Raton, Florida–based TherapeuticsMD, presented the study findings on behalf of Dr. Constantine, who was unable to attend the meeting. The rates of EC were relatively constant from 1992 to 2002 (at about 76/100,000 cases per year) but have increased 2.5% annually, with a 10% increase from 2006 to 2014, especially in women aged 55-64 years.
Use of estrogen and progestin combinations have decreased while risk factors remained constant or decreased during the same time period. However, the researchers observed a “huge increase (of 1-2.5 million U.S. women) using non-FDA approved compounded estrogen and estrogen and progesterone, which may not provide adequate endometrial protection from estrogen, a known cause of EC,” Dr. Constantine said. “Additionally, there is less progestin use subsequent to the [Women’s Health Initiative] and it is known that progestin is protective on the endometrium.”
The researchers also examined the incidence of obesity – another known risk factor for EC – and found that, although obesity has continued to increase in incidence, “it does not appear to be increasing at the same rate as EC, so [it] does not appear to be enough to explain the increase in EC from 2006,” Dr. Constantine said. “I was surprised at the rate of increase of EC from 2006 to 2014 and have also been surprised by the amount of non-FDA compounded hormone use.”
Dr. Graham characterized the increase in EC incidence as “a public health concern that is most likely multifactorial in etiology.” Contributors, she said, include the combination of an increase in obesity with an inherent increase in endogenous estrogen, decreasing progesterone use from a decrease in the use of FDA-approved hormone therapy products, and an increase in compounded hormone therapy that may not deliver adequate endometrial protection.
Dr. Constantine acknowledged certain limitations of the study, including the fact that it is “an ecological analysis, not a randomized clinical trial. It is hypothesis-generating.”
Dr. Constantine reported that she is a consultant/advisory member for TherapeuticsMD and other pharmaceutical companies. She owns stock in TherapeuticsMD. Coauthor Steven R. Goldstein, MD, reported having numerous financial relationships with pharmaceutical companies including TherapeuticsMD. Dr. Graham is an employee of TherapeuticsMD.
SAN DIEGO – Endometrial cancer (EC) rates increased after 2002, coinciding with the release of results from the Women’s Health Initiative and including a 10% spike between 2006 and 2014, according to a large analysis of national data.
“Be aware of an increase of endometrial cancer and, whenever possible, look to minimize possible inciting causes,” Ginger Constantine, MD, lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Be certain that the hormonal products that patients are taking are delivering adequate progesterone to the endometrium in those patients at an increased risk of endometrial cancer, such as those with unopposed estrogen.”
“We sought to look at possible causes for the increase of the known risk factors for EC,” she said. “What has changed in the years leading up to 2006?” To find out, she and her associates obtained EC incidence from the Surveillance, Epidemiology, and End Result Program database from 1975 through 2014. They evaluated the incidence of risk factors thought to be associated with EC, including age, obesity, race, number of menstrual cycles, gravidity and parity, metabolic syndromes, diet and exercise, and medications, including various types of hormone therapy, tamoxifen, and hormonal contraceptives.
Shelli Graham, PhD, vice president of medical affairs for Boca Raton, Florida–based TherapeuticsMD, presented the study findings on behalf of Dr. Constantine, who was unable to attend the meeting. The rates of EC were relatively constant from 1992 to 2002 (at about 76/100,000 cases per year) but have increased 2.5% annually, with a 10% increase from 2006 to 2014, especially in women aged 55-64 years.
Use of estrogen and progestin combinations have decreased while risk factors remained constant or decreased during the same time period. However, the researchers observed a “huge increase (of 1-2.5 million U.S. women) using non-FDA approved compounded estrogen and estrogen and progesterone, which may not provide adequate endometrial protection from estrogen, a known cause of EC,” Dr. Constantine said. “Additionally, there is less progestin use subsequent to the [Women’s Health Initiative] and it is known that progestin is protective on the endometrium.”
The researchers also examined the incidence of obesity – another known risk factor for EC – and found that, although obesity has continued to increase in incidence, “it does not appear to be increasing at the same rate as EC, so [it] does not appear to be enough to explain the increase in EC from 2006,” Dr. Constantine said. “I was surprised at the rate of increase of EC from 2006 to 2014 and have also been surprised by the amount of non-FDA compounded hormone use.”
Dr. Graham characterized the increase in EC incidence as “a public health concern that is most likely multifactorial in etiology.” Contributors, she said, include the combination of an increase in obesity with an inherent increase in endogenous estrogen, decreasing progesterone use from a decrease in the use of FDA-approved hormone therapy products, and an increase in compounded hormone therapy that may not deliver adequate endometrial protection.
Dr. Constantine acknowledged certain limitations of the study, including the fact that it is “an ecological analysis, not a randomized clinical trial. It is hypothesis-generating.”
Dr. Constantine reported that she is a consultant/advisory member for TherapeuticsMD and other pharmaceutical companies. She owns stock in TherapeuticsMD. Coauthor Steven R. Goldstein, MD, reported having numerous financial relationships with pharmaceutical companies including TherapeuticsMD. Dr. Graham is an employee of TherapeuticsMD.
SAN DIEGO – Endometrial cancer (EC) rates increased after 2002, coinciding with the release of results from the Women’s Health Initiative and including a 10% spike between 2006 and 2014, according to a large analysis of national data.
“Be aware of an increase of endometrial cancer and, whenever possible, look to minimize possible inciting causes,” Ginger Constantine, MD, lead study author, said in an interview prior to the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Be certain that the hormonal products that patients are taking are delivering adequate progesterone to the endometrium in those patients at an increased risk of endometrial cancer, such as those with unopposed estrogen.”
“We sought to look at possible causes for the increase of the known risk factors for EC,” she said. “What has changed in the years leading up to 2006?” To find out, she and her associates obtained EC incidence from the Surveillance, Epidemiology, and End Result Program database from 1975 through 2014. They evaluated the incidence of risk factors thought to be associated with EC, including age, obesity, race, number of menstrual cycles, gravidity and parity, metabolic syndromes, diet and exercise, and medications, including various types of hormone therapy, tamoxifen, and hormonal contraceptives.
Shelli Graham, PhD, vice president of medical affairs for Boca Raton, Florida–based TherapeuticsMD, presented the study findings on behalf of Dr. Constantine, who was unable to attend the meeting. The rates of EC were relatively constant from 1992 to 2002 (at about 76/100,000 cases per year) but have increased 2.5% annually, with a 10% increase from 2006 to 2014, especially in women aged 55-64 years.
Use of estrogen and progestin combinations have decreased while risk factors remained constant or decreased during the same time period. However, the researchers observed a “huge increase (of 1-2.5 million U.S. women) using non-FDA approved compounded estrogen and estrogen and progesterone, which may not provide adequate endometrial protection from estrogen, a known cause of EC,” Dr. Constantine said. “Additionally, there is less progestin use subsequent to the [Women’s Health Initiative] and it is known that progestin is protective on the endometrium.”
The researchers also examined the incidence of obesity – another known risk factor for EC – and found that, although obesity has continued to increase in incidence, “it does not appear to be increasing at the same rate as EC, so [it] does not appear to be enough to explain the increase in EC from 2006,” Dr. Constantine said. “I was surprised at the rate of increase of EC from 2006 to 2014 and have also been surprised by the amount of non-FDA compounded hormone use.”
Dr. Graham characterized the increase in EC incidence as “a public health concern that is most likely multifactorial in etiology.” Contributors, she said, include the combination of an increase in obesity with an inherent increase in endogenous estrogen, decreasing progesterone use from a decrease in the use of FDA-approved hormone therapy products, and an increase in compounded hormone therapy that may not deliver adequate endometrial protection.
Dr. Constantine acknowledged certain limitations of the study, including the fact that it is “an ecological analysis, not a randomized clinical trial. It is hypothesis-generating.”
Dr. Constantine reported that she is a consultant/advisory member for TherapeuticsMD and other pharmaceutical companies. She owns stock in TherapeuticsMD. Coauthor Steven R. Goldstein, MD, reported having numerous financial relationships with pharmaceutical companies including TherapeuticsMD. Dr. Graham is an employee of TherapeuticsMD.
Key clinical point:
Major finding: Rates of endometrial cancer increased 10% between 2006 and 2014.
Data source: An analysis of the Surveillance, Epidemiology, and End Result Program database.
Disclosures: Dr. Constantine reported that she is a consultant/advisory board member for TherapeuticsMD as well as other pharmaceutical companies. She also owns stock in TherapeuticsMD. Coauthor Steven R. Goldstein, MD, reported having numerous financial relationships with pharmaceutical companies including TherapeuticsMD. Dr. Graham is an employee of TherapeuticsMD.
Updated osteoporosis guideline advocates bisphosphonates, nixes estrogens
The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.
The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.
The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.
Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.
Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).
Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.
One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.
Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”
The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.
The most important recommendation in this updated ACP guideline is for clinicians to offer bisphosphonates or denosumab to women with osteoporosis.
Even though large, well-designed, randomized controlled trials amply demonstrate the effectiveness of these drugs in preventing fractures, undertreatment is rampant and is actually increasing. It appears that patients and perhaps some clinicians have the mistaken impression that bisphosphonates frequently cause serious adverse effects.
In truth, the rate of adverse effects and of serious adverse events with bisphosphonates is very low. Clinicians should educate patients about the safety of these agents.
Eric S. Orwoll, MD, is at Oregon Health and Science University, Portland. Dr. Orwoll made these remarks in an editorial accompanying the updated guideline (Ann. Intern. Med. 2017 May 8. doi: 10.7326/M17-0957). His financial disclosures are available at www.acponline.org
The most important recommendation in this updated ACP guideline is for clinicians to offer bisphosphonates or denosumab to women with osteoporosis.
Even though large, well-designed, randomized controlled trials amply demonstrate the effectiveness of these drugs in preventing fractures, undertreatment is rampant and is actually increasing. It appears that patients and perhaps some clinicians have the mistaken impression that bisphosphonates frequently cause serious adverse effects.
In truth, the rate of adverse effects and of serious adverse events with bisphosphonates is very low. Clinicians should educate patients about the safety of these agents.
Eric S. Orwoll, MD, is at Oregon Health and Science University, Portland. Dr. Orwoll made these remarks in an editorial accompanying the updated guideline (Ann. Intern. Med. 2017 May 8. doi: 10.7326/M17-0957). His financial disclosures are available at www.acponline.org
The most important recommendation in this updated ACP guideline is for clinicians to offer bisphosphonates or denosumab to women with osteoporosis.
Even though large, well-designed, randomized controlled trials amply demonstrate the effectiveness of these drugs in preventing fractures, undertreatment is rampant and is actually increasing. It appears that patients and perhaps some clinicians have the mistaken impression that bisphosphonates frequently cause serious adverse effects.
In truth, the rate of adverse effects and of serious adverse events with bisphosphonates is very low. Clinicians should educate patients about the safety of these agents.
Eric S. Orwoll, MD, is at Oregon Health and Science University, Portland. Dr. Orwoll made these remarks in an editorial accompanying the updated guideline (Ann. Intern. Med. 2017 May 8. doi: 10.7326/M17-0957). His financial disclosures are available at www.acponline.org
The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.
The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.
The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.
Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.
Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).
Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.
One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.
Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”
The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.
The American College of Physicians’ updated clinical practice guideline for treating osteoporosis strongly advocates bisphosphonates and strongly advises against estrogens or raloxifene. It was presented online May 8 in the Annals of Internal Medicine.
The new guideline is based on a review of the evidence published since the previous (2008) ACP guideline for preventing fractures in women and men with osteoporosis or low bone density and is intended to replace that document. It offers six main recommendations and several additional pointers for both clinicians and the approximately 50% of Americans older than age 50 years who are at risk for osteoporotic fracture, said Amir Qaseem, MD, PhD, lead author and vice president of clinical policy at the ACP, Philadelphia, and his associates.
The strongest recommendation, based on extensive high-quality evidence, is that clinicians offer women known to have osteoporosis pharmacologic therapy with the bisphosphonates alendronate, risedronate, or zoledronic acid, or the biologic agent denosumab, to reduce their risk of hip and vertebral fracture. Counseling on the importance of adherence despite the relative inconvenience of taking the medications and their possible adverse effects is urged, as is prescribing generic formulations whenever possible.
Raloxifene, ibandronate, and teriparatide have not been shown to reduce the risks of all types of fractures, so they are not recommended as first-line therapy. The updated guideline no longer addresses the use of calcitonin, because it is no longer used widely for osteoporosis. Similarly, it no longer addresses the use of etidronate or pamidronate, which are not approved by the Food and Drug Administration for this indication. The updated guideline added denosumab, a new biologic agent recently approved by the FDA.
Estrogens or raloxifene are not advised for established osteoporosis because good evidence shows they do not reduce fracture risk, according to the guideline. Moreover, these agents can be associated with serious harms that outweigh any potential benefits, including stroke and venous thromboembolism. This recommendation directly refutes one in the previous guideline that favored estrogen therapy, based on newer evidence, Dr. Qaseem and his associates said (Ann. Intern. Med. 2017 May 8.doi: 10.7326/M15-1361).
Four additional recommendations in the updated guideline are weaker because they are based on low-quality evidence.
One advises that the duration of pharmacologic therapy should be 5 years, although there is considerable variation in response to treatment and many patients may benefit from longer treatment. Another recommendation advises against bone mineral density monitoring during this 5-year period because current evidence shows no benefit for it.
Another recommendation advises that men who have clinically recognized osteoporosis should be offered bisphosphonate therapy to reduce their risk of vertebral fracture. The final recommendation advises clinicians to decide whether to treat “osteopenic women 65 years of age or older who are at a high risk for fracture,” based on patient preferences and the “benefits, harms, and costs of medications.”
The guideline notes that, for women who have normal bone mineral density, frequent monitoring for osteoporosis is unnecessary, because current evidence shows those with normal dual-energy x-ray absorptiometry scores do not progress to osteoporosis within 15 years. And it cautions that even though the World Health Organization’s Fracture Risk Assessment Tool scores are widely used, there is no evidence that they accurately reflect treatment efficacy.
FROM ANNALS OF INTERNAL MEDICINE
Key clinical point:
Major finding: The guideline offers six main recommendations and several additional pointers for clinicians and for those over age 50 years who are at risk for osteoporotic fracture.
Data source: A review of the evidence since the previous (2008) ACP guideline for treating osteoporosis.
Disclosures: This work was supported exclusively by the American College of Physicians. The authors’ financial disclosures are available at www.acponline.org
FDA approves abaloparatide for postmenopausal osteoporosis
The Food and Drug Administration has approved abaloparatide (Tymlos) for postmenopausal women with osteoporosis at high risk for fracture.
Abaloparatide was approved based on 18-month results from the ACTIVE trial and 6-month results from the ACTIVExtend trial. Patients in the ACTIVE trial showed an relative risk reduction of 86% for new vertebral fractures and 43% for nonvertebral fractures, compared with placebo, according to a statement from manufacturer Radius Health. Results were similar regardless of age, years since menopause, presence or absence of prior fracture (vertebral or nonvertebral), and bone mineral density at baseline.
Find the full statement on the Radius Health website.
The Food and Drug Administration has approved abaloparatide (Tymlos) for postmenopausal women with osteoporosis at high risk for fracture.
Abaloparatide was approved based on 18-month results from the ACTIVE trial and 6-month results from the ACTIVExtend trial. Patients in the ACTIVE trial showed an relative risk reduction of 86% for new vertebral fractures and 43% for nonvertebral fractures, compared with placebo, according to a statement from manufacturer Radius Health. Results were similar regardless of age, years since menopause, presence or absence of prior fracture (vertebral or nonvertebral), and bone mineral density at baseline.
Find the full statement on the Radius Health website.
The Food and Drug Administration has approved abaloparatide (Tymlos) for postmenopausal women with osteoporosis at high risk for fracture.
Abaloparatide was approved based on 18-month results from the ACTIVE trial and 6-month results from the ACTIVExtend trial. Patients in the ACTIVE trial showed an relative risk reduction of 86% for new vertebral fractures and 43% for nonvertebral fractures, compared with placebo, according to a statement from manufacturer Radius Health. Results were similar regardless of age, years since menopause, presence or absence of prior fracture (vertebral or nonvertebral), and bone mineral density at baseline.
Find the full statement on the Radius Health website.
Postmenopausal hot flashes cut by 93% with novel nonhormonal treatment
AT ENDO 2017
ORLANDO –
After 12 weeks of treatment with the oral small molecule, women had a 93% reduction in moderate to severe hot flashes, compared with a 23% reduction for those taking placebo (P less than .0001). The effects of fezolinetant were seen earlier as well, with an 88% reduction in hot flashes at 4 weeks into the trial, compared with a 12% reduction for the placebo group (P less than .001).
The eight-site study enrolled 87 patients in a double-blind, randomized, placebo-controlled trial that assessed hot flash frequency and severity at study weeks 4 and 12. Postmenopausal women had to have frequent, moderate to severe hot flashes to qualify for enrollment, and they had to be otherwise healthy.
To capture data for a secondary endpoint, participants also completed a quality of life questionnaire. Dr. Fraser and his coinvestigators tracked safety and pharmacokinetic data by measuring levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and sex hormone–binding globulin at baseline and 12 weeks, as well.
Evenly divided between study arms, 80 patients completed the trial. Two patients withdrew because of adverse events, one patient violated inclusion criteria, and the others withdrew for a variety of reasons. Mean age was similar between the two groups, at 53.7 years for those on placebo and 53.3 years for the fezolinetant group. Other anthropometric characteristics were similar, as well.
At baseline, patients taking placebo experienced a mean 10.3 moderate to severe hot flashes daily, compared with the fezolinetant group at a mean of 11.5. By study week 4, 14 of the 40 patients in the active arm had zero hot flashes, compared with 2 of 40 in the in the placebo arm, when the intention-to-treat population was examined. Hot flash severity dropped by 70% (P less than .0001).
Quality of life was assessed with the Hot Flash Related Daily Interference Scale (HFRDIS). When the two groups were compared, a significant (P less than .001) reduction in HFRDIS score was seen by week 4 and continued through to week 12 in the group on active treatment. Lower HFRDIS scores mean improved hot flash–related quality of life.
Using the Leeds Sleep Evaluation Questionnaire allowed Dr. Fraser and his colleagues to ask about how long it took patients to get to sleep while they were participating in the study, compared with their normal sleep latency. Patients taking fezolinetant reported getting to sleep significantly more quickly (P less than .01) than the placebo group. They also reported better quality of sleep (P less than .001) and a better awakening experience (P less than .05). However, they did not report feeling better after awakening (P = .08).
Women taking fezolinetant also showed significant improvement, compared with the placebo group, on other quality of life questionnaires, the Greene Climacteric Scale and the Sheehan Disability Scale. By week 8, a significant (P less than .001) improvement was seen on both scales and specifically at week 4 on the Sheehan Disability Scale.
Among the hormone biomarkers that were followed in the study, only plasma luteinizing-hormone levels dropped, compared with patients’ baseline levels. These were reduced 20% 12 hours after one of the two daily 60-mg oral doses, and 50% at 3 hours post dose, a point at which maximum serum fezolinetant concentration would be seen. These were all statistically significant reductions and expected effects of the drug’s mechanism of action.
Further pharmacokinetic analysis, said Dr. Fraser, “supports testing of once-daily dosing for vasomotor symptoms,” given that, when the drug was tested in premenopausal women in phase I clinical trials, there was no difference in peak and trough drug concentration.
The safety profile was good overall, said Dr. Fraser. No patients in the fezolinetant group reported serious treatment-emergent adverse events. “More patients reported treatment-emergent adverse events in the placebo group than in the fezolinetant group,” he said.
The NK3R antagonist is also under investigation for use in the treatment of polycystic ovary syndrome and uterine fibroids.
The study was funded by Ogeda, which employs Dr. Fraser. Another author reported serving as a clinical adviser for Ogeda.
[email protected]
On Twitter @karioakes
AT ENDO 2017
ORLANDO –
After 12 weeks of treatment with the oral small molecule, women had a 93% reduction in moderate to severe hot flashes, compared with a 23% reduction for those taking placebo (P less than .0001). The effects of fezolinetant were seen earlier as well, with an 88% reduction in hot flashes at 4 weeks into the trial, compared with a 12% reduction for the placebo group (P less than .001).
The eight-site study enrolled 87 patients in a double-blind, randomized, placebo-controlled trial that assessed hot flash frequency and severity at study weeks 4 and 12. Postmenopausal women had to have frequent, moderate to severe hot flashes to qualify for enrollment, and they had to be otherwise healthy.
To capture data for a secondary endpoint, participants also completed a quality of life questionnaire. Dr. Fraser and his coinvestigators tracked safety and pharmacokinetic data by measuring levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and sex hormone–binding globulin at baseline and 12 weeks, as well.
Evenly divided between study arms, 80 patients completed the trial. Two patients withdrew because of adverse events, one patient violated inclusion criteria, and the others withdrew for a variety of reasons. Mean age was similar between the two groups, at 53.7 years for those on placebo and 53.3 years for the fezolinetant group. Other anthropometric characteristics were similar, as well.
At baseline, patients taking placebo experienced a mean 10.3 moderate to severe hot flashes daily, compared with the fezolinetant group at a mean of 11.5. By study week 4, 14 of the 40 patients in the active arm had zero hot flashes, compared with 2 of 40 in the in the placebo arm, when the intention-to-treat population was examined. Hot flash severity dropped by 70% (P less than .0001).
Quality of life was assessed with the Hot Flash Related Daily Interference Scale (HFRDIS). When the two groups were compared, a significant (P less than .001) reduction in HFRDIS score was seen by week 4 and continued through to week 12 in the group on active treatment. Lower HFRDIS scores mean improved hot flash–related quality of life.
Using the Leeds Sleep Evaluation Questionnaire allowed Dr. Fraser and his colleagues to ask about how long it took patients to get to sleep while they were participating in the study, compared with their normal sleep latency. Patients taking fezolinetant reported getting to sleep significantly more quickly (P less than .01) than the placebo group. They also reported better quality of sleep (P less than .001) and a better awakening experience (P less than .05). However, they did not report feeling better after awakening (P = .08).
Women taking fezolinetant also showed significant improvement, compared with the placebo group, on other quality of life questionnaires, the Greene Climacteric Scale and the Sheehan Disability Scale. By week 8, a significant (P less than .001) improvement was seen on both scales and specifically at week 4 on the Sheehan Disability Scale.
Among the hormone biomarkers that were followed in the study, only plasma luteinizing-hormone levels dropped, compared with patients’ baseline levels. These were reduced 20% 12 hours after one of the two daily 60-mg oral doses, and 50% at 3 hours post dose, a point at which maximum serum fezolinetant concentration would be seen. These were all statistically significant reductions and expected effects of the drug’s mechanism of action.
Further pharmacokinetic analysis, said Dr. Fraser, “supports testing of once-daily dosing for vasomotor symptoms,” given that, when the drug was tested in premenopausal women in phase I clinical trials, there was no difference in peak and trough drug concentration.
The safety profile was good overall, said Dr. Fraser. No patients in the fezolinetant group reported serious treatment-emergent adverse events. “More patients reported treatment-emergent adverse events in the placebo group than in the fezolinetant group,” he said.
The NK3R antagonist is also under investigation for use in the treatment of polycystic ovary syndrome and uterine fibroids.
The study was funded by Ogeda, which employs Dr. Fraser. Another author reported serving as a clinical adviser for Ogeda.
[email protected]
On Twitter @karioakes
AT ENDO 2017
ORLANDO –
After 12 weeks of treatment with the oral small molecule, women had a 93% reduction in moderate to severe hot flashes, compared with a 23% reduction for those taking placebo (P less than .0001). The effects of fezolinetant were seen earlier as well, with an 88% reduction in hot flashes at 4 weeks into the trial, compared with a 12% reduction for the placebo group (P less than .001).
The eight-site study enrolled 87 patients in a double-blind, randomized, placebo-controlled trial that assessed hot flash frequency and severity at study weeks 4 and 12. Postmenopausal women had to have frequent, moderate to severe hot flashes to qualify for enrollment, and they had to be otherwise healthy.
To capture data for a secondary endpoint, participants also completed a quality of life questionnaire. Dr. Fraser and his coinvestigators tracked safety and pharmacokinetic data by measuring levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and sex hormone–binding globulin at baseline and 12 weeks, as well.
Evenly divided between study arms, 80 patients completed the trial. Two patients withdrew because of adverse events, one patient violated inclusion criteria, and the others withdrew for a variety of reasons. Mean age was similar between the two groups, at 53.7 years for those on placebo and 53.3 years for the fezolinetant group. Other anthropometric characteristics were similar, as well.
At baseline, patients taking placebo experienced a mean 10.3 moderate to severe hot flashes daily, compared with the fezolinetant group at a mean of 11.5. By study week 4, 14 of the 40 patients in the active arm had zero hot flashes, compared with 2 of 40 in the in the placebo arm, when the intention-to-treat population was examined. Hot flash severity dropped by 70% (P less than .0001).
Quality of life was assessed with the Hot Flash Related Daily Interference Scale (HFRDIS). When the two groups were compared, a significant (P less than .001) reduction in HFRDIS score was seen by week 4 and continued through to week 12 in the group on active treatment. Lower HFRDIS scores mean improved hot flash–related quality of life.
Using the Leeds Sleep Evaluation Questionnaire allowed Dr. Fraser and his colleagues to ask about how long it took patients to get to sleep while they were participating in the study, compared with their normal sleep latency. Patients taking fezolinetant reported getting to sleep significantly more quickly (P less than .01) than the placebo group. They also reported better quality of sleep (P less than .001) and a better awakening experience (P less than .05). However, they did not report feeling better after awakening (P = .08).
Women taking fezolinetant also showed significant improvement, compared with the placebo group, on other quality of life questionnaires, the Greene Climacteric Scale and the Sheehan Disability Scale. By week 8, a significant (P less than .001) improvement was seen on both scales and specifically at week 4 on the Sheehan Disability Scale.
Among the hormone biomarkers that were followed in the study, only plasma luteinizing-hormone levels dropped, compared with patients’ baseline levels. These were reduced 20% 12 hours after one of the two daily 60-mg oral doses, and 50% at 3 hours post dose, a point at which maximum serum fezolinetant concentration would be seen. These were all statistically significant reductions and expected effects of the drug’s mechanism of action.
Further pharmacokinetic analysis, said Dr. Fraser, “supports testing of once-daily dosing for vasomotor symptoms,” given that, when the drug was tested in premenopausal women in phase I clinical trials, there was no difference in peak and trough drug concentration.
The safety profile was good overall, said Dr. Fraser. No patients in the fezolinetant group reported serious treatment-emergent adverse events. “More patients reported treatment-emergent adverse events in the placebo group than in the fezolinetant group,” he said.
The NK3R antagonist is also under investigation for use in the treatment of polycystic ovary syndrome and uterine fibroids.
The study was funded by Ogeda, which employs Dr. Fraser. Another author reported serving as a clinical adviser for Ogeda.
[email protected]
On Twitter @karioakes
Key clinical point: .
Major finding: Women on fezolinetant had a 93% drop in hot flash frequency, compared with a 23% reduction for those on placebo (P less than .0001).
Data source: A phase II randomized, double-blind, placebo-controlled clinical trial of 87 postmenopausal women with moderate to severe hot flashes.
Disclosures: The study was funded by Ogeda, which employs Dr. Fraser. Another author reported serving as a clinical adviser for Ogeda.
Study shows no adverse events with long-term denosumab in postmenopausal women
Extended follow-up of postmenopausal women taking denosumab for high-risk osteoporosis in the FREEDOM trial showed no increasing rates of either common adverse events or specific adverse events identified in the original study.
“This analysis provides reassuring information regarding safety and tolerability of both short-term and longer-term treatment with denosumab,” said Nelson B. Watts, MD, of Mercy Health, Cincinnati, and his associates.
The average age of the women was 72.3 years, and about 23% had vertebral fractures at baseline. The specific, infrequent adverse events that occurred more commonly in the denosumab group than the placebo group in the original trial were malignancy, eczema/dermatitis, pancreatitis, endocarditis, delayed fracture healing, infections, opportunistic infections, and cellulitis or erysipelas. The more common adverse events associated with the active treatment, and currently listed in the prescribing information for denosumab, were back pain, pain in the extremities, musculoskeletal pain, hypercholesterolemia, and cystitis, the investigators reported (J Bone Mineral Res. 2017 Apr 3. doi: 10.1002/jbmr.3119).
“We found no evidence for a relationship between treatment with denosumab and increasing rates of either low-frequency adverse events or common adverse events in patients who were assigned to placebo in the [original] trial and received 3 years of denosumab in the extension study, and no indication of increased incidence of low-frequency adverse events and common adverse events in patients receiving denosumab in years 4-6, compared with years 1-3,” Dr. Watts and his associates wrote.
This study was funded by Amgen, maker of denosumab (Prolia). Dr. Watts reported ties to Amgen, Shire, AbbVie, Merck, Radius, Sanofi, and Osteodynamics; his associates reported ties to numerous industry sources.
Extended follow-up of postmenopausal women taking denosumab for high-risk osteoporosis in the FREEDOM trial showed no increasing rates of either common adverse events or specific adverse events identified in the original study.
“This analysis provides reassuring information regarding safety and tolerability of both short-term and longer-term treatment with denosumab,” said Nelson B. Watts, MD, of Mercy Health, Cincinnati, and his associates.
The average age of the women was 72.3 years, and about 23% had vertebral fractures at baseline. The specific, infrequent adverse events that occurred more commonly in the denosumab group than the placebo group in the original trial were malignancy, eczema/dermatitis, pancreatitis, endocarditis, delayed fracture healing, infections, opportunistic infections, and cellulitis or erysipelas. The more common adverse events associated with the active treatment, and currently listed in the prescribing information for denosumab, were back pain, pain in the extremities, musculoskeletal pain, hypercholesterolemia, and cystitis, the investigators reported (J Bone Mineral Res. 2017 Apr 3. doi: 10.1002/jbmr.3119).
“We found no evidence for a relationship between treatment with denosumab and increasing rates of either low-frequency adverse events or common adverse events in patients who were assigned to placebo in the [original] trial and received 3 years of denosumab in the extension study, and no indication of increased incidence of low-frequency adverse events and common adverse events in patients receiving denosumab in years 4-6, compared with years 1-3,” Dr. Watts and his associates wrote.
This study was funded by Amgen, maker of denosumab (Prolia). Dr. Watts reported ties to Amgen, Shire, AbbVie, Merck, Radius, Sanofi, and Osteodynamics; his associates reported ties to numerous industry sources.
Extended follow-up of postmenopausal women taking denosumab for high-risk osteoporosis in the FREEDOM trial showed no increasing rates of either common adverse events or specific adverse events identified in the original study.
“This analysis provides reassuring information regarding safety and tolerability of both short-term and longer-term treatment with denosumab,” said Nelson B. Watts, MD, of Mercy Health, Cincinnati, and his associates.
The average age of the women was 72.3 years, and about 23% had vertebral fractures at baseline. The specific, infrequent adverse events that occurred more commonly in the denosumab group than the placebo group in the original trial were malignancy, eczema/dermatitis, pancreatitis, endocarditis, delayed fracture healing, infections, opportunistic infections, and cellulitis or erysipelas. The more common adverse events associated with the active treatment, and currently listed in the prescribing information for denosumab, were back pain, pain in the extremities, musculoskeletal pain, hypercholesterolemia, and cystitis, the investigators reported (J Bone Mineral Res. 2017 Apr 3. doi: 10.1002/jbmr.3119).
“We found no evidence for a relationship between treatment with denosumab and increasing rates of either low-frequency adverse events or common adverse events in patients who were assigned to placebo in the [original] trial and received 3 years of denosumab in the extension study, and no indication of increased incidence of low-frequency adverse events and common adverse events in patients receiving denosumab in years 4-6, compared with years 1-3,” Dr. Watts and his associates wrote.
This study was funded by Amgen, maker of denosumab (Prolia). Dr. Watts reported ties to Amgen, Shire, AbbVie, Merck, Radius, Sanofi, and Osteodynamics; his associates reported ties to numerous industry sources.
FROM THE JOURNAL OF BONE AND MINERAL RESEARCH
Key clinical point: Denosumab, taken long term, is not linked with any adverse events.
Major finding: Extended follow-up of postmenopausal women taking denosumab for high-risk osteoporosis showed no increasing rates of either common adverse events or of specific adverse events identified in the original trial.
Data source: Extended (6-year) follow-up of 4,550 women in the international phase III randomized, double-blind FREEDOM trial.
Disclosures: This study was funded by Amgen, maker of denosumab. Dr. Watts reported ties to Amgen, Shire, AbbVie, Merck, Radius, Sanofi, and Osteodynamics; his associates reported ties to numerous industry sources.
Neurokinin receptor antagonist nearly halves hot flashes
ORLANDO – A novel antagonist of a neurokinin pathway effectively reduced hot flashes in postmenopausal women, according to results of a phase II trial.
The neurokinin 3 receptor (NK3R) antagonist, termed MLE4901, cut the number of hot flashes nearly in half compared to the effect of a placebo, and also improved overall menopause-related quality of life symptoms.
The medication has the potential to fulfill an unmet clinical need, since 70% of women experience hot flashes and the median duration of symptoms is more than 7 years, Julia K. Prague, MD, said at the annual meeting of the Endocrine Society.
The study results were published concurrently with Dr. Prague’s presentation (Lancet. 2017 Apr 3. doi: 10.1016/S0140-6736[17]30823-1).
Evidence from postmortem studies of postmenopausal women, said Dr. Prague, pointed to NKB (neurokinin B)/NK3R signaling as playing a role in hot flashes. The brains of these women showed hypertrophy of NKB neurons and increased neuronal activity, as well as increased NKB gene expression. The same effects were seen in monkeys whose ovaries had been removed, and the effect was reversed when the monkeys were given estrogen. 
Also, previous work has shown that administering NKB to premenopausal women gave them hot flashes (Sci Rep. 2015 Feb 6;5:8466). The preclinical work laid the groundwork for the hypothesis that taking an oral NK3R antagonist could mitigate hot flashes in menopausal women.
The randomized, placebo-controlled, double-blind 2-way crossover study enrolled 37 healthy women aged 40-62 who were at least 12 months out from their last menses. To qualify for enrollment, they needed to be experiencing at least seven hot flashes per 24 hours; the actual mean total number in the study group was 13 per 24 hours and 85 per week. A total of 28 women completed the full protocol.
The mean age of the women was 55 years, and the mean body mass index was 25.8 kg/m2. Three quarters of the women were white.
The women had an initial 2-week baseline period, during which they kept a symptom diary, and then were randomized to receive either an oral NK3R antagonist or a placebo twice daily. Then, each patient went through a 2-week washout period, after which they were crossed over to the other arm of the study. Finally, patients were monitored for a further 2 weeks after taking the study drug.
The NK3R antagonist, said Dr. Prague, “significantly reduced the total weekly number of hot [flashes] compared to placebo in the fourth week of treatment.” Patients taking placebo experienced 49.01 hot flashes per week (range, 40.81-58.86), while those taking the NK3R antagonist had 19.35 (range, 15.99-23.42, P less than .0001). This amounted to a 45% reduction in number of hot flashes compared to placebo.
Dr. Prague, a clinical research fellow at Imperial College, London, said that the treatment effect size seen was similar regardless of whether patients received the active study drug or placebo first.
Using the Menopause-Related Quality of Life questionnaire, Dr. Prague and her colleagues determined that when women were taking the NK3R antagonist, in addition to a significant reduction in vasomotor symptoms, menopause-related psychosocial symptoms were reduced by 15% (P = .0083) and physical symptoms by 19% (P = .0002). As expected for the nonhormonal medication, she said, sexual symptoms were reduced by a nonsignificant 8% (P = .24).
A subset of patients received more intensive study, with external validation of hot flashes and a series of 3-day-long stays during which an intravenous catheter was placed for blood sampling every 10 minutes.
Data from this group of patients showed that, while the NK3R antagonist did not significantly affect the number of luteinizing hormone pulses detected compared with placebo (P = .41), it did increase the mean amplitude of each pulse (P = .0243). Also, the active drug made the luteinizing hormone pulses more orderly (P = .0006 compared to placebo).
The NK3R antagonist was well tolerated. Though no serious adverse events were seen, three patients taking the NK3R antagonist did have a transient and asymptomatic elevation of transaminases without hyperbilirubinemia at 28 days after starting treatment. The elevation resolved for all patients within 90 days of stopping the medication.
The novel drug could represent “a potentially practice-changing therapeutic,” said Dr. Prague, since it “significantly relieves hot [flash] symptoms without the need for estrogen exposure.” She added that planning is underway for longer studies involving more patients.
The study was supported by AstraZeneca and Millendo Therapeutics, which are involved with manufacturing MLE4901.
[email protected]
On Twitter @karioakes
ORLANDO – A novel antagonist of a neurokinin pathway effectively reduced hot flashes in postmenopausal women, according to results of a phase II trial.
The neurokinin 3 receptor (NK3R) antagonist, termed MLE4901, cut the number of hot flashes nearly in half compared to the effect of a placebo, and also improved overall menopause-related quality of life symptoms.
The medication has the potential to fulfill an unmet clinical need, since 70% of women experience hot flashes and the median duration of symptoms is more than 7 years, Julia K. Prague, MD, said at the annual meeting of the Endocrine Society.
The study results were published concurrently with Dr. Prague’s presentation (Lancet. 2017 Apr 3. doi: 10.1016/S0140-6736[17]30823-1).
Evidence from postmortem studies of postmenopausal women, said Dr. Prague, pointed to NKB (neurokinin B)/NK3R signaling as playing a role in hot flashes. The brains of these women showed hypertrophy of NKB neurons and increased neuronal activity, as well as increased NKB gene expression. The same effects were seen in monkeys whose ovaries had been removed, and the effect was reversed when the monkeys were given estrogen.
Also, previous work has shown that administering NKB to premenopausal women gave them hot flashes (Sci Rep. 2015 Feb 6;5:8466). The preclinical work laid the groundwork for the hypothesis that taking an oral NK3R antagonist could mitigate hot flashes in menopausal women.
The randomized, placebo-controlled, double-blind 2-way crossover study enrolled 37 healthy women aged 40-62 who were at least 12 months out from their last menses. To qualify for enrollment, they needed to be experiencing at least seven hot flashes per 24 hours; the actual mean total number in the study group was 13 per 24 hours and 85 per week. A total of 28 women completed the full protocol.
The mean age of the women was 55 years, and the mean body mass index was 25.8 kg/m2. Three quarters of the women were white.
The women had an initial 2-week baseline period, during which they kept a symptom diary, and then were randomized to receive either an oral NK3R antagonist or a placebo twice daily. Then, each patient went through a 2-week washout period, after which they were crossed over to the other arm of the study. Finally, patients were monitored for a further 2 weeks after taking the study drug.
The NK3R antagonist, said Dr. Prague, “significantly reduced the total weekly number of hot [flashes] compared to placebo in the fourth week of treatment.” Patients taking placebo experienced 49.01 hot flashes per week (range, 40.81-58.86), while those taking the NK3R antagonist had 19.35 (range, 15.99-23.42, P less than .0001). This amounted to a 45% reduction in number of hot flashes compared to placebo.
Dr. Prague, a clinical research fellow at Imperial College, London, said that the treatment effect size seen was similar regardless of whether patients received the active study drug or placebo first.
Using the Menopause-Related Quality of Life questionnaire, Dr. Prague and her colleagues determined that when women were taking the NK3R antagonist, in addition to a significant reduction in vasomotor symptoms, menopause-related psychosocial symptoms were reduced by 15% (P = .0083) and physical symptoms by 19% (P = .0002). As expected for the nonhormonal medication, she said, sexual symptoms were reduced by a nonsignificant 8% (P = .24).
A subset of patients received more intensive study, with external validation of hot flashes and a series of 3-day-long stays during which an intravenous catheter was placed for blood sampling every 10 minutes.
Data from this group of patients showed that, while the NK3R antagonist did not significantly affect the number of luteinizing hormone pulses detected compared with placebo (P = .41), it did increase the mean amplitude of each pulse (P = .0243). Also, the active drug made the luteinizing hormone pulses more orderly (P = .0006 compared to placebo).
The NK3R antagonist was well tolerated. Though no serious adverse events were seen, three patients taking the NK3R antagonist did have a transient and asymptomatic elevation of transaminases without hyperbilirubinemia at 28 days after starting treatment. The elevation resolved for all patients within 90 days of stopping the medication.
The novel drug could represent “a potentially practice-changing therapeutic,” said Dr. Prague, since it “significantly relieves hot [flash] symptoms without the need for estrogen exposure.” She added that planning is underway for longer studies involving more patients.
The study was supported by AstraZeneca and Millendo Therapeutics, which are involved with manufacturing MLE4901.
[email protected]
On Twitter @karioakes
ORLANDO – A novel antagonist of a neurokinin pathway effectively reduced hot flashes in postmenopausal women, according to results of a phase II trial.
The neurokinin 3 receptor (NK3R) antagonist, termed MLE4901, cut the number of hot flashes nearly in half compared to the effect of a placebo, and also improved overall menopause-related quality of life symptoms.
The medication has the potential to fulfill an unmet clinical need, since 70% of women experience hot flashes and the median duration of symptoms is more than 7 years, Julia K. Prague, MD, said at the annual meeting of the Endocrine Society.
The study results were published concurrently with Dr. Prague’s presentation (Lancet. 2017 Apr 3. doi: 10.1016/S0140-6736[17]30823-1).
Evidence from postmortem studies of postmenopausal women, said Dr. Prague, pointed to NKB (neurokinin B)/NK3R signaling as playing a role in hot flashes. The brains of these women showed hypertrophy of NKB neurons and increased neuronal activity, as well as increased NKB gene expression. The same effects were seen in monkeys whose ovaries had been removed, and the effect was reversed when the monkeys were given estrogen.
Also, previous work has shown that administering NKB to premenopausal women gave them hot flashes (Sci Rep. 2015 Feb 6;5:8466). The preclinical work laid the groundwork for the hypothesis that taking an oral NK3R antagonist could mitigate hot flashes in menopausal women.
The randomized, placebo-controlled, double-blind 2-way crossover study enrolled 37 healthy women aged 40-62 who were at least 12 months out from their last menses. To qualify for enrollment, they needed to be experiencing at least seven hot flashes per 24 hours; the actual mean total number in the study group was 13 per 24 hours and 85 per week. A total of 28 women completed the full protocol.
The mean age of the women was 55 years, and the mean body mass index was 25.8 kg/m2. Three quarters of the women were white.
The women had an initial 2-week baseline period, during which they kept a symptom diary, and then were randomized to receive either an oral NK3R antagonist or a placebo twice daily. Then, each patient went through a 2-week washout period, after which they were crossed over to the other arm of the study. Finally, patients were monitored for a further 2 weeks after taking the study drug.
The NK3R antagonist, said Dr. Prague, “significantly reduced the total weekly number of hot [flashes] compared to placebo in the fourth week of treatment.” Patients taking placebo experienced 49.01 hot flashes per week (range, 40.81-58.86), while those taking the NK3R antagonist had 19.35 (range, 15.99-23.42, P less than .0001). This amounted to a 45% reduction in number of hot flashes compared to placebo.
Dr. Prague, a clinical research fellow at Imperial College, London, said that the treatment effect size seen was similar regardless of whether patients received the active study drug or placebo first.
Using the Menopause-Related Quality of Life questionnaire, Dr. Prague and her colleagues determined that when women were taking the NK3R antagonist, in addition to a significant reduction in vasomotor symptoms, menopause-related psychosocial symptoms were reduced by 15% (P = .0083) and physical symptoms by 19% (P = .0002). As expected for the nonhormonal medication, she said, sexual symptoms were reduced by a nonsignificant 8% (P = .24).
A subset of patients received more intensive study, with external validation of hot flashes and a series of 3-day-long stays during which an intravenous catheter was placed for blood sampling every 10 minutes.
Data from this group of patients showed that, while the NK3R antagonist did not significantly affect the number of luteinizing hormone pulses detected compared with placebo (P = .41), it did increase the mean amplitude of each pulse (P = .0243). Also, the active drug made the luteinizing hormone pulses more orderly (P = .0006 compared to placebo).
The NK3R antagonist was well tolerated. Though no serious adverse events were seen, three patients taking the NK3R antagonist did have a transient and asymptomatic elevation of transaminases without hyperbilirubinemia at 28 days after starting treatment. The elevation resolved for all patients within 90 days of stopping the medication.
The novel drug could represent “a potentially practice-changing therapeutic,” said Dr. Prague, since it “significantly relieves hot [flash] symptoms without the need for estrogen exposure.” She added that planning is underway for longer studies involving more patients.
The study was supported by AstraZeneca and Millendo Therapeutics, which are involved with manufacturing MLE4901.
[email protected]
On Twitter @karioakes
AT ENDO 2017
Key clinical point:
Major finding: The neurokinin 3 receptor antagonist reduced hot flashes from a mean of 85 per week at baseline to a mean of 49 per week.
Data source: Phase II randomized, double-blind, placebo-controlled two-way crossover study of 37 postmenopausal women with moderate to severe hot flashes.
Disclosures: The study was funded by AstraZeneca and Millendo Therapeutics, which are involved with the manufacture of the medicine, termed MLE4901.
Bioidentical hormone replacement fares well in phase III trial
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
[email protected]
On Twitter @karioakes
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
[email protected]
On Twitter @karioakes
ORLANDO – An oral combination of naturally-occurring estrogen and progesterone was found safe and effective for treatment of hot flashes in postmenopausal women with an intact uterus.
The phase III trial results represent another step toward approval of a formulation of bioidentical hormone therapy (HT) by the Food and Drug Administration.
“No similar combined HT has been approved in the U.S.; however, compounded bioidentical HT is estimated to have become the most prevalent HT by U.S. prescription volume,” Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, New York, wrote in an abstract accompanying the study. He presented his findings at the annual meeting of the Endocrine Society.
The study enrolled 1,835 patients, of whom 89% completed the efficacy portion of the study. The estrogen-progesterone combination significantly reduced hot flashes, compared with placebo (P less than .05 for all doses at 12 weeks), with the higher two of four different combination doses resulting in significant differences by study week 4. Menopause-related quality of life was also significantly improved by study week 12 for all doses (P less than .05, compared with placebo).
Up to 39 million prescriptions annually may be written for up to 2.5 million women in the United States, Dr. Lobo said. None of the currently available formulations of 17 beta-estradiol and progesterone are FDA approved. The medication studied – dubbed TX-001HR and produced by TherapeuticsMD – combines the two hormones in an oral capsule.
The REPLENISH trial was designed to evaluate the efficacy and safety of four different dose combinations of estradiol (E2) and progesterone (P4), compared with placebo, to treat moderate to severe vasomotor symptoms in postmenopausal women.
The phase III randomized, double-blind, placebo-controlled trial of the E2/P4 combination in postmenopausal women with an intact uterus had an efficacy portion of the study that lasted 12 weeks; endometrial safety was followed for 1 year in a smaller subset of patients.
The dose-ranging study design randomized women 1:1:1:1:1 to one of four combinations of E2 and P4, or to placebo. The four active treatment groups received either 1.0 mg E2/100 mg P4, 0.5 mg E2/100 mg P4, 0.5 mg E2/50 mg P4, or 0.25 mg E2/50 mg P4. There was no active comparator.
The safety portion of the study could include women whose vasomotor severity did not qualify them for the efficacy substudy; there was no placebo in this arm of the study.
Women participating in the vasomotor menopausal symptom (VMS) portion of the study kept a daily symptom diary and completed the Menopause-Specific Quality of Life (MENQOL) questionnaire as an objective measure of menopause-related symptomatology.
The study’s primary efficacy endpoints were VMS frequency and severity, tracked by measuring the mean change from baseline at study weeks 4 and 12. The secondary endpoint was the mean change in VMS frequency and severity week to week, compared with baseline. Patients were included in the modified intention-to-treat population if they took at least one dose of study drug and had at least 5 days of baseline diary data as well as at least 4 days of diary data in one on-treatment week.
The safety cohort included all women who took at least one capsule of the study drug, and tracked the incidence of endometrial hyperplasia out to 12 months for those who participated in the extended safety portion of the trial. The secondary endpoint was the incidence of other adverse events and serious adverse events.
All four dose combinations “provided statistically and clinically significant reduction in the weekly frequency of moderate to severe VMS from baseline at weeks 4 and 12, compared with placebo,” Dr. Lobo said. The lone exception, he said, was the lowest dose combination, which didn’t produce significant VMS reduction until study week 6.
Looking at the week-by-week improvement measure, the 1.0 mg E2/100 mg P4 and the 0.5 mg E2/100 mg P4 formulations improved VMS severity at weeks 4 and 12, compared with placebo.
Quality of life as measured by the MENQOL was significantly improved by all doses by study week 12, compared with placebo. Participants also reported significant improvement on the vasomotor domain of the MENQOL.
There was no endometrial hyperplasia in any study subject, nor were any malignancies detected in any study participant, Dr. Lobo said. The most frequently reported treatment-emergent adverse events were headaches, nasopharyngitis, breast tenderness, upper respiratory tract infection, nausea, back pain, and abdominal pain. Though seven serious treatment-emergent adverse events were considered treatment-related, “no unexpected safety signals were observed,” Dr. Lobo said.
To be included, postmenopausal women aged 40-65 years needed to have an intact uterus and be generally healthy, with a body mass index of less than 35 kg/m2. They also underwent an endometrial biopsy before participating. Their VMS had to occur at least seven times daily, or 50 times in a week, and be moderate to severe in intensity.
Patients with endometrial hyperplasia or melanoma, as well as women with uterine, endometrial, ovarian, or breast cancer, were excluded from the study, as were women with cardiovascular, hepatic, or renal disorders. Women with diabetes and those with thyroid disorders also were excluded.
Though women could have used sex hormone–containing or –modifying medications, they had to cease those medications for a variable washout period before beginning the study. The mean age of study participants was 55, and their mean BMI was 27. Two-thirds of the women were white.
“TX-001HR, if approved, would be a new oral hormone therapy option for postmenopausal women with moderate to severe vasomotor symptoms with an intact uterus,” Dr. Lobo said.
The drug, he said, could present an option in bioidentical hormones – one that has been evaluated for safety and efficacy – for women who are currently using “less regulated and unapproved compounded bioidentical hormone therapy.”
Dr. Lobo reported receiving research support from TherapeuticsMD, which funded the study.
[email protected]
On Twitter @karioakes
Key clinical point:
Major finding: Four different dose combinations of 17 beta estradiol and progesterone improved hot flashes and menopause-related quality of life, compared with placebo (P less than .05 for all).
Data source: Multicenter randomized, double-blind, placebo-controlled study of 1,835 postmenopausal women with an intact uterus.
Disclosures: Dr. Lobo reported receiving research funding from TherapeuticsMD, which sponsored the study.
HT use associated with lower postmenopausal coronary artery calcium scores
, and may also be linked to lower all-cause mortality, according to data presented in a poster at the annual meeting of the American College of Cardiology.
In a retrospective cohort study involving 4,286 consecutive asymptomatic postmenopausal women undergoing coronary artery calcium scanning between 1998 and 2012, researchers sought to clarify the controversial cardioprotective effects of hormone replacement therapy (HT).
After adjustment for age and cardiac risk factors, HT was associated with a higher prevalence of women with calcium artery score of 0, and a lower prevalence of women with calcium artery scores above 399.
Women taking HT also had significantly lower mortality compared with those not on HT (5.8% vs. 6.8%). After adjustment for age, cardiac risk factors, and coronary artery calcium scores, women on HT had a 30% lower long-term mortality (95% confidence interval, 0.49-0.98; P = .043).
“Hormone replacement therapy resulted in lower atherosclerosis and improved survival for all age groups and for all levels of coronary calcium,” Dr. Arnson said in a statement. “From this we do think it is beneficial, but we would need prospective or randomized studies to determine which groups might not benefit or even be harmed by this therapy.”
The women in the HT group were significantly younger than those not taking HT, and had a lower prevalence of hypertension and diabetes as well as higher average HDL cholesterol than women not taking HT.
Researchers saw a clear decrease in the number of women taking HT over the course of the study, declining from a peak of 60% in 1998 to 23% of women in 2012.
No disclosures were available.
, and may also be linked to lower all-cause mortality, according to data presented in a poster at the annual meeting of the American College of Cardiology.
In a retrospective cohort study involving 4,286 consecutive asymptomatic postmenopausal women undergoing coronary artery calcium scanning between 1998 and 2012, researchers sought to clarify the controversial cardioprotective effects of hormone replacement therapy (HT).
After adjustment for age and cardiac risk factors, HT was associated with a higher prevalence of women with calcium artery score of 0, and a lower prevalence of women with calcium artery scores above 399.
Women taking HT also had significantly lower mortality compared with those not on HT (5.8% vs. 6.8%). After adjustment for age, cardiac risk factors, and coronary artery calcium scores, women on HT had a 30% lower long-term mortality (95% confidence interval, 0.49-0.98; P = .043).
“Hormone replacement therapy resulted in lower atherosclerosis and improved survival for all age groups and for all levels of coronary calcium,” Dr. Arnson said in a statement. “From this we do think it is beneficial, but we would need prospective or randomized studies to determine which groups might not benefit or even be harmed by this therapy.”
The women in the HT group were significantly younger than those not taking HT, and had a lower prevalence of hypertension and diabetes as well as higher average HDL cholesterol than women not taking HT.
Researchers saw a clear decrease in the number of women taking HT over the course of the study, declining from a peak of 60% in 1998 to 23% of women in 2012.
No disclosures were available.
, and may also be linked to lower all-cause mortality, according to data presented in a poster at the annual meeting of the American College of Cardiology.
In a retrospective cohort study involving 4,286 consecutive asymptomatic postmenopausal women undergoing coronary artery calcium scanning between 1998 and 2012, researchers sought to clarify the controversial cardioprotective effects of hormone replacement therapy (HT).
After adjustment for age and cardiac risk factors, HT was associated with a higher prevalence of women with calcium artery score of 0, and a lower prevalence of women with calcium artery scores above 399.
Women taking HT also had significantly lower mortality compared with those not on HT (5.8% vs. 6.8%). After adjustment for age, cardiac risk factors, and coronary artery calcium scores, women on HT had a 30% lower long-term mortality (95% confidence interval, 0.49-0.98; P = .043).
“Hormone replacement therapy resulted in lower atherosclerosis and improved survival for all age groups and for all levels of coronary calcium,” Dr. Arnson said in a statement. “From this we do think it is beneficial, but we would need prospective or randomized studies to determine which groups might not benefit or even be harmed by this therapy.”
The women in the HT group were significantly younger than those not taking HT, and had a lower prevalence of hypertension and diabetes as well as higher average HDL cholesterol than women not taking HT.
Researchers saw a clear decrease in the number of women taking HT over the course of the study, declining from a peak of 60% in 1998 to 23% of women in 2012.
No disclosures were available.
FROM ACC 17
Key clinical point: Hormone replacement therapy is associated with lower coronary artery calcium scores in postmenopausal women and may also be linked to lower all-cause mortality.
Major finding: The average coronary artery calcium score was significantly lower in the 41% of women who were taking HT compared to those who weren’t (72.1 vs. 3,119.2 ).
Data source: Retrospective cohort study of 4,286 postmenopausal women undergoing coronary artery calcium scanning.
Disclosures: No disclosures were available.
Older women with remitted depression show attention bias for negative information
Older women with a history of major depressive disorder are more likely to direct their attention to negative images than women without history of MDD, researchers report. The findings follow previous research showing that individuals currently depressed or at-risk show a similar attention bias.
The current study examined 33 postmenopausal women aged 45-75 years with an emotion dot probe (EDP) task combined with fMRI scans, in addition to cognitive and depression history screening and several self-rated measures.
“We examined resting-state functional connectivity before the EDP task to assess differences in intrinsic amygdala functional connections to other brain areas between the groups,” wrote Kimberly Albert, PhD, of Vanderbilt University, Nashville, Tenn., and her coauthors (J Affect Disord. 2017 Mar 1;210:49-52).
The women in the study with a history of MDD showed greater attention facilitation to negative images, greater amygdala activity, and greater amygdala-hippocampal functional connectivity than women without a history of MDD.
“Attention bias for negative information can be seen in individuals with past MDD without inducing a negative mood state. Attention bias for negative information may be an ongoing vulnerability for MDD recurrence independent of mood state,” Dr. Albert and her coauthors wrote.
Older women with a history of major depressive disorder are more likely to direct their attention to negative images than women without history of MDD, researchers report. The findings follow previous research showing that individuals currently depressed or at-risk show a similar attention bias.
The current study examined 33 postmenopausal women aged 45-75 years with an emotion dot probe (EDP) task combined with fMRI scans, in addition to cognitive and depression history screening and several self-rated measures.
“We examined resting-state functional connectivity before the EDP task to assess differences in intrinsic amygdala functional connections to other brain areas between the groups,” wrote Kimberly Albert, PhD, of Vanderbilt University, Nashville, Tenn., and her coauthors (J Affect Disord. 2017 Mar 1;210:49-52).
The women in the study with a history of MDD showed greater attention facilitation to negative images, greater amygdala activity, and greater amygdala-hippocampal functional connectivity than women without a history of MDD.
“Attention bias for negative information can be seen in individuals with past MDD without inducing a negative mood state. Attention bias for negative information may be an ongoing vulnerability for MDD recurrence independent of mood state,” Dr. Albert and her coauthors wrote.
Older women with a history of major depressive disorder are more likely to direct their attention to negative images than women without history of MDD, researchers report. The findings follow previous research showing that individuals currently depressed or at-risk show a similar attention bias.
The current study examined 33 postmenopausal women aged 45-75 years with an emotion dot probe (EDP) task combined with fMRI scans, in addition to cognitive and depression history screening and several self-rated measures.
“We examined resting-state functional connectivity before the EDP task to assess differences in intrinsic amygdala functional connections to other brain areas between the groups,” wrote Kimberly Albert, PhD, of Vanderbilt University, Nashville, Tenn., and her coauthors (J Affect Disord. 2017 Mar 1;210:49-52).
The women in the study with a history of MDD showed greater attention facilitation to negative images, greater amygdala activity, and greater amygdala-hippocampal functional connectivity than women without a history of MDD.
“Attention bias for negative information can be seen in individuals with past MDD without inducing a negative mood state. Attention bias for negative information may be an ongoing vulnerability for MDD recurrence independent of mood state,” Dr. Albert and her coauthors wrote.
FROM THE JOURNAL OF AFFECTIVE DISORDERS