NAMS 2011 Annual Meeting

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD.  – A novel selective estrogen–receptor modulator called ospemifene was significantly more effective than placebo for reducing symptoms of vaginal dryness and dyspareunia in a study of 919 postmenopausal women.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated," said Dr. David Portman of the Columbus (Ohio) Center for Women’s Health Research.

Only estrogen-based treatments have been approved in the United States to treat VVA in postmenopausal women, but concerns about the effects of estrogen on breast and endometrial tissue have prompted doctors and patients to seek alternatives, Dr. Portman said at the annual meeting of the North American Menopause Society.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated."

"We do need to find alternatives because many of our patients still have concerns even with local estrogen," he emphasized.

Ospemifene (OSP), a selective estrogen–receptor modulator (SERM) – also referred to as a nonsteroidal estrogen–receptor agonist/antagonist – is distinct from other SERMs because its estrogenic activity occurs on the vaginal epithelium, "but not on the endometrium," said Dr. Portman.

Previous studies have shown that ospemifene is well tolerated, with a favorable pharmacologic profile in postmenopausal women with VVA, he added.

In a 12-week randomized, double-blind, placebo-controlled, phase III parallel group study, Dr. Portman and his colleagues assessed the efficacy, safety, and tolerability of ospemifene for women with moderate to severe vaginal dryness or moderate to severe dyspareunia. VVA and dyspareunia symptoms and severity were self-reported, and use of a nonhormonal vaginal lubricant was permitted as needed. Demographic characteristics were similar between the two groups.

The women ranged from 40 to 80 years of age at baseline. Those with a body mass index of 37 kg/m² or greater were excluded, as were those with clinically significant abnormal gynecologic findings other than vaginal atrophy and those using hormonal medications or other products with possible estrogenic or antiestrogenic effects within a timeframe too close to the study screening.

A total of 314 postmenopausal women who reported vaginal dryness as their primary symptom were randomized to 60 mg of OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the vaginal dryness severity score improved in the OSP group vs. the placebo group (–1.3 vs. –1.1). In addition, the percentages of superficial and parabasal cells were significantly different in the OSP group vs. the placebo group (12% vs. 3% and –32% vs. –4%, respectively). Measuring these types of cells indicates changes in the vaginal microflora, which have been shown to affect vaginal dryness and pain.

The mean change in vaginal pH was –1.01 in the OSP group, compared with –0.25 in the placebo group, respectively.

An additional 605 women who reported dyspareunia as their primary symptom were randomized to 60 mg OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the dyspareunia severity score improved in the OSP group vs. the placebo group (–1.5 vs. –1.2, P = .0001), a significant difference. In addition, the percentages of superficial cells and parabasal cells were significantly different in the OSP vs. the placebo groups (12% vs. 2% and –40% vs. 0%, respectively). The mean change in vaginal pH also differed significantly between the OSP and placebo groups (–1.0 vs. –0.06, respectively).

Overall, ospemifene had "a very clean safety profile," Dr. Portman said. The total number of treatment-emergent adverse events was not significantly different between the OSP and placebo groups (290 vs. 232). A total of 122 treatment-related adverse events occurred in the OSP group, compared with 62 in the placebo group, but the number of serious adverse events and severe adverse events were similar between the groups (6 vs. 7 and 28 vs. 29, respectively). The most common treatment-emergent adverse events in the OSP group were urinary tract infection, (8%), hot flashes (7%), and vaginal discharge (5%).

No deaths, myocardial infarctions, and or breast cancer cases were reported in any of the patients during the study period.

While not yet approved for VVA, "this investigational SERM has the potential to be an efficacious, nonestrogen oral prescription therapy for this prevalent, bothersome, and undertreated condition," Dr. Portman said.

The study was sponsored in part by Shionogi, which develops and markets ospemifene, and several coinvestigators were Shionogi employees. Dr. Portman has received consulting fees, honoraria, and/or grant support from multiple companies including Shionogi, Bayer, Boehringer Ingelheim, Teva, Warner Chilcott, and Watson Pharmaceuticals.

NATIONAL HARBOR, MD.  – A novel selective estrogen–receptor modulator called ospemifene was significantly more effective than placebo for reducing symptoms of vaginal dryness and dyspareunia in a study of 919 postmenopausal women.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated," said Dr. David Portman of the Columbus (Ohio) Center for Women’s Health Research.

Only estrogen-based treatments have been approved in the United States to treat VVA in postmenopausal women, but concerns about the effects of estrogen on breast and endometrial tissue have prompted doctors and patients to seek alternatives, Dr. Portman said at the annual meeting of the North American Menopause Society.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated."

"We do need to find alternatives because many of our patients still have concerns even with local estrogen," he emphasized.

Ospemifene (OSP), a selective estrogen–receptor modulator (SERM) – also referred to as a nonsteroidal estrogen–receptor agonist/antagonist – is distinct from other SERMs because its estrogenic activity occurs on the vaginal epithelium, "but not on the endometrium," said Dr. Portman.

Previous studies have shown that ospemifene is well tolerated, with a favorable pharmacologic profile in postmenopausal women with VVA, he added.

In a 12-week randomized, double-blind, placebo-controlled, phase III parallel group study, Dr. Portman and his colleagues assessed the efficacy, safety, and tolerability of ospemifene for women with moderate to severe vaginal dryness or moderate to severe dyspareunia. VVA and dyspareunia symptoms and severity were self-reported, and use of a nonhormonal vaginal lubricant was permitted as needed. Demographic characteristics were similar between the two groups.

The women ranged from 40 to 80 years of age at baseline. Those with a body mass index of 37 kg/m² or greater were excluded, as were those with clinically significant abnormal gynecologic findings other than vaginal atrophy and those using hormonal medications or other products with possible estrogenic or antiestrogenic effects within a timeframe too close to the study screening.

A total of 314 postmenopausal women who reported vaginal dryness as their primary symptom were randomized to 60 mg of OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the vaginal dryness severity score improved in the OSP group vs. the placebo group (–1.3 vs. –1.1). In addition, the percentages of superficial and parabasal cells were significantly different in the OSP group vs. the placebo group (12% vs. 3% and –32% vs. –4%, respectively). Measuring these types of cells indicates changes in the vaginal microflora, which have been shown to affect vaginal dryness and pain.

The mean change in vaginal pH was –1.01 in the OSP group, compared with –0.25 in the placebo group, respectively.

An additional 605 women who reported dyspareunia as their primary symptom were randomized to 60 mg OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the dyspareunia severity score improved in the OSP group vs. the placebo group (–1.5 vs. –1.2, P = .0001), a significant difference. In addition, the percentages of superficial cells and parabasal cells were significantly different in the OSP vs. the placebo groups (12% vs. 2% and –40% vs. 0%, respectively). The mean change in vaginal pH also differed significantly between the OSP and placebo groups (–1.0 vs. –0.06, respectively).

Overall, ospemifene had "a very clean safety profile," Dr. Portman said. The total number of treatment-emergent adverse events was not significantly different between the OSP and placebo groups (290 vs. 232). A total of 122 treatment-related adverse events occurred in the OSP group, compared with 62 in the placebo group, but the number of serious adverse events and severe adverse events were similar between the groups (6 vs. 7 and 28 vs. 29, respectively). The most common treatment-emergent adverse events in the OSP group were urinary tract infection, (8%), hot flashes (7%), and vaginal discharge (5%).

No deaths, myocardial infarctions, and or breast cancer cases were reported in any of the patients during the study period.

While not yet approved for VVA, "this investigational SERM has the potential to be an efficacious, nonestrogen oral prescription therapy for this prevalent, bothersome, and undertreated condition," Dr. Portman said.

The study was sponsored in part by Shionogi, which develops and markets ospemifene, and several coinvestigators were Shionogi employees. Dr. Portman has received consulting fees, honoraria, and/or grant support from multiple companies including Shionogi, Bayer, Boehringer Ingelheim, Teva, Warner Chilcott, and Watson Pharmaceuticals.

NATIONAL HARBOR, MD.  – A novel selective estrogen–receptor modulator called ospemifene was significantly more effective than placebo for reducing symptoms of vaginal dryness and dyspareunia in a study of 919 postmenopausal women.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated," said Dr. David Portman of the Columbus (Ohio) Center for Women’s Health Research.

Only estrogen-based treatments have been approved in the United States to treat VVA in postmenopausal women, but concerns about the effects of estrogen on breast and endometrial tissue have prompted doctors and patients to seek alternatives, Dr. Portman said at the annual meeting of the North American Menopause Society.

"Despite its negative impact on sexual function, psychosocial well-being, and partner relationships, vulvovaginal atrophy (VVA) frequently goes untreated."

"We do need to find alternatives because many of our patients still have concerns even with local estrogen," he emphasized.

Ospemifene (OSP), a selective estrogen–receptor modulator (SERM) – also referred to as a nonsteroidal estrogen–receptor agonist/antagonist – is distinct from other SERMs because its estrogenic activity occurs on the vaginal epithelium, "but not on the endometrium," said Dr. Portman.

Previous studies have shown that ospemifene is well tolerated, with a favorable pharmacologic profile in postmenopausal women with VVA, he added.

In a 12-week randomized, double-blind, placebo-controlled, phase III parallel group study, Dr. Portman and his colleagues assessed the efficacy, safety, and tolerability of ospemifene for women with moderate to severe vaginal dryness or moderate to severe dyspareunia. VVA and dyspareunia symptoms and severity were self-reported, and use of a nonhormonal vaginal lubricant was permitted as needed. Demographic characteristics were similar between the two groups.

The women ranged from 40 to 80 years of age at baseline. Those with a body mass index of 37 kg/m² or greater were excluded, as were those with clinically significant abnormal gynecologic findings other than vaginal atrophy and those using hormonal medications or other products with possible estrogenic or antiestrogenic effects within a timeframe too close to the study screening.

A total of 314 postmenopausal women who reported vaginal dryness as their primary symptom were randomized to 60 mg of OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the vaginal dryness severity score improved in the OSP group vs. the placebo group (–1.3 vs. –1.1). In addition, the percentages of superficial and parabasal cells were significantly different in the OSP group vs. the placebo group (12% vs. 3% and –32% vs. –4%, respectively). Measuring these types of cells indicates changes in the vaginal microflora, which have been shown to affect vaginal dryness and pain.

The mean change in vaginal pH was –1.01 in the OSP group, compared with –0.25 in the placebo group, respectively.

An additional 605 women who reported dyspareunia as their primary symptom were randomized to 60 mg OSP orally each morning or a placebo.

In the intent-to-treat population, the change in the dyspareunia severity score improved in the OSP group vs. the placebo group (–1.5 vs. –1.2, P = .0001), a significant difference. In addition, the percentages of superficial cells and parabasal cells were significantly different in the OSP vs. the placebo groups (12% vs. 2% and –40% vs. 0%, respectively). The mean change in vaginal pH also differed significantly between the OSP and placebo groups (–1.0 vs. –0.06, respectively).

Overall, ospemifene had "a very clean safety profile," Dr. Portman said. The total number of treatment-emergent adverse events was not significantly different between the OSP and placebo groups (290 vs. 232). A total of 122 treatment-related adverse events occurred in the OSP group, compared with 62 in the placebo group, but the number of serious adverse events and severe adverse events were similar between the groups (6 vs. 7 and 28 vs. 29, respectively). The most common treatment-emergent adverse events in the OSP group were urinary tract infection, (8%), hot flashes (7%), and vaginal discharge (5%).

No deaths, myocardial infarctions, and or breast cancer cases were reported in any of the patients during the study period.

While not yet approved for VVA, "this investigational SERM has the potential to be an efficacious, nonestrogen oral prescription therapy for this prevalent, bothersome, and undertreated condition," Dr. Portman said.

The study was sponsored in part by Shionogi, which develops and markets ospemifene, and several coinvestigators were Shionogi employees. Dr. Portman has received consulting fees, honoraria, and/or grant support from multiple companies including Shionogi, Bayer, Boehringer Ingelheim, Teva, Warner Chilcott, and Watson Pharmaceuticals.

NATIONAL HARBOR, MD. – Women who had a longer exposure to estradiol before menopause had a significantly lower risk of developing depression during the menopausal transition, based on data from 1,282 women.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition," said Dr. Wendy Marsh of the University of Massachusetts, Worcester.

Data from previous studies have suggested that endocrine factors in general, and estrogen levels in particular, may contribute to a woman’s susceptibility to depression during menopause, she noted.

Dr. Marsh and her colleagues reviewed data from 1,282 women participating in the Study of Women's Health Across the Nation (SWAN), a multisite, long-term epidemiologic study of women during midlife and through the menopausal transition. The women were premenopausal when they entered the study.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition."

Each additional year of premenopausal estradiol exposure conveyed a 15% reduction in risk of experiencing depression during menopause (hazard ratio, 0.85) after confounding factors including premenopausal depression, baseline age, smoking status, education, antidepressant use, ethnicity, and length of time in the study were controlled for.

The average duration of estradiol exposure was 36 years. Longer exposure was significantly associated with a lower risk of having a score of 16 or higher on the Center for Epidemiologic Studies Depression (CES-D) scale.

Estradiol has been shown to affect mood regulation, Dr. Marsh noted, but "it is unknown how such a modulatory effect during premenopausal years would lead to a protective effect against depression during the menopausal transition," she said.

Although the data are preliminary, they may provide a foundation for further research that may help clinicians identify and manage women at increased risk for depression during menopause.

"Additional analyses will further qualify and quantify other variables related to estrogen exposure, including use of oral contraceptives, pregnancies, and lactation," Dr. Marsh said at the annual meeting of the North American Menopause Society.

The Study of Women’s Health Across the Nation is supported by grants from the National Institutes of Health, the U.S. Department of Health and Human Services, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. Dr. Marsh reported having no relevant financial disclosures.

NATIONAL HARBOR, MD. – Women who had a longer exposure to estradiol before menopause had a significantly lower risk of developing depression during the menopausal transition, based on data from 1,282 women.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition," said Dr. Wendy Marsh of the University of Massachusetts, Worcester.

Data from previous studies have suggested that endocrine factors in general, and estrogen levels in particular, may contribute to a woman’s susceptibility to depression during menopause, she noted.

Dr. Marsh and her colleagues reviewed data from 1,282 women participating in the Study of Women's Health Across the Nation (SWAN), a multisite, long-term epidemiologic study of women during midlife and through the menopausal transition. The women were premenopausal when they entered the study.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition."

Each additional year of premenopausal estradiol exposure conveyed a 15% reduction in risk of experiencing depression during menopause (hazard ratio, 0.85) after confounding factors including premenopausal depression, baseline age, smoking status, education, antidepressant use, ethnicity, and length of time in the study were controlled for.

The average duration of estradiol exposure was 36 years. Longer exposure was significantly associated with a lower risk of having a score of 16 or higher on the Center for Epidemiologic Studies Depression (CES-D) scale.

Estradiol has been shown to affect mood regulation, Dr. Marsh noted, but "it is unknown how such a modulatory effect during premenopausal years would lead to a protective effect against depression during the menopausal transition," she said.

Although the data are preliminary, they may provide a foundation for further research that may help clinicians identify and manage women at increased risk for depression during menopause.

"Additional analyses will further qualify and quantify other variables related to estrogen exposure, including use of oral contraceptives, pregnancies, and lactation," Dr. Marsh said at the annual meeting of the North American Menopause Society.

The Study of Women’s Health Across the Nation is supported by grants from the National Institutes of Health, the U.S. Department of Health and Human Services, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. Dr. Marsh reported having no relevant financial disclosures.

NATIONAL HARBOR, MD. – Women who had a longer exposure to estradiol before menopause had a significantly lower risk of developing depression during the menopausal transition, based on data from 1,282 women.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition," said Dr. Wendy Marsh of the University of Massachusetts, Worcester.

Data from previous studies have suggested that endocrine factors in general, and estrogen levels in particular, may contribute to a woman’s susceptibility to depression during menopause, she noted.

Dr. Marsh and her colleagues reviewed data from 1,282 women participating in the Study of Women's Health Across the Nation (SWAN), a multisite, long-term epidemiologic study of women during midlife and through the menopausal transition. The women were premenopausal when they entered the study.

"It is unclear why some women are at increased risk of depression while undergoing the menopausal transition."

Each additional year of premenopausal estradiol exposure conveyed a 15% reduction in risk of experiencing depression during menopause (hazard ratio, 0.85) after confounding factors including premenopausal depression, baseline age, smoking status, education, antidepressant use, ethnicity, and length of time in the study were controlled for.

The average duration of estradiol exposure was 36 years. Longer exposure was significantly associated with a lower risk of having a score of 16 or higher on the Center for Epidemiologic Studies Depression (CES-D) scale.

Estradiol has been shown to affect mood regulation, Dr. Marsh noted, but "it is unknown how such a modulatory effect during premenopausal years would lead to a protective effect against depression during the menopausal transition," she said.

Although the data are preliminary, they may provide a foundation for further research that may help clinicians identify and manage women at increased risk for depression during menopause.

"Additional analyses will further qualify and quantify other variables related to estrogen exposure, including use of oral contraceptives, pregnancies, and lactation," Dr. Marsh said at the annual meeting of the North American Menopause Society.

The Study of Women’s Health Across the Nation is supported by grants from the National Institutes of Health, the U.S. Department of Health and Human Services, the National Institute of Nursing Research, and the NIH Office of Research on Women’s Health. Dr. Marsh reported having no relevant financial disclosures.

NATIONAL HARBOR, MD. –Women who used transdermal ­estrogen had a 30% lower risk of ­venous thromboembolism than did patients who used oral estrogen, based on data collected from more than 50,000 women, said Eric
Beresford, Pharm.D., of Novartis.

The observation is limited, how­ever, by the lack of data on specific estrogen doses in the oral estrogen users. Further, the data were not adjusted for the participants’ weights or BMIs.

Transdermal estrogen has the ­potential to reduce VTE risk by ­delivering unmetabolized estradiol ­directly to the bloodstream, he said.

Women who used transdermal estrogen had a 30% lower risk of venous thromboembolism than did patients who used oral estrogen, based on data from more than 50,000 women.

"Women treated with oral estrogen–containing hormone therapy have an increased risk of developing venous thromboembolism," according to data from previous studies, said Eric Beresford, Pharm.D., of Novartis. Dr. Beresford presented the findings at the annual meeting of the North American Menopause Society.

Transdermal estrogen has the potential to reduce VTE risk by delivering unmetabolized estradiol directly to the bloodstream, he explained.

In retrospective, matched-cohort study, Dr. Beresford and colleagues compared VTE incidence for up to 90 days in 27,018 women who began taking oral estrogen only, and in 27,018 who began using a high-dose estradiol transdermal system (ETS) between January 2002 and October 2009. The data were collected from the Thomson Reuters MarketScan database of health insurance claims.

The mean age of the women was 49 years, and 22% of them had menopausal or postmenopausal disorders.

Overall, 115 women (0.40 events per 100 person-years) in the ETS group developed VTE, compared with 164 women (0.56 events per 100 person-years) in the oral estrogen group; this difference was statistically significant (P = .006).

The incidence of hospitalization-related VTE events was significantly lower in the ETS group, compared with the oral estrogen group (24 vs. 44, respectively). The number of events per 100 person-years was 0.08 and 0.15, respectively.

VTE was defined as at least one diagnosis code for deep vein thrombosis or pulmonary embolism. Women with a prior VTE diagnosis were excluded from the study.

When shown on a Kaplan-Meier curve, the rates of VTE in the ETS group at 6, 12, and 24 months after the start of therapy were 0.24%, 0.42%, and 0.68%, respectively. The rates of VTE in the oral estrogen group were 0.31%, 0.59%, and 1.13%, respectively. The differences between the two groups were statistically significant (P = .006).

The differences in VTE rates between the two groups were significant with EST doses of either 0.075 mg/day or 0.1 mg/day, Dr. Beresford noted. The women in the oral estrogen hormone therapy group were taking a variety of brands of oral estrogen replacements in various dosages; the study was not designed to compare ETS with specific oral estrogen doses, he added.

The most common concomitant medications were antihypertensives, which were taken by 11% of the women in each group. The most common risk factor for VTE was surgical resection of abdominal or pelvic cancer (24%) and other major surgery (17%).

The findings were limited by the lack of information about the participants’ weight or body mass index, which can affect the risk of thrombotic events, and by the observational nature of the study, Dr. Beresford said.

However, the results suggest that "women receiving ETS have a significantly lower incidence of VTE and hospitalization-related VTE than [do] women receiving oral estrogen–only hormone therapy," he said. More research is needed to assess transdermal estrogen as an option for women at increased risk for VTE.

The study was sponsored by Novartis and several of the coinvestigators are employed by Novartis.

NATIONAL HARBOR, MD. –Women who used transdermal ­estrogen had a 30% lower risk of ­venous thromboembolism than did patients who used oral estrogen, based on data collected from more than 50,000 women, said Eric
Beresford, Pharm.D., of Novartis.

The observation is limited, how­ever, by the lack of data on specific estrogen doses in the oral estrogen users. Further, the data were not adjusted for the participants’ weights or BMIs.

Transdermal estrogen has the ­potential to reduce VTE risk by ­delivering unmetabolized estradiol ­directly to the bloodstream, he said.

Women who used transdermal estrogen had a 30% lower risk of venous thromboembolism than did patients who used oral estrogen, based on data from more than 50,000 women.

"Women treated with oral estrogen–containing hormone therapy have an increased risk of developing venous thromboembolism," according to data from previous studies, said Eric Beresford, Pharm.D., of Novartis. Dr. Beresford presented the findings at the annual meeting of the North American Menopause Society.

Transdermal estrogen has the potential to reduce VTE risk by delivering unmetabolized estradiol directly to the bloodstream, he explained.

In retrospective, matched-cohort study, Dr. Beresford and colleagues compared VTE incidence for up to 90 days in 27,018 women who began taking oral estrogen only, and in 27,018 who began using a high-dose estradiol transdermal system (ETS) between January 2002 and October 2009. The data were collected from the Thomson Reuters MarketScan database of health insurance claims.

The mean age of the women was 49 years, and 22% of them had menopausal or postmenopausal disorders.

Overall, 115 women (0.40 events per 100 person-years) in the ETS group developed VTE, compared with 164 women (0.56 events per 100 person-years) in the oral estrogen group; this difference was statistically significant (P = .006).

The incidence of hospitalization-related VTE events was significantly lower in the ETS group, compared with the oral estrogen group (24 vs. 44, respectively). The number of events per 100 person-years was 0.08 and 0.15, respectively.

VTE was defined as at least one diagnosis code for deep vein thrombosis or pulmonary embolism. Women with a prior VTE diagnosis were excluded from the study.

When shown on a Kaplan-Meier curve, the rates of VTE in the ETS group at 6, 12, and 24 months after the start of therapy were 0.24%, 0.42%, and 0.68%, respectively. The rates of VTE in the oral estrogen group were 0.31%, 0.59%, and 1.13%, respectively. The differences between the two groups were statistically significant (P = .006).

The differences in VTE rates between the two groups were significant with EST doses of either 0.075 mg/day or 0.1 mg/day, Dr. Beresford noted. The women in the oral estrogen hormone therapy group were taking a variety of brands of oral estrogen replacements in various dosages; the study was not designed to compare ETS with specific oral estrogen doses, he added.

The most common concomitant medications were antihypertensives, which were taken by 11% of the women in each group. The most common risk factor for VTE was surgical resection of abdominal or pelvic cancer (24%) and other major surgery (17%).

The findings were limited by the lack of information about the participants’ weight or body mass index, which can affect the risk of thrombotic events, and by the observational nature of the study, Dr. Beresford said.

However, the results suggest that "women receiving ETS have a significantly lower incidence of VTE and hospitalization-related VTE than [do] women receiving oral estrogen–only hormone therapy," he said. More research is needed to assess transdermal estrogen as an option for women at increased risk for VTE.

The study was sponsored by Novartis and several of the coinvestigators are employed by Novartis.

NATIONAL HARBOR, MD. –Women who used transdermal ­estrogen had a 30% lower risk of ­venous thromboembolism than did patients who used oral estrogen, based on data collected from more than 50,000 women, said Eric
Beresford, Pharm.D., of Novartis.

The observation is limited, how­ever, by the lack of data on specific estrogen doses in the oral estrogen users. Further, the data were not adjusted for the participants’ weights or BMIs.

Transdermal estrogen has the ­potential to reduce VTE risk by ­delivering unmetabolized estradiol ­directly to the bloodstream, he said.

Women who used transdermal estrogen had a 30% lower risk of venous thromboembolism than did patients who used oral estrogen, based on data from more than 50,000 women.

"Women treated with oral estrogen–containing hormone therapy have an increased risk of developing venous thromboembolism," according to data from previous studies, said Eric Beresford, Pharm.D., of Novartis. Dr. Beresford presented the findings at the annual meeting of the North American Menopause Society.

Transdermal estrogen has the potential to reduce VTE risk by delivering unmetabolized estradiol directly to the bloodstream, he explained.

In retrospective, matched-cohort study, Dr. Beresford and colleagues compared VTE incidence for up to 90 days in 27,018 women who began taking oral estrogen only, and in 27,018 who began using a high-dose estradiol transdermal system (ETS) between January 2002 and October 2009. The data were collected from the Thomson Reuters MarketScan database of health insurance claims.

The mean age of the women was 49 years, and 22% of them had menopausal or postmenopausal disorders.

Overall, 115 women (0.40 events per 100 person-years) in the ETS group developed VTE, compared with 164 women (0.56 events per 100 person-years) in the oral estrogen group; this difference was statistically significant (P = .006).

The incidence of hospitalization-related VTE events was significantly lower in the ETS group, compared with the oral estrogen group (24 vs. 44, respectively). The number of events per 100 person-years was 0.08 and 0.15, respectively.

VTE was defined as at least one diagnosis code for deep vein thrombosis or pulmonary embolism. Women with a prior VTE diagnosis were excluded from the study.

When shown on a Kaplan-Meier curve, the rates of VTE in the ETS group at 6, 12, and 24 months after the start of therapy were 0.24%, 0.42%, and 0.68%, respectively. The rates of VTE in the oral estrogen group were 0.31%, 0.59%, and 1.13%, respectively. The differences between the two groups were statistically significant (P = .006).

The differences in VTE rates between the two groups were significant with EST doses of either 0.075 mg/day or 0.1 mg/day, Dr. Beresford noted. The women in the oral estrogen hormone therapy group were taking a variety of brands of oral estrogen replacements in various dosages; the study was not designed to compare ETS with specific oral estrogen doses, he added.

The most common concomitant medications were antihypertensives, which were taken by 11% of the women in each group. The most common risk factor for VTE was surgical resection of abdominal or pelvic cancer (24%) and other major surgery (17%).

The findings were limited by the lack of information about the participants’ weight or body mass index, which can affect the risk of thrombotic events, and by the observational nature of the study, Dr. Beresford said.

However, the results suggest that "women receiving ETS have a significantly lower incidence of VTE and hospitalization-related VTE than [do] women receiving oral estrogen–only hormone therapy," he said. More research is needed to assess transdermal estrogen as an option for women at increased risk for VTE.

The study was sponsored by Novartis and several of the coinvestigators are employed by Novartis.

NATIONAL HARBOR, MD. – Use of a combination of bazedoxifene and conjugated estrogens had no significant impact on breast density (a potential risk factor for breast cancer) in postmenopausal women, based on data from the SMART-5 trial.

"Preclinical studies have suggested that the selective estrogen receptor modulator (SERM) bazedoxifene (BZA) prevents estrogen-induced stimulation of breast tissue," said Dr. JoAnn V. Pinkerton of the University of Virginia, Charlottesville. The findings were presented at the annual meeting of the North American Menopause Society.

The Selective Estrogens, Menopause, and Response to Therapy (SMART)-5 study was a 1-year, randomized, double-blind, placebo-controlled, phase III study of healthy postmenopausal women with a uterus who sought treatment for vasomotor symptoms, Dr. Pinkerton said. A subset of 940 women from this study took part in a breast density substudy to assess changes in breast density after a year of treatment with BZA/conjugated estrogens, compared to other treatment or a placebo.

The women underwent mammograms at baseline and again after 1 year of treatment. Changes in breast density were assessed using an analysis of covariance (ANCOVA) model.

After 1 year, the mean adjusted change in breast density from baseline was –0.38% in the women who were received 20 mg BZA/0.45 mg conjugated estrogens, –0.44 in the women who received 20 mg BZA/0.625 conjugated estrogens, –0.24% in the women who received 20 mg BZA alone, 1.60% in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate, and –0.32% in the women who received a placebo.

The only significant difference in breast density either within group or versus placebo occurred in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate.

In addition, BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg showed noninferiority to placebo for breast density at 1 year, Dr. Pinkerton noted.

Four abnormal mammograms were seen in the 20 mg BZA/0.45 mg conjugated estrogens group, two in the 20 mg BZA/0.625 conjugated estrogens group, one in the 20 mg BZA alone group, three in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, and one in the placebo group.

Two cases of breast cancer were reported in the 20 mg BZA/0.45 mg conjugated estrogens group, compared to one case in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, one case in the placebo group, and none in the other groups.

The mean age of the women was 54 years, and they were menopausal from 4 to 5 years. Approximately 90% were white. The demographics were similar among all five groups.

Overall, there was no significant difference in the incidence of breast-related adverse events among the groups.

The findings are consistent with those from a previous retrospective study of the SMART-5 data, said Dr. Pinkerton.

"The favorable breast effects seen with BZA 20 mg/CE 0.45 mg and 0.625 mg in this prospective evaluation are a potential advantage of BZA/CE over conventional estrogen/progestin therapy," for postmenopausal women with a uterus, she said.

The study was sponsored by Wyeth Research, now a division of Pfizer, and several of the study coinvestigators are Pfizer employees. Dr. Pinkerton has received fees given to the University of Virginia. She has served as a consultant to Pfizer, Teva, Depomed, and Novo Nordisk, received grants or research support from Pfizer, Depomed, and EndoCeutics, and served on the data safety monitoring board for Boehringer Ingelheim.

NATIONAL HARBOR, MD. – Use of a combination of bazedoxifene and conjugated estrogens had no significant impact on breast density (a potential risk factor for breast cancer) in postmenopausal women, based on data from the SMART-5 trial.

"Preclinical studies have suggested that the selective estrogen receptor modulator (SERM) bazedoxifene (BZA) prevents estrogen-induced stimulation of breast tissue," said Dr. JoAnn V. Pinkerton of the University of Virginia, Charlottesville. The findings were presented at the annual meeting of the North American Menopause Society.

The Selective Estrogens, Menopause, and Response to Therapy (SMART)-5 study was a 1-year, randomized, double-blind, placebo-controlled, phase III study of healthy postmenopausal women with a uterus who sought treatment for vasomotor symptoms, Dr. Pinkerton said. A subset of 940 women from this study took part in a breast density substudy to assess changes in breast density after a year of treatment with BZA/conjugated estrogens, compared to other treatment or a placebo.

The women underwent mammograms at baseline and again after 1 year of treatment. Changes in breast density were assessed using an analysis of covariance (ANCOVA) model.

After 1 year, the mean adjusted change in breast density from baseline was –0.38% in the women who were received 20 mg BZA/0.45 mg conjugated estrogens, –0.44 in the women who received 20 mg BZA/0.625 conjugated estrogens, –0.24% in the women who received 20 mg BZA alone, 1.60% in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate, and –0.32% in the women who received a placebo.

The only significant difference in breast density either within group or versus placebo occurred in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate.

In addition, BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg showed noninferiority to placebo for breast density at 1 year, Dr. Pinkerton noted.

Four abnormal mammograms were seen in the 20 mg BZA/0.45 mg conjugated estrogens group, two in the 20 mg BZA/0.625 conjugated estrogens group, one in the 20 mg BZA alone group, three in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, and one in the placebo group.

Two cases of breast cancer were reported in the 20 mg BZA/0.45 mg conjugated estrogens group, compared to one case in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, one case in the placebo group, and none in the other groups.

The mean age of the women was 54 years, and they were menopausal from 4 to 5 years. Approximately 90% were white. The demographics were similar among all five groups.

Overall, there was no significant difference in the incidence of breast-related adverse events among the groups.

The findings are consistent with those from a previous retrospective study of the SMART-5 data, said Dr. Pinkerton.

"The favorable breast effects seen with BZA 20 mg/CE 0.45 mg and 0.625 mg in this prospective evaluation are a potential advantage of BZA/CE over conventional estrogen/progestin therapy," for postmenopausal women with a uterus, she said.

The study was sponsored by Wyeth Research, now a division of Pfizer, and several of the study coinvestigators are Pfizer employees. Dr. Pinkerton has received fees given to the University of Virginia. She has served as a consultant to Pfizer, Teva, Depomed, and Novo Nordisk, received grants or research support from Pfizer, Depomed, and EndoCeutics, and served on the data safety monitoring board for Boehringer Ingelheim.

NATIONAL HARBOR, MD. – Use of a combination of bazedoxifene and conjugated estrogens had no significant impact on breast density (a potential risk factor for breast cancer) in postmenopausal women, based on data from the SMART-5 trial.

"Preclinical studies have suggested that the selective estrogen receptor modulator (SERM) bazedoxifene (BZA) prevents estrogen-induced stimulation of breast tissue," said Dr. JoAnn V. Pinkerton of the University of Virginia, Charlottesville. The findings were presented at the annual meeting of the North American Menopause Society.

The Selective Estrogens, Menopause, and Response to Therapy (SMART)-5 study was a 1-year, randomized, double-blind, placebo-controlled, phase III study of healthy postmenopausal women with a uterus who sought treatment for vasomotor symptoms, Dr. Pinkerton said. A subset of 940 women from this study took part in a breast density substudy to assess changes in breast density after a year of treatment with BZA/conjugated estrogens, compared to other treatment or a placebo.

The women underwent mammograms at baseline and again after 1 year of treatment. Changes in breast density were assessed using an analysis of covariance (ANCOVA) model.

After 1 year, the mean adjusted change in breast density from baseline was –0.38% in the women who were received 20 mg BZA/0.45 mg conjugated estrogens, –0.44 in the women who received 20 mg BZA/0.625 conjugated estrogens, –0.24% in the women who received 20 mg BZA alone, 1.60% in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate, and –0.32% in the women who received a placebo.

The only significant difference in breast density either within group or versus placebo occurred in the women who received 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate.

In addition, BZA 20 mg/CE 0.45 mg and BZA 20 mg/CE 0.625 mg showed noninferiority to placebo for breast density at 1 year, Dr. Pinkerton noted.

Four abnormal mammograms were seen in the 20 mg BZA/0.45 mg conjugated estrogens group, two in the 20 mg BZA/0.625 conjugated estrogens group, one in the 20 mg BZA alone group, three in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, and one in the placebo group.

Two cases of breast cancer were reported in the 20 mg BZA/0.45 mg conjugated estrogens group, compared to one case in the 0.45 mg conjugated estrogens/1.5 mg medroxyprogesterone acetate group, one case in the placebo group, and none in the other groups.

The mean age of the women was 54 years, and they were menopausal from 4 to 5 years. Approximately 90% were white. The demographics were similar among all five groups.

Overall, there was no significant difference in the incidence of breast-related adverse events among the groups.

The findings are consistent with those from a previous retrospective study of the SMART-5 data, said Dr. Pinkerton.

"The favorable breast effects seen with BZA 20 mg/CE 0.45 mg and 0.625 mg in this prospective evaluation are a potential advantage of BZA/CE over conventional estrogen/progestin therapy," for postmenopausal women with a uterus, she said.

The study was sponsored by Wyeth Research, now a division of Pfizer, and several of the study coinvestigators are Pfizer employees. Dr. Pinkerton has received fees given to the University of Virginia. She has served as a consultant to Pfizer, Teva, Depomed, and Novo Nordisk, received grants or research support from Pfizer, Depomed, and EndoCeutics, and served on the data safety monitoring board for Boehringer Ingelheim.