Meeting News Coverage

Novel options now available for treatment of vasomotor symptoms

Menopausal women now have more FDA-approved options for vasomotor symptoms than just a few years ago, according to JoAnn V. Pinkerton, MD.

During a presentation at The North American Menopause Society’s Annual Meeting, Pinkerton said clinicians now have the ability to utilize ospemifene (Osphena, Shionogi Inc.) for dyspareunia; combination bazedoxifene/conjugated estrogens (Duavee, Pfizer); or low-dose mesylate salt of paroxetine (Brisdelle, Noven Therapeutics) — the very first nonhormonal therapy indicated for hot flashes.

“These are alternatives for postmenopausal women with a uterus who need to avoid progesterone,” Pinkerton, a professor of obstetrics and gynecology and director of the Midlife Health Center at the University of Virginia, told Endocrine Today. “This provides new, much needed options for women. The FDA has done it; they’ve come up to bat.”

JoAnn V. Pinkerton, MD 

JoAnn V. Pinkerton

The first nonhormonal therapy

Two phase 3 trials previously demonstrated that low-dose mesylate salt of paroxetine (LDMP) reduced the mean weekly frequency and severity of vasomotor symptoms and was well tolerated among those assigned the drug.

“For women who are not candidates for oral HT, we have the first FDA-approved nonhormonal treatment for hot flashes,” Pinkerton said.

Pinkerton presented new data on the effect of sleep by LDMP compared with placebo. 

“There was a decreased number of nighttime awakenings and improved duration of sleep; there were less sleep interferences and improved difficulty in sleeping,” Pinkerton said. “What was not [previously] published is there were no weight gains and no effect on libido.”

The number of nighttime awakenings due to vasomotor symptoms were reduced greater by LDMP compared with placebo at baseline, weeks 4, 12 and 24 (all P<.005), according to data.

Combination therapy and dyspareunia

Also new to the menopausal armamentarium is combination bazedoxifene/conjugated estrogens for the treatment of hot flashes, prevention of vaginal changes, bone loss without increasing breast tenderness, breast density, breast cancer, uterine stimulation or bleeding.

This tissue selective estrogen complex is a novel menopausal therapy that pairs a selective estrogen receptor modulator with one or more estrogens. Conjugated estrogens/bazedoxifene (CE/BZA) is one such therapy that has been shown to effectively treat vasomotor symptoms and preserve bone mineral density while protecting the endometrium in postmenopausal women with a uterus, according to data presented by Pinkerton.

The SMART clinical trials evaluated hot flashes, vaginal atrophy, dyspareunia and BMD. Pinkerton said the drug reduced hot flash frequency and severity; significantly improved vasomotor symptoms and sleep disturbances.

However, she said the mechanism of sleep improvements remains unclear.

Besides hot flashes, women with menopause also can develop dyspareunia. One new therapy for this indication is ospemifene, according to Pinkerton.

“For women who have vaginal dryness who are not candidates for either systemic or vaginal estrogen, we have a new serum which targets and improves vaginal pain with intercourse,” she said.

PAGE BREAK

Off-label gabapentin therapy

Besides these novel treatments, Pinkerton presented new data on extended-release gabapentin (Serada, Depomed), indicated for the treatment of menopausal hot flashes.

Pinkerton served as a primary investigator for BREEZE 3, a multicenter phase 3 clinical trial consisting of 600 menopausal women (mean age 54 years). The researchers assessed the efficacy and safety of the nonhormone, non-antidepressant, gabapentin extended release (G-ER) 1,800 mg daily in a divided dose (600 mg in the morning and 1,200 mg in the evening) compared with placebo.

“The population studied had approximately 11 severe hot flashes per day on average; with a high rate of sleep disturbances,” Pinkerton said. “The data demonstrated that at 12 weeks, there was a significant decrease in hot flashes. However, it did not meet the FDA request for a decrease to just two hot flashes per day.”

Women assigned to gabapentin had significantly greater reductions in mean hot flash frequency and severity compared with those assigned to placebo (frequency: week 4, –1.7, P<.0001; week 12, –1.14, P=.0007; severity: week 4, –0.21, P<.0001; week 12, –0.19, P=.012), according to data published in the journal Menopause. Similar reductions continued up to week 24, Pinkerton said. Women assigned to gabapentin tended to report their symptoms were “much” or “very much” improved (week 12: 58% vs. 44%, P=.0008; week 24: 76% vs. 55%, P<.0001), according to data.

“We also looked at the prevalence of dizziness and somnolence, which is a major side effect of menopause. We found that although at week 1 there was significant difference in both dizziness and somnolence, it decreased rapidly and continued at that level for the duration of the study,” Pinkerton said.

The FDA has not approved the drug and its future remains uncertain, Pinkerton said. – by Samantha Costa

For more information:

Pinkerton JV. Menopause. 2013;doi:10.1097/GME.0b013e3182a7c073.

Pinkerton JV. Plenary symposium 2: Hot flashes – more than just a minor annoyance. Beyond hormone therapy: innovative options for treatment of hot flashes; Posters 82-83. Presented at: the North American Menopause Society 24th Annual Meeting; Oct. 9-12, 2013; Dallas.

Disclosure: Pinkerton reports consultancy, research and/or travel fees from Bionova, Depomed, Endoceutics, Noven, Novo Nordisk, Pfizer and Shionogi.

Menopausal women now have more FDA-approved options for vasomotor symptoms than just a few years ago, according to JoAnn V. Pinkerton, MD.

During a presentation at The North American Menopause Society’s Annual Meeting, Pinkerton said clinicians now have the ability to utilize ospemifene (Osphena, Shionogi Inc.) for dyspareunia; combination bazedoxifene/conjugated estrogens (Duavee, Pfizer); or low-dose mesylate salt of paroxetine (Brisdelle, Noven Therapeutics) — the very first nonhormonal therapy indicated for hot flashes.

“These are alternatives for postmenopausal women with a uterus who need to avoid progesterone,” Pinkerton, a professor of obstetrics and gynecology and director of the Midlife Health Center at the University of Virginia, told Endocrine Today. “This provides new, much needed options for women. The FDA has done it; they’ve come up to bat.”

JoAnn V. Pinkerton, MD 

JoAnn V. Pinkerton

The first nonhormonal therapy

Two phase 3 trials previously demonstrated that low-dose mesylate salt of paroxetine (LDMP) reduced the mean weekly frequency and severity of vasomotor symptoms and was well tolerated among those assigned the drug.

“For women who are not candidates for oral HT, we have the first FDA-approved nonhormonal treatment for hot flashes,” Pinkerton said.

Pinkerton presented new data on the effect of sleep by LDMP compared with placebo. 

“There was a decreased number of nighttime awakenings and improved duration of sleep; there were less sleep interferences and improved difficulty in sleeping,” Pinkerton said. “What was not [previously] published is there were no weight gains and no effect on libido.”

The number of nighttime awakenings due to vasomotor symptoms were reduced greater by LDMP compared with placebo at baseline, weeks 4, 12 and 24 (all P<.005), according to data.

Combination therapy and dyspareunia

Also new to the menopausal armamentarium is combination bazedoxifene/conjugated estrogens for the treatment of hot flashes, prevention of vaginal changes, bone loss without increasing breast tenderness, breast density, breast cancer, uterine stimulation or bleeding.

This tissue selective estrogen complex is a novel menopausal therapy that pairs a selective estrogen receptor modulator with one or more estrogens. Conjugated estrogens/bazedoxifene (CE/BZA) is one such therapy that has been shown to effectively treat vasomotor symptoms and preserve bone mineral density while protecting the endometrium in postmenopausal women with a uterus, according to data presented by Pinkerton.

The SMART clinical trials evaluated hot flashes, vaginal atrophy, dyspareunia and BMD. Pinkerton said the drug reduced hot flash frequency and severity; significantly improved vasomotor symptoms and sleep disturbances.

However, she said the mechanism of sleep improvements remains unclear.

Besides hot flashes, women with menopause also can develop dyspareunia. One new therapy for this indication is ospemifene, according to Pinkerton.

“For women who have vaginal dryness who are not candidates for either systemic or vaginal estrogen, we have a new serum which targets and improves vaginal pain with intercourse,” she said.

PAGE BREAK

Off-label gabapentin therapy

Besides these novel treatments, Pinkerton presented new data on extended-release gabapentin (Serada, Depomed), indicated for the treatment of menopausal hot flashes.

Pinkerton served as a primary investigator for BREEZE 3, a multicenter phase 3 clinical trial consisting of 600 menopausal women (mean age 54 years). The researchers assessed the efficacy and safety of the nonhormone, non-antidepressant, gabapentin extended release (G-ER) 1,800 mg daily in a divided dose (600 mg in the morning and 1,200 mg in the evening) compared with placebo.

“The population studied had approximately 11 severe hot flashes per day on average; with a high rate of sleep disturbances,” Pinkerton said. “The data demonstrated that at 12 weeks, there was a significant decrease in hot flashes. However, it did not meet the FDA request for a decrease to just two hot flashes per day.”

Women assigned to gabapentin had significantly greater reductions in mean hot flash frequency and severity compared with those assigned to placebo (frequency: week 4, –1.7, P<.0001; week 12, –1.14, P=.0007; severity: week 4, –0.21, P<.0001; week 12, –0.19, P=.012), according to data published in the journal Menopause. Similar reductions continued up to week 24, Pinkerton said. Women assigned to gabapentin tended to report their symptoms were “much” or “very much” improved (week 12: 58% vs. 44%, P=.0008; week 24: 76% vs. 55%, P<.0001), according to data.

“We also looked at the prevalence of dizziness and somnolence, which is a major side effect of menopause. We found that although at week 1 there was significant difference in both dizziness and somnolence, it decreased rapidly and continued at that level for the duration of the study,” Pinkerton said.

The FDA has not approved the drug and its future remains uncertain, Pinkerton said. – by Samantha Costa

For more information:

Pinkerton JV. Menopause. 2013;doi:10.1097/GME.0b013e3182a7c073.

Pinkerton JV. Plenary symposium 2: Hot flashes – more than just a minor annoyance. Beyond hormone therapy: innovative options for treatment of hot flashes; Posters 82-83. Presented at: the North American Menopause Society 24th Annual Meeting; Oct. 9-12, 2013; Dallas.

Disclosure: Pinkerton reports consultancy, research and/or travel fees from Bionova, Depomed, Endoceutics, Noven, Novo Nordisk, Pfizer and Shionogi.

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