The drug gabapentin, originally developed to fight seizures, can also significantly reduce hot flashes in postmenopausal women, a multinational clinical trial has found. If approved by the Food and Drug Administration for the purpose, gabapentin would offer women a non-hormonal treatment alternative to estrogen therapy.
The development of alternatives is important because up to 75 percent of women experience hot flashes associated with menopause and 25 percent of those need treatment. Currently, the FDA approves only hormone therapy for relief of hot flashes.
“However, many women are not candidates or choose not to take hormone therapy because of the small increased risk of breast cancer and other health conditions,” said Dr. JoAnn Pinkerton, professor of obstetrics and gynecology, director of the University of Virginia’s Midlife Health Center and principal investigator of the study for the U.Va. School of Medicine. The increased risk is of particular concern for women who have had breast cancer or who are at high risk for breast cancer.
“Right now the only FDA-approved treatment we have for women’s bothersome menopausal hot flashes is estrogen therapy,” Pinkerton said. “Women need non-hormonal alternatives. They need choice.”
Although not yet FDA-approved for the purpose, antidepressants are sometimes used as non-hormonal alternatives to treat hot flashes and other menopause symptoms. However, they affect mood and carry common side effects.
The gabapentin study examined the drug’s effect on 600 postmenopausal women with moderate to severe hot flashes. It found that extended-relief gabapentin significantly reduced both the frequency and severity of hot flashes when compared with a placebo. Improvement was seen at one month, three months and six months, with most women reporting their hot flashes were “much improved” or “very much improved” at six months.
The drug was found to be well-tolerated, with only 5 percent of trial participants discontinuing use because of adverse symptoms such as dizziness and sleepiness.
Pinkerton, a past president of the North American Menopause Society, recently presented the gabapentin findings at the society’s annual meeting in Florida. U.Va. was a key site for the trial, for which U.Va. was reimbursed research costs. Pinkerton has received consulting fees contracted through U.Va. from Depomed, the maker of gabapentin.
In addition to the gabapentin trial, Pinkerton has been U.Va.’s principal investigator in the recent trials of two other potential hot flash treatments. One of these is an alternative estrogen product that combines conjugated estrogen with an anti-estrogen, bazedoxifene, that omits progesterone. Unlike traditional hormone treatment, this alternative estrogen product was not seen to stimulate the growth of tumors in the breast. The combination relieved moderate to severe hot flashes, improved sleep and vaginal dryness and prevented bone loss without stimulating either the breast or the uterus. It is now being evaluated by the FDA.
Pinkerton was also U.Va.’s principal investigator in the trial of the non-hormonal antidepressant desvenlafaxine, a serotonin-norepinephrine reuptake inhibitor. The 12-week trial found rapid symptom reduction with significant reduction in the number and severity of moderate to severe hot flashes associated with menopause. However, in September 2011, the FDA denied the application to approve desvenlafaxine for moderate to severe vasomotor symptoms of menopause such as hot flashes. (It is already available for the treatment of major depressive disorder under the brand name Pristiq.)
The findings of that trial were presented in 2011 at the annual meeting of American College of Obstetricians and Gynecologists in Washington, D.C., and have just been published online in the journal Menopause. The results from the yearlong safety and efficacy study of desvenlafaxine will be published soon in Menopause.