Low-dose estradiol and low-dose venlafaxine were both effective and well-tolerated in a trial comparing them with placebo as treatments for vasomotor symptoms (VMS) in peri- and postmenopausal women, according to an article published online May 26 in JAMA Internal Medicine.
The trial results mean that women who do not want to, or cannot, take estrogen for VMS have another treatment option, which already has been commonly prescribed off-label.
Hadine Joffe, MD, from the Department of Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and colleagues conducted a randomized 3-group, double-blind clinical trial involving 339 peri- and postmenopausal women with at least 2 VMS per day (mean, 8.1/day).
Researchers recruited participants from 3 clinical network sites of Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH), a research network funded by the National Institutes of Health testing treatments for menopause-related symptoms. They recruited participants aged 40 to 62 years in Boston; Philadelphia, Pennsylvania; and Seattle, Washington, between December 5, 2011, and October 15, 2012.
Patient Satisfaction Higher With Estradiol
The researchers randomly assigned participants to treatment with estradiol (0.5 mg/day; n = 97), venlafaxine (75 mg/day; n = 96), or placebo (n = 146). Participants took identical-appearing pills once a day for 8 weeks.
The researchers collected data during a telephone screen, 3 clinic-based visits (at screening, at randomization, and at 8 weeks), and 2 telephone assessments (at 1 and 4 weeks). Participants completed questionnaires at baseline and at 8 weeks, and they recorded VMS and vaginal bleeding patterns in diaries twice a day for 3 weeks before randomization and throughout the 8 weeks of study.
Overall, 319 of the 339 participants adhered to medication schedules and 318 provided complete diaries at 8 weeks, about 94% for each point.
The researchers found that mean VMS frequency decreased 52.9% for women taking estradiol, going to 3.9 per day (95% confidence interval [CI], 2.9 - 4.9); 47.6% for women taking venlafaxine, going to 4.4 per day (95% CI, 3.5 - 5.3); and 28.6% for women taking placebo, going to 5.5 per day (95% CI, 4.7 - 6.3).
Estradiol reduced the VMS frequency by 2.3 more per day than placebo (P < .001), and venlafaxine reduced the VMS frequency by 1.8 more per day than placebo (P = .005). Estrogen therapy reduced VMS frequency by 0.6 more per day than venlafaxine, which, after statistical modeling, translates to a 15.2% greater reduction, the researchers write.
Of 319 women rating treatment satisfaction, 70.3% were satisfied with estrogen therapy, 51.1% were satisfied with venlafaxine treatment, and 38.4% were satisfied with placebo. The difference in satisfaction between estradiol and placebo was statistically significant (P < .001), but not that between venlafaxine and placebo (P = .06).
Adverse Event Profile Should Be Considered
Four patients in the estrogen group withdrew from treatment because of adverse events, and 5 in the venlafaxine group and 2 in the placebo group also withdrew, for a total of 11 participants (3.2%). Participants reported insomnia as the most frequent adverse event for estrogen therapy, and fatigue for venlafaxine and placebo. Three participants reported suicidal ideation during the study: 2.5% for estrogen therapy, 0.7% for placebo, and none for venlafaxine.
The findings extend results of previous placebo-controlled trials regarding effectiveness of low-dose serotonin norepinephrine reuptake inhibitors, the researchers write, and in a trial with racially diverse cohort (in which a third of the patients were black).
"Treatment decisions should weigh the risk profile of each agent for each individual woman, taking into account her risk factor status and personal preferences regarding treatment options," the authors conclude.
"Some products may be better than others for individual women," Margery Gass, MD, a gynecologist at the Cleveland Clinic Center for Specialized Women's Health and executive director of the North American Menopause Society in Ohio, told Medscape Medical News.
"Women and clinicians might end up using venlafaxine more often as a result of this study. It does demonstrate that venlafaxine did fairly well compared to estrogen and better than placebo, so that's good news. For the women who don't want to use hormone therapy or cannot use it for health reasons, venlafaxine would be a good option."
She pointed out that the US Food and Drug Administration approved the selective serotonin reuptake inhibitor paroxetine as a treatment for hot flashes last year. "Paroxetine was approved for hot flashes in a smaller dose than what's been on the market for depression. It provides another good option for women besides the hormone therapy. Clinicians have been prescribing venlafaxine off-label along with other [selective serotonin reuptake inhibitors] and [serotonin norepinephrine reuptake inhibitors] for a number of years, because there have been earlier reports of beneficial effects of these drugs on vasomotor symptoms."
This research was supported by the National Institute on Aging. Dr. Joffe has reported receiving research support from the National Institutes of Health and Cephalon/Teva and serving as a consultant for Noven. Various coauthors have reported serving as a consultant for Amgen and Bayer HealthCare Pharmaceuticals, receiving research grants from the University of Massachusetts Center for Outcomes Research; receiving research support from the National Institutes of Health, Astra-Zeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Ortho-McNeil Janssen, Pfizer, Sunovion Pharmaceuticals, the National Institute of Mental Health, Otsuka Pharmaceuticals, Forest Laboratories, Bionovo, and Xanodyne Pharmaceuticals, and the National Institute on Aging; receiving financial compensation for serving as a consultant on the data monitoring committee for Merck Sharpe & Dohme; receiving financial compensation from New England Research Institutes for consulting work related to a research study of vulvovaginal atrophy; receiving financial compensation from the Pfizer advisory board for consultancy; receiving royalties for serving as the textbook editor for the second edition of Women and Health; receiving financial compensation from Noven and PamLab for consultancy work. Dr. Gass has disclosed no relevant financial relationships.
JAMA Intern Med. Published online May 26, 2014. Abstract
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Cite this: Estradiol, Venlafaxine Both Effective Against Hot Flashes - Medscape - Jun 02, 2014.