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JAMA Intern Med. 2014 Jul;174(7):1058-66. doi: 10.1001/jamainternmed.2014.1891.

Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial.

Author information

1
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts2Department of Psychosocial Oncology and Palliative Care, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts3Department of Psychi.
2
MsFLASH Data Coordinating Center, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle.
4
Division of Epidemiology and Community Health, Department of Medicine, Veterans Affairs Health System, Minneapolis, Minnesota7Department of Medicine, University of Minnesota, Minneapolis.
5
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
6
Group Health Research Institute, Seattle, Washington.
7
Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia10Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
8
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston.
9
Division of Research, Kaiser Permanente of Northern California, Oakland.
10
School of Nursing, Indiana University, Indianapolis.

Abstract

IMPORTANCE:

Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial to date.

OBJECTIVE:

To determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms (VMS).

DESIGN, SETTING, AND PARTICIPANTS:

In total, 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites between December 5, 2011, and October 15, 2012.

INTERVENTIONS:

Participants were randomized to double-blind treatment with low-dose oral 17β-estradiol (0.5 mg/d) (n = 97), low-dose venlafaxine hydrochloride extended release (75 mg/d) (n = 96), or placebo (n = 146) for 8 weeks.

MAIN OUTCOMES AND MEASURES:

The primary outcome was the mean daily frequency of VMS after 8 weeks of treatment. Secondary outcomes were VMS severity, bother, and interference with daily life. Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments.

RESULTS:

Compared with baseline, the mean VMS frequency at week 8 decreased to 3.9 (95% CI, 2.9-4.9) VMS per day (52.9% reduction) in the estradiol group, to 4.4 (95% CI, 3.5-5.3) VMS per day (47.6% reduction) in the venlafaxine group, and to 5.5 (95% CI, 4.7-6.3) VMS per day (28.6% reduction) in the placebo group. Estradiol reduced the frequency of symptoms by 2.3 more per day than placebo (P < .001), and venlafaxine reduced the frequency of symptoms by 1.8 more per day than placebo (P = .005). The results were consistent for VMS severity, bother, and interference. Low-dose estradiol reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P = .09). Treatment satisfaction was highest (70.3%) for estradiol (P < .001 vs placebo), lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine (P = .06 vs placebo). Both interventions were well tolerated.

CONCLUSIONS AND RELEVANCE:

Low-dose oral estradiol and venlafaxine are effective treatments for VMS in women during midlife. While the efficacy of low-dose estradiol may be slightly superior to that of venlafaxine, the difference is small and of uncertain clinical relevance.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01418209.

PMID:
24861828
PMCID:
PMC4179877
DOI:
10.1001/jamainternmed.2014.1891
[Indexed for MEDLINE]
Free PMC Article

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