Low-dose oral estrogen and venlafaxine demonstrate efficacy and tolerability for menopausal vasomotor symptoms

Low-dose oral estrogen and venlafaxine are effective treatments for vasomotor symptoms of hot flashes and night sweats in women during midlife, with a possible small advantage for estrogen, a study found.

To determine the efficacy and tolerability of oral estrogen and venlafaxine in alleviating menopause symptoms, researchers recruited 339 perimenopausal and postmenopausal women with at least 2 bothersome symptoms per day (mean, 8.1 per day) between December 2011 and October 2012. 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.

The primary outcome was the mean daily frequency of symptoms after 8 weeks of treatment. Secondary outcomes were symptoms' severity, bother, and interference with daily life. Intention-to-treat analyses compared the change in symptom frequency. Results appeared at JAMA Internal Medicine on May 26.

Compared with baseline, at week 8, the mean symptom frequency in the estrogen group decreased 52.9% to 3.9 symptoms per day (95% CI, 2.9 to 4.9 symptoms per day). In the venlafaxine group, symptoms decreased 47.6% to 4.4 symptoms per day (95% CI, 3.5 to 5.3 symptoms per day). In the placebo group, symptoms decreased 28.6% to 5.5 per day (95% CI, 4.7 to 6.3 symptoms per day). Estrogen reduced the frequency of symptoms by 2.3 more incidents per day than placebo (P<0.001), and venlafaxine reduced the frequency of symptoms by 1.8 more per day than placebo (P=0.005). Low-dose estrogen reduced the frequency of symptoms by 0.6 more per day than venlafaxine (P=0.09).

The results were consistent for symptom severity, bother, and interference. Treatment satisfaction was highest (70.3%) for estrogen (P<0.001 vs. placebo), lowest (38.4%) for placebo, and intermediate (51.1%) for venlafaxine (P=0.06 vs. placebo). Both interventions were well tolerated, and 11 participants (3.2%) stopped treatment because of adverse events (4 with estrogen, 5 with venlafaxine, and 2 with placebo.)

No statistically significant interactions of treatment effects were observed with age, race/ethnicity, body mass index, smoking, menopausal status, symptom duration, or baseline symptom level frequency for venlafaxine or estrogen versus placebo (P>0.05 for all).

“The results of this trial provide clinically relevant data about the magnitude of the effect of low-dose oral ET [estrogen therapy] and an SNRI [serotonin-norepinephrine reuptake inhibitor] in improving VMS [vasomotor symptom] frequency, severity, bother, and interference in the same population of symptomatic women, enabling standardization of baseline symptom profiles of treated participants for the first time to date,” the authors wrote. “Our findings extend the results of previous placebo-controlled trials of these individual treatments alone by demonstrating that SNRIs have a meaningful therapeutic effect on VMS, which is in the range of that with low-dose ET.”