Both low-dose and micro-dose 17β-oestradiol are effective for postmenopausal hot flushes
G A Bachmann
Dr G A Bachmann, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ, USA;
Does micro-dose 17β-oestradiol reduce the frequency and severity of hot flushes in symptomatic postmenopausal women?
randomised, placebo-controlled trial.
blinded (patients, clinicians, and data collectors).
48 centres in the US.
425 healthy postmenopausal women ⩾40 years of age (mean age 53 y) who had an average of ⩾7 moderate or severe hot flushes per day for ⩾1 week during screening. Women taking hormone therapy or other drugs that might affect vasomotor symptoms underwent a wash-out period. Exclusion criteria included abnormal Pap test result, abnormal vaginal bleeding, and history of thrombophlebitis or thromboembolic disorder.
transdermal patches delivering 17β-oestradiol (E2), 0.023 mg/day, plus levonorgestrel, 0.0075 mg/day (low dose, n = 145); E2, 0.014 mg/day (micro dose, n = 147); or no E2 (placebo, n = 133). Patches were replaced weekly.
frequency and severity of moderate and severe hot flushes, proportion of women who responded to treatment (⩾75% or ⩾90% reduction in hot flush frequency), and adverse events.
84% (intention-to-treat analysis).
All 3 groups showed gradual improvement in hot flushes over the study period. At 12 weeks, both the frequency and severity of hot flushes were reduced in the 2 active treatment groups compared with the placebo group (table). More women taking low-dose or micro-dose E2 responded to treatment than those taking placebo (table). Adverse events were similar in the 3 groups.
In symptomatic postmenopausal women, both low-dose (0.023 mg/d) and micro-dose (0.014 mg/d) 17β-oestradiol reduced hot flush frequency and severity more than placebo.
A modified version of this abstract appears in Evidence-Based Medicine.
Bachmann GA, Schaefers M, Uddin A, et al. Lowest effective transdermal 17β-estradiol dose for relief of hot flushes in postmenopausal women: a randomized controlled trial. Obstet Gynecol 2007;110:771–9.
Clinical impact ratings: Family/General practice 6/7; Women’s health 6/7
Hot flushes, night sweats, and other vasomotor symptoms affect approximately 75% of perimenopausal and early postmenopausal women.1 Although benign, they cause suffering in many women and are a common reason for seeking medical advice. Hormone therapy (HT) has been the traditional treatment of choice for menopausal hot flushes. However, use of HT has markedly decreased since the well-publicised Women’s Health Initiative trials showed a small but statistically significant increase in risk of serious adverse outcomes, including myocardial infarction, stroke, breast cancer, and thromboembolic events in women taking HT.2 Alternatively, lifestyle changes, natural phyto-oestrogens, and medications such as selective serotonin reuptake inhibitors and gabapentin have gained popularity. However, many women with severe vasomotor symptoms continue to initiate or continue HT. To minimise risks while maximising benefits, transdermal HT has been suggested as a safer alternative to oral HT.
The randomised trial by Bachmann et al examined the efficacy and side effects of the lowest available strength transdermal oestrogen preparation. The authors concluded that micro-dose transdermal oestrogen offers effective vasomotor symptom relief comparable with more widely studied low-dose transdermal preparations. Response was not influenced by women’s weight and occurred within 4–8 weeks of initiation, allowing for quick assessment of efficacy. Limitations of this trial include exclusion of non-healthy women and lack of direct comparison to “gold standard” oral regimens.
Supporting the traditional pharmacological principle of “start low, titrate slow,” micro-dose transdermal oestrogen is a viable option for consideration in the treatment of menopausal symptoms. Whatever approach is adopted, women should be counselled extensively on the risks and benefits of all available treatment options for vasomotor symptoms.