Transdermal oestrogen is recommended for women with hot flushes and night sweats, when pharmacological treatment is needed. Lowest possible dose should be used for women who do not have major contraindications. However, if the woman has an intact uterus, progestagens have to be added to the treatment.
The recommendation is strong because of large effect size on patient-important outcomes: hot flushes and night sweats may deteriorate sleep and working ability and strongly decrease quality of life. Contraindications and balance between benefits and harms should be carefully discussed.
A systematic review 3 determined the effectiveness of low-dose transdermal estrogen versus placebo in postmenopausal women with at least 7 hot flashes per day and/or at least 50 hot flashes per week. 9 studies met all inclusion criteriawere included (7 had low risk of bias). Low-dose transdermal estrogen in all dose ranges was more likely than placebo to decrease the daily number of hot flashes.Results were divided into three groups by decreasing estrogen dose range (0.037 to 0.045 mg, 0.020 to 0.029 mg, and 0.003 to 0.125 mg). The mean daily decrease in the number of hot flashes from baseline was 9.36, 7.91, and 7.07, respectively. The mean daily decrease in the placebo groups was 5.07.8 studies reported P values comparing each estrogen dose to placebo; all were significant at P < 0.05.
In a randomized, double-blind, placebo-controlled, multicenter, parallel-group study 1 postmenopausal women with at least 60 hot flushes per week applied 0.87 g/d (n=136), 1.7 g/d (n=142), or 2.6 g/d (n=69) estradiol (E2) gel or placebo gel (n=137) topically for 12 weeks.With increasing E2 doses, mean trough serum E2 increased from 17 to 29 pg/mL. By weeks 3-5, E2 gel reduced moderate-to-severe hot flush rate by at least 7 hot flushes per day (P<.001) and reduced the severity score (P<.01). The numbers needed to treat for benefit for an 80% and 100% decrease in hot flush number were 3.2 and 6.3 for the 0.87-g/d group and 1.3 and 2.3 for the 2.6-g/d group. At week 12, vaginal pH was more acidic and vaginal maturation index more mature compared with placebo (P<.001). The lowest dose improved most bothersome vulvovaginal atrophy symptoms (P<.05). Estradiol gel was well tolerated at the site of application and produced no unexpected adverse effects. The 0.87 g/d dose (delivering an estimated 0.0125 mg E2 daily) produced fewest adverse events.
In a randomized, double-blind, placebo-controlled, multi-centre trial 2, healthy postmenopausal women (mean age 53 years, mean time since menopause 9 years) with moderate or severe hot flushes (at least seven per day for at least 1 week, or at least 50 per week) applied transdermal patches with a nominal delivery of 0.014 mg/d 17β-estradiol (micro-dose; n=147), or placebo (n=133) for 12 weeks. A third group of women used transdermal patches delivering 0.023 mg/d 17β-estradiol and 0.0075 mg/d levonorgestrel (low-dose E2/levonorgestrel; n=145). Mean weekly frequencies of moderate and severe hot flushes were significantly reduced with low-dose E2/levonorgestrel (-51.80; P<0.001) but also with micro-dose E2 (-38.46; P<0.001) as compared to placebo. Severity scores were also significantly reduced with both treatments compared with placebo. At week 12 endpoint, 41% of women receiving micro-dose E2 were treatment responders (75% or more reduction from baseline in hot flush frequency; P=0.003 compared with 24% placebo). There were no differences between active treatments and placebo regarding adverse events.
A umbrella review 4 summarized evidence on the benefits and harms of HT across diverse health outcomes. Vasomotor symptoms improved (frequency: RR 0.43, 95% CI 0.33 to 0.57; 9 trials, n=1104, p < 0.001; severity: RR 0.29, 95% CI 0.17 to 0.50; 7 trials, n=503, p = 0.002) and urinary incontinence (RR 0.82, 95% CI 0.62 to 1.09; 13 trials, n=16 999).
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