The recommendation is strong because there is evidence of effect on fracture prevention, and because of large effect size on hot flushes and night sweats that may deteriorate sleep and working ability and strongly decrease quality of life.
A meta-analysis «Zhu L, Jiang X, Sun Y et al. Effect of hormone therapy on the risk of bone fractures: a systematic review and meta-analysis of randomized controlled trials. Menopause 2016;23(4):461-70. »1 included 28 studies with a total of 33426 participants and 2516 fractures cases. The overall relative risk with menopausal hormone therapy (HT) compared to placebo was 0.74 (95% CI, 0.69 to 0.80) for total fractures, 0.72 (95% CI 0.53 to 0.98) for hip fractures, and 0.63 (95% CI 0.44 to 0.91) for vertebral fractures. Estradiol led to greater decrease in the risk of total fractures compared with conjugated equine estrogens (P = .01). There was greater reduction in total fracture risk in trials of follow-up less than 36 months than that of follow-up more than 36 months (P = 0.003). No increase in the incidence of total cancer events but an increase in the incidence of thrombus was found to be associated with HT.
A Cochrane review «Long‐term hormone therapy for perimenopausal and postmenopausal women»1 «Bofill Rodriguez M, Yong LN, Mirkov S, et al. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2025;11(11):CD004143. »2 included 1 trial comparing hormone therapy (HT) with placebo concerning clinical fractures. Risk was decreased with HT compared to placebo: oestrogen-only HT (RR 0.73, 95% CI 0.65 to 0.80; 1 study, n=10 739); combined continuous HT (RR 0.78, 95% CI 0.71 to 0.86; 1 study, n=16 608).
Comment: The certainty of evidence is downgraded by indirectness (only 31% of the study participants were 50 to 59 years of age at baseline, mean participant age was 63 years).