Estrogen and bones after menopause: a reappraisal of data and future perspectives

Menopausal hormone therapy (MHT) is effective in preventing menopause-related bone loss and decreasing vertebral, non-vertebral and hip fracture risk. MHT contains estrogens that exert both antiosteoclastic and osteoanabolic effects. These effects are dose-dependent, as even ultra-low doses preserve or increase bone mineral density. The transdermal route of administration is effective on cancellous and cortical bone, although fracture data are still lacking. Hormone replacement therapy is the treatment of choice to preserve skeletal health in women with premature ovarian insufficiency and early menopause. MHT can be considered in women aged < 60 years or within 10 years since menopause as, in this population, benefits outweigh possible risks, such as breast cancer and cardiovascular events. Despite the ensuing bone loss after MHT discontinuation, a residual antifracture effect persists. However, in women at risk of fracture, subsequent antiosteoporotic therapy may be needed, either with an antiosteoclastic or osteoanabolic agent. In any case, longitudinal data from randomized controlled trials comparing different estrogen doses and routes of administration, as well as designating the optimal treatment strategy after MHT discontinuation, are needed to elucidate these issues further.