A review of menopausal hormone therapy: Recalibrating the balance of benefit and risk

Abstract

While menopausal hormone therapy (MHT) was initially marketed to women of menopausal age to prolong youth, it has endured a tumultuous history evaluating the risk-to-benefit ratio. In response to evidence that MHT may confer cardioprotective effects, 2 landmark randomized controlled trials tested this hypothesis, and both were stopped prematurely due to increased incident cancers and cardiovascular events, creating much controversy and confusion. As women and physicians grew reticent to use MHT, most symptomatic menopausal women remained untreated. Further evaluation of available data has since lent support for the “timing hypothesis,” which posits that younger women may not be at risk of adverse events following the use of MHT and may instead experience a survival advantage. Most recently, the 18-year follow-up data of postmenopausal women in the Women’s Health Institute trial did not show any change in long-term survival associated with the use of MHT at any age. More recent studies have evaluated alternative treatments for high-risk women, including lower doses and newer formulations of MHT, along with combined new therapies such as selective estrogen receptor modulators, antidepressants, and exercise therapies, which are effective in reducing vasomotor symptoms and improving menopause-specific quality of life. These alternatives provide new options to symptomatic women who are unable or unwilling to take conventional MHT and allow for more person-centered decision making strategies to support women through the menopause.