A heartfelt message, estrogen replacement therapy: use it or lose it

Abstract

The issue of cardiovascular and cognitive health in women is complex. During the premenopausal phase of life, women have healthy blood pressure levels that are lower than those of age-matched men, and they have less cardiovascular disease. However, in the postmenopausal stage of life, blood pressure in women increases, and they are increasingly susceptible to cardiovascular disease, cognitive impairments, and dementia, exceeding the incidence in men. The major difference between pre- and postmenopausal women is the loss of estrogen. Thus, it seemed logical that postmenopausal estrogen replacement therapy, with or without progestin, generally referred to as menopausal hormone treatment (MHT), would prevent these adverse sequelae. However, despite initially promising results, a major randomized clinical trial refuted the benefits of MHT, leading to its falling from favor. However, reappraisal of this study in the framework of a "critical window," or "timing hypothesis," has changed our perspective on the benefit-to-risk ratio of MHT, and this review discusses the historical, current, and future approaches to MHT.

Keywords: Alzheimer’s disease; cancer; cardiovascular disease; cognitive function; dementia; estrogen; estrogen replacement therapy; estrogen-progestin therapy; menopausal hormone therapy; progesterone; route of administration.

Fig. 1.

Relative and attributable risks for breast cancer and cardiovascular death with estrogen replacement therapy (ERT). The incidence of breast cancer is based on statistics from the National Cancer Institute website (https://www.cancer.gov/types/breast/risk-fact-sheet; accessed August 6, 2018). The incidence of cardiovascular disease deaths was derived from Lloyd-Jones et al. (83). The estimate of the relative risk for breast cancer and coronary heart disease with ERT was from Santen and Petroni (136) but can vary considerably based on the type of ERT agents, routes of administration, duration of therapy, followup period, and individual risk factors.