Comparison of estrogens and selective estrogen receptor modulators (SERMs) used for menopausal hormone therapy.

Abstract

A variety of natural and synthetic steroidal estrogens, as well as selective estrogen receptor modulators (SERMs), are used for menopausal hormone therapy (MHT) by oral and/or parenteral routes of administration. Two of the most widely used estrogens for MHT are conjugated equine estrogens (CEE) and estradiol (E2); other estrogens include esterified estrogens, piperazine estrone sulfate, estriol, estetrol (E4), E2 valerate, and ethinyl estradiol. Commonly used SERMs include tamoxifen, raloxifene, ospemifene, lasofoxifene, and bazedoxifene. These agents vary widely in their affinities for the estrogen receptors and in their pharmacokinetics, leading to differences in clinical utility. The estrogens are highly effective in treating vasomotor symptoms (VMS) and genitourinary syndrome of menopause (GSM), and they have a beneficial effect on bone density. While some SERMs are approved for osteoporosis prevention and treatment, they have variable effects on VMS and GSM. Studies show that CEE reduces breast cancer risk, but the risk is increased when CEE or E2 are combined with a synthetic progestogen. Tamoxifen and raloxifene are used as breast cancer chemopreventive agents. Although studies suggest a cardioprotective effect of estrogen when administered in early menopause, they are currently not used for this indication. Some estrogens and SERMs may increase the risk of venous thromboembolism by increasing procoagulant factors and decreasing anticoagulant factors. Lastly, E4 has emerged as a novel estrogen with beneficial effects on VMS, GSM, and bone, and neutral effects on the breast and hemostatic factors. A personalized approach, based on each woman's biological profile, is recommended to guide the choice of MHT.