Use of SERMs for treatment in postmenopausal women

• FDA approved selective estrogen receptor modulators (SERMs) prevent and treat breast cancer, osteoporosis and dyspareunia.
• SERMs have varying agonist and antagonist activities at the level of the estrogen receptor (ER) in target tissues.
• Targeted agonist effects of SERMs are hot flashes, lipids, bone, vagina, and brain.
• Antagonist SERM effects are desired in breast and endometrium.
• The first tissue selective estrogen complex (TSEC) pairs the SERM bazedoxifene with conjugated equine estrogens.

Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have varying estrogen agonist and antagonist activities in different tissues, most likely due to the receptor conformation changes associated with that SERM's binding and the subsequent effect on transcription. Clinical trials aim to differentiate amongst SERMs on selected target tissues for use in postmenopausal women including effects on breast, bone, cardiovascular venous thrombosis risk, endometrium, vagina, vasomotor symptoms, and brain. This paper describes differences in clinical effects on selected target tissues of SERMs that are approved, discontinued or in development. FDA approved SERMs include tamoxifen and toremifene used for prevention and treatment of breast cancer, raloxifene approved for prevention and treatment of osteoporosis and prevention of invasive breast cancer, and ospemifene approved for treatment of dyspareunia from menopausal vaginal atrophy. The FDA approved first tissue selective estrogen complex (TSEC) a pairing of conjugated equine estrogens with the SERM, bazedoxifene. This pairing reduces the risk of endometrial hyperplasia that can occur with the estrogenic component of the TSEC without the need for a progestogen in women with a uterus. It also allows for the estrogenic benefits on relief of hot flashes and prevention of bone loss without stimulating the breast or the endometrium. In clinical practice, the tissue-selective actions of SERMs, alone or paired with estrogens, allow for individualization in meeting the treatment needs of postmenopausal women by providing targeted tissue effects.This article is part of a Special Issue entitled ‘Menopause’.