An overview of current and emerging SERMs.

Selective estrogen receptor modulators (SERMs) are compounds that exhibit tissue-specific estrogen receptor (ER) agonist or antagonist activity, and are used for various indications, including treatment of breast cancer, osteoporosis, and menopausal symptoms. Endometrial safety has been a key differentiator between SERMs in clinical practice. For example, tamoxifen exhibits ER agonist activity in the uterus, resulting in an increased risk of endometrial hyperplasia and malignancy, whereas raloxifene and bazedoxifene have neutral effects on the uterus. Based on their efficacy and long-term safety, SERMs are increasingly being prescribed for women who cannot tolerate other treatment options and for younger women at an increased risk of fracture who may remain on therapy for long periods of time. Continuing advances in the understanding of SERM mechanisms of action and structural interactions with the ER may lead to the development of new agents and combinations of agents to provide optimal treatments to meet the varying needs of postmenopausal women. One such example is the tissue selective estrogen complex, which partners a SERM with 1 or more estrogens, with the aim of blending the desired estrogen-receptor agonist activities of estrogens on vasomotor symptoms, vulvar-vaginal atrophy, and loss of bone mass with the tissue selectivity of a SERM.