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.