Tissue-selective estrogen complexes for postmenopausal women

Abstract

Although hormone therapy using estrogens plus progestogens (EPT) is effective for the management of menopausal symptoms (e.g., vasomotor symptoms and vulvar/vaginal atrophy) and prevention/treatment of postmenopausal osteoporosis, EPT is associated with safety and tolerability concerns. A new alternative to EPT is the tissue selective estrogen complex (TSEC), which partners a selective estrogen receptor modulator (SERM) with one or more estrogens and is designed to treat menopausal symptoms and prevent postmenopausal osteoporosis without the tolerability concerns associated with EPT. The first TSEC to reach advanced clinical development is a combination of the SERM bazedoxifene (BZA) with conjugated estrogens (CE). BZA has been shown to inhibit the stimulatory activity of CE on uterine tissue and breast in vitro and in vivo. In clinical studies, BZA/CE treatment has been associated with significant improvements in menopausal symptoms including hot flushes and vulvar/vaginal atrophy and significant increases in bone mineral density, coupled with reductions in bone turnover marker levels and improvements in sleep and health-related quality of life. Additionally, BZA/CE has been shown to have a neutral effect on endometrial and breast tissue because BZA inhibits the stimulatory effects of estrogens in tissue-selective fashion in these 2 organs. Taken together, results of these preclinical and clinical studies indicate that the benefits of estrogens for treating menopausal symptoms are maintained with BZA/CE without endometrial or breast stimulation, resulting in a safe and effective treatment for symptomatic postmenopausal women.

Keywords: BMD; BZA; Bazedoxifene; CE; EPT; ER; LAS; LDL-C; MCF-7; MENQOL; MS-TSQ; Menopause Symptoms Treatment Satisfaction Questionnaire; Menopause-Specific Quality of Life; Michigan Cancer Foundation-7; Osteoporosis; RLX; SERM; SERMs; SMART; Selective estrogens, Menopause, And Response to Therapy; TSEC; TSECs; VMS; VTE; VVA; Vasomotor symptoms; Vulvar/vaginal atrophy; bazedoxifene; bone mineral density; conjugated estrogens; estrogen receptor; estrogen-progestin therapy; lasofoxifene; low-density lipoprotein cholesterol; raloxifene; selective estrogen receptor modulator; tissue selective estrogen complex; vasomotor symptoms; venous thromboembolic event; vulvar/vaginal atrophy.