The evolving role of oral hormonal therapies and review of conjugated estrogens/bazedoxifene for the management of menopausal symptoms

Abstract

This review describes the evolving role of oral hormone therapy (HT) for treating menopausal symptoms and preventing osteoporosis, focusing on conjugated estrogens/bazedoxifene (CE/BZA). Estrogens alleviate hot flushes and prevent bone loss associated with menopause. In nonhysterectomized women, a progestin should be added to estrogens to reduce the risk of endometrial cancer. Use of HT declined since the Women's Health Initiative (WHI) studies showed that HT does not prevent coronary heart disease (CHD) and that conjugated estrogens/medroxyprogesterone acetate increased the risk of invasive breast cancer after nearly 5 years of use. However, re-analyses of the WHI data suggest that some risks (eg, CHD, all-cause mortality) may be reduced when HT is initiated in women <60 years of age and <10 years since menopause, compared with later. CE/BZA is the first menopausal HT without a progestogen for nonhysterectomized women. Instead, BZA, a selective estrogen receptor modulator, in combination with CE, protects against estrogenic effects on uterine and breast tissue. Data from 5 large, randomized clinical trials show that CE/BZA reduces hot flush frequency/severity, prevents bone loss, reduces bone turnover, improves the vaginal maturation index and ease of lubrication, and improves some measures of sleep and menopause-specific quality of life. In studies of up to 2 years, there was no increase in endometrial hyperplasia, vaginal bleeding, breast density, or breast pain/tenderness compared with placebo. Venous thromboembolism and stroke are risks of all estrogen-based therapies. The choice of HT should be individualized, with consideration of the risk/benefit profile and tolerability of therapy, as well as patient preferences.

Bazedoxifene as a novel GP130 inhibitor for Colon Cancer therapy

“…The FDA-approved drug bazedoxifene, known as a selective estrogen modulator, is currently used for the postmenopausal osteoporosis [23]. Recently, using multiple-ligand simultaneous docking and drug repositioning, we identified bazedoxifene as a novel small-molecule inhibitor of GP130 [24].…”

Prevention Strategies in Endometrial Carcinoma

“…CE/BZA has been studied in five RCTs involving more than 7500 women and no increase in endometrial hyperplasia was found. It may be an option for women who poorly tolerate the side effects of progestins [ 45 •].…”

MicroRNA-34a inhibits cells proliferation and invasion by downregulating Notch1 in endometrial cancer

“…These may be due to absorption of exogenous hormone, obesity, late menopause, high pressure, etc [ 3 ]. Patients are generally treated with surgery [ 4 ], and in some cases, a combination of chemotherapy, radiotherapy, and hormone therapy [ 5 ]. The five-year survival rate in patients was only approximately 80%, while about 15-20% develop metastasis [ 6 ].…”