[Third generation selective estrogen receptor modulators: benefits beyond bone. II, endometrial action]

Area of Science:

• Endocrinology
• Oncology
• Pharmacology

Background:

• Selective estrogen receptor modulators (SERMs) aim to replicate estrogen's benefits while mitigating risks, particularly endometrial cancer associated with earlier agents like tamoxifen.
• Third-generation SERMs, including lasofoxifene (LFX) and bazedoxifene (BZA), were developed to improve endometrial safety.
• Bazedoxifene (BZA) is the only third-generation SERM currently in clinical use.

Purpose of the Study:

• To evaluate the endometrial effects of third-generation SERMs, focusing on bazedoxifene (BZA).
• To assess BZA's efficacy in preventing endometrial cancer and hyperplasia, especially when co-administered with estrogens.

Main Methods:

• Review of experimental and clinical data on SERMs, particularly BZA, LFX, and raloxifene (RLX).
• Analysis of a 7-year pivotal study on BZA's effect on endometrial adenocarcinoma incidence.
• Examination of a clinical trial assessing BZA and conjugated equine estrogens (CEE) for hot flush prevention and its impact on endometrial hyperplasia.

Main Results:

• BZA exhibits neutral or anti-estrogenic effects on the endometrium in experimental models.
• BZA demonstrated a significantly lower incidence of endometrial adenocarcinoma compared to placebo in a long-term study.
• BZA, at doses of 20mg or higher, significantly reduced the risk of endometrial hyperplasia when combined with CEE.

Conclusions:

• Bazedoxifene (BZA) shows a favorable endometrial safety profile, acting as an anti-estrogen.
• BZA represents a promising therapeutic option with a reduced risk of endometrial adverse events compared to placebo and earlier SERMs.
• BZA's efficacy in preventing endometrial hyperplasia when combined with estrogens warrants further investigation for menopausal hormone therapy.