Estradiol and Micronized Progesterone: A Narrative Review About Their Use as Hormone Replacement Therapy

Abstract

Hormone replacement therapy (HRT) currently represents the first-line treatment to manage and reduce menopausal symptoms. Standard regimens generally combine 17β-estradiol (E2) or conjugated equine estrogens (CEEs) with micronized progesterone (P4) or synthetic progestins. While synthetic progestins ensure endometrial protection against estrogen-induced stimulation of the endometrium, their impact on metabolic, cardiovascular, skeletal, and cognitive systems is heterogeneous and not always beneficial. In contrast, progesterone, as a micronized preparation (P4), allows for more physiological effects because it is chemically identical to endogenous progesterone. This narrative review provides an updated overview of the clinical benefits of HRT regimens based on E2/P4, with a focus on their impact on endometrial thickness, venous thromboembolism (VTE), cardiovascular diseases (CVDs), breast cancer risk, cognitive effects, bone protection, and quality of life (QoL).