What is the Origin of Progesterone Monotherapy?

The concept arose from the need to counteract the proliferative effect of unopposed estrogen on the endometrium, a risk identified in early hormone replacement therapy studies. The term "monotherapy" simply denotes the use of a single drug. The clinical application expanded as the non-reproductive, neuro-modulatory, and bone-protective roles of progesterone were better understood, justifying its use in specific therapeutic contexts.

What is the Mechanism of Progesterone Monotherapy?

When used for endometrial protection, progesterone acts by binding to nuclear progesterone receptors in endometrial cells, inducing secretory changes and promoting shedding, thus preventing excessive cell proliferation. As a neurosteroid, it also interacts with GABA-A receptors in the brain, contributing to its anxiolytic and sleep-promoting effects, which are independent of estrogen. The therapeutic mechanism is highly receptor-specific, targeting distinct physiological outcomes.

Progesterone Monotherapy

Meaning

Progesterone monotherapy is a clinical treatment protocol that involves the administration of progesterone or a progestin as the sole hormonal agent, without concurrent use of estrogen or other sex steroids. This strategy is primarily employed in women with an intact uterus who are receiving estrogen replacement to prevent endometrial hyperplasia, or in certain cases of luteal phase defect or specific mood disorders. The goal is to leverage progesterone’s unique physiological effects while minimizing exposure to other hormones.

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What Are the Long-Term Effects of Progesterone Monotherapy?

Progesterone monotherapy, particularly with micronized forms, generally shows a favorable long-term profile on metabolic, cardiovascular, and cognitive health.

∞ Progesterone Monotherapy
∞ Oral Micronized Progesterone
∞ Perimenopause