What is the Origin of Progesterone Depletion?

The term combines 'progesterone,' a name derived from its function as a progestational steroid, meaning "for gestation," and 'depletion,' referring to the act of exhausting a supply. The clinical recognition of this state became widespread with the development of precise hormonal assays and the understanding of the specific role of progesterone in the menstrual cycle and central nervous system function.

What is the Mechanism of Progesterone Depletion?

The primary mechanism involves the reduced output from the corpus luteum as ovarian function declines, leading to an anovulatory cycle, which is the hallmark of perimenopause. Additionally, chronic stress elevates ACTH, prioritizing the synthesis of cortisol from cholesterol via the adrenal glands, thereby diverting the common precursor pregnenolone away from the progesterone synthesis pathway. This hormonal imbalance can lead to a state of estrogen dominance, where the unopposed action of estrogen contributes to a range of undesirable physiological and psychological symptoms.

Progesterone Depletion

Meaning

Progesterone Depletion refers to a clinically significant reduction in the circulating levels of the steroid hormone progesterone, primarily synthesized in the corpus luteum of the ovaries and the adrenal glands. This state is a common occurrence during the perimenopausal transition and can be a consequence of chronic stress, which shunts steroid precursors toward cortisol production, a phenomenon known as the “pregnenolone steal.” Clinically, depletion is associated with symptoms such as sleep disturbances, anxiety, and menstrual irregularities, reflecting its critical role as a neurosteroid and its balancing effect on estrogen.