Recurrent Secretion of Progesterone in Large Amounts: An Endocrine/Metabolic Disorder Unique to Young Women?*

THE purpose of this review is to examine four separate but related issues that we believe are important for an overall understanding of progesterone secretion, metabolism, and action. These four propositions are as follows: 1) Recurrent ovulation and progesterone secretion/withdrawal (and thence menstruation) for long times may not be the biological evolutionary norm for young women. 2) The recurrent secretion/withdrawal of progesterone is unique to young women (during the luteal phase of the ovarian cycle and during pregnancy). At these times, the rate of progesterone secretion is greater than that of any other steroid hormone in women or men. 3) Progesterone and metabolites thereof may act by way of progesterone receptor-independent mechanisms to effect physiological and possibly pathophysiological processes; and, progesterone receptor-mediated actions not yet defined may also affect the well-being of women. 4) Bioactive metabolites of progesterone (in nonconjugated form) that are produced in extrahepatic tissues may be available to cellular sites of action.