Metabolites of progesterone are measured in urine, including 5b-pregnanediol and 5a-pregnanediol. 5b-pregnanediol is inactive in the body but is the major metabolite of progesterone. 5a-pregnanediol is often a metabolite of more interest, as it can cross the blood brain barrier and up-regulate GABA activity and is considered neuroprotective to the brain. Both taken together represent the major metabolic end points for progesterone and can be used to represent total progesterone production.
Progesterone is produced by the corpus luteum following ovulation and to a lesser extent by the adrenal glands in both sexes. While found in the urine in small amounts, progesterone can be seen as a clinical marker of luteul activity and theraputic oral progesterone administration. The most important progesterone metabolite, pregnanediol (PDL), can serve as a urinary marker for endogenous progesterone levels and as an indicator of ovulation. PDL exists as two isomers, 5a-pregnanediol and 5b-pregnanediol. 5b-pregnanediol represents the majority end point of endogenous progesterone metabolism and appears to have little activity within the body, while 5α-pregnanediol, the lesser metabolite of PDL, can cross the blood brain barrier and may partially agonize GABA-A receptors. This action is possibly due to its role as an immediate precursor to allopregnanolone. Allopregnanolone is a potent neuroactive steroid capable of binding the GABA-A receptor often leading to sedative and anxiolytic action. The calming action of allopregnanolone is often seen with orally supplemented progesterone, as the liver metabolizes a large portion of oral progesterone to the neuroactive steroid allopregnanolone.
5a-Pregnanediol (male)
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