Allopregnanolone (Post-menopausal)

Allopregnanolone is a downstream metabolite of progesterone considered a neurosteroid due to its ability to influence the GABA-A receptor, creating anxiolytic effects. Elevated levels can be seen with high endogenous progesterone as well as exogenous oral supplementation of progesterone.

Low levels of allopregnanolone can be seen with low progesterone, anovulatory cycles, the use of oral contraceptives containing ethinyl estradiol and levonorgestrel, and decreased 5-alpha reductase HSD3A activity.

Allopregnanolone is a downstream metabolite of progesterone considered a neurosteroid due to its ability to influence the GABA-A receptor, creating anxiolytic effects.

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, 5α-pregnanediol and 5β-pregnanediol.

5β-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.