20ñ-Dihydroprogesterone (20ñ-DHP), also known as 20ñ-hydroxyprogesterone (20ñ-OHP), is a naturally occurring, endogenous progestogen. It is a metabolite of progesterone, formed by the 20ñ-hydroxysteroid dehydrogenases (20ñ-HSDs) AKR1C1, AKR1C2, and AKR1C3 and the 17ò-hydroxysteroid dehydrogenase (17ò-HSD) HSD17B1. 20ñ-DHP can be transformed back into progesterone by 20ñ-HSDs and by the 17ò-HSD HSD17B2. HSD17B2 is expressed in the human endometrium and cervix among other tissues. In animal studies, 20ñ-DHP has been found to be selectively taken up into and retained in target tissues such as the uterus, brain, and skeletal muscle.
20ñ-DHP has very low affinity for the progesterone receptor and is much less potent as a progestogen in comparison to progesterone, with about one-fifth of the relative progestogenic activity. It has also been found to act as an aromatase inhibitor and to inhibit the production of estrogen in breast tissue in vitro.
A single 200-mg oral dose of micronized progesterone has been found to result in peak levels of 20ñ-DHP of around 1 ng/mL after 2 hours. In another study however, peak levels of 20ñ-DHP were around 10 ng/mL during therapy with 300 mg/day oral micronized progesterone. 20ñ-DHP is formed from progesterone in the liver and in target tissues such as the endometrium. It appears to be more slowly eliminated than progesterone.
Levels of 5ñ-DHP have been quantified.