The primary role of progesterone is to balance the strong effects of estrogen. Progesterone metabolites are measured and reflect progesterone levels well because very little progesterone is found in urine, so b-Pregnanediol is typically used as a surrogate marker because it is the most abundant metabolite, but we also test the corresponding a-pregnanediol. The average of the two metabolites is reported for progesterone.

The total serum progesterone on the Dutch test is a calculated value based on urine pregnanediol. Progesterone has 2 primary metabolites: b-Pregnanediol and a-Pregnanediol. Each one of them represents about half of the progesterone that is being produced. If you are supplementing with oral/sublingual progesterone the serum correlation is not a valid concept. 

What does Progesterone do?

- Helps with sleep and anxiety (alpha metabolites) via GABA-a receptors

- Antagonist to the mineralocorticoid receptor

- Prepares the uterus for implantation

- When pregnant, it decreases the maternal immune system to prevent attack on the fetus, the fall of progesterone on delivery triggers breast milk ‘let down’

- Its neurosteroid ALLO helps with sex drive

- Supports normal development of neurons in the brain

- Often given at high doses immediately after TBI or stroke to protect brain

- Enhances serotonin receptors in brain

- Reduces spasms and relaxes smooth muscle especially in the lungs/uterus

- Reduces gall bladder activity (high estrogen increased risk for GB disease)

- Often used as a medication to counter hyperplasia of uterine cells

While variations in progesterone levels may be perfectly normal, sometimes a high reading is cause for further testing.