a-Pregnanediol is a metabolite of progesterone.
Progesterone is present in men but at a much lower level than found in premenopausal women. Progesterone is known as a female hormone, but males need progesterone to produce testosterone. Its function involves the development of sperm.
Pregnanediol is the major progesterone metabolite, and is present in appreciable quantities in the urine. Progesterone is not excreted in urine in detectable quantities. Thus, values of progesterone are very well “tracked” by pregnanediol values, and this value is an adequate reflection of free progesterone.
Alpha– and beta–Pregnanediol are usually used as surrogate markers, because they are the most abundant metabolites.
Natural production by the testes and adrenals in men starts to decrease with aging and can lead to an imbalance, not only of progesterone, but also lead to decreased testosterone and an increase of estrogen.
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.
References:
-https://www.ncbi.nlm.nih.gov/pubmed/15669543
-http://digital.csic.es/bitstream/10261/166820/1/Prog.%20Neurobiol%202014.pdf
Symptoms of low progesterone in males include:
-Low progesterone levels in men can lead to hair loss.
-Low libido
-Hair loss
-Weight gain
-Fatigue
-Depression
-Gynecomastia, which is breast development in males
-Erectile dysfunction
-Impotence
-Bone loss
-Muscle loss
Men with low progesterone levels have a higher risk of developing:
-Osteoporosis
-Arthritis
-Prostate cancer
-Prostatism – difficulties with urination as a result of obstruction, typically associated with an enlarged prostate gland
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If just one of the metabolites is high, his total progesterone in serum may be normal, or the patient could have a metabolic preference pushing the bulk of his metabolites one direction.
5a-reductase makes the a-pregnanediol metabolite and can be higher with inflammation, insulin resistance or obesity. Not much is known about the 5b-reductase enzyme, which makes b-pregnanediol.
Progesterone in men is positively associated with inflammation and tends to rise in response to higher testosterone production, high stress, and high cortisol.
High progesterone in men is also seen with liver issues.
→ Working on the root cause is the best approach.
If oral progesterone OR pregnenolone supplementation are used, please be aware these will increase progesterone metabolites in the urine due to first pass metabolism, but serum progesterone may not be elevated to the same degree as the urine implies.
5A-PD is a minor urinary metabolite of progesterone. Increased levels may be due to high levels of progesterone or pregnenolone, progesterone supplementation, or adrenocorticohyperplasia. 5A-PD may agonize GABA-A receptors.
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