Androgen Receptor binding, T/DHT/Pregnenolone/Progesterone

Your thoughts on the affinity for binding to our androgen receptors? I was doing some personal research for an appt with Dr Saya re: my use of Pregnenolone TD that he prescribed.
I was reading that Pregnenolone/Progesterone may have a higher affinity to androgen receptors, higher than T and DHT. I'm going to be drawing labs on Preg/Prog and seeing what my levels are with the TD cream. It's something I may reduce or eliminate based on the labs but also don't want either of those two binding to receptors over my T/DHT if I can help it.

I have read that Progesterone is a known inhibitor of the enzyme 5-alpha-reductase, which converts testosterone into dihydrotestosterone (DHT). I have taken it in the past and it did seem to have the effect of reducing my already very low libido. Now that is a sample size of one and nothing to hang your hat on to be sure. But at the same time, Progesterone antagonizes estrogen and some guys have used it to help with 'man boobs' according to a few sites that I have found, including this one.

Pregnenolone on the other hand doesn't have that effect (not that I can find in any studies that I have found, anyway) and I like it for its relaxing and anti-anxiety effects.

I will be curious to what Dr. Saya recommends as well!

Im having a DHT problem we're treating with a TD cream I use on the scrotum so I've been wondering this very thing for a few months.

Vince Carter said:

Your thoughts on the affinity for binding to our androgen receptors? I was doing some personal research for an appt with Dr Saya re: my use of Pregnenolone TD that he prescribed.
I was reading that Pregnenolone/Progesterone may have a higher affinity to androgen receptors, higher than T and DHT. I'm going to be drawing labs on Preg/Prog and seeing what my levels are with the TD cream. It's something I may reduce or eliminate based on the labs but also don't want either of those two binding to receptors over my T/DHT if I can help it.

Click to expand...

Good stuff and good thoughts, Vince. I'll try to hit on all of them here for everyone's benefit and we can certainly discuss in more detail when you and I chat directly.

First, ERO is absolutely correct...progesterone can act as an inhibitor of 5-AR, but it is a WEAK inhibitor unless at high levels. Similar to the progestin like effect of 19-nor testosterone derivatives (nandrolone)...we all know the negative impact that nandrolone can have on libido, erections, etc (deca d**k), but that is dose dependent and typically worse/more pronounced at higher dosages.

I haven't personally seen any data of pregnenolone binding to androgen receptors with a stronger affinity than T/DHT. In fact, I am only aware of pregnenolone binding with MUTATED androgen receptors in some forms of prostate cancer (again, mutated androgen receptors, not the native receptors).

Progesterone is interesting, but typically binds to the progesterone receptor. The progesterone receptor IS the closest structurally to the androgen receptor and I have heard of androgen receptor binding, but again have not seen anything convincing that shows it binding with a stronger affinity than the androgens themselves (as we would expect). Further, the concentrations of progesterone are so much less in the male body than the concentrations of androgens that the "mass effect" of the androgens is overwhelming. I don't believe progesterone (at physiologic MALE levels) has much of a chance to be of clinical significance in interacting with the androgen receptors given its inherent disadvantages in the male body (and its affinity for its own receptor).

Outstanding, Dr Saya...many thanks.

Great information as always Dr Saya! Thank you