Supraphysiological Testosterone levels increase 5AR & Adiol-G activity in certain men.

Therapeutic Efforts Pharmaceutical
#1

Not only was 5AR activity increased, but so were Adiol-G levels in certain men.

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. Higher 5α-reductase activity in oligozoospermic men administered supraphysiological doses of testosterone

FULL TEXT: andrologyjournal.org/cgi/rep … /4/366.pdf

The administration of exogenous testosterone (T) to eugonadal men causes suppression of gonadotropin secretion and thus of spermatogenesis.

This is currently being investigated as a possible method of hormonal male contraceptive, but complete suppression of spermatogenesis to azoospermia is induced in only 50-70% of Caucasian men ; the remainder maintain a low rate of spermatogenesis. The basis for this polymorphism in response is unclear.

The enzyme 5α-reductase (5αR) converts T to dihydrotestosterone (DHT) and is important in determining the magnitude of the androgen stimulus in some tissues. We investigated whether the maintenance of spermatogenesis in men remaining oligozoospermic while receiving suppressive doses of T is associated with evidence of increased 5αR activity.

Thirty-three normal men were given 200 mg T enanthate (TE), im, weekly in a clinical trial of hormonal male contraception. The MCR of T (MCRT) and the conversion ratio of T to DHT (CRT-DHT) were measured by infusion of [3H]T, plasma levels of DHT and androstanediol glucuronide (AdiolG) were measured by RIA, and 24-h urinary steroid metabolites were measured by capillary column gas chromatography.

Sperm density decreased in all men ; 18 achieved azoospermia by 20 weeks of treatment, and the remainder had a mean sperm density of 2.0 ± 0.8 x 106/mL at that time. This treatment caused increases in plasma T levels and MCRT, but with no differences between azoospermic and oligozoospermic responders.

There were no differences in CRT-DHT, plasma DHT, or AdiolG before treatment, but after 16 weeks, CRT-DHT had increased in the oligozoospermic responders, but not in the azoospermic responders. TE treatment increased plasma DHT and AdiolG levels in both groups, but the increases in both 5αR metabolites were significantly greater in the oligozoospermic responders.

Urinary excretion of etiocholanolone and androsterone was increased after 16 weeks of TE treatment, but did not differ between the two groups, andetiocholanolone/androsterone ratios did not differ greatly from unity. There was no change in urinary excretion of tetrahydrocortisol, allo-tetrahydrocortisol, or cortisone after 16 weeks of TE treatment in either group.

These results suggest that after TE administration there is a selective increase in 5αR activity in those men who remain oligozoospermic, but not in those becoming azoospermic. This difference in the androgenic milieu may underlie the incomplete suppression in the oligozoospermic responders, in whom a low rate of spermatogenesis is maintained despite the apparent absence of gonadotropins.

#2

This looks like T increases 5AR activity but makes you infertile( azoospermia or oligospermia). The question is after ceasing external T supplementation does a high level of 5AR activity remain and do you become fertile again. This seems a bit too risky to try due to infertility issues, at least in my opinion.

#3

Yes, of course TRT has risks. By its very nature, it can (and likely will) make you infertile while on it… as noted in the report, they are testing TRT as a potential male contraceptive. Unless you take hCG (LH analogue) concurrently with TRT, TRT will shut down your sperm production, since your pituitary senses the extraneous Testosterone and stops sending LH/FSH signals to the testes to make endogenous Testosterone/maintain spermatogenesis.

I wasn’t suggesting people jump on TRT, I was simply pointing out the fact they noted elevated 5AR and Adiol-G levels in certain men who took supraphysiological doses of Testosterone. In addition, despite taking TRT, for some reason these particular men did not experience a complete shutdown in sperm production – as noted in the report, the elevated 5AR/Adiol-G was a possible explanation for why.

Don’t know about 5AR activity remaining elevated (my guess is no), but if endogeneous T production comes online after TRT (could take months or more), then likely fertility would come back as well.

However, there are reports of guys having to resort to Clomid etc to try and jumpstart this process after discontinuing TRT, same as steroid users do after coming off a cycle, and it is by no means 100% guaranteed when messing with such things (especially for a long time).

#4

TRT is indeed risky. As much as i say i want to do it, i am not sure yet, and i will try more alternatives before. I will hang on and see what Dr. Crisler says.

#5

Definitely going to get Adiol-G measured. Ideally it would be in a low T state. After 3 weeks off of clomiphene I dropped down to 500 ish (from 700 to 1050 ng/dL). Don’t think I completely restarted, but still higher than the 150-350 range I had been previously absent TRT or clomiphene. Thing is I was hoping to restart clomiphene at a lower (less frequent) dose.

Would be interesting to “tune” endogenous T production to say a certain level of Adiol G (wonder what we should target, mid range?)

Mew, I found this yesterday but you had already beat me to posting it - this is a very nice article indeed - appreciate your efforts- kazman

#6

what is your T-leve now? you are saying that your T-level rose to 500ish from 150 ish ?
so why not give another shot clomid maybe this time it goes to 700ish?

#7

Boston, this is probably why Jacobs is pursuing this route.

#8

You very well could be right. He’s also told the story a couple of times of bombarding a patient with thyroid hormone that would kill a normal person until she became sensitive to it again. He said people thought he was crazy and tried to bring him up on malpractice charges.

Wonder how this would have a synergetic effect with oxytocin?

Its gonna be some guy just like Jacobs who finally helps us -wicked smart and a renegade.

#9

Hi Mew, sorry to dig up that old thread, that had stayed in a corner of my head since I read it.
As I asked my uro a spergogram yesterday, he accepted in order to calm me down, but insisted on the fact there were 2 different pathways : the spermatogenesis commanded by FSH and the testosterone production impulsed by LH. Actually, in my case, I have a fucked up LH response, but my FHS is OK.
So, are you really affirmative about TRT shutting down the whole system, including sperm production ? If there is a retrocontrol process while on TRT, shouldn’t it just hit the LH, in a normal pattern ?

#10

I now quote myself !
I saw another endo today, she confirmed me TRT reduced balls size and shot down your fertility : she made it short but according to her vulgarization speech, the sperm elaborated while on synthetic testosterone isn’t as good as endogenous one for reproduction purposes.