Does hCG boost libido by stimulating 5-alpha-reductase?

FunkOdyssey · Aug 7, 2023

I started a previous thread to unravel the mystery of why hCG improves libido in some men, which generated some good discussion but didn't reach any firm conclusions:

Libido: hCG vs higher T / E2

When people say that hCG improves libido, it seems like a huge confounding factor to me that it also substantially increases your testosterone level and especially your E2, while reducing the T/E2 ratio. Has anyone achieved the same or very similar levels of T and E2 both on and off hCG to...

www.excelmale.com

Now comes a youtube video from Cortex Labs that claims hCG improves libido by stimulating 5-AR activity and increasing DHT production:

This actually sounds plausible to me for a few reasons:

My ratio of Free T to DHT increased on testosterone injections compared to my natural baseline. In one case, I tested a below baseline DHT with a free T that was almost double baseline.
There seems to be a theme with the endocrine system where hormones that stimulate the secretion of downstream hormones also stimulate the metabolism of those downstream hormones into more active versions. For example, TSH increases the conversion of T4 into T3, so people on T4 only therapy with suppressed TSH may have below baseline production of T3. This is hypothesized to cause poor outcomes and continued hypothyroid symptoms.
My libido on injections is pretty garbage except for a short while after dose increases.
My libido on cream with the high DHT levels was much better.
People that are suffering long-term sexual dysfunction from the use of 5-AR inhibitors, SSRIs, accutane, etc seem to report more success with hCG than TRT.

Has anyone tested their DHT levels with and without hCG and observed differences at comparable free T levels? Or a significant change in the ratio of Free T to DHT?

I think this guy may be onto something and he has inspired me to start taking hCG seriously as worthy of experimentation. He expresses some controversial ideas around absolute levels of estradiol being more important than the T:E2 ratio and the need to control E2 (particularly to gain the best results from hCG) that I think are worth discussing also.

Nelson Vergel · Aug 7, 2023

I agree. It's a great hypothesis. Yes, hCG increases DHT, E2 and free T. But I think the increased libido I experience goes beyond just an effect of E2, free T and DHT. There must be some LH-like effect on receptors in the brain.

madman · Aug 7, 2023

Pros and cons of using TRT vs HCG for treatment low-t symptoms

Human chorionic gonadotropin treatment: a viable option for management of secondary hypogonadism and male infertility (2020) Julius Fink, Brad J. Schoenfeld, Anthony C. Hackney, Takahiro Maekawa & Shigeo Horie Abstract Introduction: Low testosterone and its symptoms is a condition affecting...

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8. Side effects of HCG treatment

Since HCG treatment raises serum testosterone levels, it can lead to similar side effects as seen in direct TRT, including gynecomastia, high blood pressure, acne, hair loss and raises in estrogen potentially leading to gynecomastia. However, unlike supplementation with supraphysiological doses of testosterone as seen in doping, physiological serum testosterone increases triggered by HCG supplementation only rarely result in side effects (Table 2). Moreover, as compared to TRT, HCG treatment seems to have fewer side effects with regard to affecting hematocrit, estradiol, prostate volume, and PSA increases [15]. Interestingly, serum testosterone seems to peak at 72 hours post HCG injection and significantly correlates with estradiol peaks observed 24 hours after injection [38]. Therefore similar to TRT, even though not in line with guidelines, ancillary drugs such as aromatase inhibitors, selective estrogen receptor modulators, or 5α-reductase inhibitors are used off-label in some rare cases of severe side effects due to increased serum estradiol or DHT levels.

Tips to Dial In Test C + HCG Protocol

I just had bloodwork done after 4 months on this protocol: 1) 45mg of test cypionate 2x weekly (90mg total per week) 2) 500IU of Pregnyl 2x weekly (1,000IU total per week) My labs are attached. The free T didn't show up on the PDF but it's 823 pmol/L, which is well above the reference range of...

www.excelmale.com

*Take-home point:

A replacement regimen with combined hCG/rFSH mimics physiologic steroid hormone profiles better than a substitution with exogenous testosterone. The documented differences in steroid profiles on testosterone replacement in hypogonadal males with absent or severely reduced endogenous LH and FSH secretion may have long-term consequences for health and wellbeing. Specifically, body composition, bone health, glucose, and lipid metabolism, salt and water balance, cognition, mood, sleep, and sexual function could be affected. The steroidogenic differences could also be relevant for gonadotropin-suppressive treatments with long-acting testosterone preparations in males with primary hypogonadism. To what extent this hypothesis is true, should be addressed in future clinical studies.

Effect of TRT vs hCG/FSH on upstream hormone pathways.

The role of gonadotropins in testicular and adrenal androgen biosynthesis pathways -insights from males with congenital hypogonadotropic hypogonadism on hCG/rFSH and on testosterone replacement SUMMARY Objective: To delineate the role of gonadotropins in male androgen biosynthesis pathways...

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Combined treatment of CHH males with hCG and rFSH resulted in steroid hormone profiles similar to those of healthy men, but this was not the case, while exogenous testosterone was used for replacement. Serum steroid hormone levels on the different treatment modalities in CHH males and matched controls are summarized in Table 1 and plotted individually in Figure 3 and Figure 4. While CHH patients were on T substitution, decreased serum concentrations of some members of the classical Δ4 pathway of androgen biosynthesis (progesterone (p=0.0104), 17-OH-progesterone (17 OHP) (p<0.0001)) and of the alternative T pathway steroid androstenediol (p=0.004)) were observed, compared to controls. The marker steroid of the backdoor DHT pathway androstandiol (p=0.025), was slightly increased.

The testosterone metabolites DHT and 17-ß estradiol (E2), the Δ5 steroid 17-pregnenolone, the sulfated form of the Δ5 pathway steroid dehydroepiandrosterone DHEA, i.e. dehydroepiandrosterone sulfate (DHEAS), androstenedione (A4) and all measured 11-oxygenated C19 androgens (11-keto-testosterone (11-K-T), 11-keto-dihydro-testosterone (11-K-DHT) and 11-keto-androstenedione (11-K-A4)) were comparable to those of controls.

By contrast, normal concentrations were found for most steroid hormones in the serum of CHH males, while they were on hCG/rFSH replacement. Specifically, steroid profiles resembled those of healthy male controls, regarding the Δ 4 pathway of androgen biosynthesis (17-OHP) and the metabolite DHT, the marker steroid of an alternative T pathway via androstenediol, the Δ5 pathway steroids Δ5 steroid 17- pregnenolone, DHEAS and A4 and all aforementioned 11-oxygenated C19 androgens (11-K-A4, 11-K-T, 11-K-DHT). Serum progesterone was slightly decreased (p=0.0104), the testosterone metabolite E2 and the backdoor DHT pathway steroid androstanediol were increased (both p<0.0001).

Our results indicate that the treatment of CHH males with gonadotropins results in steroid hormone profiles similar to those of healthy men, with few exceptions (E2, progesterone). However, this is not the case using a regimen based on exogenous testosterone. If testosterone is applied, steroidogenic pathways in testicles of CHH males remain unstimulated. By contrast, if hCG +rFSH are used, the LHCG receptor in Leydig cells is activated 14. In response, multiple steroids of the classical steroidogenic cascade are synthesized by the gonads, including the classic potent androgens T and DHT. This explains the differences observed in serum steroid levels in CHH males on the two different replacement regimens.

Limitations

One limitation of the present study, regarding the investigation of gonadotropin-effects is that hCG was used to replace LH. This substance may have slightly different properties regarding the activation of LHCG receptors 55. However, at present, rLH is not licensed for clinical use in males.

Summarized results and conclusions

These biochemical studies of serum steroid hormone patterns in CHH males on two different androgenic replacement regimens contribute to our knowledge of human steroidogenesis, specifically androgen production and it's regulation. Gonadotropins contribute to steroid production along the classic Δ4 pathway, by stimulation of 17-OHP production. In addition, gonadotropins co-activate an alternative pathway of T biosynthesis from DHEA via androstenediol.

However, Δ5 biosynthesis of 17-OH-pregnenolone, DHEA(S) seems fully gonadotropin-independent, and the production of androstenedione is largely gonadotropin-independent. Thus, an “adrenal-peripheral tissues-testicular collaboration” regarding androgen synthesis by classic or alternative pathways seems possible.

The 11-oxygenated C19 androgen pathway is activated independently of gonadotropins. The activity of the three DHT backdoor pathways (converging in androstanediol biosynthesis) is not increased by gonadotropins.

A replacement regimen with combined hCG/rFSH mimics physiologic steroid hormone profiles better than a substitution with exogenous testosterone. The documented differences in steroid profiles on testosterone replacement in hypogonadal males with absent or severely reduced endogenous LH and FSH secretion may have long term consequences for health and wellbeing. Specifically, body composition, bone health, glucose, and lipid metabolism, salt and water balance, cognition, mood, sleep, and sexual function could be affected. The steroidogenic differences could also be relevant for gonadotropin-suppressive treatments with long-acting testosterone preparations in males with primary hypogonadism. To what extent this hypothesis is true, should be addressed in future clinical studies.

Figure 4

-Serum steroid hormone concentrations of CHH males from alternative/backdoor pathways of androgen biosynthesis

-Serum androstenediol concentrations, representing the alternative pathway of testosterone formation, in CHH males on hCG/rFSH and T replacement, compared to those of healthy controls.

-Serum androstanediol concentrations, representing the backdoor pathway of DHT formation in CHH males, on gonadotropin and T replacement, and in healthy controls.

-Serum 11K T and 11 K DHT concentrations, representing the 11-oxygenated C19 androgen pathway in CHH males, on gonadotropin and T replacement, and in healthy controls.

DHT

DHT serum levels were comparable to controls in CHH males during hCG/rFSH replacement but were slightly increased after the patients were switched to exogenous testosterone, indicating that the pathways of DHT production are more active if exogenous testosterone is provided. DHT is known to result mainly from 5-alpha reduction of testosterone 45 and from the aforementioned backdoor pathway in adrenal and prostatic tissues. DHT exerts the strongest bioactivity on the AR 46.

17ß-estradiol

17ß-estradiol (E2), a major metabolite of testosterone, was found to be slightly elevated as compared to controls while patients were undergoing gonadotropin replacement. About 50-75 % of circulating E2 is derived from extragonadal aromatization of testosterone by fat, bone, brain, testes and other tissues 47. Although we matched for serum T in both cohorts, mean serum T levels were slightly higher during gonadotropin application, compared to the situation during T treatment. This explains why T was aromatized to a greater extent during hCG/rFSH substitution. Alternatively, the higher E2 levels could be interpreted as an enhancement of aromatase activity by hCG/rFSH. E2 acts on estrogen receptors alpha and beta (ERα and ERβ) that are present in reproductive organs, brain, bone, blood vessels, liver, and skin and breast tissue. Many biologic effects, hitherto attributed to testosterone are conveyed by estradiol: estrogen action is important for the regulation of spermatogenesis; E2 is involved in the regulation of the somatotropic axis, it mediates epiphyseal closure in bones, improves bone mineralization and bone microarchitecture, decreases fat mass, thereby favoring lean body mass. In addition, it positively affects glucose metabolism by enhancing insulin sensitivity and conveys vasomotor stability 48-50.

Frizzle · Jan 8, 2024

FunkOdyssey said:
My libido on injections is pretty garbage except for a short while after dose increases.

My libido on cream with the high DHT levels was much better.

People that are suffering long-term sexual dysfunction from the use of 5-AR inhibitors, SSRIs, accutane, etc seem to report more success with hCG than TRT.

I know you both injected T SubQ and IM, did you notice a difference in libido between SubQ and IM? inject T with hCG, IM spikes my libido and mood but gives me some acne.

FunkOdyssey · Jan 8, 2024

Frizzle said:
I know you both injected T SubQ and IM, did you notice a difference in libido between SubQ and IM? inject T with hCG, IM spikes my libido and mood but gives me some acne.

I'm glad you bumped these past conclusions of mine so I can add some context. I only briefly reached a max of something like 13 ng/dl free T on injections when I used them in the past. I'm trying higher doses now and seeing some better results. I just changed protocols recently though so any conclusions would be premature.

My past trials were almost all IM injections with just a bit of SC propionate at the end. For my current run of TRT I've been on SC injections only.

If you are seeing a spike of libido and mood with IM, and without a corresponding dip of libido/mood that comes later, I would stay with IM. Or in other words, if your libido and mood "area under the curve" are higher with IM, then stick with it.

You might be benefiting from the extra fluctuation and sharper post-injection rise. Or, with IM you are able to hit a threshold value of Free T and/or metabolites that activate a libido and mood improvement -- in this case, you could also hit that level with SC if you reduced injection frequency or raised your dose.

Frizzle · Jan 9, 2024

Thanks for your reply, I hope your new protocol will work for you. Would be nice to have some libido and good mood I can imagine

.

I’m still dialing in and I suspect my dose is too low. At this moment I’m only taking 12mg Test-cyp plus 100iu HCG daily. As we know post Accutane guys are often under responders to Test.

Mastodont · Jan 9, 2024

So it does seem according to that study that hcg is not a DHT booster, since higher dht was found on exogenous t compared with gonadotropins group.

FunkOdyssey · Jan 9, 2024

Mastodont said:
So it does seem according to that study that hcg is not a DHT booster, since higher dht was found on exogenous t compared with gonadotropins group.

Yes, I didn't notice that before but you're right. You can't compare to the result of the exogenous T group though -- many of them were on T gel and we know what that does boost DHT. You can compare to the control group though, and observe that the hCG/FSH and control groups have almost identical T

HT ratios.

I guess the mystery of hCG boosting libido in some men remains unsolved then.

Mastodont · Jan 10, 2024

FunkOdyssey said:
Yes, I didn't notice that before but you're right. You can't compare to the result of the exogenous T group though -- many of them were on T gel and we know what that does boost DHT. You can compare to the control group though, and observe that the hCG/FSH and control groups have almost identical THT ratios.

I guess the mystery of hCG boosting libido in some men remains unsolved then.

Thanks for pointing that out, i missed the gel part.

Fernando Almaguer · Jan 10, 2024

I think its still a mystery but having fuller balls can give you more umf down there at least for me.

FunkOdyssey · Jan 10, 2024

FunkOdyssey said:
I guess the mystery of hCG boosting libido in some men remains unsolved then.

Actually as I think about it more, the hCG/FSH group matching the T / DHT ratio of the controls might actually confirm a DHT boosting effect relative to injections, if injections reduce that ratio. This study wasn't able to inform us about the T / DHT ratio of men on injections because the exogenous T group included gel users. Maybe we can find another study with data on that. I know that as I said in the first post of the thread, my personal T / DHT ratio is, in fact, reduced on injections.

You citizen scientist types could also help answer this question if you can provide any of the following from your personal labs: baseline T / DHT, injections T / DHT, injection + hCG T / DHT ratios.

Mastodont · Jan 10, 2024

FunkOdyssey said:
Actually as I think about it more, the hCG/FSH group matching the T / DHT ratio of the controls might actually confirm a DHT boosting effect relative to injections, if injections reduce that ratio. This study wasn't able to inform us about the T / DHT ratio of men on injections because the exogenous T group included gel users. Maybe we can find another study with data on that. I know that as I said in the first post of the thread, my personal T / DHT ratio is, in fact, reduced on injections.

You citizen scientist types could also help answer this question if you can provide any of the following from your personal labs: baseline T / DHT, injections T / DHT, injection + hCG T / DHT ratios.

At least in my country, dht is so expensive that people rarely test it

magnus68 · Jan 10, 2024

FunkOdyssey said:
I'm glad you bumped these past conclusions of mine so I can add some context. I only briefly reached a max of something like 13 ng/dl free T on injections when I used them in the past. I'm trying higher doses now and seeing some better results. I just changed protocols recently though so any conclusions would be premature.

My past trials were almost all IM injections with just a bit of SC propionate at the end. For my current run of TRT I've been on SC injections only.

If you are seeing a spike of libido and mood with IM, and without a corresponding dip of libido/mood that comes later, I would stay with IM. Or in other words, if your libido and mood "area under the curve" are higher with IM, then stick with it.

You might be benefiting from the extra fluctuation and sharper post-injection rise. Or, with IM you are able to hit a threshold value of Free T and/or metabolites that activate a libido and mood improvement -- in this case, you could also hit that level with SC if you reduced injection frequency or raised your dose.

Is your libido still good on HCG/test? what dosages are you taking

Does hCG boost libido by stimulating 5-alpha-reductase?

FunkOdyssey

Seeker of Wisdom

Libido: hCG vs higher T / E2

Nelson Vergel

Founder, ExcelMale.com

madman

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Pros and cons of using TRT vs HCG for treatment low-t symptoms

Tips to Dial In Test C + HCG Protocol

Effect of TRT vs hCG/FSH on upstream hormone pathways.

Frizzle

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FunkOdyssey

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Mastodont

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FunkOdyssey

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Fernando Almaguer

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