Is it possible to reduce Inhibin?

[phalloguy100]

I’ve been reading a lot about testicular atrophy and how to increase testicular size. It appears that FSH could affect size way more than LH because it affects the size of tubules which take up more volume than the individual cells that produce testosterone. But as you all know… FSH is very expensive. HCG can be found much cheaper but that takes the place of LH, not FSH. Clomid, Gonadorelin (GNRH), kispeptin, etc. can increase both LH and FSH but eventually the FSH feedback loop thru Inhibin kicks in.

So… I wonder… is there a way to decrease inhibin B, or slow its effect on the HPTA axis, in order to increase FSH to supraphysiological levels temporarily? Long enough to recover testicular size.

And before you suggest it, yes, I am on hcg.

 

[madman]

I’ve been reading a lot about testicular atrophy and how to increase testicular size. It appears that FSH could affect size way more than LH because it affects the size of tubules which take up more volume than the individual cells that produce testosterone. But as you all know… FSH is very expensive. HCG can be found much cheaper but that takes the place of LH, not FSH. Clomid, Gonadorelin (GNRH), kispeptin, etc. can increase both LH and FSH but eventually the FSH feedback loop thru Inhibin kicks in.

So… I wonder… is there a way to decrease inhibin B, or slow its effect on the HPTA axis, in order to increase FSH to supraphysiological levels temporarily? Long enough to recover testicular size.

And before you suggest it, yes, I am on hcg.

Key points here!

*hCG will be the main driver as it mimics LH which stimulates the Leydig cells in the testes to produce ITT (intratesticular testosterone) which is CRITICAL for the MAINTENANCE of GERM CELLS/SEMINIFEROUS TUBULES let alone fertility.

*Spermatogenesis is largely dependent on the action of FSH on Sertoli cells COUPLED WITH HIGH INTRA-TESTICULAR TESTOSTERONE CONCENTRATIONS. Within the seminiferous tubules, only SERTOLI CELLS POSSESS RECEPTORS for BOTH FSH and TESTOSTERONE. Numerous signaling pathways are activated when FSH binds to FSH receptors on these cells. It acts SYNERGISTICALLY with TESTOSTERONE to increase fertility and the efficiency of spermatogenesis [6]. The inhibition of LH release by exogenous testosterone leads to the suppression of endogenous testosterone production by the Leydig cells. The DECREASED INTRA-TESTICULAR TESTOSTERONE COMBINED with the SUPPRESSION of FSH leads to DECREASED GERM CELL SURVIVAL and MATURATION (Fig.1).

*Testosterone is also required in maintaining connections between Sertoli cells and the haploid spermatid germ cells. Round spermatids are initially connected to Sertoli cells via desmosomes. As the spermatids mature and elongate, the desmosomes are replaced with stronger, specialized adherens junctions called ectoplasmic specializations, which are maintained until the release of mature sperm. Testosterone aids in this process and increases the efficiency of germ cell attachment to Sertoli cells. Testosterone is also essential for the release of mature spermatozoa from Sertoli cells. It has been shown that in the absence of testosterone stimulation, sperm are not released but are instead phagocytized by Sertoli cells [7].

* Since 80% of testicular volume consists of germinal epithelium and seminiferous tubules, a reduction in these cells is usually manifested by testicular atrophy and this reflects the loss of both spermatogenesis and Leydig cell function




There is no way to avoid testicular atrophy when using exogenous T without the addition of HCG or hCG + FSH.

Your only option would be nasal T gel (Natesto) as it will have a minimal impact due to PK/dosing protocol being the least suppressive when it comes to the HPTA

Use of hCG without FSH will still have a big impact on minimizing/preventing testicular atrophy.

Far bigger impact than FSH without hCG as ITT is critical.

hCG is the go to when it comes to minimizing/preventing testicular atrophy.

If anything combining FSH with hCG will improve the quality/quantity of sperm which is made by the germ/Sertoli cells in the testes as FSH acts directly upon such.

It can also help with improving testicular volume when combined with hCG although hCG will be the main driver as it mimics LH which stimulates the Leydig cells in the testes to produce ITT (intratesticular testosterone) which is critical for the maintenance of germ cells/seminiferous tubules let alone fertility.

The majority of the testicular volume (80-90%) is made up of germ cells/seminiferous tubules.

The use of exogenous testosterone will shut down the HPTA/LH/FSH/iTT (intratesticular testosterone) resulting in atrophy of these tubules.

WHAT MEN SHOULD KNOW ABOUT TESTICULAR SHRINKAGE AND TESTOSTERONE THERAPY

If you're considering testosterone replacement therapy, understanding its effects on testicular size is crucial. Learn why shrinkage occurs, the treatments available to mitigate this side effect, and why testicle size usually has minimal impact on your overall health. Urologist John Smith, MD...

www.excelmale.com

Fertility maintenance or restoration in men before, during, and after TRT or AAS

Fertility Preservation in Hypogonadal Men (2018) Robert J. Carrasquillo and Ranjith Ramasamy Introduction Testicular failure is defined as the impairment or loss of both the endocrine functions of the testis (production of testosterone, or T) and exocrine function (production of...

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Absolute minimum dose of HCG for fertility?

Is there any data on what the minimal dosage of hcg is to keep 'the guys' working while on TRT? I'm asking this because hcg seems to rise estrogen and I'd like to keep that to a minimum. Also, I might want to have kids later but not exactly now, so I'm looking for a guideline for the minimal...

www.excelmale.com

 

[madman]

Women’s Birth Control vs TRT as Contraceptives and Potential Infertility

There is generally no fear of women permanently losing their fertility when they start birth control, even though birth control (generally a mix of estradiol and progesterone) is intended to shut down a woman’s HPG axis, leads to the lack of ovarian stimulation, and leads to ovarian shrinkage...

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INTRODUCTION

Testosterone is a pleiotropic hormone that plays various physiological roles in the development of male genitalia in utero and during puberty. Classically, testosterone is a hormone associated with masculinity. Testosterone is used as a treatment for males with late-onset hypogonadism, a condition in men who experience symptoms caused by a decrease in serum testosterone. Symptoms associated with low testosterone can include decreased libido, decreased muscle mass, depressed mood, and/or erectile dysfunction. The use of testosterone replacement therapy (TRT) among men over the age of 40 years has increased more than 3-fold over the last decade [1].

Exogenous testosterone comes in various preparations and each form carries various risks. Along with an increase in hematocrit, a major adverse effect of TRT is diminished sperm production because of the decreased intra-testicular concentration of testosterone and suppression of the hypothalamic-pituitary-gonadal (HPG) axis [2-4]. Suppression of follicle-stimulating hormone (FSH) release from the pituitary gland impairs sperm production and suppression of luteinizing hormone (LH) release inhibits intra-testicular testosterone production

The purpose of this review is to evaluate the contraceptive effect of testosterone, discuss how the use of exogenous testosterone can negatively impact a man’s fecundity, and identify the importance of family planning in men who are planning to receive TRT.




The exogenous administration of testosterone suppresses the release of gonadotropins (FSH and LH) to levels below that required for spermatogenesis. Spermatogenesis is largely dependent on the action of FSH on Sertoli cells coupled with high intra-testicular testosterone concentrations. Within the seminiferous tubules, only Sertoli cells possess receptors for both FSH and testosterone. Numerous signaling pathways are activated when FSH binds to FSH receptors on these cells. It acts synergistically with testosterone to increase fertility and the efficiency of spermatogenesis [6]. The inhibition of LH release by exogenous testosterone leads to the suppression of endogenous testosterone production by the Leydig cells. The decreased intra-testicular testosterone combined with the suppression of FSH leads to decreased germ cell survival and maturation (Fig. 1).

Intra-testicular testosterone is required in spermatogenesis for the formation of the blood-testis barrier (BTB). The BTB is a series of tight and adherens junctions between the Sertoli cells that separates postmeiotic germ cells in the adluminal compartment of the seminiferous tubules from the basal compartment containing the blood supply. During spermatogenesis, the BTB is disrupted and reformed as preleptotene spermatocytes pass through this barrier. In the absence of testosterone stimulation, spermatogenesis can only proceed as far as the prophase 1-leptotene stage of meiosis [7].

Testosterone is also required in maintaining connections between Sertoli cells and the haploid spermatid germ cells. Round spermatids are initially connected to Sertoli cells via desmosomes. As the spermatids mature and elongate, the desmosomes are replaced with stronger, specialized adherens junctions called ectoplasmic specializations, which are maintained until the release of mature sperm. Testosterone aids in this process and increases the efficiency of germ cell attachment to Sertoli cells. Testosterone is also essential for the release of mature spermatozoa from Sertoli cells. It has been shown that in the absence of testosterone stimulation, sperm are not released but are instead phagocytized by Sertoli cells [7].

Ultimately, the low intra-testicular testosterone results in decreased proliferation of spermatogonia, defects in spermiation of mature spermatozoa by Sertoli cells, and accelerated apoptosis of spermatozoa [8- 11]. Since 80% of testicular volume consists of germinal epithelium and seminiferous tubules, a reduction in these cells is usually manifested by testicular atrophy and this reflects the loss of both spermatogenesis and Leydig cell function [12,13].

 

[Cataceous]

...
So… I wonder… is there a way to decrease inhibin B, or slow its effect on the HPTA axis, in order to increase FSH to supraphysiological levels temporarily? Long enough to recover testicular size.
...

It's an interesting question. Assuming Wikipedia is up-to-date—not always a given—not much is known about how inhibin works. Speculation is that it involves "competing with activin for binding to activin receptors and/or binding to inhibin-specific receptors." If it's the former then blocking inhibin would seem to be more of a challenge. You'd need a drug that selectively attaches to inhibin and blocks its action on the activin receptor. If inhibin works through inhibin-specific receptors then there probably are substances that can block the receptors and prevent activation by inhibin. However, it seems unlikely this has been explored if the existence of the receptors themselves is uncertain.

On the production side, which occurs in Sertoli cells, there appears to be indirect stimulation by androgens. Wiki cites this work, though it's kind of old. "The cellular interaction is proposed in which LH acts on Leydig cells to stimulate androgen production which in turn acts on peritubular cells to regulate [testicular paracrine factor] PModS production which subsequently can act on Sertoli cells to control inhibin production." Presumably reducing androgens is undesirable, so then you'd need to see what's known about PModS.

ChatGPT doesn't seem to do any better. The anticlimactic conclusion is that a cursory search reveals little about ways to safely and effectively reduce inhibin activity.

 

[Vince]

You can buy fsh through safe meds an India pharmacy. I believe it's about $27 per injection.

 

[phalloguy100]

Thanks guys. So what I'm reading in the articles above is that both FSH and intra-testicular testosterone are needed for spermatogenesis, and in particular, for Steroli and germ cell function. But, many other hormones and processes are also requried for spermatogenesis - transferrin, TSH, estradiol (after aconversion to 1,7-beta-estradiol), androgen-binding protein, inhibin, activins, etc.

But what if one wasn't interested in complete/mature spermatogenesis, but rather only the structure, size and proliferation of Steroli cells and seminiferous tubules? ITT would still play a role in the structure (the glue that holds them together and fills with fluid), but wouldn't FSH alone affect their health and size? So in theory... wouldn't FSH be more likely to increase testicular size (without regard to sperm production) than LH?

Has there ever been a study that compares FSH, LH, TT, Estradiol levels to adult testicular size?

(And @Vince good to know Safmeds4All carries cheap FSH!!!)