Are there any problems with having zero gonadotrophin?

[Henry]

I've been on TRT for 6 years now and I have no complaints. It's been wonderful for me. I'm on 4 pumps of Androgel daily with 500iu's of HCG every other day.

I remember reading, a long time ago, that HCG is recommended with TRT and one of the reasons is that it'll activate LH receptors across the body. I know that TRT brings down your LH and FSH down to zero but I've always wondered, are there any long term issues with having zero LH and FSH?

I know there are people who are on TRT with no HCG and they are doing very well but I'm just curious about the zero LH and FSH. I know that it might drop your sperm count or shrink your balls but are there any other problems or does the body just adjust to no gonadotrophins and just goes on?

Thanks

 

[sh1973]

I’ve been on trt going on 11 years and haven’t used hcg. My biggest hurdle has been lack of libido but the few times I tried hcg it didn’t help. I feel better without it. I’m not sure anyone can answer your question entirely bu to my knowledge there’s no harm. If you don’t mind me asking do your levels get high enough for symptom resolution with the Androgel? I used it in the beginning with really good luck but had to stop it due to insurance coverage.

 

[Henry]

Hi,
I got up to 1400 on Androgel but that's with 4 pumps and 500iu's of HCG every other day. Androgel has been very good to me and it's worked for the past several years.

 

[Cataceous]

Some references below hinting at possible wider effects of LH. It's also not just the gonadotropins that are suppressed by TRT. Further upstream you have GnRH and kisspeptin, both of which may have additional functions.

Lei ZM, Rao CV, Kornyei JL, Licht P, Hiatt ES. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology 1993;132(5):2262-70. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain.​

​

LH from anterior pituitary and hCG from placenta bind to a common receptor in gonadal and nongonadal reproductive tissues. There have been numerous examples suggesting that the brain may also contain hCG/LH receptors, yet there has been no evidence for their existence so far. We now demonstrate by reverse transcription-nested polymerase chain reaction and northern blotting that the rat brain contains hCG/LH receptor mRNA. ...​

​

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​

Yang E-J, Nasipak BT, Kelley DB. Direct action of gonadotropin in brain integrates behavioral and reproductive functions. Proceedings of the National Academy of Sciences 2007;104(7):2477-82. Direct action of gonadotropin in brain integrates behavioral and reproductive functions​

​

Essential roles for gonadotropins in gonadal development and reproduction are well established. Over the past decade, however, the expression of luteinizing hormone receptor (LHR) has also been reported in the brain of various mammals and birds. Although suggestive, it has not yet been determined whether this expression pattern supports a novel function for gonadotropins. Here, we demonstrate a CNS-mediated role of gonadotropins in a reproductive behavior: the courtship songs of the South African clawed frog, Xenopus laevis. Male advertisement calling in this species depends on a nongonadal action of gonadotropin. ...​

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Kokk K, Kuuslahti M, Keisala T, et al. Expression of LH Receptors in the Mouse Penis. J Androl:jandrol.109.008623. Expression of LH Receptors in the Mouse Penis -- Kokk et al., 10.2164/jandrol.109.008623 -- Journal of Andrology ​

​

The role of luteinizing hormone (LH) in the regulation of normal reproductive functions in males and females is quite well established. Besides the expression of LH receptors in the target cells in gonads, it has been found in several extragonadal organs. There is no information about the expression of LH receptors in the penis up to now. The aim of present study is to investigate the expression of LH receptor in the mouse penis to see if LH effects are possible in the penis. BALB/c mice were used as donors of normal penis and testis tissue. Immunocytochemistry, Western blotting and quantitative RT-PCR reactions were used for the detection of the LH receptor. Positive immunoreaction for LH receptors was present in the nuclei of urethral epithelium and endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis. Western blotting experiments demonstrated the presence of LH antigen at Mr = 97.4 and 78 kD. Quantitative RT- PCR reactions confirmed the expression of LH receptor in the penis. Our results show that LH receptor is expressed in the body of the mouse penis, thus it may directly regulate functions of penile tissue.​

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Wikipedia (LH receptor):​

LHCGR have been found in many types of extragonadal tissues, and the physiologic role of some has remained largely unexplored. Thus receptors have been found in the uterus, sperm, seminal vesicles, prostate, skin, breast, adrenals, thyroid, neural retina, neuroendocrine cells, and (rat) brain.[6]​

 

[Henry]

Thank you for the amazing read.

 

[antelopers]

Some references below hinting at possible wider effects of LH. It's also not just the gonadotropins that are suppressed by TRT. Further upstream you have GnRH and kisspeptin, both of which may have additional functions.

Lei ZM, Rao CV, Kornyei JL, Licht P, Hiatt ES. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology 1993;132(5):2262-70. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain.​

​

LH from anterior pituitary and hCG from placenta bind to a common receptor in gonadal and nongonadal reproductive tissues. There have been numerous examples suggesting that the brain may also contain hCG/LH receptors, yet there has been no evidence for their existence so far. We now demonstrate by reverse transcription-nested polymerase chain reaction and northern blotting that the rat brain contains hCG/LH receptor mRNA. ...​

​

-----------

​

Yang E-J, Nasipak BT, Kelley DB. Direct action of gonadotropin in brain integrates behavioral and reproductive functions. Proceedings of the National Academy of Sciences 2007;104(7):2477-82. Direct action of gonadotropin in brain integrates behavioral and reproductive functions​

​

Essential roles for gonadotropins in gonadal development and reproduction are well established. Over the past decade, however, the expression of luteinizing hormone receptor (LHR) has also been reported in the brain of various mammals and birds. Although suggestive, it has not yet been determined whether this expression pattern supports a novel function for gonadotropins. Here, we demonstrate a CNS-mediated role of gonadotropins in a reproductive behavior: the courtship songs of the South African clawed frog, Xenopus laevis. Male advertisement calling in this species depends on a nongonadal action of gonadotropin. ...​

-----------

Kokk K, Kuuslahti M, Keisala T, et al. Expression of LH Receptors in the Mouse Penis. J Androl:jandrol.109.008623. Expression of LH Receptors in the Mouse Penis -- Kokk et al., 10.2164/jandrol.109.008623 -- Journal of Andrology ​

​

The role of luteinizing hormone (LH) in the regulation of normal reproductive functions in males and females is quite well established. Besides the expression of LH receptors in the target cells in gonads, it has been found in several extragonadal organs. There is no information about the expression of LH receptors in the penis up to now. The aim of present study is to investigate the expression of LH receptor in the mouse penis to see if LH effects are possible in the penis. BALB/c mice were used as donors of normal penis and testis tissue. Immunocytochemistry, Western blotting and quantitative RT-PCR reactions were used for the detection of the LH receptor. Positive immunoreaction for LH receptors was present in the nuclei of urethral epithelium and endothelial cells of cavernous spaces in the corpus cavernosum and corpus spongiosum penis. Western blotting experiments demonstrated the presence of LH antigen at Mr = 97.4 and 78 kD. Quantitative RT- PCR reactions confirmed the expression of LH receptor in the penis. Our results show that LH receptor is expressed in the body of the mouse penis, thus it may directly regulate functions of penile tissue.​

--------

Wikipedia (LH receptor):​

LHCGR have been found in many types of extragonadal tissues, and the physiologic role of some has remained largely unexplored. Thus receptors have been found in the uterus, sperm, seminal vesicles, prostate, skin, breast, adrenals, thyroid, neural retina, neuroendocrine cells, and (rat) brain.[6]​

Is it possible that the LH receptors need much less stimulation if they don't have to produce testosterone, and that there is still a miniscule amount of LH circulating, that while undetectable with our current testing methods, is still sufficient for these other purposes?

 

[Henry]

Is it possible that the LH receptors need much less stimulation if they don't have to produce testosterone, and that there is still a miniscule amount of LH circulating, that while undetectable with our current testing methods, is still sufficient for these other purposes?

I'm wondering too. Also, does FSH play a factor? Are there any others that are suppressed?

 

[Cataceous]

Is it possible that the LH receptors need much less stimulation if they don't have to produce testosterone, and that there is still a miniscule amount of LH circulating, that while undetectable with our current testing methods, is still sufficient for these other purposes?

I don't know for sure, but it seems unlikely. My impression is that in general the level of receptor activation is proportional to hormone concentration. So minimal concentration, minimal action.

... Also, does FSH play a factor? Are there any others that are suppressed?

It appears that in males the FSH receptor has so far been found only on Sertoli cells. This may limit the effects of low FSH to testicular atrophy and attenuated spermatogenesis.

As I mentioned above, other upstream hormones are suppressed by TRT.

 

[antelopers]

I don't know for sure, but it seems unlikely. My impression is that in general the level of receptor activation is proportional to hormone concentration. So minimal concentration, minimal action.


It appears that in males the FSH receptor has so far been found only on Sertoli cells. This may limit the effects of low FSH to testicular atrophy and attenuated spermatogenesis.

As I mentioned above, other upstream hormones are suppressed by TRT.

I get what you're saying, but then wouldn't every single person on TRT eventually run into issues without using an LH analogue of some sort? I'd imagine the vast majority of TRT patients are not on HCG.

 

[Cataceous]

I get what you're saying, but then wouldn't every single person on TRT eventually run into issues without using an LH analogue of some sort? I'd imagine the vast majority of TRT patients are not on HCG.

From this we might hope that stimulation of these receptors isn't vital in most cases. But that doesn't preclude subtle problems. Or not so subtle: Nelson says he has no libido without hCG. I find the sexual experience diminished in quality when I'm not on hCG. We will need large, long-term studies to find out whether LH suppression is causing other issues.

 

[antelopers]

From this we might hope that stimulation of these receptors isn't vital in most cases. But that doesn't preclude subtle problems. Or not so subtle: Nelson says he has no libido without hCG. I find the sexual experience diminished in quality when I'm not on hCG. We will need large, long-term studies to find out whether LH suppression is causing other issues.

I have the same response to HCG as you guys. It does present other problems as well which could probably be fixed with the correct dose and frequency of HCG and T.

It's frustrating to talk to friends of mine who have never even heard of LH, HCG, Leydig cells, and take 100mg of ugl test once a week and have zero issues at all lol.

 

[Cataceous]

I have the same response to HCG as you guys. It does present other problems as well which could probably be fixed with the correct dose and frequency of HCG and T.

It's frustrating to talk to friends of mine who have never even heard of LH, HCG, Leydig cells, and take 100mg of ugl test once a week and have zero issues at all lol.

I am a bit envious of those who do well on simple protocols. But even if I could go back I'd be troubled by the thoughts of possible long-term harm from suppression of all those hormones. The neurogenesis aspects of GnRH in particular got my attention.

I do wonder whether or not the right "dose and frequency" of hCG can be found. Or does the long half-life mean it's never going to be quite right? When you lower the dose enough to stop skewing your estradiol balance will you still get the benefits?

 

[antelopers]

I am a bit envious of those who do well on simple protocols. But even if I could go back I'd be troubled by the thoughts of possible long-term harm from suppression of all those hormones. The neurogenesis aspects of GnRH in particular got my attention.

I do wonder whether or not the right "dose and frequency" of hCG can be found. Or does the long half-life mean it's never going to be quite right? When you lower the dose enough to stop skewing your estradiol balance will you still get the benefits?

I wonder the same thing. Although it's close, it's not exactly the same LH and it seems to drive estrogen up pretty high for me, and while I have found less side effects at lower more frequent doses (EOD vs twice a week for example), I've also felt that the benefits have been blunted.

 

[Willyt]

I am curious about this issue too and whether it would explain why many of us suffer from decreased libido and emotional flatness when on TRT

 

[slicktop]

It's frustrating to talk to friends of mine who have never even heard of LH, HCG, Leydig cells, and take 100mg of ugl test once a week and have zero issues at all lol.

Well, not to split hairs, but there's a difference between not reporting any issues, not being aware of any issues, and not having any issues. Or even, not having any issues *yet*. I'd bet good money a 28 year old taking 100mg of UGL test once a week would find different results with that same protocol when he's 40.

 

[Cataceous]

I am curious about this issue too and whether it would explain why many of us suffer from decreased libido and emotional flatness when on TRT

I think it's quite likely that the missing hormones are at least part of this. I also suspect that having testosterone well above our natural prime levels may sometimes be a factor.

 

[Henry]

I think it's quite likely that the missing hormones are at least part of this. I also suspect that having testosterone well above our natural prime levels may sometimes be a factor.

I’m wondering if HCG can replace those missed hormones or are there more? It looks like FSH, IGF and kisspeptin are missing too

 

[slicktop]

I’m wondering if HCG can replace those missed hormones or are there more? It looks like FSH, IGF and kisspeptin are missing too

IGF? That's an odd one. I've been on TRT for two years and my IGF is way high. I actually took several tests to make sure I didn't have a brain tumor it's so high (425+).

 

[Henry]

IGF? That's an odd one. I've been on TRT for two years and my IGF is way high. I actually took several tests to make sure I didn't have a brain tumor it's so high (425+).

I read that while google searching. It could be wrong. I’m just trying to see what I’m missing out on and to be honest, it doesn’t seem like much. If a person could handle HCG, they might be pretty much covered

 

[Cataceous]

I’m wondering if HCG can replace those missed hormones or are there more? It looks like FSH, IGF and kisspeptin are missing too

HCG may replace the missing LH if it doesn't create too many problems via an estrogen imbalance. Kisspeptin and GnRH are also suppressed with TRT and have the potential to act directly on our brains. FSH is suppressed but appears unable to directly influence how we feel. IGF-1 is more prone to increasing with TRT, according to the literature.