Fertility with HCG + SERM? HMG/rhFSH Impossible to get in Australia

[Adamsapple]

Hi all,

Firstly, thanks to Nelson and all on the forum for sharing the breadth of your knowledge online, it's taught and helped me so much. I was hoping I could pick your brains about a specific fertility protocol used by Dr. Ramasamy (interviewed by Nelson on podcast).

Mainly, it is HCG 2000iu EOD with Clomid 50mg.

I've read conflicting things about just HCG and SERM being ineffective to restart HPTA with HCG suppressing LH and the effect of this on producing sperm. There are (few) studies that show HCG and Clomid therapy have helped men regain spermatogenesis over the longer term I.e. ramasamy, lipshultz but sperm were deformed in one. It begs the question if HCG supresses FSH production and SERMs can counteract this is anyway?

For background, My wife and I are now trying to get pregnant. I tested azoospermic while on TRT 180mg test E/week in early Feb. I stopped test enanthate on 15 Feb. On 4 March, after test clearing my system- I started Clomid 50mg EOD and Tamoxifen 20mg daily.

I initially started SERMs with HCG, planning to stop HCG and continue with just SERMs. I just had a doctor prescribe me HCG for longer term testosterone maintenance. I am interested but, will using HCG (without HMG) stop me from making sperm , even with alongside serm?

I'm 34 using test on and off since early 20s, have a naturally low test baseline of around 10ng/dl. I'm planning to get to the bottom of why with my endocrinologist but fertility is priority now.

I restarted sperm production after two years on and off, last in 2020 it took 3.5 months for me to get to 10mil sperm count using standard pct and clomid. But that period really took a toll on my personal and professional life. I'm wondering if I can use HCG to help me with sides of SERMs and throughout the PCT. I got bloods done on TRT and have a script ready to check all fertility markers.

I am reaching out because I'm at ends - there is really no option to even get SERMs prescribed by a fertility specialist or Endocrinologist here (both which I'm seeing).

Thanks so much in advance! If anyone is an expert in this area, happy to pay for a consultation over a zoom call.

 

[Adamsapple]

Bump

 

[aneuman]

I've read conflicting things about just HCG and SERM being ineffective to restart HPTA with HCG suppressing LH and the effect of this on producing sperm.

tigermvmt,​

First thing, HCG does not "suppress LH". HCG mimics LH and because it stimulates the Leydig cells to produce more testosterone, there's an increase in estradiol, which through a negative feedback mechanism involving the pituitary and the hypothalamus, causes the anterior pituitary to reduce the production of LH. For this to work, your Leydig cells must maintain certain level of vitality. Complete testicular failure could render this treatment ineffective.

Clomid, or more specific, the enclomiphene citrate portion of clomid (62%) is selective estrogen receptor modulator that blocks that feedback mechanism I mentioned earlier and simulates lack of estrogen, which causes the hypothalamus to increase production of GnRH and the pituitary to release more LH, which increases testosterone, and FSH, which increases sperm production. For this to work, both your hypothalamus and pituitary must maintain some level of functionality, otherwise, it doesn't matter much you block the negative feedback, it won't result in increased LH/FSH.

The combination of HCG and Clomid (or just enclomiphene citrate) is effective in most cases if the HPG is still functional at some level in all three aspects (Hypothalamus, Pituitary, Gonads)

I have read that for fertility reasons, HCG doses are very high and similar to the ones you mentioned, but I have no experience with such a high dose/frequency.

On 4 March, after test clearing my system- I started Clomid 50mg EOD and Tamoxifen 20mg daily.

Clomid and tamoxifen (2 SERMS) seems like overkill, but your doctor should probably has a reason regarding why this combination.

I am interested but, will using HCG (without HMG) stop me from making sperm , even with alongside serm?

I do not think HCG will "stop" you from naming sperm, as a matter of fact, HCG mono therapy is usually the treatment for infertile men with doses as high as 5000 IU several times a week.

I'm wondering if I can use HCG to help me with sides of SERMs and throughout the PCT. I got bloods done on TRT and have a script ready to check all fertility markers.

I'm not sure which "sides of SERM" you're trying to avoid. HCG also has side effects, on some people more than others, there's no such thing as a free lunch. If getting your wife pregnant is your objective, there may be some small price to pay.

I am reaching out because I'm at ends - there is really no option to even get SERMs prescribed by a fertility specialist or Endocrinologist here (both which I'm seeing).

I can't comment of why you can't access SERMs "there". Those are prescription medications that need to be ordered by a doctor. There're gray and black markets for everything out there but I'd stay out of it, or at least that's why I'd do.

Bottom line, depending on the reasons why you are currently infertile (testicular failure, pituitary dysfunction, etc) the combination of HCG and Clomid could work very well. In many cases, and I'm oversimplifying here, if your testicles work well but your pituitary does not, HCG alone could be a good option. If your testicles work well and your pituitary is lazy, Clomid should work well. A combination should work well in most cases. If both your pituitary and testicles are completely dysfunctional, then I have no options for you, but adoption might be a good alternative. In any case, only blood work and the evaluation of a specialist could determine your specific situation and the appropriate course of action.

Good luck

 

[Adamsapple]

Thanks very much, @aneuman for such a comprehensive response. Extremely useful.

Sorry, I should've clarified I'm aware of how each HCG and Clomid work in isolation, I mean to ask about the effects on the hypothalamus and pituarity signalling of FSH while both HCG and Clomid are acting in your system.

Since the sertoli cells produce sperm when it is signalled from presence of both testosterone and FSH; I just wanted to make sure HCG use did not result in a negative feedback mechanism on producing FSH (noting I can't access HMG/rFSH). From what you've said, it seems it won't and Clomid will play a role in helping with raising FSH.

I am hopeful that it is secondary hypogonadism, and my hypothalamus and pituitary are functioning, given I have lost and regained fertility several times in the past decade with coming on/off testosterone.

Many thanks again, this has put my mind at ease to continue with the protocol.

Side note that it's not always the case that doctors globally help or know what's best. In Australia we are extremely regulated, conservative and stuck in the 1990s for treatment of AAS induced male infertility - the standard procedure is to just wait after coming off testosterone (ignoring the fact it can take 12 months for spermatozoa without intervention). Only some endocrinologists and urologists are recently starting to prescribe SERMs for secondary Hypogonadism. My doctors say HCG is not permitted to be prescribed for male fertility. I've been lucky because of male health clinics somehow are still able to prescribe it for low testosterone. I stopped test a month ago and am willing to do whatever it takes but not when the common practice across average standard of healthcare overseas can produce better health outcomes for me and my family.

 

[aneuman]

My doctors say HCG is not permitted to be prescribed for male fertility.

It's curious, because hCG if one of the few treatments that are FDA approved for male infertility. SERMS are not, by the way, and are used off label.

Medical treatment of male infertility

From the article above

The most important thing to understand is that HCG is not "suppressive" in the sense that it will strangle your pretuitary, take it hostage, and force it not to produce LH/FSH. It will simply bypass the need for the pituitary to produce LH and as a result, the pituitary will produce less LH. If this is maintained for a long time, there might be some permanent effect.

Enclomiphene citrate (whether pure or as part of clomid) will block such an effect on the pituitary and fool it into believing there's not enough estradiol, so it will try to increase the production of LH to increase testosterone to bring estradiol to normal levels

I'm currently using low dose HCG and Enclomipohene citrate and both LH and FSH are at the top of the normal range, and I'm 60 btw.

Good luck.

 

[Adamsapple]

Thanks again - unfortunately there is a lot of misinformation on the internet about HCG; this clears it up for me and honestly has reduced my stress levels tenfold.

The FDA equivalent body in Australia is called the Therapeutic Goods Administration (TGA) and yes, they have approved HCG for male infertility (summary here):

The issue is that the first course of action from my (+ others, from what I hear) fertility specialist and endocrinologist is to wait three months after exogenous testosterone has been eliminated, then re-test FSH, LH and testosterone. Only then if hormones are clearly below the baseline; they will consider adding gonadotropin treatment. So instead of suffering three months of trauma/family grievance, I've opted to approach a clinic for low testosterone and have been prescribed HCG in a roundabout way. (I've also presented both physicians with three sets of blood panels showing that my testosterone levels are below baseline.)

Great to hear it's working for you. I am trying to get my hands on some enclomiphene citrate from receptorchem UK - you would've thought a trans-isomer of clomid would be more widely available by now.

 

[Adamsapple]

It's curious, because hCG if one of the few treatments that are FDA approved for male infertility. SERMS are not, by the way, and are used off label.

Medical treatment of male infertility

From the article above

View attachment 30107

The most important thing to understand is that HCG is not "suppressive" in the sense that it will strangle your pretuitary, take it hostage, and force it not to produce LH/FSH. It will simply bypass the need for the pituitary to produce LH and as a result, the pituitary will produce less LH. If this is maintained for a long time, there might be some permanent effect.

Enclomiphene citrate (whether pure or as part of clomid) will block such an effect on the pituitary and fool it into believing there's not enough estradiol, so it will try to increase the production of LH to increase testosterone to bring estradiol to normal levels

I'm currently using low dose HCG and Enclomipohene citrate and both LH and FSH are at the top of the normal range, and I'm 60 btw.

Good luck.

Hi again!
After 1 month of HPTA recovery: on HCG 1500 IU EOD and Clomid 50mg daily:
LH and FSH are up from zero to 1.7 and 2.0 IU/L.
Testosterone from zero to 14.8 nmol/L!

The only thing is my SHBG is quite high at 84 nmol/L, so free testosterone is very low at about 150 pmol/L.

Do you think the SHBG might still be levelling out after extended time on test therapy? I've also just switched to Enclomiphene 12.5 mg/day and continuing with the HCG EOD. I expect the testosterone and LH/FSH will keep increasing.

Is your SHBG elevated on your protocol?

Thanks

 

[aneuman]

Hi again!
After 1 month of HPTA recovery: on HCG 1500 IU EOD and Clomid 50mg daily:
LH and FSH are up from zero to 1.7 and 2.0 IU/L.
Testosterone from zero to 14.8 nmol/L!

The only thing is my SHBG is quite high at 84 nmol/L, so free testosterone is very low at about 150 pmol/L.

Do you think the SHBG might still be levelling out after extended time on test therapy? I've also just switched to Enclomiphene 12.5 mg/day and continuing with the HCG EOD. I expect the testosterone and LH/FSH will keep increasing.

Is your SHBG elevated on your protocol?

Thanks

First, congrats on your restart!

Two things I can get from this, first, your Leydig cells appear to be responding to HCG and are producing testosterone.NSecond, Your pituitary/hypothalamus seem to be waking up with Clomid. Based on my particular experience, your LH should continue to go up in the following months. Some fertility doctors say that treatment with clomid (alone) requires at least 6 months

Usually hormones require quite some time to find balance, about 3 monghs or so, sometimes more, and making changes in the middle will lead you make the wrong adjustments.

Was this protocol ordered by a professional or is it something you’re trying on your own? 1500 IU of HCG EOD seems a bit high but not unheard of for fertility reasons.

Consider that your Leydig cells are been pushed to produced testosterone by HCG, while simultaneously you have awaken your pituitary produce LH, that means that your testicles might be soon overstimulated by concurrently having HCG and LH hitting them. According to some theories on this forum, that could lead to desensitization of the Leydig cells, which could result in decreased testosterone, in the long run. Whether this is true or not I do not know, but the explanation sounds like it could possible.

On the other hand, SHBG is a bit high and seems to be outside normal parameters which tend to be around 77 nmol/L, mostly in old males. I do not have an advise for you other than see a doctor, and see whether he or she thinks this is a concern.

In my experience, HCG tends to increase SHBG. when I was using 600 IU 3/week my SHBG went up to 68; normal values for me are around 40. Currently I’m using 250 IU 3/week + Enclomiphene citrate and SHBG is at 58.

Ultimately, there’re a lot of feedback mechanisms, some of them understood better than others that cause SHBG to go up more in some people higher than others, whether this is good or bad I don’t know.

In any case, I’m glad that your restart is working, just make sure you don’t overdo it and end up causing more harm than good. In a couple of months probably you and your wife can have your baby and everything will be worth its while.

One question for you though, how are you feeling with this protocol? Any side effects?

 

[Adamsapple]

First, congrats on your restart!

Two things I can get from this, first, your Leydig cells appear to be responding to HCG and are producing testosterone.NSecond, Your pituitary/hypothalamus seem to be waking up with Clomid. Based on my particular experience, your LH should continue to go up in the following months. Some fertility doctors say that treatment with clomid (alone) requires at least 6 months

Usually hormones require quite some time to find balance, about 3 monghs or so, sometimes more, and making changes in the middle will lead you make the wrong adjustments.

Was this protocol ordered by a professional or is it something you’re trying on your own? 1500 IU of HCG EOD seems a bit high but not unheard of for fertility reasons.

Consider that your Leydig cells are been pushed to produced testosterone by HCG, while simultaneously you have awaken your pituitary produce LH, that means that your testicles might be soon overstimulated by concurrently having HCG and LH hitting them. According to some theories on this forum, that could lead to desensitization of the Leydig cells, which could result in decreased testosterone, in the long run. Whether this is true or not I do not know, but the explanation sounds like it could possible.

On the other hand, SHBG is a bit high and seems to be outside normal parameters which tend to be around 77 nmol/L, mostly in old males. I do not have an advise for you other than see a doctor, and see whether he or she thinks this is a concern.

In my experience, HCG tends to increase SHBG. when I was using 600 IU 3/week my SHBG went up to 68; normal values for me are around 40. Currently I’m using 250 IU 3/week + Enclomiphene citrate and SHBG is at 58.

Ultimately, there’re a lot of feedback mechanisms, some of them understood better than others that cause SHBG to go up more in some people higher than others, whether this is good or bad I don’t know.

In any case, I’m glad that your restart is working, just make sure you don’t overdo it and end up causing more harm than good. In a couple of months probably you and your wife can have your baby and everything will be worth its while.

One question for you though, how are you feeling with this protocol? Any side effects?

Thanks, I tell you what, it's been a ride that I won't soon forget. Appreciate your help which provided confidence to continue my plan and to address it with doctors.

I sought the HCG from an online doctor, who prescribed 1000 IU 3x a week for low testosterone. After reviewing two meta-analyses and several individual human studies on secondary HH, I chose to dose a bit higher. In many cases, doses of 2000 IU EOD were used with Clomid for upwards of 3 months.

I'm now seeing an Endocrinologist who has prescribed 1500 IU 3x a week for male infertility - I've switched and will continue with this reduced dose for the next 6 weeks, at which point doc requested another blood test and a semen analysis done.

I raised concerns about elevated SHBG with the Endo, he similarly stated that hormones might be balancing out over months and that SHBG may drop in response to the expected further increase in testosterone.

My wife and I need to get on with IVF quickly for other reasons, so the fertility doctor (doc #3) has asked that I get a semen analysis next week. I thought this was too early but the doc says since it's not natural conception, I don't need to wait for a full recovery and the highest sperm count possible, they need a smaller number of healthy sperm to can find a few ideal ones for IVF to work (1 per embryo frozen).

I hope desensitisation doesn't become an issue but don't think it's likely from the studies I've seen run over months and given the fertility protocol is FDA/TGA approved. If SHBG doesn't drop at the next blood test, I may suggest to the Endo to reduce the HCG; since things are up and running again, there's probably only a need for a lower maintenance dose to ensure sperm keep producing healthily (and possible harm that can harm come from overstimulation).

I finally feel normal now. The only issues are that my sex drive is hardly there, I do get morning wood sometimes but my general sexual appetite and ability to get an erection are quite reduced (comparing to a normal, pre-TRT state). I've held onto muscle though lost a fair bit of strength and have gained fat in the 'estrogenic' areas. But I can tell the situation keeps improving as time goes on, and have accepted that my body is something that I fix later, less important to me now than health and family. I think switching to Enclo two weeks ago has helped a lot with my mental state. As expected at the start of protocol, the Clomid and zero test really hit me, for 2-3 weeks I had insomnia, was often sad/pessimistic, fatigued, zero sex drive, crazy mood swings.

 

[aneuman]

Thanks, I tell you what, it's been a ride that I won't soon forget. Appreciate your help which provided confidence to continue my plan and to address it with doctors.

Thanks @Adamsapple. I'm glad I was able to help in this respect. I feel uneasy offering medical advise as I do not have any medical training at all, although I've spent quite some time at the library some time ago (yes, you got that right, the library) and now read a lot on PubMed and other well-respected literature regarding the endocrine system -which I'm fascinated by- and particularly male hormones for different reasons. If my experience helped you get advise and get better, that makes me happy.

I'm now seeing an Endocrinologist who has prescribed 1500 IU 3x a week for male infertility - I've switched and will continue with this reduced dose for the next 6 weeks, at which point doc requested another blood test and a semen analysis done.

This is a frequent fertility treatment protocol I've found in my readings. You mentioned that you wanted to follow Dr. Ramasamy's protocol. I know Dr. Ramasamy personally and I have read a lot of the research he's done in this area, so HCG + clomid is something that has been used a lot for fertility reasons. I do not have any personal experience in protocols for fertility, so any comment would be based on literature I've read.

I raised concerns about elevated SHBG with the Endo, he similarly stated that hormones might be balancing out over months and that SHBG may drop in response to the expected further increase in testosterone.

As I mentioned earlier, HCG tends to increase my SHBG even at much lower doses (750 IU a week, 250 IU x 3) so it doesn't surprise me that it goes even higher with a higher dose, what I cannot say is whether that has any consequences other than higher sequestration of testosterone. I'm glad you endocrinologist has reviewed it and found no reasons of concern. Keep an eye on it.

My wife and I need to get on with IVF quickly for other reasons, so the fertility doctor (doc #3) has asked that I get a semen analysis next week. I thought this was too early but the doc says since it's not natural conception, I don't need to wait for a full recovery and the highest sperm count possible, they need a smaller number of healthy sperm to can find a few ideal ones for IVF to work (1 per embryo frozen).

Best of luck. I'm sure you'll be a dad soon.

I hope desensitisation doesn't become an issue but don't think it's likely from the studies I've seen run over months and given the fertility protocol is FDA/TGA approved. If SHBG doesn't drop at the next blood test, I may suggest to the Endo to reduce the HCG; since things are up and running again, there's probably only a need for a lower maintenance dose to ensure sperm keep producing healthily (and possible harm that can harm come from overstimulation).

Yes, that's something that I've read here and in some other literature bit is more a speculation or a hypothesis of what could happen and I don't think there's much evidence to support it. In any case I wanted you to be aware of this possibility.

Keep in mind that most of the talk and advice you'll find on this forum is NOT for fertility reasons. Your protocol probably needs to be substantially different from most people who are here simply to raise their T level for a variety of reasons, but don't care much about fertility. The best path forward is to monitor closely the levels of testosterone, estradiol, SHBG AND FSH. You need to increase your FSH to a level in which you start producing sperm again, not only testosterone. Clomid is the one that's going to help with that

As you said, as your system starts to recover, you may need less support and hopefully everything starts working well again, but for now, you may need to keep this protocol until you reach your goal.

I finally feel normal now. The only issues are that my sex drive is hardly there, I do get morning wood sometimes but my general sexual appetite and ability to get an erection are quite reduced (comparing to a normal, pre-TRT state).

That's great! I'm really happy, and yes, I know what you mean, that's life.

Wish you the best and let us know how you name the baby!

Best of luck.

 

[Adamsapple]

I'm not surprised, your interest seems to have provided a wealth of knowledge on the topic.

Good point about perspectives of those choosing to go on TRT. For my current issue, I've looked at posts, studies, articles with primary focus on achieving fertility. Guess this will lend itself to increasing natural testosterone but perhaps not to levels many here would feel is inadequate.

Hoping this SHBG drops so I can see an improvement in quality of life from freed up T. See what the bloods look like, and what the doctors think, in a few weeks.

Baby names! Bit further down the track but excited for when we get there. You sound like you have some experience...!

Thanks again

 

[tomlikesbeetroot]

Just to let you know, FSH/HMG to my knowledge is only needed if to improve the quality of sperm, the LH/HCG will be sufficient to increase the sperm count. Once you have the sperm count increased you can undertake a test to determine if quality is an issue.

If sperm quality is an issue, then here in Australia you can get Gonal-F from any pharmacy as long as you can find a doctor who can prescribe it. It will need to be a private script for this purpose so it is a bit expensive.

But for all of these SERMS/HCG/HMG there are plenty of UGL sources online that will ship to Australia. It is possible that it might be seized by customs but not always, in my history >90% of packages get through. Once I even had a box of clomid delivered with a note saying it had been opened and inspected by customs, but they let it through.

 

[Adamsapple]

rFSH (FSH) is literally the acts as a signal to the testes to produce sperm. LH/HCG signals the testes mainly to produce testosterone, through this process, production of sperm and FSH can also increase. HMG has both LH and FSH.

In addition to needing adequate levels of both LH and FSH to produce healthy sperm, the count and quality of sperm you produce depends on many factors. As an example, deficiency in Vit E, D, C will result in poor sperm quality (motility, morphology, count) and antioxidants like glutathione and carnitine can improve sperm morphology and motility further.

Here are some studies showing FSH improves fertility - sperm count, motility and morphology:
HMG is as good as recombinant human FSH in terms of oocyte and embryo quality: a prospective randomized trial

Frontiers | Clinical Use of FSH in Male Infertility

The established clinical indication for FSH use in male infertility is the treatment of patients with hypogonadotropic hypogonadism for stimulation of sperma...

www.frontiersin.org

 

[Adamsapple]

Just to let you know, FSH/HMG to my knowledge is only needed if to improve the quality of sperm, the LH/HCG will be sufficient to increase the sperm count. Once you have the sperm count increased you can undertake a test to determine if quality is an issue.

If sperm quality is an issue, then here in Australia you can get Gonal-F from any pharmacy as long as you can find a doctor who can prescribe it. It will need to be a private script for this purpose so it is a bit expensive.

But for all of these SERMS/HCG/HMG there are plenty of UGL sources online that will ship to Australia. It is possible that it might be seized by customs but not always, in my history >90% of packages get through. Once I even had a box of clomid delivered with a note saying it had been opened and inspected by customs, but they let it through.

UGL is the last (never a) resort imo - half of it is fake, if it's really you can't verify how much you're getting and you can't guarantee long-term, customs as you say, HPLC certificates can be faked, don't really have time to trial and error when sperm takes up to 3 months to mature (as well as other people involved). Once you test infertile, can get HCG from doctors relatively easily and a lot cheaper than UGL.

 

[tomlikesbeetroot]

UGL is the last (never a) resort imo - half of it is fake, if it's really you can't verify how much you're getting and you can't guarantee long-term, customs as you say, HPLC certificates can be faked, don't really have time to trial and error when sperm takes up to 3 months to mature (as well as other people involved). Once you test infertile, can get HCG from doctors relatively easily and a lot cheaper than UGL.

Agreed, though I was just unsure what it meant where the title said HMG/rhFSH impossible to get in Australia. Gonal-F is what we have received, but our clinic also mentions Menopur or Puregon as other options in this class.
All available here in Australia, so I figured it was just a difficulty in obtaining a script.

 

[Adamsapple]

Agreed, though I was just unsure what it meant where the title said HMG/rhFSH impossible to get in Australia. Gonal-F is what we have received, but our clinic also mentions Menopur or Puregon as other options in this class.
All available here in Australia, so I figured it was just a difficulty in obtaining a script.

Sorry mate, missed your reply - thanks for letting me know. My experience was different. Who prescribed the Gonal-F ?