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HELP! Still shooting blanks after 3 years on hCG and 9 months on hCG + Clomid

John99Test

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I was shooting blanks for about 2 years. Reproductive endo did a shot to test sertoli cells. It was one shot but I can't recall the name. Test indicated they were functioning and he rx'd 20,000iu per week of hcg. Thankfully, insurance paid for all of it and we explored gonal-f but my response was good enough that it was necessary. He added clomid and anastrozole. He even suggested I consider a sperm donor just in case and admittedly, that wasn't an option. Folic acid was also prescribed. I stuck with the regimen for about 15 months and in NOV20, I had a daughter. I felt great with that combo and have a beautiful and healthy little girl.
Would love to work with your doc. Can you DM their contact info
 

Needmassquick

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Any chance you're primary? That would explain the lack of results. I'd drop the hCG down to 200iu daily since too much causes high E2 production and that damages the Leydig cells making them less responsive.

What's your Clomid dose? Too much will also shut down your response to it. I'd take 25mg daily max but that was too much for me. I started having estrogen issues and my testicles shrank again.

Hey Bad Rad, can you explain where you saw that too much clomid will shut down your response? I've read 7-8 studies on clomid and enclomiphene now and in all cases higher doses resulted in higher responses (more LH/FSH).

Have you read the studies? Almost all studies on HCG and fertility use 1000-3000iu of HCG 3x per week
Too much hCG will shut down the Leydig cells. After 1000iu dose there is about 96 hours of refractory when the testes won't respond to another dose. 500iu has a 3 day active life. I'd cut that dose way back and do it daily. hCG should last about 30 days mixed before degrading. You can freeze any unused hCG without issues.

You can try 10-20mg Test and 200iu hCG daily as it may help. That's my preferred TRT schedule for myself. Most docs prescribe way too much hCG and the localized E2 production will inhibit your response to hCG. The only fix is a lower dose since SERMs/AI won't affect the E2 in the testes.

Primary means your testicles stopped responding to LH/FSH initially. Pretty uncommon compared to secondary that is a LH/FSH issue.

Where are you getting this information? Dr. Crisler, Dr. McClain, and Dr. O'Connor (basically the big 3 in the TRT world) all say the leydig cell desensitization is a myth with no evidence supporting it


By the way for those reading, I have been on 25mg enclomiphene every day for 3 weeks now. No noticeable side effects other than that my libido is even higher than normal.
 

Needmassquick

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I was shooting blanks for about 2 years. Reproductive endo did a shot to test sertoli cells. It was one shot but I can't recall the name. Test indicated they were functioning and he rx'd 20,000iu per week of hcg. Thankfully, insurance paid for all of it and we explored gonal-f but my response was good enough that it was necessary. He added clomid and anastrozole. He even suggested I consider a sperm donor just in case and admittedly, that wasn't an option. Folic acid was also prescribed. I stuck with the regimen for about 15 months and in NOV20, I had a daughter. I felt great with that combo and have a beautiful and healthy little girl.

Holy crap that's a lot of HCG
 

bad rad

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Hey Bad Rad, can you explain where you saw that too much clomid will shut down your response? I've read 7-8 studies on clomid and enclomiphene now and in all cases higher doses resulted in higher responses (more LH/FSH).

Have you read the studies? Almost all studies on HCG and fertility use 1000-3000iu of HCG 3x per week


Where are you getting this information? Dr. Crisler, Dr. McClain, and Dr. O'Connor (basically the big 3 in the TRT world) all say the leydig cell desensitization is a myth with no evidence supporting it


By the way for those reading, I have been on 25mg enclomiphene every day for 3 weeks now. No noticeable side effects other than that my libido is even higher than normal.
I've been traveling so late to respond. I'm still looking for the Clomid study but I believe I originally read it from a Swale post. Here's one on hCG showing better response to multiple, lower doses vs one big dose. Even the package inserts for hCG have what appears to random recommendations. I wouldn't call it desensitization but there's an effective dosing threshold. I've read so many studies at this point trying to find the best approach it's absurd.

 

bad rad

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Here's a little info on Clomid lowering sperm counts in some men due to excessive dosing. I'll keep looking for the pituitary studies.

Ross et al. reported one of their 53 patients on high dose CC (100 mg 3 times per week) had a decrease in sperm motility, however, demonstrated rapid improvement when the dose was reduced to 50 mg every other day.37 There was also another case report by Pasqualotto et al. that found three patients of their cohort becoming azoospermic after treatment, with only return to severe oligospermia after clomiphene discontinuation.36,38 It will be interesting to note whether future studies using a nonracemic mixture of pure enclomiphene will avoid these occasional negative effects.

 

bad rad

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Finally found the doses recommended and wow, I really wish the original posts and recommendation I read had listed them too. I would expect major side effects at that dose. The referenced studies are in the discussion.

I guess in the end I'm a moderate doses guy and lean towards less is more if able to. I have tried high doses of these drugs before and have terrible side effects, hence my recommendations. It's usually more comfortable to increase doses if needed than lower them due to side effects.

At low doses (25–50 mg/day), clomiphene is reportedly ineffective in prepubertal boys, but stimulates gonadotropin secretion in pubertal and adult males. At high doses (500 mg/day), clomiphene suppresses gonadotropin secretion even in normal adult males.

 

bad rad

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Some more reading on why too much hCG is basically wasted. Once the testes are maximally stimulated they don't respond to additional doses until they "get a break" per se.

Of note, doses of hCG above ~2000 IU are associated with pharmacological levels of plasma hCG and result in the Leydig cell being refractory to additional doses of hCG.14, 17

 

Needmassquick

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I've been traveling so late to respond. I'm still looking for the Clomid study but I believe I originally read it from a Swale post. Here's one on hCG showing better response to multiple, lower doses vs one big dose. Even the package inserts for hCG have what appears to random recommendations. I wouldn't call it desensitization but there's an effective dosing threshold. I've read so many studies at this point trying to find the best approach it's absurd.


This is a great study and really shows why smaller doses more frequently are better, crazy how much higher estrogen got relative to testosterone with the single dose. But again this doesn't show desensitization of the leydig cells.
 

Needmassquick

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Here's a little info on Clomid lowering sperm counts in some men due to excessive dosing. I'll keep looking for the pituitary studies.

Ross et al. reported one of their 53 patients on high dose CC (100 mg 3 times per week) had a decrease in sperm motility, however, demonstrated rapid improvement when the dose was reduced to 50 mg every other day.37 There was also another case report by Pasqualotto et al. that found three patients of their cohort becoming azoospermic after treatment, with only return to severe oligospermia after clomiphene discontinuation.36,38 It will be interesting to note whether future studies using a nonracemic mixture of pure enclomiphene will avoid these occasional negative effects.


Yea I have seen that study by Pasqualotto. It is unique, hard to explain why that would happen as it contrasts with other research. Hopefully if it is a potential problem I would avoid it with Enclomiphene.

It's also odd as there is no mention of the clomid dose used here, so you can't really say it's due to "excessive dosing" as we have no idea what the dosing was. They also had high-normal FSH the entire time, even off Clomid, so I'm wondering why they were infertile in the first place and why it was presumed that clomid would help if they already had normal gonadotropins.

I will note that if you look at the discussion section below, this is precisely why I was challenging people about it being of any benefit to me, and this is also why all doctors I've spoken to on the topic have said it wouldn't benefit me. Very little evidence for it especially if already taking HCG and FSH:

"Discussion
Clomiphene citrate is a nonsteroidal antiestrogen that binds to hypothalamic estrogen receptors and weakens the negative feedback mechanism of LHRH secretion by estrogens. This leads to increased secretion of FSH and LH. The increased LH stimulates production of T by Leydig cells, whereas FSH and T stimulate Sertoli cells and germinal cells (1). On the basis of four trials that evaluated the effect of this drug in unexplained infertility, CC has a small and nonsignificant effect, producing 1 additional pregnancy in 76 CC cycles compared with untreated control cycles (2). A randomized, double-blind, multicenter study from the World Health Organization evaluated 109 couples with idiopathic male infertility and failed to show any improvement in pregnancy rates after 6 months of treatment with CC (3). The potential side effects of this drug include headaches, nausea, visual disturbances, dizziness, abdominal discomfort, mouth ulcers, and cataract formation (3).This study shows that there is a real possibility for a decrease in semen quality, even azoospermia, after the use of CC in patients with severe idiopathic oligospermia. Therefore, the benefits of empiric treatment with CC must be balanced with the possible undesirable effects, such as azoospermia. "
 

Needmassquick

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Some more reading on why too much hCG is basically wasted. Once the testes are maximally stimulated they don't respond to additional doses until they "get a break" per se.

Of note, doses of hCG above ~2000 IU are associated with pharmacological levels of plasma hCG and result in the Leydig cell being refractory to additional doses of hCG.14, 17


It's another great link, but again there's a huge difference between saying that a higher dose will actually prevent it from working (leydig cell desensitization) and that it just won't produce additional results. I'd caution about telling other posters that, as it makes this confusing topic even more confusing. Additionally, they only tested testosterone levels at Day 1, 2 and 3. I would guess that if this was continued for weeks on end the 4000iu group would almost certainly have the highest testosterone levels. As I mentioned earlier some studies have as high as 3000-6000iu several times per week to get sufficient testosterone levels.

Speaking of, anyone have word from the OP? He's one of the only cases I've seen where it just did not work at all even after years. Definitely makes me worried about my own case too. Still zero change in testicle size.
 

bad rad

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This is a great study and really shows why smaller doses more frequently are better, crazy how much higher estrogen got relative to testosterone with the single dose. But again this doesn't show desensitization of the leydig cells.
Did you notice the difference in serum testosterone levels? The smaller doses almost doubled the testes output.

I think part of the confusion is people interchangeably use desensitization and refractory period. There is definitely a refractory period for hCG usage as additional doses show no increase in serum testosterone. This, per other studies, is related to the increase in intra-testicular E2 as they point to it reducing sensitivity to hCG.
 

bad rad

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It's also odd as there is no mention of the clomid dose used here, so you can't really say it's due to "excessive dosing" as we have no idea what the dosing was. They also had high-normal FSH the entire time, even off Clomid, so I'm wondering why they were infertile in the first place and why it was presumed that clomid would help if they already had normal gonadotropins.
The dose started at 100mg x3 weekly and reduced to 50mg EOD.
 

Needmassquick

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The dose started at 100mg x3 weekly and reduced to 50mg EOD.

That was the study that showed reduced sperm motility. The Pasqualotto study (which is mostly a case report) is the one that actually showed a decrease in sperm count and does not report clomid dose as far as I can see.
 

Needmassquick

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Did you notice the difference in serum testosterone levels? The smaller doses almost doubled the testes output.

I think part of the confusion is people interchangeably use desensitization and refractory period. There is definitely a refractory period for hCG usage as additional doses show no increase in serum testosterone. This, per other studies, is related to the increase in intra-testicular E2 as they point to it reducing sensitivity to hCG.
The smaller doses doubled the testes output in terms of area under the curve because it was the same total iu of HCG spread out over 5 days instead of one large bolus on 1 day. That is not an example of desensitization.

If they did 5x300iu and then 5x1500iu and the latter showed lower total testosterone then that would be desensitization. But that is not the case. 5x1500iu would absolutely show higher total testosterone compared to 5x300iu. It would not be 5x as much of course, as there are diminishing returns.
 

beast405

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Well I can say if it were me, I would just go fully natty and live healthy for a maybe a few years, take or do anything that is considered natural ways to increase testosterone simply like your vits and mins and exercise. 6 years a while to be on but I think you could slowly start to bring it back. when taking stuff you got to cycle, TRT should be more for those who have decided to not have kids anymore
I have to disagree with your last statement. There’s nothing healthy about having low test. I feel trt should be for anybody with less than optimal hormone levels. And majority of the time people can still have kids while on trt with the help of hmg and hcg. Besides there’s nothing really “natural” that’s going to raise your testosterone to any real degree.
 

beast405

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Like I and others have said bro. Hmg is the key !
 

Kaladryn

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The first thing to do is drop the TRT completely, give the body 6 months to 1.5 years to come back, THEN start fertility treatments.
 

Needmassquick

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The first thing to do is drop the TRT completely, give the body 6 months to 1.5 years to come back, THEN start fertility treatments.

Why not start the fertility treatments (HCG/FSH) when coming off the TRT?
 

Kaladryn

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Why not start the fertility treatments (HCG/FSH) when coming off the TRT?
You need to give the body time to multiply leydig cells before stimulating them or you will just desensitize the receptors. Sure many people can stay on TRT while doing fertility treatments, but that is because they still have enough leydig cells left to begin with.
 

pickapeck

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Yea I have seen that study by Pasqualotto. It is unique, hard to explain why that would happen as it contrasts with other research. Hopefully if it is a potential problem I would avoid it with Enclomiphene.

It's also odd as there is no mention of the clomid dose used here, so you can't really say it's due to "excessive dosing" as we have no idea what the dosing was. They also had high-normal FSH the entire time, even off Clomid, so I'm wondering why they were infertile in the first place and why it was presumed that clomid would help if they already had normal gonadotropins.

I will note that if you look at the discussion section below, this is precisely why I was challenging people about it being of any benefit to me, and this is also why all doctors I've spoken to on the topic have said it wouldn't benefit me. Very little evidence for it especially if already taking HCG and FSH:

"Discussion
Clomiphene citrate is a nonsteroidal antiestrogen that binds to hypothalamic estrogen receptors and weakens the negative feedback mechanism of LHRH secretion by estrogens. This leads to increased secretion of FSH and LH. The increased LH stimulates production of T by Leydig cells, whereas FSH and T stimulate Sertoli cells and germinal cells (1). On the basis of four trials that evaluated the effect of this drug in unexplained infertility, CC has a small and nonsignificant effect, producing 1 additional pregnancy in 76 CC cycles compared with untreated control cycles (2). A randomized, double-blind, multicenter study from the World Health Organization evaluated 109 couples with idiopathic male infertility and failed to show any improvement in pregnancy rates after 6 months of treatment with CC (3). The potential side effects of this drug include headaches, nausea, visual disturbances, dizziness, abdominal discomfort, mouth ulcers, and cataract formation (3).This study shows that there is a real possibility for a decrease in semen quality, even azoospermia, after the use of CC in patients with severe idiopathic oligospermia. Therefore, the benefits of empiric treatment with CC must be balanced with the possible undesirable effects, such as azoospermia. "
Adding in Clomid is not in line with the purpose of this protocol. If you were to attemp a restart hCG would be run, then adding in Clomid and then phasing out hCG. Finally the Clomid would be phased out. Then after evaluation possibly a second round.
 

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