HCG question for Bill Roberts and Dr. Scally...

[Jeton]

please comment on the HCG protocol i'm using if u have a moment. i chose this forum over Men's Health as my history is a bit more gonzo than is usual for that forum, but move it if u feel the need...


first some history:

about 6 weeks into starting my first course of medication for HIV, i had a baseline total T test that showed a result around 450-500. this was late February 2004...i was dropping weight n wanted help keeping it on, but was afraid of injections and orals, so i was rx'd 1 packet/day of Androgel. in July 04 i switched to Testim n upped it to 2 tubes a day, as my own t production had apparently shut down (shrunken nuts, no T bloodwork tho). in Oct 04 my doc cut me off, saying i regained the weight i'd lost n she didn't wanna endanger her license. neither she, the clinic or I had any knowledge of "PCT"....

then, nothing....in the 2nd half of 2005 my nuts returned to their normal size, but i felt like shit n started to get fat. weighed 160lbs at start of meds in jan 04...132lbs 6 weeks later when starting T...160lbs when i went off Testim in Oct 2004, pretty lean n a bit ripped.

by March, 2006 i was 195lbs at 32%bf, n my Total T tested out at *27*. i started 1 packet a day of Androgel n light exercise...pushed toward heavy cardio by summer 06 n got down to 165lbs at 15% bf, but still felt sucky n got retested...my Total T in Oct 06 was only 55. At this point i requested to switch to injections, n was put on 200mg T cyp/week. in April 2007 i added 200mg/wk of deca to the injections. i did NOT know about cycling, i stayed on deca along with t cyp until a few months into joining Meso in June-ish 09, n dropped the deca from continual use...(i regained the ability to orgasm in less than 30 min). by mid 09 i had also completed 3 months of Femara to kill off some focal gyno n added 1/4 Arimidex 3x/wk. by the end of 2009 my doctor upped me to 400mg/wk of t cyp, and it helped me add more weight. i have since added 2 tubes a day of testim about 2 months ago, which is definitely an improvement in terms of energy n sense of well-being. i am still on Adex .25mg 3x/wk

it's a lot of T to be on, but my own circumstances r special enuff to warrant it: i lose weight very easily, generally dropping 10-20 pounds anytime i have a serious case of diarrhea, with several instances of dropping over 30 pounds, and anytime i'm off HIV meds it only takes me 6 months to drop to AIDS-level immune strength n half a million viral load.


anyway, on to the HCG question: i want my nuts back. i want the option of having children if i so eventually desire, but more importantly, i'm sick of carrying around peanuts in my sack...it's very distressing, even depressing. even 1 packet a day of Androgel shrunk my nuts in Spring 2004 and Spring 2006.

My doc agreed to Rx me 20,000 IUs of HCG, n suggested a protocol of 5,000 IUs per week in weekly injections. However, based on Bill Roberts HCG article on Meso, and Dr Crisler's lo-dose HCG protocol, yesterday i started a protocol of 1,000 IUs daily. I have enuff to continue this for 30 days since i waited until my refill to start, n then would drop down to 500IUs a day or less. i inject T twice weekly, n had hoped to get down eventually to 500 IUs 4x/wk, 1 and 2 days b4 each T injection...i might just keep the injections daily tho, given the Testim.

i do not want to desensitize my nuts to HCG, but i've also been shut down pretty much since March 2004. in terms of recovering testicle size n function, what do you guys think of the protocol i'm following? should i tweak it?

 

[Bill Roberts]

At the time of writing my HCG profile, the standard for bb'ing use was injections of 5000 IU at a time. When I put in the profile a top limit of 1000 IU at a time, actually my opinion was that that was still too high and I never wrote that for anyone's cycles, but I didn't know it for a fact to be too high, either. Since it was still a very major reduction from the then-norm, I thought it was reasonable to draw the line there.

However, while an individual injection could still be 1000 IU in some instances -- as a one-day frontload though I prefer 500 IU for that, or if for some reason injection frequency is weekly which it shouldn't be -- a total of 7000 IU per week I'm now quite convinced to be too much.

250 IU/day or 500 IU every other day is I think a reasonable maximum. The evidence is consistent with (but does not prove) the receptors being nearly saturated at that point.

Massive doses have been used medically but this is, I believe, a matter of a need for prolonged duration of action with a short-acting drug. This can be achieved by administering an amount which is a gross excess in the earlier part of its duration of action. But the better approach by far is to administer an appropriate amount at a frequency no less than the half-life of the drug, and preferably more frequently than that.

HCG has a biphasic half-life, with the first part of it being short, so every other day or at the least, 3x/week is about as much as the injections should optimally be spaced.

 

[Jeton]

At the time of writing my HCG profile, the standard for bb'ing use was injections of 5000 IU at a time. When I put in the profile a top limit of 1000 IU at a time, actually my opinion was that that was still too high and I never wrote that for anyone's cycles, but I didn't know it for a fact to be too high, either. Since it was still a very major reduction from the then-norm, I thought it was reasonable to draw the line there.

However, while an individual injection could still be 1000 IU in some instances -- as a one-day frontload though I prefer 500 IU for that, or if for some reason injection frequency is weekly which it shouldn't be -- a total of 7000 IU per week I'm now quite convinced to be too much.

250 IU/day or 500 IU every other day is I think a reasonable maximum. The evidence is consistent with (but does not prove) the receptors being nearly saturated at that point.

Massive doses have been used medically but this is, I believe, a matter of a need for prolonged duration of action with a short-acting drug. This can be achieved by administering an amount which is a gross excess in the earlier part of its duration of action. But the better approach by far is to administer an appropriate amount at a frequency no less than the half-life of the drug, and preferably more frequently than that.

HCG has a biphasic half-life, with the first part of it being short, so every other day or at the least, 3x/week is about as much as the injections should optimally be spaced.

THANK YOU SO MUCH!!

however, more questions (if i may):

today was my 2nd dose at 1000 IU's...given that i've been deeply hypogonadal since 2004 and definitely NOT anytime b4 then, do u think i should drop down to the 500 IU's per day dose by tomorrow or would there be some advantage to using the 1000iu dose a bit longer?

my whole idea was to taper down to 325IUs 4-5x/week eventually n maintain it there for as long as i'm on twice weekly injections of T...

 

[Bill Roberts]

I would drop it. No problem has been caused thus far, so there's definitely not anything to be concerned with there, but the only extra thing that might result from the higher dose is more desensitization. Such a dosage is a far greater level of stimulation than occurs with natural LH.

 

[Jeton]

I would drop it. No problem has been caused thus far, so there's definitely not anything to be concerned with there, but the only extra thing that might result from the higher dose is more desensitization. Such a dosage is a far greater level of stimulation than occurs with natural LH.

thank you Bill, i appreciate your help more than i can express.


one last question (pleeease):

would u be able to suggest a time-frame by which i should expect to see some visible progress in terms of testicular size? a month? 6 months? 6 weeks? 6 years?

 

[snuff-sann]

I personally think that HCG won't do anything for you at this moment.
HCG stimulates the leydig-cells. Leydig-cells only make up about 10% of the total testicular volume.
I know a guy from Holland who suffers from the same problem. He's seeing an endocrinologist.
That endo prescribes him Nolvadex, 20mg/d for 3 months. Nothing else. The guy in on TRT.

I will explain.
HCG is responsible for high testosteron-spikes and because of that more will be aromatized, so more estrogen.
More estrogen will counteract the FSH release that is responsible for the size of the testes, for about 90%.
To be honest HMG is really what you need, unfortunately that's extremely expensive.
So without HMG there is another way to solve the problem.
By blocking the estrogen. That will give FSH free play to get the testes back to size.
If after 3 months your testes won't be back to their normal size you can always try to get HMG.

Good luck.

 

[Jeton]

I personally think that HCG won't do anything for you at this moment.
HCG stimulates the leydig-cells. Leydig-cells only make up about 10% of the total testicular volume.
I know a guy from Holland who suffers from the same problem. He's seeing an endocrinologist.
That endo prescribes him Nolvadex, 20mg/d for 3 months. Nothing else. The guy in on TRT.

I will explain.
HCG is responsible for high testosteron-spikes and because of that more will be aromatized, so more estrogen.
More estrogen will counteract the FSH release that is responsible for the size of the testes, for about 90%.
To be honest HMG is really what you need, unfortunately that's extremely expensive.
So without HMG there is another way to solve the problem.
By blocking the estrogen. That will give FSH free play to get the testes back to size.
If after 3 months your testes won't be back to their normal size you can always try to get HMG.

Good luck.

did u notice that i'm on arimidex .25mg 3x/week? do u think that's sufficient?

 

[Michael Scally MD]

I disagree that 1,000 IU is excessive for HPTA restoration. In fact, in the many many patients I treated for returning HPTA function, 500 IU was far too inadequate. I am talking about QOD to Q3D dosing. I agree that QD dosing is not worthwhile. The objective is to achieve maximal testes stimulation. On this point, testing is the ONLY method to determine effectiveness. On desensitization, at 2,500 IU or less, I never saw any sign of desensitization. On higher doses, 5,000 IU, I saw it once. It should be mentioned that the duration for use is typically no more than 1 month. A longer duration should use a lesser dose, but, again, testing is key. You can start at 500 IU, but if the response is insufficient, I would NOT hesitate to increase the dose (TT < 450). An important consideration for this are very few studies dealing with AIH. I do think there is a role for hMG. [This is half the battle! There is still the requirement for restoring LH & FSH.]


The following study measured testes size. TESTICULAR SIZE - Subcutaneous doses of 1000–2500 IU hCG applied twice a week and 75–150 IU hMG applied three times a week. Testicular size after 5–12 months of therapy bilateral testicular volumes increased from an initial mean of 6.86ml (group Ia) to 14.96ml (Ia); 4.46ml (group Ib) to 15.36ml (Ib); and 14.06ml (group II) to 28.36ml (II).

Buchter D, Behre HM, Kliesch S, Nieschlag E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998;139(3):298-303. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases -- Buchter et al. 139 (3): 298 -- European Journal of Endocrinology

Stimulatory therapy with either GnRH or gonadotropins is an effective treatment to induce spermatogenesis and achieve paternity in men with secondary hypogonadism. However, there is still uncertainty about the optimal treatment modality and schedule, the duration of treatment necessary and the influence of interfering factors such as maldescended testes. We have extended our previous series of men treated for secondary hypogonadism and now present our therapeutic experience with 42 cases. Twenty-one patients with hypothalamic disorders (11 with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with hypopituitarism (group II) were treated with hCG/hMG. A total of 5 7 treatment courses were initiated for induction of spermatogenesis, 36 of these for the purpose of induction of pregnancy in the female partner. Bilateral testicular volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by the appearance of sperm in the ejaculate was induced in 54/57 courses. Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not preclude patients with IHH or KalS from gaining fertility under therapy and spermatogenesis could be successfully initiated even in some individuals with bilateral maldescended testes. In general there was a tendency for a longer duration of therapy until induction of spermatogenesis in patients with a history of bilateral cryptorchidism. However, this did not reach statistical significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH there were no statistically significant differences in terms of duration to appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years spermatogenesis could be induced. In repeatedly treated patients stimulation of spermatogenesis tended to be faster while time until induction of pregnancy was significantly shorter in the second treatment course. In conclusion, GnRH or hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It remains to be determined whether highly purified urinary gonadotropin preparations or recombinant LH and FSH will provide therapeutic advantages.

 

[Michael Scally MD]

did u notice that i'm on arimidex .25mg 3x/week? do u think that's sufficient?

The use of an AI muddles the picture when monitoring for testes function. I find it important to stop all AI when using hCG (and/or hMG) to restore testes function. The decreases degradation from an AI prevents a clear picture for the T synthesis.

 

[Jeton]

The use of an AI muddles the picture when monitoring for testes function. I find it important to stop all AI when using hCG (and/or hMG) to restore testes function. The decreases degradation from an AI prevents a clear picture for the T synthesis.

well, what about a scenario like mine, where i intend to rely on exogenous T? if high E2 is gonna slow down size-growth, and exogenous T delivery will continue long-term anyway, why sacrifice growth on the altar of studying my internal T function?

 

[Jeton]

I disagree that 1,000 IU is excessive for HPTA restoration. In fact, in the many many patients I treated for returning HPTA function, 500 IU was far too inadequate. I am talking about QOD to Q3D dosing. I agree that QD dosing is not worthwhile. The objective is to achieve maximal testes stimulation. On this point, testing is the ONLY method to determine effectiveness. On desensitization, at 2,500 IU or less, I never saw any sign of desensitization. On higher doses, 5,000 IU, I saw it once. It should be mentioned that the duration for use is typically no more than 1 month. A longer duration should use a lesser dose, but, again, testing is key. You can start at 500 IU, but if the response is insufficient, I would NOT hesitate to increase the dose (TT < 450). An important consideration for this are very few studies dealing with AIH. I do think there is a role for hMG. [This is half the battle! There is still the requirement for restoring LH & FSH.]


The following study measured testes size. TESTICULAR SIZE - Subcutaneous doses of 1000–2500 IU hCG applied twice a week and 75–150 IU hMG applied three times a week. Testicular size after 5–12 months of therapy bilateral testicular volumes increased from an initial mean of 6.86ml (group Ia) to 14.96ml (Ia); 4.46ml (group Ib) to 15.36ml (Ib); and 14.06ml (group II) to 28.36ml (II).

Buchter D, Behre HM, Kliesch S, Nieschlag E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998;139(3):298-303. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases -- Buchter et al. 139 (3): 298 -- European Journal of Endocrinology

Stimulatory therapy with either GnRH or gonadotropins is an effective treatment to induce spermatogenesis and achieve paternity in men with secondary hypogonadism. However, there is still uncertainty about the optimal treatment modality and schedule, the duration of treatment necessary and the influence of interfering factors such as maldescended testes. We have extended our previous series of men treated for secondary hypogonadism and now present our therapeutic experience with 42 cases. Twenty-one patients with hypothalamic disorders (11 with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with hypopituitarism (group II) were treated with hCG/hMG. A total of 5 7 treatment courses were initiated for induction of spermatogenesis, 36 of these for the purpose of induction of pregnancy in the female partner. Bilateral testicular volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by the appearance of sperm in the ejaculate was induced in 54/57 courses. Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not preclude patients with IHH or KalS from gaining fertility under therapy and spermatogenesis could be successfully initiated even in some individuals with bilateral maldescended testes. In general there was a tendency for a longer duration of therapy until induction of spermatogenesis in patients with a history of bilateral cryptorchidism. However, this did not reach statistical significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH there were no statistically significant differences in terms of duration to appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years spermatogenesis could be induced. In repeatedly treated patients stimulation of spermatogenesis tended to be faster while time until induction of pregnancy was significantly shorter in the second treatment course. In conclusion, GnRH or hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It remains to be determined whether highly purified urinary gonadotropin preparations or recombinant LH and FSH will provide therapeutic advantages.

is there something disadvantageous about QD dosing? if the frequency itself doesn't bother me personally, wouldn't 500 IUs QD be better than 1000 IUs QOD or 1500 IUs Q3D from a purely pharmacological perspective ?

btw, my intense thanks to u as well Doc, i've been nervous about bringing this all up here but it was my great hope that u'd both answer me with ur full consideration. i appreciate it greatly. THANK YOU.

 

[Bill Roberts]

The above study doesn't disagree with what I said because of the specific protocols it looked at.

The first employed 2x/week dosing. I don't recommend that, because due to the biphasic nature of the half-life of HCG there actually is a quite substantial drop between injections in this case.

I understand that with the general population, compliance with ED or EOD dosing, or even 3x/week, is inferior to once-weekly or twice-weekly but regardless, the study looked at different protocols than I recommend, which allow levels to fall more (thereby requiring higher peaks for similar AUC) and of course since injection frequency is less, injection amount is greater.

BB'ers don't have trouble with EOD injection protocols or even ED with an insulin syringe.

Absolutely the 75-150 IU 3x/week was inadequate. I'd never have recommended it.

I don't think the study by any means shows that 1000 IU/day is called for, or, if injecting every other day as one of the options I recommend, that 1000 IU per injection is needed, or contradicts that 250 IU/day is entirely appropriate and effective.

But yes, for the non-bb'er, every-day or every-other-day dosing seems, apparently, just too much for their delicate little souls and for best results in the real world with medical patients a doctor must take their compliance or likely lack thereof into account.

 

[Jeton]

The above study doesn't disagree with what I said because of the specific protocols it looked at.

The first employed 2x/week dosing. I don't recommend that, because due to the biphasic nature of the half-life of HCG there actually is a quite substantial drop between injections in this case.

I understand that with the general population, compliance with ED or EOD dosing, or even 3x/week, is inferior to once-weekly or twice-weekly but regardless, the study looked at different protocols than I recommend, which allow levels to fall more (thereby requiring higher peaks for similar AUC) and of course since injection frequency is less, injection amount is greater.

BB'ers don't have trouble with EOD injection protocols or even ED with an insulin syringe.

Absolutely the 75-150 IU 3x/week was inadequate. I'd never have recommended it.

I don't think the study shows that 1000 IU/day is called for, or, if injecting every other day as one of the options I recommend, that 1000 IU per injection is needed.

so u think ED dosing would work best, but with a dose around 250 IUs?

 

[Bill Roberts]

Yes, I would use that.

But if you want to use 500 IU/daily for a month "just to be sure" then although I think it is twice as much as is necessary for best results with daily dosing, as Dr Scally says there won't be an issue with regard to desensitization if that is for only say 4 weeks. If there is any difference in adverse effect it would be with regards to possibly having somewhat higher estrogen as a result. This is unproven but it does at least seem that there's higher incidence of high estrogen levels or estrogen related problems for any given situation when a lot of HCG is being used vs a more moderate amount being used.

However, I would not go to the 1000 IU/daily: that is just definitely over the top, though nowhere near as badly over the top as bb'ers used to routinely do, and a few still do.

 

[Jeton]

Yes, I would use that.

But if you want to use 500 IU/daily for a month "just to be sure" then although I think it is twice as much as is necessary for best results with daily dosing, as Dr Scally says there won't be an issue with regard to desensitization if that is for only say 4 weeks. If there is any difference in adverse effect it would be with regards to possibly having somewhat higher estrogen as a result. This is unproven but it does at least seem that there's higher incidence of high estrogen levels or estrogen related problems for any given situation when a lot of HCG is being used vs a more moderate amount being used.

However, I would not go to the 1000 IU/daily: that is just definitely over the top, though nowhere near as badly over the top as bb'ers used to routinely do, and a few still do.

[)] THANK YOU again Bill, I can see ur reading my mind now...

 

[swifto]

I disagree that 1,000 IU is excessive for HPTA restoration. In fact, in the many many patients I treated for returning HPTA function, 500 IU was far too inadequate. I am talking about QOD to Q3D dosing. I agree that QD dosing is not worthwhile. The objective is to achieve maximal testes stimulation. On this point, testing is the ONLY method to determine effectiveness. On desensitization, at 2,500 IU or less, I never saw any sign of desensitization. On higher doses, 5,000 IU, I saw it once. It should be mentioned that the duration for use is typically no more than 1 month. A longer duration should use a lesser dose, but, again, testing is key. You can start at 500 IU, but if the response is insufficient, I would NOT hesitate to increase the dose (TT < 450). An important consideration for this are very few studies dealing with AIH. I do think there is a role for hMG. [This is half the battle! There is still the requirement for restoring LH & FSH.]


The following study measured testes size. TESTICULAR SIZE - Subcutaneous doses of 1000–2500 IU hCG applied twice a week and 75–150 IU hMG applied three times a week. Testicular size after 5–12 months of therapy bilateral testicular volumes increased from an initial mean of 6.86ml (group Ia) to 14.96ml (Ia); 4.46ml (group Ib) to 15.36ml (Ib); and 14.06ml (group II) to 28.36ml (II).

Buchter D, Behre HM, Kliesch S, Nieschlag E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998;139(3):298-303. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases -- Buchter et al. 139 (3): 298 -- European Journal of Endocrinology

Stimulatory therapy with either GnRH or gonadotropins is an effective treatment to induce spermatogenesis and achieve paternity in men with secondary hypogonadism. However, there is still uncertainty about the optimal treatment modality and schedule, the duration of treatment necessary and the influence of interfering factors such as maldescended testes. We have extended our previous series of men treated for secondary hypogonadism and now present our therapeutic experience with 42 cases. Twenty-one patients with hypothalamic disorders (11 with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with hypopituitarism (group II) were treated with hCG/hMG. A total of 5 7 treatment courses were initiated for induction of spermatogenesis, 36 of these for the purpose of induction of pregnancy in the female partner. Bilateral testicular volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by the appearance of sperm in the ejaculate was induced in 54/57 courses. Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not preclude patients with IHH or KalS from gaining fertility under therapy and spermatogenesis could be successfully initiated even in some individuals with bilateral maldescended testes. In general there was a tendency for a longer duration of therapy until induction of spermatogenesis in patients with a history of bilateral cryptorchidism. However, this did not reach statistical significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH there were no statistically significant differences in terms of duration to appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years spermatogenesis could be induced. In repeatedly treated patients stimulation of spermatogenesis tended to be faster while time until induction of pregnancy was significantly shorter in the second treatment course. In conclusion, GnRH or hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It remains to be determined whether highly purified urinary gonadotropin preparations or recombinant LH and FSH will provide therapeutic advantages.

No AI + HCG?

What about the increase in endogenous T and negative feedback at the hypothalamus... If the testes are responsive?


What about the increase in E2 and PgR that HCG also brings at higher doses?