(Secondary) Hypogonadism, Strategies, Fertility, etc.

[hfk101]

To all:

I am 26 years old, white, male. Physiology doctoral student, undergraduate degree in ex. phys.

Always been an athlete. Martial arts through H.S. Wrestled in high school and college. Competed in PLing during college and still trained as a PLer for my first two years of doctoral research. However, I noticed a general trend toward lethargy, incomplete recovery, etc. since I've been a doctoral student (in my 4th year now), and used to chalk it up to my time/energy investment in lab work. Until my bout with hepatitis three months ago (see below).

I was diagnosed with hypogonadotropic hypogonadism ~8 weeks ago, when my levels of T, FT, LH, and FSH were all pitifully below the low end of the reference range. The T and FT levels were actually follow-ups to some initial tests done a month prior, when they were also low. But the main reason for these prior blood tests was I had an acute bout of hepatitis. Since then, my pancytopenic phenotype has rendered me extremely lethargic (hematocrit ~28), immunocompromised (WBC ~2.0, neutrophils 650), and feeling pretty much a waste of life to be honest. While my liver enzymes returned from the 1000's to high-normal ranges, my lethargy and suppressed bone marrow persisted.

Anyways, in addition to my PCP, I've been regularly seeing an endo and a haematologist. The endo and haematologist both agreed some form of T replacement would be in order, to stimulate my otherwise unresponsive marrow as well as to generally restore well-being/libido/etc. Thing is, I'm only 26 and my wife and I desire to have children. So straight up T replacement wasn't a viable option as far as fertility is concerned (at least according to the endo). Around a month ago, I started on prescription hCG at a dose of 1500 iu/3 times per week, as per my endo's specs. We will taper the dose down to 1000 iu/3x per week starting this week, and then in two weeks, hopefully 500. I got my T levels rechecked this past week, and they are above the upper limit of the reference range (not dramatic, but nice). SHBG has gone up to compensate, and my FT levels reflect this (low-normal end of the reference range).

So my questions to anyone who wouldn't mind offering some advice/opinions/concerns etc:
1) Is my doctor's strategy effective from both a short- and long-term approach to handling secondary hypogonadism? Remember, that at this time, my wife and I really desire to conceive. I did have a semen analysis performed prior to the hCG. As expected, low sperm count and those that do exist don't seem to be all that "energetic," (low mobility etc.)
2) What would you advise as a practical means of HRT pre-conception and post-conception (when, I assume, I can be put on some form of straight T)?

Thanks for reading and/or any help you can provide.

Sincerely,
HFK

 

[ciobl]

do you have the labs available ? hcg and clomid might do it for you.

would you mind posting the labs ?

 

[hfk101]

I haven't got the exact details handy, but this should help:

Before Starting hCG ~4500 iu/week (3x1500 iu) administered IM:
T = 1148 (low; range starts ~2220)
FT = 1 (low; range starts at ~28)
SHBG = 82 (high; range ends 71)
LH = 0.9 (low; range starts 1.7)
FSH = 1.0 (low; range starts 3.1)
Prolactin = 12.3 (normal; range = 2.8-13.1)
GH = 4.89 (high; range ends 1)
IGF-1 = low (forget values) (perhaps some form of GH resistance in liver? I was on supplemental GH as a child for short stature...prior to puberty)

1 month into hCG @4500 iu/week:
T = 9500 (high; range end 6800)
SHBG = 101 (high; range ends 71)
FT = 48 (normal; range b/t 28-86)

I am now on 3000 hCG/week (3x1000 iu injections per week). Will assay for T, FT, and E2 in two weeks, as well as get another semen analysis performed. The E2 was after my request (nipples getting a little tender, I'm sure due to the excess T aromatization to E). Doc won't prescribe a SERM or aromatase inhibitor tho.

Hope this helps,
HFK

PS: These are only the measures I've had done relative to hormones. I have had many other labs performed that are specific to my CBC, ALT, AST, EPO, LDH, etc.

 

[ciobl]

in my personal opinion i think you are on the right path with him...

your estrogen is probably way up there, like you said and...... with shbg in that range, more likely it is.

i don't understand why he wouldn't give you any serm......you have to keep an eye on the t/e ratio....

for example, clomid has effects on fsh that hcg wouldn't ? following me ? and at the same time restarts the whole transmission.....

as you know, the only transmission you are concerned right now is the hpga...hope you are not having any problems with the thyroid...so the hypothalamic pituitary gonadal axis is the only one you should focus on.....( in my opinion and i am not in the medical field...)
but at the same time keeping an eye on estrogen levels is crucial.......

 

[hfk101]

Thanks for your advice ciobl...

So should l potentially look into getting ahold of clomid elsewhere as an adjunct to hCG?

Also, I forgot to report above that my TSH and Thyroid levels came back in the normal range (TSH a little highish; T a little lowish; but pretty much normal).

Thanks,
HFK

 

[ciobl]

androgen supplementation lowers tsh, t3... so down the road everything will look better, hopefully

about the clomid, talk to your doctor first....see what he has to say about it.....then let us know what he thinks and why he does/doesn't recommend clomid....he's the one that knows you better than all of us, right ?

...you still need to keep an eye on e2 though....throw some zinc or nettle root extract, just to be safe...don't go much with the zinc, get a pill cutter and every day or so throw 1/2 1/4 down your system....

....listen to your body...and tell him....talk to him...morning wood, libido, energy, mood

 

[Weatherlite]

Ok, first off TRT will NOT cause you to become sterile! Your endo is wrong on that. The only way exogenous T will cause sterility is if it's abused. Yes, your sperm count may go down with TRT but you can still get your wife pregnant.

Second, with what your endo is doing you may become sterile! Sounds crazy I know but eventually you will desensitize your leydig cells with doses that high. Without that intratesticular T your testicles aren't going to be producing much sperm at all. There are a few guys I know of who do HcG only (Davidz is one if I recall) and they get their T levels right up to the high end of the range on less than 800IU's a week! Some even less than that!

If you aree truely interested in some form of HRT I would recommend going with a traditional route involving some form of T and after a while adding in very small doses of HcG (200-500IU's per week total). You will remain VERY fertile and will feel better than you will on an HcG only regimen.

Last but not least, Clomid is OK for short term use but can cause vision problems long term.

 

[ciobl]

weather in 2 weeks his doctor is bringing down the dose to 500....that will restart the whole thing....don't be so paranoid

 

[hfk101]

Weatherlite,

As Ciobl mentions, my endo plans to drop the dose to 500 iu in two weeks. I believe she is really trying to give my system a hefty jump-start before the tapering protocol.

I would like to use (read: not abuse) T replacement concomitantly with hCG, but I don't think my endo's buying. She's so inured to the literature regarding former AAS users and not individuals using TRT to regain or optimize T levels. So, I'm not exactly sure what to do at this point. I figure hCG alone is fine for now, especially with a tapering protocol, since we're finally doing something to improve my otherwise dismal hormonal milieu. However, I will be looking to fine tune things in the near future (re: SERM/AI and/or T replacement).

Thanks for your (and Ciobl's) help,
HFK

 

[hfk101]

On that note:

What are everyone else's thoughts regarding straight T replacement when fertility (and intratesticular T secretion) is a concern?

(I may have to make this a new thread)

HFK

 

[love_en]

Unless you are completely primary hypogonadal: testicles are dead. T will not make you sterile. Many researchers have played with using T as a male birth control. Even at 200mg depot T per week, too many men are still fertile. At the normal TRT dose of 100mg per week I doubt it is a problem. There is a joke going around the steroid message boards. What do you call a man who relies on T as a contraceptive? Daddy!. Add 250 iu HCG and shutdown of the testes is not a problem. But, like Weatherlite said, high dose shots of HCG will damage your testicles and cause sterility, not to mention primary hypogonadism.

 

[bassack]

love_en,

Do you have a study, or any anecdotal evidence to which you can point me supporting your assertion about HCG causing sterility?

 

[hfk101]

And to add: How long does it take hCG (in high doses) to cause sterility and/or testicular damage?

I'd be interested in some literature on this that I could take to my endo. As well, something tangible validating the efficacy of T supplementation on fertility in secondary hypogonadism.

Thanks,
HFK

 

[BRICK]

IMO T replacement when trying to increase sperm count is a big mistake. Stay away from the T until you and your wife conceive. I went through my own situation b4 my son was born. I had been on TRT with Androgel when my wife and I decided to try for a child. We tried for a year with no luck. I went to have a sperm count check which showed a count of next to nothing. I went to see an Endo and he immediately told me to get off the Androgel. He said that my count would always remain down as long as i was on the T. We tried HCG and Clomid for about 3 months and BINGO....my wife was able to conceive!! It winds up that the HCG and Clomid brought up my sperm count considerably but only got my T levels to 140 ng/dl (very low). So I went back on TRT since those T levels were not acceptable. Hope this helps.

 

[hfk101]

Thank you Brick & love_en,

These are exactly the issues/personal stories I was hoping to read about. I realize that, due to the glaring paucity of published data in this field, we have little other than conjecture and pragmatic appraisal to go on.

I would welcome any other opinions (scientific or otherwise) on this topic. While I don't think I will stray from my endo's specs for the moment (hCG only; tapering to ~1500 iu total/week (3 shots)), I am thinking long-term here.

Thanks,
HFK

 

[1cc]

IMO T replacement when trying to increase sperm count is a big mistake. Stay away from the T until you and your wife conceive. I went through my own situation b4 my son was born. I had been on TRT with Androgel when my wife and I decided to try for a child. We tried for a year with no luck. I went to have a sperm count check which showed a count of next to nothing. I went to see an Endo and he immediately told me to get off the Androgel. He said that my count would always remain down as long as i was on the T. We tried HCG and Clomid for about 3 months and BINGO....my wife was able to conceive!! It winds up that the HCG and Clomid brought up my sperm count considerably but only got my T levels to 140 ng/dl (very low). So I went back on TRT since those T levels were not acceptable. Hope this helps.

Brick,

How much Clomid and HCG did you do in that 3 months? Did you have to take anything else with it?

 

[DavidZ]

How long does it take hCG (in high doses) to cause sterility and/or testicular damage? I'd be interested in some literature on this that I could take to my endo.

Here are two studies from Medline. Also, see my Primer sticky at the top of this forum. In particular, see Chapter 2.


J Clin Endocrinol Metab. 1982 Jul;55(1):76-80. Related Articles, Links

Testicular responsiveness to chronic human chorionic gonadotropin administration in hypogonadotropic hypogonadism.

D'Agata R, Vicari E, Aliffi A, Maugeri G, Mongioi A, Gulizia S.

Steroidogenic responsiveness to long term hCG administration (1500 U three times a week for 23 months) was characterized in 8 males with hypogonadotropic hypogonadism (HH). During hCG treatment, testosterone (T), which was in the prepuberal range under basal conditions, rose considerably to the upper end of the normal range and remained at that level during the 23 months of observation. A 2.5-fold increase was observed in serum levels of 17 beta-estradiol (E2) an increment less than seen with T. The increment in 17 alpha-hydroxyprogesterone was also lower than that in T throughout the study; thus, the 17 alpha-hydroxyprogesterone to T ratio, despite continuous hCG administration, remained low. Serum androstenedione was slightly increased during hCG therapy. No significant changes were observed in serum levels of dehydroepiandrosterone. These data indicate that continuous long term hCG administration stimulated T levels in HH, with a relatively small change in E2. The kinetics of the T and E2 responses to 2000 U hCG, evaluated after 23 months of therapy, indicated that the testicular response was markedly reduced. No increment in T levels was observed at 24 h; the maximal response occurred at 48 h. This pattern of T response supports the idea that partial testicular desensitization occurs in HH patients receiving chronic treatment with hCG.

PMID: 6210708

*********************************************************

Horm Metab Res. 1987 May;19(5):216-21. Related Articles, Links

Testicular responsiveness following chronic administration of hCG (1500 IU every six days) in untreated hypogonadotropic hypogonadism.

Balducci R, Toscano V, Casilli D, Maroder M, Sciarra F, Boscherini B.

The observation that the testosterone (T) response to a single intramuscular injection of hCG is prolonged suggests that currently used regimens (2-3 injections per week) to stimulate endogenous androgen secretion in hypogonadotropic hypogonadism (HH) patients have to be reassessed. Moreover, during the last few years, Leydig cell steroidogenic desensitization has been found after massive doses of hCG. The aim of the present investigation, carried out in 6 HH patients who showed no signs of puberty, was to study the effect of 1500 IU hCG administered every six days over a period of one year to induce the onset of pubertal development. To evaluate the kinetics of the response of T, 17 alpha-hydroxyprogesterone (17 alpha-OHP) and 17 beta-oestradiol (E2), blood samples were taken basally and 1, 2, 4 and 6 days after drug injection. This dynamic study was performed after the first injection and after the 4th and 12th month of treatment. During this one year time period, a progressive increase in testicular size was observed. Comparing plasma T levels (mean +/- SE) before the first injection (11.2 +/- 4.7 ng/dl) with the corresponding values at the 4th (38.7 +/- 10.5 ng/dl) and 12th months (99.5 +/- 19.9 ng/dl) of therapy, a progressive and significant increase was observed. T reached a maximum elevation 58 hours after hCG injection at the 4th month (198.3 +/- 42 ng/dl; P less than 0.01) and at the 12th month (415.6 +/- 62.6 ng/dl; P less than 0.05), whereas it remained unchanged following the first hCG injection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 3583230

 

[chap]

personally, I think the 500 iu shot 3 x a week is still too much and will cause a big surge in estradiol

100 iu a day has been found to be a very effective dose for most of us that have tried it

I am confused a bit by the studies in the above post that seem to say that there is a delayed effect of 2 days from HCG, where I seem to remember reading other studies that say that peak testicular stimulation from HCG occurs in 5 or 6 hours. What is the truth of the matter. Also, many of us here have found that HCG is as good at estrogen production as it is at testosterone production.

 

[DavidZ]

Also, many of us here have found that HCG is as good at estrogen production as it is at testosterone production.

I have heard this said a few times, but have not seen any scientific data to support it.

Excess T causes excess E2. I suspect that overuse of HCG causes excess E2, rather than HCG itself.

I am confused a bit by the studies in the above post that seem to say that there is a delayed effect of 2 days from HCG, where I seem to remember reading other studies that say that peak testicular stimulation from HCG occurs in 5 or 6 hours. What is the truth of the matter.

Large doses of HCG produce 2 T peaks: one about 2 to 7 hours after the shot and a second peak about 48 to 72 hours after the shot. See the article below.

************************************************

J Clin Endocrinol Metab. 1985 Nov;61(5):926-32. Related Articles, Links

Self-priming effect of luteinizing hormone-human chorionic gonadotropin (hCG) upon the biphasic testicular response to exogenous hCG. I. Serum testosterone profile.

Ulloa-Aguirre A, Mendez JP, Diaz-Sanchez V, Altamirano A, Perez-Palacios G.

The present study was conducted to investigate whether the early (2-8 h) testicular response to a single dose of exogenous hCG depends on previous exposure to LH activity. Four different groups of subjects were studied: 1) four normal adult men [Tanner stage-G5 (T-G5)] and one late pubertal subject (T-G4); 2) normal prepubertal (T-G1) and early- and midpubertal boys (T-G2 and T-G3) (n = 4-6 each); 3) five patients with hypogonadotropic hypogonadism (HH); and 4) two patients with the complete form of the androgen insensitivity syndrome. Each subject received an im injection of hCG (40 IU/kg) on day 1 and blood samples were drawn before and 1-8, 24, 48, and 72 h after injection. At 96 h, a second dose of hCG was given (80 IU/kg) and blood samples were obtained at the same times as after the first hCG dose. Serum testosterone (T) was measured by RIA. The first dose of hCG evoked a biphasic response of serum T in groups T-G2 to T-G5 as well as in the two patients with the complete form of the androgen insensitivity syndrome. The early peak was at 2-7 h, whereas the late T peak was at 48-72 h after injection. In T-G1 children and in patients with HH, the early response did not occur [T-G1, from 129 +/- 43 (SEM) to 288 +/- 127 pg/ml (P greater than 0.05); HH, 79 +/- 18 to 107 +/- 12 (P greater than 0.05) pg/ml], and the late peak was attenuated as compared with the pubertal boys. There were not significant differences in the responses of the T-G1 and the HH groups. After the second dose, all groups had biphasic T responses, although they varied in magnitude. These results demonstrate that previous exposure to LH activity is an obligatory prerequisite for the early peak of the hCG-mediated biphasic testicular response, and that a single dose of hCG has a priming effect that is sufficient to ensure a biphasic response to a second dose of hCG given 96 h later.

PMID: 4044781

 

[painman]

My Doc prescribed 300 iu daily. He bows to my direction knowing I have more time to research than he does so he shouldn't mind when I tell him I lowered it to 200 iu every other day. I do my first labs this week, after two weeks of hcg and if needed I'll up it. It will be good to see if I get a response at this level though.

100 iu is it enough to "restart" the pituitary or just maintainence dose? I am hoping hcg restarts things and I can go without anything but nutrition in a month or so.

Maybe a higher dose is needed to restart things in comparison to just manage it?


Like you I am also interested in how long and how fast it kicks in.

Thanks.

personally, I think the 500 iu shot 3 x a week is still too much and will cause a big surge in estradiol

100 iu a day has been found to be a very effective dose for most of us that have tried it

I am confused a bit by the studies in the above post that seem to say that there is a delayed effect of 2 days from HCG, where I seem to remember reading other studies that say that peak testicular stimulation from HCG occurs in 5 or 6 hours. What is the truth of the matter. Also, many of us here have found that HCG is as good at estrogen production as it is at testosterone production.