HCG induces germ cell apoptosis in testis

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    HCG induces germ cell apoptosis in testis


    At only a 100ius a day?!


    Apoptosis. 2007 Jul;12(7):1173-82.

    hCG treatment raises H(2)O (2) levels and induces germ cell apoptosis in rat testis.

    Gautam DK, Misro MM, Chaki SP, Chandra M, Sehgal N.

    Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, 110067, India.

    The clinical significance of exogenous hCG treatment is to stimulate steroidogenesis and spermatogenesis in the testis. However, the pathogenesis of detrimental effects on the testis arising out of chronic hCG treatment is yet to be clearly ascertained. In the present study we have shown that hCG treatment (100 IU/day) to rats for 30 days raises testicular oxidative stress leading to germ cell apoptosis and impairment of spermatogenesis. The treatment raises testicular H(2)O(2) levels along with increase in lipid peroxidation and concomitant decrease in the enzymatic antioxidant activities like superoxide dismutase, catalase and glutathione-s-transferase. The rise in the number of apoptotic germ cells was associated with up regulation of Fas protein expression and caspase-3 activity in the testis. However, serum testosterone which was elevated by 15 days of hCG treatment declined to pretreatment levels by 30 days. No significant alteration in serum gonadotropins was observed. The above findings indicate that the pathogenesis of deleterious effects following chronic hCG treatment is due to increase in testicular oxidative stress with high H(2)O(2) availability leading to apoptosis among germ cells.

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    100IUs to a rat would be like giving 1,000,000IUs to a human, how was it even still alive during this experiment?
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    Good call. So how much does a rat weigh, 200 grams?

    Is there a calculation one could do to find an equivalent dose in humans?
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    Quote Originally Posted by Jupiter View Post
    At only a 100ius a day?!


    Apoptosis. 2007 Jul;12(7):1173-82.

    hCG treatment raises H(2)O (2) levels and induces germ cell apoptosis in rat testis.

    Gautam DK, Misro MM, Chaki SP, Chandra M, Sehgal N.

    Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, 110067, India.

    The clinical significance of exogenous hCG treatment is to stimulate steroidogenesis and spermatogenesis in the testis. However, the pathogenesis of detrimental effects on the testis arising out of chronic hCG treatment is yet to be clearly ascertained. In the present study we have shown that hCG treatment (100 IU/day) to rats for 30 days raises testicular oxidative stress leading to germ cell apoptosis and impairment of spermatogenesis. The treatment raises testicular H(2)O(2) levels along with increase in lipid peroxidation and concomitant decrease in the enzymatic antioxidant activities like superoxide dismutase, catalase and glutathione-s-transferase. The rise in the number of apoptotic germ cells was associated with up regulation of Fas protein expression and caspase-3 activity in the testis. However, serum testosterone which was elevated by 15 days of hCG treatment declined to pretreatment levels by 30 days. No significant alteration in serum gonadotropins was observed. The above findings indicate that the pathogenesis of deleterious effects following chronic hCG treatment is due to increase in testicular oxidative stress with high H(2)O(2) availability leading to apoptosis among germ cells.
    while the study may be a good study in overdosing, do you have concerns about HCG that are based on your experience?
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    Thanks for the replies.

    My concern is that on testosterone replacement i have no symptoms of gynecomastia, yet on shots of just 250ius 2x/wk of hcg symptoms become apparent in just a few weeks.

    I guess im just trying to find out if the hcg shots for me are worth it.

    recently i switched to 100ius a day to try to minimize the side effects and then i saw this study. of course 100ius to a rat is much different than to a human.
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    Quote Originally Posted by Jupiter View Post
    Good call. So how much does a rat weigh, 200 grams?

    Is there a calculation one could do to find an equivalent dose in humans?
    If the rat weighs 400grams and a human weighs 80kgs, it would be the equivilent to 20,000IUs per day or 140,000IUs per week, if you were to go by weight.

    btw HCG is known to aromatase more than testosterone.
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    Thanks ItsHectic.

    That makes sense.

    I have always wondered since hcg causes increased aromatase intratesticularly if an AI would make a difference. Would one need to use a SERM in the case of hcg induced gyno?
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    Quote Originally Posted by Jupiter View Post
    Thanks ItsHectic.

    That makes sense.

    I have always wondered since hcg causes increased aromatase intratesticularly if an AI would make a difference. Would one need to use a SERM in the case of hcg induced gyno?

    would it first make sense to lower the dose of HCG?
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    Yes, but would there be much benefit in going lower than 100iu a day?

    If you think there is (I know you have a wealth of knowledge in this field) let me know.

    Thanks for your responses.
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    Quote Originally Posted by Jupiter View Post
    Yes, but would there be much benefit in going lower than 100iu a day?

    If you think there is (I know you have a wealth of knowledge in this field) let me know.

    Thanks for your responses.
    I've play with different schemes of using HCG. I started with Swale's original protocol of 100 mg Test. Cyp and 250 iu HCG and days 5 and 6. I loved the cognitive effect (due to raising pregnenolone levels) but my libido was over the top. Then I switched to 60-80 Test. Cyp and 100 iu HCG on days 2,3,4,5,6. I did this for months and there was bloating. There was still a mild but noticeable cognitive effect and less intrusive libido. For the past 3 months, I've been doing 60 mg Test Cyp and 150-100 iu of HCG on days 5 and 6. No bloating. I really am commited to minimally effective dosing of these chemical. My own experience in this area is the best I can offer you.
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    Thanks for sharing, very interesting.

    My concern of less than 700iu/wk was due to the study that follows.

    It seems that in testosterone induced suppression, 125iu EOD only brings men within 25% baseline, 250iu EOD within 7% baseline and 500iu EOD over 26% baseline, during concurrent use.

    So my thinking is that one would need around a 1000iu/wk (Im sure someone with better math skills could figure out the exact dose to be at baseline with the info above).

    Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression.

    Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, Sutton PR, Wright WW, Brown TR, Yan X, Zirkin BR, Jarow JP.

    Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA. a-coviello@northwestern.edu

    In previous studies of testicular biopsy tissue from healthy men, intratesticular testosterone (ITT) has been shown to be much higher than serum testosterone (T), suggesting that high ITT is needed relative to serum T for normal spermatogenesis in men. However, the quantitative relationship between ITT and spermatogenesis is not known. To begin to address this issue experimentally, we determined the dose-response relationship between human chorionic gonadotropin (hCG) and ITT to ascertain the minimum dose needed to maintain ITT in the normal range. Twenty-nine men with normal reproductive physiology were randomized to receive 200 mg T enanthate weekly in combination with either saline placebo or 125, 250, or 500 IU hCG every other day for 3 wk. ITT was assessed in testicular fluid obtained by percutaneous fine needle aspiration at baseline and at the end of treatment. Baseline serum T (14.1 nmol/liter) was 1.2% of ITT (1174 nmol/liter). LH and FSH were profoundly suppressed to 5% and 3% of baseline, respectively, and ITT was suppressed by 94% (1234 to 72 nmol/liter) in the T enanthate/placebo group. ITT increased linearly with increasing hCG dose (P < 0.001). Posttreatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group, and 26% greater than baseline in the 500 IU hCG group. These results demonstrate that relatively low dose hCG maintains ITT within the normal range in healthy men with gonadotropin suppression. Extensions of this study will allow determination of the ITT concentration threshold required to maintain spermatogenesis in man.
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    Quote Originally Posted by Jupiter View Post
    Thanks for sharing, very interesting.

    My concern of less than 700iu/wk was due to the study that follows.

    It seems that in testosterone induced suppression, 125iu EOD only brings men within 25% baseline, 250iu EOD within 7% baseline and 500iu EOD over 26% baseline, during concurrent use.

    So my thinking is that one would need around a 1000iu/wk (Im sure someone with better math skills could figure out the exact dose to be at baseline with the info above).

    Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression.

    Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, Sutton PR, Wright WW, Brown TR, Yan X, Zirkin BR, Jarow JP.

    Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA. a-coviello@northwestern.edu

    In previous studies of testicular biopsy tissue from healthy men, intratesticular testosterone (ITT) has been shown to be much higher than serum testosterone (T), suggesting that high ITT is needed relative to serum T for normal spermatogenesis in men. However, the quantitative relationship between ITT and spermatogenesis is not known. To begin to address this issue experimentally, we determined the dose-response relationship between human chorionic gonadotropin (hCG) and ITT to ascertain the minimum dose needed to maintain ITT in the normal range. Twenty-nine men with normal reproductive physiology were randomized to receive 200 mg T enanthate weekly in combination with either saline placebo or 125, 250, or 500 IU hCG every other day for 3 wk. ITT was assessed in testicular fluid obtained by percutaneous fine needle aspiration at baseline and at the end of treatment. Baseline serum T (14.1 nmol/liter) was 1.2% of ITT (1174 nmol/liter). LH and FSH were profoundly suppressed to 5% and 3% of baseline, respectively, and ITT was suppressed by 94% (1234 to 72 nmol/liter) in the T enanthate/placebo group. ITT increased linearly with increasing hCG dose (P < 0.001). Posttreatment ITT was 25% less than baseline in the 125 IU hCG group, 7% less than baseline in the 250 IU hCG group, and 26% greater than baseline in the 500 IU hCG group. These results demonstrate that relatively low dose hCG maintains ITT within the normal range in healthy men with gonadotropin suppression. Extensions of this study will allow determination of the ITT concentration threshold required to maintain spermatogenesis in man.

    my last draw on the above was 669 total, 100 free. E2 was 22. This all works for me. Now another source of my testosterone is HGH. Igf-1 was 260.
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    Excelent numbers!

    Sounds like what you are doing is working, as a side note, is the amount of hcg you are taking keeping your testicles from atrophying?
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    Quote Originally Posted by Jupiter View Post
    Excelent numbers!

    Sounds like what you are doing is working, as a side note, is the amount of hcg you are taking keeping your testicles from atrophying?
    that also.
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    Thanks for all the info, you have been a great help.
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    Quote Originally Posted by Jupiter View Post
    Yes, but would there be much benefit in going lower than 100iu a day?

    If you think there is (I know you have a wealth of knowledge in this field) let me know.

    Thanks for your responses.
    100IU per day - 750 per week

    Dr Johns protocol of 2 shots @250Iu - 500IU per week.

    So yea, lower dosage.

    Don't blame hcG on E issues, it is mildly elevating E ONLY BECAUSE IT IS RAISING T. This is essential.

    You probably need an AI
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    100ius a day is 700ius a week, but I get your point.

    I am on 1mg arimidex, twice weekly.

    And its definitely not the increase in testosterone causing the issue, I have taken, in the past, 500mgs of testosterone a week for months with no AI and never had an issue with gyno, so I know its the intra testicular aromatization thats causing the problem.

    I'll drop down to 500ius a week and see what happens.
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    "so I know its the intra testicular aromatization thats causing the problem."

    Well at least you know your not primary

    It seems to me that hcG is doing its job - maintaining baseline testical functioning and preventing leydig cell death.

    Hmmm, already on a whopping 2mg of adex per week and still aromitization issues? Adex is self limiting, meaning it only will work to such a point to decrease aromitization.
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    Thanks for the reply plymouth city.

    A few questions for you or anyone else:

    1. what is primary and what is secondary (i should know and think i have an idea but want to be sure)?

    2. How does one know when hcg is maintaining function (testicle size)?

    3. Could someone expound on preventing leydig cell death (use it or lose it)?

    4. Is one to understand that regardless of the amount of arimidex used, it will only stop conversion to a point?

    Thanks for everyone's help, this is a great board with great members to share ideas with.
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    Quote Originally Posted by Jupiter View Post
    Thanks for the reply plymouth city.

    A few questions for you or anyone else:

    1. what is primary and what is secondary (i should know and think i have an idea but want to be sure)?

    2. How does one know when hcg is maintaining function (testicle size)?

    3. Could someone expound on preventing leydig cell death (use it or lose it)?

    4. Is one to understand that regardless of the amount of arimidex used, it will only stop conversion to a point?

    Thanks for everyone's help, this is a great board with great members to share ideas with.
    A quick summary

    1. Primary - Nutts are broken. Secondary - Pituitary broken.

    2. Testicals return, or at least increase, in size. Some note increased seminal fluid, better orgasms.

    3. Leydig cells are cells within the testes. Without a proper LH- FSH signal, leydig cells do not respond. If shutdown for long enough, they die. This is common in people on T with no hcG.

    4. Yes. Arimidex is self limiting. Regardless of dosage. Which is why even on a whopping 2mg your only getting so much AI action. At this point, something stronger and Dr monitored needs to be added, like very very small dose femura, etc.
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    Thanks plymouth city for the help.
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    Quote Originally Posted by plymouth city View Post
    A quick summary

    1. Primary - Nutts are broken. Secondary - Pituitary broken.

    2. Testicals return, or at least increase, in size. Some note increased seminal fluid, better orgasms.

    3. Leydig cells are cells within the testes. Without a proper LH- FSH signal, leydig cells do not respond. If shutdown for long enough, they die. This is common in people on T with no hcG.

    4. Yes. Arimidex is self limiting. Regardless of dosage. Which is why even on a whopping 2mg your only getting so much AI action. At this point, something stronger and Dr monitored needs to be added, like very very small dose femura, etc.

    This is important information.

    Supporting research would help.

    I suspect people like Phil and HAN may have different personal experience.

    When increasing Arimidex dose may be wise to
    account for half-life
    and
    do blood tests.
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    Thanks for your input Dr John.

    Do you feel the following link has any relevance in this discussion?

    Down and Up regulation of Leydig cells - Anabolic Steroids and Bodybuilding
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    Quote Originally Posted by Dr. John View Post
    2mg per week is not a "whopping" dose. I have seen men on TRT require a mg per day. You can drive E low enough to be unhealthy with Arimidex--therefore it is not "self-limiting".

    At this time, I do not favor the use of suicide inhibitors. Their endocrine pathway disruption is too harsh.
    Dr John, with what the price of arimidex is now, I call 2mg a whopping dose What is it now, 8 bucks a 1mg pill? And people have to take one a day?

    What I mean by arimidex being "self limiting" is taken the wrong way I wanted to express it. I mean that it only works to a point in some individuals, given a standard 1-2mg per week dose. Doubling 1mg to 2 mg will only work so much. At 8 bucks a pop, shouldn't we work to try something stronger before we start getting out of control price wise?

    I remember my original Dr telling me that given my E level, and adding on 100mg of T per week + hcG, that arimidex, cost wise, wouldn't be worth it. I didn't understand that then. I do now.
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    How can you put a price on your health?

    Arimidex is a cancer medication with no competition(arimidex has taken over nolva afaik) they could charge $50 a pill if they want. Give it afew years and a much cheaper generic brand will be out.
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    You wouldn't necessarily just correlate by weight when comparing human to rat dosing. You have to consider the ~6x greater metabolism. A human dose conversion from a rat would be approximately 1/6th the rat dose.
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    Quote Originally Posted by ItsHectic View Post
    How can you put a price on your health?

    .
    You do know that, I would say at least, 25% of guys on TRT are getting their adex online threw research labs because they cannot afford a script for adex right?

    I bet that number would be closer to 90% if the rest knew they could do so
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    Exactly plymouth city.

    Amazing how much the pharmaceutical companies can charge when the raw powders are a fraction of the price.

    Did anyone see 60 minutes last Sunday?
  

  
 

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