Best HCG Dose for Men on TRT: Two Studies That Used HCG with Testosterone

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Nelson Vergel

Note:HCG mimics LH but it is not LH and it's not picked up by the LH blood test. In fact, it suppresses LH like endogeneous testosterone does. But the amazing thing that the study below found is that HCG can increase sperm production and quality even in the absence of LH AND FSH. Most researchers believed that without FSH there was no possible sperm production.

The second study shows that testosterone inside the testicles (instratesticular testosterone or ITT) has to reach a certain amount for Sertoli cells to "wake up" to produce sperm. TRT actually decreases testosterone inside the cells by an unknown mechanism. HCG doses under 300 IU along with TRT may not normalize intratesticular testosterone since 250 IU produced an ITT 7% below baseline. 500 IU produced ITT 25% above normal. The Baylor study below used the 500 IU dose.

Conclusion: Do not use anything below 500 IU if you want to normalize your ITT while on TRT. No studies have been done on twice per week injection frequency, but that dose may work to prevent testicular atrophy (anecdotally). Three times per week or more may be needed to preserve fertility while on TRT. However, 33% of men (mostly older and who have been on TRT the longest prior to introducing hCG) do not respond as well to TRT+hCG when it comes to sperm quantity and quality. Those men may be better off on hCG+FSH.

Testosterone+ HCG Preserves Healthy Sperm in Men on Testosterone Replacement Therapy (Injections and gels)

Tung-Chin Hsieh, Alexander W. Pastuszak, Kathleen Hwang and Larry I. Lipshultz*,†

From the Division of Urology, University of California-San Diego (TCH), San Diego, California, Scott Department of Urology, Baylor College of Medicine (AWP, LIL), Houston, Texas, and Department of Urology (KH), Brown University School of Medicine, Providence, Rhode Island

Purpose: Testosterone replacement therapy results in decreased serum gonadotropins (hormones produced by the pituitary gland- LH and FSH- that jump start testicular function) and intratesticular testosterone (inside the testicles), and impairs spermatogenesis (sperm production), leading to azoospermia (no viable sperm) in 40% of patients. However, intratesticular testosterone can be maintained during testosterone replacement therapy with co-administration of low dose human chorionic gonadotropin, which may support continued spermatogenesis in patients on testosterone replacement therapy.

Materials and Methods: We retrospectively reviewed the records of hypogonadal men treated with testosterone replacement therapy and concomitant low dose human chorionic gonadotropin(HCG). Testosterone replacement consisted of daily topical gel or weekly intramuscular injection with intramuscular human chorionic gonadotropin (500 IU) every other day. Serum and free testosterone,estradiol, semen parameters and pregnancy rates were evaluated before and during therapy.

Results: A total of 26 men with a mean age of 35.9 years were included in the study. Mean followup was 6.2 months. Of the men 19 were treated with injectable testosterone and 7 were treated with transdermal gel. Mean serum hormone levels before vs during treatment were testosterone 207.2 vs 1,055.5 ng/dl (p<0.0001), free testosterone 8.1 vs 20.4 pg/ml (p = 0.02) and estradiol 2.2 vs 3.7 pg/ml (p = 0.11). Pretreatment semen parameters were volume 2.9 ml, density 35.2 million per ml, motility 49.0% and forward progression 2.3. No differences in semen parameters were observed during greater than 1 year of followup. No impact on semen parameters was observed as a function of testosterone formulation. No patient became azoospermic during concomitant testosterone replacement and human chorionic gonadotropin therapy. Nine of 26 men contributed to pregnancy with the partner during followup.

Conclusions: Low dose human chorionic gonadotropin appears to maintain semen parameters in hypogonadal men on testosterone replacement therapy. Concurrent testosterone replacement and human chorionic gonadotropin use may preserve fertility in hypogonadal males who desire fertility preservation while on testosterone replacement therapy.


Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression


Coviello AD, et al. J Clin Endocrinol Metab. 2005.


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.


The Use of HCG to Prevent / Reverse Testicular Shrinkage and Preserve Fertility
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Nelson Vergel

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Nelson Vergel

To find out if sperm count is normalized in men using hCG plus TRT, several studies have found that 17OH-P blood level is correlated to intratesticular testosterone (ITT) required for the testicles to make sperm, so testing for this hormone could not only save time while optimizing HCG dose/frequency but also eliminate the need to perform testicular aspirations, a very difficult procedure to do. Sperm count does not stabilize until 6-8 weeks after starting hCG plus TRT, so knowing your 17OH-progesterone blood level can give you a quick way to determine if your hCG dose and frequency is adequate.

This test uses liquid chromatography/mass spectrometry (LC/MS) the most accurate method for hormone testing.

The use of testosterone replacement therapy (TRT) increases blood levels of testosterone but, surprisingly, it decreases the level of testosterone inside the testicles (Intratesticular testosterone or ITT). ITT is key for proper sperm production. This ITT decrease is due to the LH and FSH shut down that occurs with TRT. This shut down decreases ITT and sperm production in men on TRT. These two gonadotropins are required to maintain healthy levels of ITT and, thus, sperm production. Some men on TRT become infertile because of this issue. ITT levels are usually ten times higher than regular blood levels. Having high testosterone blood levels on TRT have no positive effect on ITT. Only increasing LH or FSH can increase ITT. That is where hCG comes in...

Several studies have found that using human chorionic gonadotropin (hCG) while on TRT can normalize ITT and sperm production in some men (older age and longer pre-exposure to testosterone predicted poorer response). However, the optimum dose and frequency of hCG vary in every man. Fortunately, there are several ways to determine if the dose/frequency of hCG while on TRT is effective: Performing a sperm count/quality test (which requires a 3 month wait period) and/or measuring an upstream hormone to testosterone called 17-hydroxyprogesterone (17OH-P) (which can be measured within 2 weeks of starting hCG). TRT decreases 17OH-P and other upstream hormones due to the shut down of LH. Since hCG mimics LH, using hCG plus TRT may normalize upstream hormones like 17OH-P.

Several studies have found that 17OH-P blood level is correlated to ITT, so testing for this hormone could save time in optimizing HCG dose while waiting for a required 3-month sperm test. The 17OH-P test can also eliminate the need to perform testicular aspirations to measure ITT, which is a very difficult procedure to do and which is reserved to research settings. A study found that a 17OH-P level greater than 6.5 nmol/L (or 215 ng/dL) was found to normalize ITT while using HCG doses of 500 IU every other day plus testosterone enanthate injections given at 200 mg/week. However, only testing sperm count/quality after 3 months of hCG initiation makes it possible to know for sure if HCG is effective in improving fertility in men. As men get older and as they are exposed to longer periods on TRT, their response to HCG may decrease. These men may need combination approaches using clomiphene and/or FSH (follicle stimulating hormone).


Amory et al. Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in gonadotropin suppressed normal men receiving various dosages of human chorionic gonadotropin. Fertility and Sterility. Vol. 89, No. 2, February 2008

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