Safety of hCG for Men with Hypogonadal Symptoms and Testosterone >300 ng/dL

[madman]

Safety of Human Chorionic Gonadotropin Monotherapy for Men with Hypogonadal Symptoms and Testosterone >300 ng/dL (2022)
QRainer, RPai, TMasterson


Introduction

Human chorionic gonadotropin (hCG) is homologous to luteinizing hormone (LH) and is known to stimulate endogenous testosterone (T) production and may be an option for testosterone replacement therapy (TRT). Current guidelines recommend TRT for men with two T levels <300 ng/dl and symptoms of low T. A challenging patient population are men with symptoms of low T who do not meet biochemical criteria for TRT as there are no current treatments recommendations. We hypothesize that hCG may be a safe and effective therapy for men with hypogonadal symptoms and T >300ng/dl.


Objective

Our objective was to evaluate for symptom improvement and side effects of hCG monotherapy in men with hypogonadal symptoms and T >300 ng/dL.


Methods

We retrospectively reviewed the charts of 31 men treated with hCG monotherapy for hypogonadal symptoms with a T average (latest two lab results) >300 ng/dL who had follow-up labs at least 1 month after initiation of hCG therapy. We evaluated changes in hormones [T, LH, follicle-stimulating hormone (FSH), and estradiol], hematocrit (HCT), glycated hemoglobin (A1c), and prostate-specific antigen (PSA). Results are presented as means standard deviation. Student t-test was used to compare pre-and post-treatment values, significance was set at p=0.05. We also evaluated the incidence of thromboembolic events, including stroke, deep vein thrombosis, and myocardial infarction.


Results

The average age of patients was 49.0±15.8 years with a BMI of 28.6±4.8 kg/m2. Average follow-up after starting hCG therapy was 292 days, range 77 to 857 days. The average weekly hCG dosage was 1500 IU. Serum T increased from 431.27±117.22 ng/dL to 461.05 ±185.19 ng/dL (p=0.61, n=31). No change was seen in FSH (6.79±10.85 to 7.12±12.07 mIU/mL, n=8), PSA (1.55±1.44 to 1.90±1.81 ng/mL, n=10), HCT (43.43±2.27 to 44.48±2.86 %, n=12), estradiol (27.44±6.92 to 30.63±10.25 pg/mL, n=8), or A1c (6.15±0.95 to 6.33±0.93 %,n=4). A statistically significant decrease was seen in LH (4.93±1.98 to 3.66±1.85 mIU/mL,n=11). When evaluated for improvement of erectile dysfunction (ED, n=22), low libido (n=25), and low energy (n=19), 86%, 80%, and 79% of patients reported improvement of each symptom, respectively. All patients with ED were noted to be on another medication or therapy specifically for ED. No thromboembolic events were observed.


Conclusions

Weekly hCG dosing appears to safely improve hypogonadal symptoms even with baseline T levels >300 ng/dL. No changes were noted in HCT, PSA, A1c and no thromboembolic events were recorded.

 

[Nelson Vergel]

Umm. This shows to me (which I knew already) that 1500 IU per week of hCG does not work. FSH and LH should have decreased a lot more. These men were undertreated.

Total T only went up slightly.

A dose of 1000 IU three times per week of hCG is the minimum dose to use as monotherapy. And many men need 1500 IU injections instead of 1000 IU.

I am glad the men had improvements in libido even with suboptimal dosing.

These doctors work at University of Miami Miller School of Medicine. I wonder what Dr Ramasamy thinks of this.

 

[madman]

Pros and cons of using TRT vs HCG for treatment low-t symptoms

Human chorionic gonadotropin treatment: a viable option for management of secondary hypogonadism and male infertility (2020) Julius Fink, Brad J. Schoenfeld, Anthony C. Hackney, Takahiro Maekawa & Shigeo Horie Abstract Introduction: Low testosterone and its symptoms is a condition affecting...

www.excelmale.com

5.2 Effects on serum testosterone

A weekly dosage of 4500IU spread over 3 weekly injections has shown to lead to normal testosterone levels in isolated HH men [27]. Another study showed that single injections of 400IU, 2000IU, and 4000IU of HCG led to significant serum testosterone concentrations in hypogonadal as well as eugonadal males without differences among the groups after administration [28]. In hypogonadal men, 400IU, 2000IU, and 4000IU of HCG increased testosterone from about 200 to 400 ng/dl. In eugonadal men, 400IU, 2000IU, and 4000IU of HCG led to an increase from about 450 to 700 ng/dl in testosterone [28]. Interestingly, higher doses of HCG did not lead to greater testosterone level increases [28]. Another study showed similar results, with no differences in serum testosterone after single injections of 1500, 3000, or 4500IU of HCG, with testosterone increasing 24 hours post-injection and peaking 3-4 days later [29]. Serum testosterone peaked 3 days after injection [28].

From the above information, it can be suggested that low dose HCG (~500IU) injected 3 times per week can restore healthy serum and intratesticular testosterone levels in HH patients. The higher dosages used in infertility treatment to trigger sperm production might not be necessary if the goal is to increase serum testosterone levels. That is, combined treatment with HCG followed by rFSH might also be potent in order to induce fertility [21].

Indeed, HCG dosages used in the treatment of infertility can range from 3,000 to 10,000 IU 2-3 times per week [30]. One study showed that 3-6 months (1000 IU 3 times/week or 2000IU 2 times/week) of HCG treatment in 100 males with hypogonadotropic hypogonadism leads to normal serum testosterone concentrations despite the fact that 81 patients remained azoospermic [31]. These data show that low dose HCG treatment is very effective in restoring normal serum testosterone levels, however, spermatogenesis might require higher dosages of HCG. The exact mechanism by which HCG affects sperm production besides testosterone increase is not completely understood yet and needs further investigation. We summarized studies involving HCG treatment on testosterone and/or fertility parameters in Table 1.




10. Conclusion

HCG therapy is an effective treatment for patients suffering from infertility, often restoring healthy sperm production. However, HCG also increases serum and intratesticular testosterone levels, making it a prime candidate to treat patients with secondary hypogonadism. Even though the cost and injection frequency might be slightly higher as compared to TRT, HCG alone or used with TRT might be the best option for patients who desire to have children in the future. Depending on the response to HCG alone, concomitant TRT might be necessary to bring serum testosterone levels to the desired levels. Responses of serum testosterone levels seem to be independent of the dose of HCG and to peak 3 days post-injection. Therefore, low doses of ~400 IU HCG injected every 3 days intramuscularly or subcutaneously might lead to a significant increase of serum and intratesticular testosterone with few daily fluctuations in levels. Indeed, high dosages commonly seen in the treatment of male infertility going as high as 5000 IU several times per week might be unnecessary if the goal is not to increase sperm production but rather to increase testosterone only. In summary, HCG might be a safe, affordable, and effective method to restore healthy testosterone levels in males suffering from secondary hypogonadism. Nonetheless, further clinical trials should be carried out to demonstrate and elucidate the benefits of HCG therapy.




11. Expert opinion


*The HPG axis seems responsive to HCG in a similar fashion as LH and self-regulates the testosterone production within the testes in an amount of independent manner. Doses of HCG as low as 400 IU seem to significantly increase serum testosterone levels and even with dosages, 10 times that amount (4000 IU), the serum testosterone elevations seem similar to that of a 400 IU dosage (i.e., remaining within the physiological range). Rather than sensing the amount of HCG and accordingly producing testosterone, even small amounts of HCG seem to maximize the response for testosterone production within the testes probably due to receptor sensitivity.

 

[Nelson Vergel]

From the above information, it can be suggested that low dose HCG (~500IU) injected 3 times per week can restore healthy serum and intratesticular testosterone levels in HH patients.

That is actually not true. That dose only works with background TRT therapy used in combination. The data we have on intratesticular T and 17-OH-progesterone:

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

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...

www.excelmale.com

 

[Wilson7]

Umm. This shows to me (which I knew already) that 1500 IU per week of hCG does not work. FSH and LH should have decreased a lot more. These men were undertreated.

Total T only went up slightly.

A dose of 1000 IU three times per week of hCG is the minimum dose to use as monotherapy. And many men need 1500 IU injections instead of 1000 IU.

I am glad the men had improvements in libido even with suboptimal dosing.

These doctors work at University of Miami Miller School of Medicine. I wonder what Dr Ramasamy thinks of this.

Nelson, also suggests effects of LH that go beyond just increasing T and why adding HCG to HRT is beneficial as it suppresses LH. Thoughts?

 

[Nelson Vergel]

Nelson, also suggests effects of LH that go beyond just increasing T and why adding HCG to HRT is beneficial as it suppresses LH. Thoughts?