Dr. Ron’s Research Review – October 9, 2013

© 2013

This week’s research review focuses on hCG.

Does hCG increase estradiol levels in men?

Yes.

hCG causes a general increase in steroid hormone production. In men, the hCG stimulation test with assessment of serum testosterone is used for evaluation of testicular function. The increase in serum estradiol levels 24 hours after a single hCG injection may also be useful as a measure of Leydig cell function. (Meier, Christ-Crain et al. 2005)

A study published in The Journal of Clinical Endocrinology and Metabolism showed that very low-dose hCG (0, 15, 60, or 125 IU sc every other day) in normal men with experimental gonadotropin deficiency caused a dose-dependent increase in intratesticular testosterone. (Roth, Page et al. 2010)

An article published in the Journal of Urology described the co-administration of low-dose hCG (500 IU IM every other day) with testosterone replacement therapy in men to preserve spermatogenesis. (Hsieh, Pastuszak et al. 2013)

Dr. Ron


Articles

Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy

            (Hsieh, Pastuszak et al. 2013) Download

PURPOSE: Testosterone replacement therapy results in decreased serum gonadotropins and intratesticular testosterone, and impairs spermatogenesis, leading to azoospermia 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. 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.

Serum estradiol after single dose hCG administration correlates with Leydig cell reserve in hypogonadal men: reassessment of the hCG stimulation test

            (Meier, Christ-Crain et al. 2005) Download

The hCG stimulation test with assessment of serum testosterone (T) is used for evaluation of testicular function. This retrospective study was undertaken to estimate the diagnostic value of stimulated estradiol (E2) levels in the assessment of Leydig cell function. Serum T and E2 before and after repeated daily hCG injections in 23 adult men with clinically suspected or established primary hypogonadism were studied. After hCG administration serum T increased gradually with peak levels after 72 hours (delta84%, p=0.003). In contrast, serum E2 concentrations reached their maximal levels 24 hours after the first injection (delta168%, p=0.001). Serum T and E2 responses were more attenuated in men with LH > or =17 IU/L as compared to men with lower LH levels. Peak E2 levels after 24 hours correlated significantly with peak T levels after 3 days. We conclude that the increase in serum E2 levels 24 hours after a single hCG injection is an useful additional measure of Leydig cell function. Assessment of E2 increments would render the test procedure more practical, less time-consuming and more cost-effective than assessing peak T levels after 72 hours.

Dose-dependent increase in intratesticular testosterone by very low-dose human chorionic gonadotropin in normal men with experimental gonadotropin deficiency

            (Roth, Page et al. 2010) Download

CONTEXT AND OBJECTIVE: In men with infertility secondary to gonadotropin deficiency, treatment with relatively high dosages of human chorionic gonadotropin (hCG) stimulates intratesticular testosterone (IT-T) biosynthesis and spermatogenesis. Previously we found that lower dosages of hCG stimulated IT-T to normal. However, the minimal dose of hCG needed to stimulate IT-T and the dose-response relationship between very low doses of hCG and IT-T and serum testosterone in normal men is unknown. DESIGN, SETTING, PATIENTS, AND INTERVENTION: We induced experimental gonadotropin deficiency in 37 normal men with the GnRH antagonist acyline and randomized them to receive one of four low doses of hCG: 0, 15, 60, or 125 IU sc every other day or 7.5 g daily testosterone gel for 10 d. Testicular fluid was obtained by percutaneous aspiration for steroid measurements at baseline and after 10 d of treatment and correlated with contemporaneous serum hormone measurements. RESULTS: Median (25th, 75th percentile) baseline IT-T was 2508 nmol/liter (1753, 3502 nmol/liter). IT-T concentrations increased in a dose-dependent manner with very low-dosage hCG administration from 77 nmol/liter (40, 122 nmol/liter) to 923 nmol/liter (894, 1017 nmol/liter) in the 0- and 125-IU groups, respectively (P<0.001). Moreover, serum hCG was significantly correlated with both IT-T and serum testosterone (P<0.01). CONCLUSION: Doses of hCG far lower than those used clinically increase IT-T concentrations in a dose-dependent manner in normal men with experimental gonadotropin deficiency. Assessment of IT-T provides a valuable tool to investigate the hormonal regulation of spermatogenesis in man.


References

Hsieh, T. C., A. W. Pastuszak, et al. (2013). "Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy." J Urol 189(2): 647-50. [PMID: 23260550]

Meier, C., M. Christ-Crain, et al. (2005). "Serum estradiol after single dose hCG administration correlates with Leydig cell reserve in hypogonadal men: reassessment of the hCG stimulation test." Clin Lab 51(9-10): 509-15. [PMID: 16285473]

Roth, M. Y., S. T. Page, et al. (2010). "Dose-dependent increase in intratesticular testosterone by very low-dose human chorionic gonadotropin in normal men with experimental gonadotropin deficiency." J Clin Endocrinol Metab 95(8): 3806-13. [PMID: 20484472]