This recent study is a follow up of their published work, "Coviello AD, Matsumoto AM, Bremner WJ, et al. Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression. J Clin Endocrinol Metab 2005;90(5):2595-602." There is a discussion of this paper, including abstract, found here: https://thinksteroids.com/community/threads/134284785
I have to applaud the authors for the follow up study. I have not had the time to read the new study, but it incorporates an improved study design that I stated was a reason why the prior study was poor! In the prior study, the treatment group used was TE administration as the method to induce a decreased LH (i.e., hypogonadism). I stated a much better model would be the use of a GnRH agonist/antagonist. The new study makes use of the GnRH antagonist acyline.
From the study Introduction: We previously used this technique to examine the dose-response relationship between hCG as a proxy for LH and IT-T in normal men. However, although the doses of hCG in our previous work were lower than those used to treat patients with hypogonadotropic hypogonadism, IT-T concentrations were similar to those in untreated normal men. In addition, our previous work relied on exogenous testosterone to suppress the hypothalamic-pituitary- gonadal axis, and there was concern that the exogenous testosterone could potentially increase IT-T concentrations.
Therefore, in this study, we experimentally induced low levels of IT-T in normal men using the GnRH antagonist, acyline, and subsequently stimulated testicular testosterone biosynthesis with very low doses of hCG, lower than we used previously. In addition, we included a group of men treated with exogenous testosterone to determine whether treatment with testosterone would affect intratesticular steroid concentrations. In this way, we sought to ascertain the dose response relationship between very low doses of LH-like stimulation and IT-T in man.
Roth MY, Page ST, Lin K, et al. Dose-Dependent Increase in Intratesticular Testosterone by Very Low-Dose Human Chorionic Gonadotropin in Normal Men with Experimental Gonadotropin Deficiency. J Clin Endocrinol Metab:jc.2010-0360.
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.
I have to applaud the authors for the follow up study. I have not had the time to read the new study, but it incorporates an improved study design that I stated was a reason why the prior study was poor! In the prior study, the treatment group used was TE administration as the method to induce a decreased LH (i.e., hypogonadism). I stated a much better model would be the use of a GnRH agonist/antagonist. The new study makes use of the GnRH antagonist acyline.
From the study Introduction: We previously used this technique to examine the dose-response relationship between hCG as a proxy for LH and IT-T in normal men. However, although the doses of hCG in our previous work were lower than those used to treat patients with hypogonadotropic hypogonadism, IT-T concentrations were similar to those in untreated normal men. In addition, our previous work relied on exogenous testosterone to suppress the hypothalamic-pituitary- gonadal axis, and there was concern that the exogenous testosterone could potentially increase IT-T concentrations.
Therefore, in this study, we experimentally induced low levels of IT-T in normal men using the GnRH antagonist, acyline, and subsequently stimulated testicular testosterone biosynthesis with very low doses of hCG, lower than we used previously. In addition, we included a group of men treated with exogenous testosterone to determine whether treatment with testosterone would affect intratesticular steroid concentrations. In this way, we sought to ascertain the dose response relationship between very low doses of LH-like stimulation and IT-T in man.
Roth MY, Page ST, Lin K, et al. Dose-Dependent Increase in Intratesticular Testosterone by Very Low-Dose Human Chorionic Gonadotropin in Normal Men with Experimental Gonadotropin Deficiency. J Clin Endocrinol Metab:jc.2010-0360.
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.
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