Journal of Andrology Testis Workshop 2009
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Published-Ahead-of-Print December 3, 2009
Journal of Andrology 2009, DOI:10.2164/jandrol.109.009035

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LH, Non-SHBG Testosterone and Estradiol Levels during Testosterone Replacement of Hypogonadal Men: Further Evidence that Steroid Negative Feedback Increases as Men Grow Older

Stephen J. Winters * and Chenxi Wang

* To whom correspondence should be addressed. E-mail: sjwint01{at}louisville.edu.

Previous evidence suggests that the testicular negative feedback control of GnRH-LH secretion may change as men age, and may thereby contribute to the hypogonadism that occurs as men grow older. To pursue this idea, we analyzed the results for 35 men with primary hypogonadism who were participants in an open-label multicenter study of testosterone replacement. LH, SHBG and total and free T and E concentrations were measured in blood samples at baseline and after 2% testosterone gel was applied daily for 2 wks. A 24h pharmacokinetic profile for T and E was obtained at the end of week 2. Age was a strong predictor of LH suppression during testosterone replacement (r = -0.46), and the effect could not be explained by obesity, SHBG or higher levels of total or non-SHBG testosterone or estradiol during treatment. In fact, both LH and non-SHBG testosterone levels were lower (p<0.05) in older men receiving testosterone treatment. In addition, the strongest association overall was between the percent decline in LH and non-SHBG estradiol concentrations (r = -0.39). These data provide further evidence that suppression of LH secretion during testosterone treatment is greater as men age, and are consistent with the hypothesis that the hypogonadism of aging men is partly due to a change in gonadotropin negative feedback regulation. These results further suggest that estrogen receptor signaling might contribute to this effect.


Key words: Androgen • Andropause • estradiol • luteinizing hormone • sex hormone binding globulin






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