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Feedback Inhibition of Gonadotropins by Testosterone in Men With Hypogonadotropic Hypogonadism: Comparison to the Intact Pituitary-Testicular Axis in Primary Hypogonadism

ILAN SHIMON^*,

ALEXANDRA LUBINA^,

MALKA GORFINE

JACOB ILANY^,

From the ^* Institute of Endocrinology and Metabolism, Rabin Medical Center, Beilinson Campus, Petach Tikva; the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; the Institute of Endocrinology, Sheba Medical Center, Tel Hashomer; and the Department of Mathematics, Bar-Ilan University, Ramat Gan, Israel.

Correspondence to: Dr Ilan Shimon, Institute of Endocrinology and Metabolism, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel (e-mail: ilanshi{at}clalit.org.il).

Men with hypogonadotropic hypogonadism (HH) due to hypothalamic-pituitary disease present with low serum testosterone levels combined with undetectable, low, or normal gonadotropin levels. Treatment consists of testosterone replacement to reverse the symptoms of androgen deficiency. The aim of this study was to examine the dynamics and feedback inhibition of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in relation to testosterone in 38 men with HH treated with testosterone. Findings were compared with 11 men with primary hypergonadism (PH). Testosterone replacement led to a suppression of FSH levels from 2.8 IU/L at baseline to 1.1 IU/L and to a suppression of LH levels from 2.3 to 0.8 IU/L. There was a linear correlation between levels of FSH and LH (after natural log transformation for both) and testosterone levels in both the HH and PH groups. However, the differences in intercepts and slopes between the groups were significant. To determine whether nonsuppressed FSH or LH during testosterone replacement reduces the probability of eugonadism, as reflected by normal testosterone levels, gonadotropin levels were measured and categorized as low (<0.5 IU/L), medium (0.5-2 IU/L), and high levels (>2 IU/L). The higher FSH or LH levels were found to significantly decrease the chance for achieving eugonadism. In conclusion, in men with HH due to hypothalamic-pituitary disease or injury, the pituitary-testicular hormonal axis maintains its physiological negative feedback between testosterone and gonadotropins. Thus, gonadotropin levels in men with HH might be useful, together with testosterone concentrations, for assessing the adequacy of androgen replacement.

     Key words: FSH, LH, androgen replacement