Effect of Massive Weight Loss on Hypothalamic Pituitary-Gonadal Function in Obese Men*

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Abstract
To study the ability of weight loss to reverse the hyperestrogenemia-induced hypogonadotropic hypogonadism that occurs in obese men, we measured the 24-h mean plasma free and total estradiol (E2), total estrone, FSH, LH, and free and total testosterone concentrations in 11 healthy obese men (100–305% above desirable body weight) and again 5–39 months later after weight loss of 26–129 kg and restabilization at the new weight. Weight loss produced significant increases in mean plasma total testosterone [240 ±116 (±sd, 8.5 ± 4.0) to 377 ± 113 ng/dL (13.0 ± 4.0 nmol/L); P < 0.01], free testosterone [9.5 ± 5.0 (329 ± 173) to 13.4 ± 4.3 ng/dL (464 ± 149 pmol/L); P < 0.025], and FSH (6.5 ± 4.7 to 10.9 ± 8.5 IU/L; P < 0.025). Plasma LH was lower than levels in normal men before and after weight loss and did not change significantly (10.3 ± 4.8 and 10.8 ± 6.8 IU/L, respectively). There was no change in plasma total E2 [54 ± 26 (196 ± 94) to 50 ± 13 pg/mL (180 ± 50 pmol/L)], free E2 [1.48 ± 0.7 (5.37 ± 2.54) to 1.33 ± 0.42 pg/mL (4.83 ± 1.45 pmol/L)], or total estrone [75 ± 38 (280 ± 140) to 82 ± 24 (300 ± 90) pmol/L], and sex hormone-binding globulin rose from 9.2 ± 3.2 to 12.9 ± 5.4 nmol/L (P < 0.005). The increases in plasma free and total testosterone and sex hormonebinding globulin were proportional to the degree of weight loss. Thus, the hypogonadotropic hypogonadism was largely reversed by the weight loss without any decrease in hyperestrogenemia, its presumed cause. We postulate a change in hypothalamicpituitary function with weight loss, such that GnRH-gonadotropin secretion becomes less sensitive to suppression by a given amount of estrogen.

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