0021-972X/88/6605-1019$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1988 by The Endocrine Society Vol. 66, No. 5 Printed in U.S.A. Effect of Massive Weight Loss on Hypothalamic Pituitary-Gonadal Function in Obese Men* GLADYS W. STRAIN, BARNETT ZUMOFF, LORRAINE K. MILLER, WILLIAM ROSNER, CHARLES LEVIT, MARCIA KALIN, RICHARD J. HERSHCOPF, AND ROBERT S. ROSENFELD Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Medical Center, New York, New York 10003; and the Mount Sinai School of Medicine of the City of New York, Rockefeller University, and the Division of Endocrinology, Department of Medicine, St. Luke's-Roosevelt Medical Center, New York, New York 10032 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 (E 2 ), 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 E 2 [54 ± 26 (196 ± 94) to 50 ± 13 pg/mL (180 ± 50 pmol/L)], free E 2 [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 hormone- binding 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 hypothalamic- pituitary function with weight loss, such that GnRH-gonadotro- pin secretion becomes less sensitive to suppression by a given amount of estrogen. (J Clin Endocrinol Metab 66: 1019, 1988) W E HAVE described a syndrome of hyperestroge- nemia-induced hypogonadotropic hypogonadism (HHG) in obese men (1). The HHG can be normalized by giving drugs that reduce plasma estrogen levels (2), which suggests that the hormonal abnormalities are a consequence of the obesity rather than a condition that antedates the obesity. Definitive support for this conclu- sion would be provided by demonstrating that massive weight loss reversed the hormonal abnormalities in obese men. Stanik et al. (3) studied the hormonal changes in modestly obese men who reduced their weight to normal levels; they found that the hyperestrogenemia was indeed normalized and that the serum testosterone concentra- tion rose substantially, but they did not measure gonad- otropin levels. In this report, we describe the hormonal changes occurring in 11 markedly obese men who achieved massive weight loss but remained very obese. The men had a pronounced rise in plasma testosterone Received June 8,1987. Address requests for reprints to: Dr. Gladys W. Strain, Department of Medicine, Beth Israel Medical Center, New York, New York 10003. * This work was supported in part by Grants AM-30978 and DK- 28562 from the NIH. (T) and FSH levels, but, in contrast to the findings of Stanik et al. (3), no change in plasma estrogen levels. Materials and Methods Subjects Eleven healthy, markedly obese men, aged 20-50 yr [mean, 34 ± 11 (±SD) yr] and ranging from 100-305% above desirable (ideal) body weight (mean, 167 ± 74%), were studied with respect to their 24-h mean plasma estrone (E0, free and total estradiol (E 2 ), LH, FSH, sex hormone-binding globulin (SHBG), and free and total T concentrations before and 17 ± 17 months after massive weight loss (53 ± 36 kg; range, 26- 130) produced by caloric restriction on individualized dietary protocols. At the time of the second study, their weights had been stable at the new lower level, i.e. weights did not vary ±2 kg over several weeks, but they were all still very obese (93 ± 32% above desirable body weight). One man was studied at intervals during a 130-kg weight loss. None of the men had any significant acute or chronic disease, including diabetes mellitus and hypertension, and none was taking any medication. As a control, 14 normal men, 8 ± 8% above desirable body weight and aged 35 ± 12 yr, were studied with respect to the above- listed hormones. Informed consent was obtained from all men. 1019 The Endocrine Society. Downloaded from press.endocrine.org by [William Rosner] on 27 December 2013. at 08:22 For personal use only. No other uses without permission. . All rights reserved.