Journal of Clinical Endocrinology & Metabolism, Vol 78, 549-554, Copyright © 1994 by Endocrine Society

ARTICLES

Effects of a reduction in circulating insulin by metformin on serum dehydroepiandrosterone sulfate in nondiabetic men

JE Nestler, NA Beer, DJ Jakubowicz and RM Beer
Department of Internal Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.

Evidence suggests that hyperinsulinemic insulin resistance may reduce serum levels of the adrenal steroid dehydroepiandrosterone (DHEA) sulfate in humans. This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administration of the biguanide metformin. A total of 28 nondiabetic men were studied. The study group consisted of 16 obese and hypertensive men, and the control group of 12 nonobese and normotensive men. The men were studied at baseline and after the oral administration of 500 mg metformin, 3 times daily, for 21 days. Metformin administration resulted in significant reductions in serum insulin levels and concurrent increases in serum DHEA sulfate levels in both groups of men. The mean fasting serum DHEA sulfate concentration rose by 48% in the obese hypertensive men (from 5.9 +/- 0.8 to 8.7 +/- 0.7 mumol/L; P < 0.02) and by 80% in the nonobese normotensive men (from 3.5 +/- 0.5 to 6.3 +/- 0.9 mumol/L; P < 0.05). When the results from both groups were combined, changes in serum DHEA sulfate levels (i.e. day 21 value minus day 0 value) correlated positively with baseline fasting serum insulin levels (r = 0.44; P = 0.02; n = 28). Moreover, changes in fasting serum DHEA sulfate levels correlated inversely with changes in fasting serum insulin levels (r = -0.38; P < 0.05; n = 28). These findings lend further credence to the idea that insulin acts as a physiological regulator of DHEA sulfate metabolism and lowers circulating DHEA sulfate concentrations in men.

This article has been cited by other articles:

				J.-P. Baillargeon, J. E. Nestler, R. E. Ostlund, T. Apridonidze, and E. Diamanti-Kandarakis Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism Hum. Reprod., June 1, 2008; 23(6): 1439 - 1446. [Abstract] [Full Text] [PDF]

				R.-R. Wu, J.-P. Zhao, X.-F. Guo, Y.-Q. He, M.-S. Fang, W.-B. Guo, J.-D. Chen, and L.-H. Li Metformin Addition Attenuates Olanzapine-Induced Weight Gain in Drug-Naive First-Episode Schizophrenia Patients: A Double-Blind, Placebo-Controlled Study Am J Psychiatry, March 1, 2008; 165(3): 352 - 358. [Abstract] [Full Text] [PDF]

				J.-P. Baillargeon, E. Diamanti-Kandarakis, R. E. Ostlund Jr, T. Apridonidze, M. J. Iuorno, and J. E. Nestler Altered D-Chiro-Inositol Urinary Clearance in Women With Polycystic Ovary Syndrome Diabetes Care, February 1, 2006; 29(2): 300 - 305. [Abstract] [Full Text] [PDF]

				J.-P. Baillargeon, M. J. Iuorno, D. J. Jakubowicz, T. Apridonidze, N. He, and J. E. Nestler Metformin Therapy Increases Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator in Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 242 - 249. [Abstract] [Full Text] [PDF]

				G. Guercio, M. A. Rivarola, E. Chaler, M. Maceiras, and A. Belgorosky Relationship between the GH/IGF-I Axis, Insulin Sensitivity, and Adrenal Androgens in Normal Prepubertal and Pubertal Boys J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1162 - 1169. [Abstract] [Full Text] [PDF]

				J. E. Nestler, D. J. Jakubowicz, W. S. Evans, and R. Pasquali Effects of Metformin on Spontaneous and Clomiphene-Induced Ovulation in the Polycystic Ovary Syndrome N. Engl. J. Med., June 25, 1998; 338(26): 1876 - 1880. [Abstract] [Full Text] [PDF]

				L. Ibanez, N. Potau, M. Zampolli, S. RiquE, P. Saenger, and A. Carrascosa Hyperinsulinemia and Decreased Insulin-Like Growth Factor-Binding Protein-1 Are Common Features in Prepubertal and Pubertal Girls with a History of Premature Pubarche J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2283 - 2288. [Abstract] [Full Text] [PDF]

				J. E. Nestler and D. J. Jakubowicz Decreases in Ovarian Cytochrome P450c17{alpha} Activity and Serum Free Testosterone after Reduction of Insulin Secretion in Polycystic Ovary Syndrome N. Engl. J. Med., August 29, 1996; 335(9): 617 - 623. [Abstract] [Full Text] [PDF]