Investigating the Regulation of Reproductive Hormones in Adult Men

Summary

The purpose of the research study is to learn more about the regulation of reproductive hormones in adult men. We would like to understand what role testosterone and estradiol play in controlling the release of LH (lutenizing hormone) and FSH (follicle stimulating hormone). Testosterone and estradiol come from the testes, and LH and FSH are released from a gland in the head called the pituitary. Men involved in the study will have detailed evaluations that involve overnight stays in the hospital and frequent blood sampling. The men in the study will also be receiving medications that affect the levels of various hormones in the body. This will allow the researchers to learn how various hormones influence each other. Men that participate in the study will receive medical evaluations and monetary compensation. Information gathered from this study will help in the development of new treatments for infertility and potentially new hormonal forms of contraception.

Timeline

Start

1995-07

Primary completion

2007-02

Completion

2007-02

Publications

• Background Howards SS. Treatment of male infertility. N Engl J Med. 1995 Feb 2;332(5):312-7. doi: 10.1056/NEJM199502023320507. No abstract available.
• Background Ying SY. Inhibins, activins, and follistatins: gonadal proteins modulating the secretion of follicle-stimulating hormone. Endocr Rev. 1988 May;9(2):267-93. doi: 10.1210/edrv-9-2-267.
• Background Khoury RH, Wang QF, Crowley WF Jr, Hall JE, Schneyer AL, Toth T, Midgley AR Jr, Sluss PM. Serum follistatin levels in women: evidence against an endocrine function of ovarian follistatin. J Clin Endocrinol Metab. 1995 Apr;80(4):1361-8. doi: 10.1210/jcem.80.4.7714112.
• Background Hayes FJ, Hall JE, Boepple PA, Crowley WF Jr. Clinical review 96: Differential control of gonadotropin secretion in the human: endocrine role of inhibin. J Clin Endocrinol Metab. 1998 Jun;83(6):1835-41. doi: 10.1210/jcem.83.6.4884.
• Background Santen RJ. Is aromatization of testosterone to estradiol required for inhibition of luteinizing hormone secretion in men? J Clin Invest. 1975 Dec;56(6):1555-63. doi: 10.1172/JCI108237.
• Background Winters SJ, Janick JJ, Loriaux DL, Sherins RJ. Studies on the role of sex steroids in the feedback control of gonadotropin concentrations in men. II. Use of the estrogen antagonist, clomiphene citrate. J Clin Endocrinol Metab. 1979 Feb;48(2):222-7. doi: 10.1210/jcem-48-2-222. No abstract available.
• Background Matsumoto AM, Bremner WJ. Modulation of pulsatile gonadotropin secretion by testosterone in man. J Clin Endocrinol Metab. 1984 Apr;58(4):609-14. doi: 10.1210/jcem-58-4-609.
• Background Finkelstein JS, Whitcomb RW, O'Dea LS, Longcope C, Schoenfeld DA, Crowley WF Jr. Sex steroid control of gonadotropin secretion in the human male. I. Effects of testosterone administration in normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab. 1991 Sep;73(3):609-20. doi: 10.1210/jcem-73-3-609.
• Background Finkelstein JS, O'Dea LS, Whitcomb RW, Crowley WF Jr. Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab. 1991 Sep;73(3):621-8. doi: 10.1210/jcem-73-3-621.
• Background Bagatell CJ, Dahl KD, Bremner WJ. The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl. 1994 Jan-Feb;15(1):15-21.
• Background Groome NP, Illingworth PJ, O'Brien M, Pai R, Rodger FE, Mather JP, McNeilly AS. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996 Apr;81(4):1401-5. doi: 10.1210/jcem.81.4.8636341.
• Background Majumdar SS, Mikuma N, Ishwad PC, Winters SJ, Attardi BJ, Perera AD, Plant TM. Replacement with recombinant human inhibin immediately after orchidectomy in the hypophysiotropically clamped male rhesus monkey (Macaca mulatta) maintains follicle-stimulating hormone (FSH) secretion and FSH beta messenger ribonucleic acid levels at precastration values. Endocrinology. 1995 May;136(5):1969-77. doi: 10.1210/endo.136.5.7720645.
• Background Culler MD, Negro-Vilar A. Passive immunoneutralization of endogenous inhibin: sex-related differences in the role of inhibin during development. Mol Cell Endocrinol. 1988 Aug;58(2-3):263-73. doi: 10.1016/0303-7207(88)90163-3.
• Background Veldhuis JD, Johnson ML. Cluster analysis: a simple, versatile, and robust algorithm for endocrine pulse detection. Am J Physiol. 1986 Apr;250(4 Pt 1):E486-93. doi: 10.1152/ajpendo.1986.250.4.E486.
• Background Heel RC, Brogden RN, Carmine A, Morley PA, Speight TM, Avery GS. Ketoconazole: a review of its therapeutic efficacy in superficial and systemic fungal infections. Drugs. 1982 Jan-Feb;23(1-2):1-36. doi: 10.2165/00003495-198223010-00001. No abstract available.
• Background Pont A, Graybill JR, Craven PC, Galgiani JN, Dismukes WE, Reitz RE, Stevens DA. High-dose ketoconazole therapy and adrenal and testicular function in humans. Arch Intern Med. 1984 Nov;144(11):2150-3.
• Background Sonino N. The use of ketoconazole as an inhibitor of steroid production. N Engl J Med. 1987 Sep 24;317(13):812-8. doi: 10.1056/NEJM198709243171307. No abstract available.
• Background Van Tyle JH. Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use. Pharmacotherapy. 1984 Nov-Dec;4(6):343-73. doi: 10.1002/j.1875-9114.1984.tb03398.x.
• Background Lewis JH, Zimmerman HJ, Benson GD, Ishak KG. Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. Gastroenterology. 1984 Mar;86(3):503-13.
• Background Duarte PA, Chow CC, Simmons F, Ruskin J. Fatal hepatitis associated with ketoconazole therapy. Arch Intern Med. 1984 May;144(5):1069-70.
• Background van Dijke CP, Veerman FR, Haverkamp HC. Anaphylactic reactions to ketoconazole. Br Med J (Clin Res Ed). 1983 Dec 3;287(6406):1673. doi: 10.1136/bmj.287.6406.1673. No abstract available.
• Background Janssen PA, Symoens JE. Hepatic reactions during ketoconazole treatment. Am J Med. 1983 Jan 24;74(1B):80-5. doi: 10.1016/0002-9343(83)90519-3.
• Results Pitteloud N, Dwyer AA, DeCruz S, Lee H, Boepple PA, Crowley WF Jr, Hayes FJ. Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab. 2008 Mar;93(3):784-91. doi: 10.1210/jc.2007-2156. Epub 2007 Dec 11.
• Results Boepple PA, Hayes FJ, Dwyer AA, Raivio T, Lee H, Crowley WF Jr, Pitteloud N. Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function. J Clin Endocrinol Metab. 2008 May;93(5):1809-14. doi: 10.1210/jc.2007-2450. Epub 2008 Feb 12.
• Results Pitteloud N, Dwyer AA, DeCruz S, Lee H, Boepple PA, Crowley WF Jr, Hayes FJ. The relative role of gonadal sex steroids and gonadotropin-releasing hormone pulse frequency in the regulation of follicle-stimulating hormone secretion in men. J Clin Endocrinol Metab. 2008 Jul;93(7):2686-92. doi: 10.1210/jc.2007-2548. Epub 2008 Apr 29.

Drugs

Indications