Matthew S. Wosnitzer, M.D. is a Male Reproductive Medicine Fellow in the Department of Urology, Weill Cornell Medical College in New York, NY. His research work focuses on genetics and molecular biology of male infertility and the role of opioids and novel immunomodulators in iatrogenic hypogonadism.
Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome†
Article first published online: 18 JAN 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Medical and Neurodevelopmental Aspects of XXY and Related Multiple X Conditions
Volume 163, Issue 1, pages 16–26, 15 February 2013
How to Cite
Wosnitzer, M. S. and Paduch, D. A. (2013), Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome. Am. J. Med. Genet., 163: 16–26. doi: 10.1002/ajmg.c.31350
How to Cite this Article: Wosnitzer MS, Paduch DA. 2013. Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome. Am J Med Genet Part C Semin Med Genet 163C: 16–26.
- Issue published online: 28 JAN 2013
- Article first published online: 18 JAN 2013
- The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust
- Robert Dow Foundation
- Klinefelter syndrome;
- testosterone surge;
- testosterone replacement therapy;
- aromatase inhibitors;
- nonobstructive azoospermia;
- Leydig cells;
- Sertoli cells;
- germ cells
47, XXY or Klinefelter syndrome (KS), the most common chromosomal aberration in males, is characterized by either absolute or relative hypogonadism with frequent decline in serum testosterone (T) following the onset of puberty. Decreased T levels are the result of testicular dysfunction with decrease in size of Leydig cells, and loss of germs and Sertoli cells leading to tubular hyalinization. Increase in estradiol results from over-expression of aromatase CYP19. Deficient androgen production and observed varied response of end-organs to T leads to delayed progression of puberty with decreased facial/body hair, poor muscle development, osteoporosis, and gynecomastia. It is possible that hypogonadism and excessive estradiol production contribute to emotional and social immaturity, and specific learning disabilities in KS. Based on the authors' experience and literature review, early fertility preservation and hormonal supplementation may normalize pubertal development, prevent metabolic sequelae of hypogonadism, and have a positive effect on academic and social development. No randomized clinical trials are available studying the effects of T supplementation on reproductive or cognitive issues in KS. Aggressive T supplementation (topical gel) and selective use of aromatase inhibitors may be considered at the onset of puberty with careful follow-up and titration to reach age-specific high-normal physiologic serum values. The decision to institute hormonal therapy should be part of a multidisciplinary approach including physical, speech, behavioral, and occupational therapy. © 2013 Wiley Periodicals, Inc.