Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome

Authors

  • Matthew S. Wosnitzer,

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    • 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.

  • Darius A. Paduch

    Corresponding author
    • Department of Urology, Weill Cornell Medical College, 525 East 68th Street, Starr 900, New York, NY 10065.
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    • Darius A. Paduch, M.D., Ph.D. is Associate Professor of Urology and Reproductive Medicine at Weill Cornell Medical College in New York, NY. He is an internationally recognized expert in genetics and reproductive endocrinology of male infertility and hypogonadism, Klinefelter syndrome, sexual medicine, and virology of genital tract.


  • 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.

Abstract

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.

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