To the Editor:
The authors thank Dr. Oates for his insightful comments (1) on our article, “Successful testicular sperm retrieval in adolescents with Klinefelter syndrome (KS) treated with at least 1 year of topical testosterone and aromatase inhibitor,” which summarize the key messages of the article (2). First of all, the goal of this study was not to advocate for the routine use of testosterone therapy in affected adolescents, and our results should not be used as this clinical approach in the absence of more data. Secondly, the study was not designed to compare rates of surgical sperm retrieval in adolescence versus adulthood, or in the setting of hormone therapy versus without it. And thirdly, the viability and utility of the retrieved and cryopreserved sperm remain to be determined. We acknowledge these limitations in the manuscript. Nevertheless, our results suggest that surgical sperm retrieval is possible in adolescents with KS, despite receiving treatment with aromatase inhibitor and topical testosterone therapy, offering additional information for patients interested in future fertility.
In addition to the above, Dr. Oates discusses potential effects of aromatase inhibitor on bone density, cautioning that post-menopausal women with ER-positive breast cancer demonstrate significant bone loss on aromatase inhibitors. We believe that it is important to recognize the differences between post-menopausal women and adolescent males with KS. Specific evaluation of the effects of aromatase inhibitors in young males has already been published.
The effect of aromatase inhibitors therapy on bone metabolism was evaluated in adolescent boys with idiopathic short stature. Anastrozole use in these boys over a 12-month period did not have any detrimental effect on bone density, despite a decrease in serum estrogen concentrations (3, 4). In fact, no changes in serum concentrations of osteocalcin and alkaline phosphatase, or in rates of bone calcium deposition and resorption, were noted following anastrozole therapy in one series (5). Thus, with regard to the adolescent male population, published evidence does not suggest an association between aromatase inhibitor use and loss of bone density. Concern that aromatase treatment will result in clinically significant adverse effects on bone density appears to be very limited.
Akanksha Mehta, M.D., Darius A. Paduch, M.D., Ph.D., Peter N. Schlegel, M.D.
Department of Urology, Weill Medical College of Cornell University, New York, New York
1. Oates B. Invited commentary on “Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor.” Fertil and Steril 2013, in press.
2. Mehta A, Bolyakov A, Roosma J, Schlegel PN, Paduch DA. Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor. Fertil Steril 2013, in press.
3. Mauras N, Welch S, Rini A, Klein KO. An open label 12-month pilot trial on the effects of the aromatase inhibitor anastrozole in growth hormone (GH)-treated GH deficient adolescent boys. J Pediatr Endocrinol Metab 2004;17:1597-606.
4. Wickman S, Kajantie E, Dunkel L. Effects of suppression of estrogen action by the p450 aromatase inhibitor letrozole on bone mineral density and bone turnover in pubertal boys. J Clin Endocrinol Metab 2003;88:3785-93.
5. Mauras N, O’Brien KO, Klein KO, Hayes V. Estrogen suppression in males: metabolic effects. J Clin Endocrinol Metab 2000;85:2370-7.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.08.001