Virilization in two pre-pubertal children exposed to topical androgen

Danielle Nelson; Josephine Ho; Danièle Pacaud; David Stephure

doi:10.1515/jpem-2013-0127

Article

Virilization in two pre-pubertal children exposed to topical androgen

Danielle Nelson , Josephine Ho , Danièle Pacaud and David Stephure

Published/Copyright: May 24, 2013

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 26 Issue 9-10

Abstract

Androgen replacement therapy for male hypogonadism may be prescribed utilizing intramuscular, oral or more recently, topical formulations. With topical formulations, there is a risk of person-to-person transmission if appropriate precautions are not taken. We describe two cases of virilization in pre-pubertal children following passive transfer of paternal topical testosterone. A 21 month old male was referred with a 6 week history of pubic hair, phallic growth, and linear growth spurt. Genital examination revealed Tanner stage 2 pubic hair and Tanner stage 3 phallic development, which was discordant with the pre-pubertal testicular size (2 mL bilaterally). A 3 year 8 month old girl was referred for a 2 month history of increasing pubic hair development. Examination revealed Tanner stage 2 pubic hair and Tanner stage 1 breast development. Both of these patients had fathers who had been diagnosed with hypogonadism and were being treated with topical androgen gel therapy, which they applied to their arms and chest before bed. In addition, both patients often slept with their parents resulting in skin-to-skin contact. Investigations were consistent with gonadotropin independent virilization with both patients demonstrating elevated testosterone levels. Testosterone levels returned to normal pre-pubertal levels with no further development of secondary sexual characteristics following discontinuation of exposure to topical testosterone. Precautions must be taken to prevent person-to-person transfer of topical steroids. With the increasing popularity of topical steroids for the treatment of low testosterone, it is imperative that these therapies be prescribed and utilized judiciously to prevent harm, specifically gonadotropin-independent virilization.

Keywords: testosterone; topical; virilization

Corresponding author: Josephine Ho, Faculty of Medicine, Department of Pediatrics, Section of Pediatric Endocrinology, University of Calgary, Alberta Children’s Hospital, 2888 Shaganappi Trail NW, Calgary, T3B 6A8, Canada, Phone: +1-403-955-7819, Fax: +1-403-955-5001, E-mail: Josephine.ho@albertahealthservices.ca

The authors would like to gratefully acknowledge the patients and their family who have agreed to share their cases for this report.

Conflict of interest statement

The authors have no conflicts of interest to declare related to this report.

References

1. Beas F, Vargas L, Spada RP, Merchak N. Pseudoprecocious puberty in infants caused by a dermal ointment containing estrogens. J Pediatr 1969;75:127–30.10.1016/S0022-3476(69)80113-7Search in Google Scholar

2. Saenz de Rodriguez CA, Bongiovanni AM, Conde de Borrego L. An epidemic of precocious development in Puerto Rican children. J Pediatr 1985;107:393–6.10.1016/S0022-3476(85)80513-8Search in Google Scholar

3. Tiwary CM. Premature sexual development in children following the use of estrogen- or placenta-containing hair products. Clin Pediatr (Phila) 1998;37:733–9.10.1177/000992289803701204Search in Google Scholar PubMed

4. Weber WW, Grossman M, Thom JV, Sax J, Chan JJ, et al. Drug contamination with diethylstilbestrol. Outbreak of precocious puberty due to contaminated isonicocinic acid hydrazide (INH). N Engl J Med 1963;268:411–5.10.1056/NEJM196302212680804Search in Google Scholar PubMed

5. Zimmerman PA, Francis GL, Poth M. Hormone-containing cosmetics may cause signs of early sexual development. Mil Med 1995;160:628–30.10.1093/milmed/160.12.628Search in Google Scholar

6. Yu YM, Punyasavatsu N, Elder D, D’Ercole AJ. Sexual development in a two-year-old boy induced by topical exposure to testosterone. Pediatrics 1999;104:e23.10.1542/peds.104.2.e23Search in Google Scholar PubMed

7. Kunz GJ, Klein KO, Clemons RD, Gottschalk ME, Jones KL. Virilization of young children after topical androgen use by their parents. Pediatrics 2004;114:282–4.10.1542/peds.114.1.282Search in Google Scholar PubMed

8. Franklin SL, Geffner ME. Precocious puberty secondary to topical testosterone exposure. J Pediatr Endocrinol Metab 2003;16:107–10.Search in Google Scholar

9. Svoren BM, Wolfsdorf JI. Sexual development in a 21 month-old boy caused by testosterone contamination of a topical hydrocortisone cream. J Pediatr Endocrinol Metab 2005;18: 507–10.Search in Google Scholar

10. Lewis T, Goldstein I. Transfer of topical testosterone preparations to children or spouses. J Sex Med 2009;6: 2649–52.10.1111/j.1743-6109.2009.01478.xSearch in Google Scholar PubMed

11. Stephen MD, Jehaimi CT, Brosnan PG, Yafi M. Sexual precocity in a 2-year-old boy caused by indirect exposure to testosterone cream. Endocr Pract 2008;14:1027–30.10.4158/EP.14.8.1027Search in Google Scholar PubMed

12. Brachet C, Vermeulen J, Heinrichs C. Children’s virilization and the use of a testosterone gel by their fathers. Eur J Pediatr 2005;164:646–7.10.1007/s00431-005-1714-zSearch in Google Scholar PubMed

13. Bhowmick SK, Ricke T, Rettig KR. Sexual precocity in a 16-month-old boy induced by indirect topical exposure to testosterone. Clin Pediatr (Phila) 2007;46:540–3.10.1177/0009922806296651Search in Google Scholar

14. Cavender RK, Fairall M. Precocious puberty secondary to topical testosterone transfer: a case report. J Sex Med 2011;8:622–6.10.1111/j.1743-6109.2010.02082.xSearch in Google Scholar

15. Basaria S, Wahlstrom JT, Dobs AS. Clinical review 138: anabolic-androgenic steroid therapy in the treatment of chronic diseases. J Clin Endocrinol Metab 2001;86:5108–17.10.1210/jcem.86.11.7983Search in Google Scholar

16. Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ, et al. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients – 2002 update. Endocr Pract 2002;8:440–56.10.4158/EP.8.6.439Search in Google Scholar

17. Conway AJ, Handelsman DJ, Lording DW, Stuckey B, Zajac JD. Use, misuse and abuse of androgens. The Endocrine Society of Australia consensus guidelines for androgen prescribing. Med J Aust 2000;172:220–4.10.5694/j.1326-5377.2000.tb123913.xSearch in Google Scholar

18. Cuzin B, Giuliano F, Jamin C, Legros JJ, Lejeune H, et al. [Investigation, treatment and surveillance of late-onset hypogonadism in males: the official guidelines of the International Society for the Study of the Aging Male (ISSAM) with comments]. Prog Urol 2004;14:1–14.Search in Google Scholar

19. Franklin SL. Effects of unintentional exposure of children to compounded transdermal sex hormone therapy. Pediatr Endocrinol Rev 2011;8:208–12.Search in Google Scholar

20. Kirschner MA. Hirsutism and virilism in women. Spec Top Endocrinol Metab 1984;6:55–93.Search in Google Scholar

21. Kathiresan AS, Carr BR, Attia GR. Virilization from partner’s use of topical androgen in a reproductive-aged woman. Am J Obstet Gynecol 2011;205:e3–4.10.1016/j.ajog.2011.02.017Search in Google Scholar

22. Merhi ZO, Santoro N. Postmenopausal virilization after spousal use of topical androgens. Fertil Steril 2007;87:976.e13–5.10.1016/j.fertnstert.2006.07.1547Search in Google Scholar

23. Klugo RC, Cerny JC. Response of micropenis to topical testosterone and gonadotropin. J Urol 1978;119:667–8.10.1016/S0022-5347(17)57584-9Search in Google Scholar

24. Ahmed SR, Boucher AE, Manni A, Santen RJ, Bartholomew M, et al. Transdermal testosterone therapy in the treatment of male hypogonadism. J Clin Endocrinol Metab 1988;66:546–51.10.1210/jcem-66-3-546Search in Google Scholar PubMed

25. Wilson JD, Walker JD. The conversion of testosterone to 5 alpha-androstan-17 beta-ol-3-one (dihydrotestosterone) by skin slices of man. J Clin Invest 1969;48:371–9.10.1172/JCI105994Search in Google Scholar PubMed PubMed Central

26. Herman-Giddens ME, Sandler AD, Friedman NE. Sexual precocity in girls. An association with sexual abuse? Am J Dis Child 1988;142:431–3.10.1001/archpedi.1988.02150040085025Search in Google Scholar

27. Guthrie RD, Smith DW, Graham CB. Testosterone treatment for micropenis during early childhood. J Pediatr 1973;83:247–52.10.1016/S0022-3476(73)80484-6Search in Google Scholar

28. Soliman AT, AlLamki M, AlSalmi I, Asfour M. Congenital adrenal hyperplasia complicated by central precocious puberty: linear growth during infancy and treatment with gonadotropin-releasing hormone analog. Metabolism 1997;46:513–7.10.1016/S0026-0495(97)90186-4Search in Google Scholar

29. Husmann DA, Cain MP. Microphallus: eventual phallic size is dependent on the timing of androgen administration. J Urol 1994;152:734–9.10.1016/S0022-5347(17)32694-0Search in Google Scholar

30. McMahon DR, Kramer SA, Husmann DA. Micropenis: does early treatment with testosterone do more harm than good? J Urol 1995;154:825–9.10.1016/S0022-5347(01)67175-1Search in Google Scholar

31. Sutherland RS, Kogan BA, Baskin LS, Mevorach RA, Conte F, et al. The effect of prepubertal androgen exposure on adult penile length. J Urol 1996;156:783–7; discussion 787.10.1016/S0022-5347(01)65814-2Search in Google Scholar

Received: 2013-3-28

Accepted: 2013-4-18

Published Online: 2013-05-24

Published in Print: 2013-10-01

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Articles in the same Issue

https://doi.org/10.1515/jpem-2013-0127

Keywords for this article

testosterone; topical; virilization