ESPE Abstracts (2015) 84 P-3-1150

Physiological Dose Reverse Rhythm Testosterone Treatment Abolishes the Development of Permanent Gynaecomastia in Adolescent Boys with 47,XXY Klinefelter Syndrome

Gary Butler


Department of Adolescent Endocrinology, University College London Hospital, London, UK


Background: Gynaecomastia (GM) is common in boys with Klinefelter syndrome (KS) during adolescence due to the higher diurnal oestradiol–testosterone ratio in early-to-mid puberty. The physiological mid-late pubertal rise in testosterone (T) causes the GM to disappear in chromosomally normal boys, but GM persists in boys with KS if this rise in T is blunted.

Aims and objectives: We aimed to examine the effect of routine T supplementation in boys with KS ascertained antenatally or clinically on the development and persistence of GM.

Methods: The presence of GM was routinely ascertained in consecutively referred KS boys to a specialist multidisciplinary clinic. 29 boys were over 11 year. Once puberty had started and GM identified and recorded using Tanner breast staging and measurement of cross sectional breast disc diameter, either oral T undecanoate (TU – Restandol) 40 mg or transdermal T (Tostran) 20 mg was commenced each morning. T was administered in the morning, in reverse rhythm, in order to counterbalance the physiological decline of T concentrations in the afternoon/evening which is known to be more marked in boys with KS.

Results: 8/29 boys developed GM. Two did not adhere to treatment and the GM persisted. In the other six, GM stages B2-B3 with breast discs diameter range 1–3 cm appeared at mean age 12.8 year (range 11.4–14.2 year) and at puberty stages G2–G3. Only one had a high BMI (+3 SD). GM resolved completely within a mean of 1.1 year on treatment (range 0.2–1.9 year). Physiological T replacement was continued. Transient recurrence in 1/6 boys was ablated with a physiological TU dose increase. No major adverse effects were noted.

Conclusion: Reverse rhythm T, using a morning administration regimen started at the onset of GM and then given continuously in physiological dose increments, abolishes the development of permanent GM in adolescent boys with KS.

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