Endocrine Abstracts

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

Aim: As a previous longitudinal RCT of testosterone in boys with KS identified by birth screening had found no persistence of GM in treated boys, we examined the effect of routine testosterone supplementation in boys with KS ascertained antenatally or clinically on the persistence of GM. Testosterone was administered each morning, in reverse rhythm, in order to counterbalance the usual rapid decline of testosterone concentrations in the afternoon/evening in the physiological diurnal rhythm of normal puberty, which is known to be more marked in boys with KS.

Methods: The presence of GM was routinely ascertained in boys with KS consecutively referred to and followed up in a specialist multidisciplinary KS Clinic. 29 of the boys were over 11 years. Once puberty had started and GM identified and recorded using Tanner breast staging and measurement of cross sectional disc diameter, either oral testosterone undecanoate (TU; Restandol) 40 mg or transdermal testosterone (Tostran) 20 mg was commenced each morning.

Results: Eight out of the 29 boys developed GM. Two did not comply with the treatment and the GM persisted. In the remaining six, GM stages B2–B3 with breast discs diameter range 1–3 cm appeared at mean age 12.8 years (range 11.4–14.2 years) and at puberty stages G2–G3. Only one had a high BMI (+3 S.D.). GM resolved completely within a mean of 1.1 years on treatment (range 0.2–1.9 years). Physiological testosterone replacement was continued. Transient recurrence in one boy was ablated with a physiological TU dose increase. No major adverse effects were noted.

Conclusion: Reverse rhythm testosterone, 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.