Endocrine Abstracts

Background: Klinefelter syndrome (KS), karyotype 47XXY, affects 1 in 650 males. Subjects develop primary gonadal failure requiring life-long testosterone replacement. Many different testosterone formulations are available and long-term monitoring is necessary to avoid secondary polycythaemia.

Objective: To investigate the effect of testosterone formulations used in KS subjects and estimate frequency of association with secondary polycythaemia.

Method: A single institution retrospective review of the hospital database was undertaken to identify KS subjects. Collated data included formulation of testosterone replacement and evidence of secondary polycythaemia – defined as either a haemoglobin > 170 g/l or a haematocrit > 0.54 l/l.

Results: 83 subjects with KS were identified. 72 subjects (87%) took some form of testosterone or hCG. Of these 72 subjects, 34 (47%) took testosterone undecanoate (Nebido), 7 (10%) took testosterone esters (Sustanon), 23 (32%) took topical testosterone gel (Testogel or Tostran) and 8 (11%) took Pregnyl/Gonasi. 10 of 72 (14%) subjects had evidence of polycythaemia at some point during follow-up. In 2 subjects, both the haemoglobin and haematocrit were raised; only the haemoglobin was raised in the remaining 8 subjects. 7 subjects took testosterone undecanoate (intervals: 13 weekly(1); 12 weekly(4); 10 weekly(1) and 750 mg 20 weekly(1)) and 3 took daily testosterone gel subjects (Testogel(2) and Tostran(1)) – 20.5% of subjects taking testosterone undecanoate and 13% of subjects taking testosterone gel developed polycythaemia. 2 subjects (one taking Nebido, the other Testogel) required venesection as treatment for polycythaemia, with others only requiring dose alteration.

Conclusion: A significant minority of KS subjected developed polycythaemia whilst on testosterone therapy. Testosterone undecanoate appears to be associated with the highest risk despite published data reporting a relatively low risk with this preparation. In the KS cohort, avoidance of polycythaemia is important given the increasing risk of venous thromboembolic disease with age.