Platelet aggregation in Klinefelter syndrome is not aggravated by testosterone replacement therapy: A longitudinal follow-up study

Background: Men with Klinefelter syndrome (KS) are routinely offered testosterone replacement therapy (TRT) suggested to potentially promote platelet aggregation and increase cardiovascular risk. Objective: We investigated platelet aggregation in men with KS before and during TRT. Materials and methods: Forty-one adult men with KS participated, of which 20 had no history of TRT at baseline, with 15 completing follow-up after 18 months TRT. Further, we included 21 adult men with KS on long-term TRT (>10 years) and a male reference population. We assessed platelet impedance aggregometry using adenosine diphosphate (6.5 μM), thrombin-receptor-activating-peptide-6 (TRAP 32 μM), and arachidonic acid (ASPI 0.5 mM) as agonists in KS compared to a male reference population and stratified by route of TRT administration. Results: Platelet aggregation among men with KS at baseline or during TRT was not increased compared with the male reference population. For all three agonist, no change was seen in platelet aggregation in KS at follow-up compared with baseline (p ≥ 0.2). Platelet aggregation was not associated with total testosterone and furthermore, platelet count was not affected by treatment with testosterone. Men with KS treated with testosterone gel showed slightly increased TRAP- and ASPI-induced platelet aggregation compared with those treated with testosterone injection (p = 0.02 and p = 0.04, respectively). Discussion and conclusions: We observed normal platelet aggregation in men with KS before TRT and following both short and long term treatment. Our findings do not support an independent role of platelets in driving the cardiovascular risk in KS.