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

Platelet aggregation in men with Klinefelter syndrome at baseline was not increased compared with the male reference population.

• 41 adult men with KS participated in the study
• 20 men with KS had no history of TRT at baseline
• Platelet impedance aggregometry was used with three agonists: adenosine diphosphate (6.5 μM), thrombin-receptor-activating-peptide-6 (TRAP 32 μM), and arachidonic acid (ASPI 0.5 mM)
• Comparison was made against a male reference population

Testosterone replacement therapy did not increase platelet aggregation in men with Klinefelter syndrome after 18 months of treatment.

• 15 men with KS completed follow-up after 18 months of TRT
• For all three agonists, no change was seen in platelet aggregation at follow-up compared with baseline (p ≥ 0.2)
• 21 additional adult men with KS on long-term TRT (>10 years) were also included and showed no increased platelet aggregation

Platelet aggregation was not associated with total testosterone levels, and platelet count was not affected by testosterone treatment.

• No association was found between platelet aggregation and total testosterone
• Platelet count remained unaffected by testosterone treatment
• This finding held across both short-term (18 months) and long-term (>10 years) TRT

Men with Klinefelter syndrome treated with testosterone gel showed slightly higher TRAP- and ASPI-induced platelet aggregation compared with those treated with testosterone injection.

• TRAP-induced platelet aggregation was higher in gel-treated vs. injection-treated men (p = 0.02)
• ASPI-induced platelet aggregation was higher in gel-treated vs. injection-treated men (p = 0.04)
• The difference was described as 'slightly increased' and was stratified by route of TRT administration

The study findings do not support an independent role of platelets in driving cardiovascular risk in Klinefelter syndrome.

• Normal platelet aggregation was observed in men with KS before TRT and following both short- and long-term treatment
• Despite men with KS being routinely offered TRT which was suggested to potentially promote platelet aggregation and increase cardiovascular risk, no such effect was observed
• The authors conclude that platelets do not independently drive cardiovascular risk in KS