Pubertal testis volume, age at pubertal onset, and adolescent blood pressure: Evidence from Hong Kong's "Children of 1997" birth cohort

Objectives: A warning from Health Canada suggests that testosterone increases blood pressure (BP). No evidence from large randomized controlled trials is available, and observational studies are confounded by ill-health lowering serum testosterone. To address the evidence gap, we assessed the association of pubertal testicular volume, as a reflection of testosterone production, with BP. Methods: We examined whether testicular volume was associated with sex-, age-, and height-standardized BP z-score at similar to 13 years in a population-representative Chinese birth cohort (n=5195, 63% follow-up). We used age at pubertal onset, determined as the earliest age when Tanner stage II for genitalia, breast, or pubic hair, or testicular volume of 4 mL occurred, as control exposures. These exposures were expected to produce findings different from testicular volume because they are not direct measures of testosterone. They were used to ascertain specificity of exposure and to detect residual confounding. Results: Greater testicular volume was associated with higher systolic BP by 0.03 z-score, which is equivalent to 1.40 mm Hg per standard deviation of testicular volume (95% CI 0.02-0.04), adjusted for infant characteristics, socioeconomic position, and childhood body mass index. Similarly adjusted, earlier pubertal onset was not associated with higher systolic BP z-score in boys or girls. Conclusions: Greater pubertal testicular volume is related to higher BP, consistent with a potential role of androgens in the higher BP in boys than girls that emerges during puberty. Our finding provides preliminary evidence supportive of more definitive studies to clarify the warning on testosterone from Health Canada.