Prenatal Testosterone Associates with Blood Pressure in Young Adults: A Prospective Cohort Study

Abstract

Preclinical evidence suggests that adult blood pressure (BP) may be modified by the prenatal endocrine environment. Specifically, in several animal models, higher prenatal testosterone exposure increases the risk of hypertension in later life. We investigated the prospective association between prenatal testosterone levels (as measured in umbilical cord blood) and BP at 20 to 27 years in 434 participants from the Raine Study. As expected, median bioavailable testosterone, the fraction of total testosterone either free or bound to serum albumin, was higher in males than females (0.12 [Q1-Q3, 0.09-0.19] versus 0.07 [Q1-Q3, 0.05-0.1] nmol/L; P<0.001). Mean (SD) systolic BP was 122.9 (±12.3) and 110.9 (±9.5) mm Hg at age 20 years and 122.4 (±11) and 111.2 (±9.1) mm Hg at 27 years in males and females, respectively. Using hierarchical mixed-effects models, higher cord blood bioavailable testosterone concentrations were associated with higher levels of systolic BP (P=0.007) and diastolic BP (P=0.002) in young adults at 20 and 27 years, after adjusting for change in BP over time and potential confounders. In these models, one SD increase in bioavailable testosterone equated to a 1 mm Hg increase in systolic BP (regression coefficient, 11.1 [95% CI, 4.1-21.11]) and diastolic BP (regression coefficient, 10.15 [95% CI, 3.67-15.93]). There was no significant difference detected between males and females in the association between bioavailable testosterone and adult BP. These data from a large unselected population indicate that higher fetal testosterone levels in late pregnancy are associated with higher BP in young adulthood.