Abstract
Objective: Animal studies have shown intrauterine androgen exposure leads to offspring adult cardiovascular dysfunction, including hypertension. In humans, androgens in umbilical cord blood at birth reflect the androgen environment in pregnancy. In a population-based sample studied from in utero, we aimed to explore the association between prenatal testosterone exposure and BP in young adulthood. Design and method: In the Raine Study cohort, data was available on umbilical cord blood androgens and on BP, anthropometric and socio-behavioural information in 387 participants at 20 years and 319 at 27 years. Total testosterone was measured using liquid chromatography-tandem mass spectrometry; free testosterone, by empirical method (Sartorius et al.); and sex hormone binding globulin, by ELISA. Bioavailable testosterone (BioT; nmol L) was calculated employing the formula: BioT = free testosterone + albumin-bound testosterone. We employed hierarchical linear mixed effects regression, with maximum likelihood estimation, to assess the association of BioT with blood pressure at 20 and 27 years adjusting for potential confounders. Results: Umbilical cord BioT levels were significantly higher in males than in females (0.14 [95%CI 0.13; 0.16] vs 0.08 [95%CI 0.07; 0.09] nM/L; p < 0.001). Mean systolic BP were 122.9 (95%CI 121.3; 124.6) and 110.5 (95%CI 109.1; 111.9) mmHg at 20 years, and 122.4 (95%CI 120.7; 124.1) and 111.2 (95%CI 109.8; 112.7) mmHg at 27 years, in males and females, respectively. Longitudinal regression models showed higher BioT levels were positively associated with systolic BP (coefficient: 16.1 [95% CI: 1.8; 30.4]; p = 0.027) at both 20 and 27 years, after adjusting for BMI, sex and hormone contraceptive use. This translates to a 1 mmHg increase in systolic BP for a 1 standard deviation increase in BioT. There was no difference in this association between sexes. Conclusions: To our knowledge, this is the first population-based study that shows testosterone in umbilical cord blood at birth is significantly associated with systolic BP in young adulthood. Our data support previous findings in animal studies of a causal relationship. The data suggest that higher testosterone levels in utero may increase the risk of hypertension later in life.
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