Is there a gender difference in the associations of birthweight and adult hypothalamic-pituitary-adrenal axis activity?

Objective: increased hypothalamic–pituitary–adrenal (HPA) axis activity in men of low birthweight may be an important link between early life and the adult metabolic syndrome. In animal models females are more sensitive than males to HPA axis programming, but whether gender influences susceptibility in humans is unknown. Design: birth cohort study. Methods: we studied 106 women aged 67–78 years, from Hertfordshire, UK, in whom birthweight was recorded. Negative feedback sensitivity was assessed by an overnight low-dose (0.25 mg) dexa-methasone suppression test, and adrenal sensitivity by a low-dose (1 µg) ACTH1 – 24 stimulation test. Cortisol and its metabolites were analysed in a 24 h urine collection. Data were compared with previously published identical measurements in 205 men aged 66–77 years from the same cohort. Results: in women, plasma cortisol levels after dexamethasone were lower (P < 0.0001) and peak cortisol following ACTH1 – 24 were higher (P < 0.0001) than in men, suggesting a more responsive HPA axis. As in men, women with lower birthweight had enhanced plasma cortisol responses to ACTH1 – 24 (P = 0.05 for trend) but no difference in plasma cortisol after dexamethasone or in urinary cortisol metabolite excretion. The strength of the association in women was not different from that in men; a 1 lb decrease in birthweight was associated with an incremental rise in cortisol of 12.6 nmol/l (95% confidence interval (CI) 1.4, 23.8) in men, P = 0.03, and 14.8 nmol/l (95% CI –0.4, 29.9) in women, P = 0.05 (P = 0.82 for birthweight x gender interaction). In a combined analysis of men and women adjusted for gender (n = 302), a 1 lb decrease in birthweight was associated with a 13.4 nmol/l (95% CI 4.5, 22.4) greater incremental rise in plasma cortisol, P = 0.003. Conclusions: associations between lower birthweight and increased HPA axis activity are similar in men and women, supporting the hypothesis that HPA axis activation is an important mechanism underlying programming of adult disease

Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life

Background: The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain. Objectives: To examine the effect of birth weight, early postnatal growth, and pre- and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm. Design and methods: Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre- and postnatal corticosteroids administration using multiple linear regression analyses. Results: Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (beta: -0.865, 95% confidence interval (CI): -1.254 to -0.476) and in men (beta: -0.758, 95% CI: -1.247 to -0.268) and with serum Adione concentrations in women (beta: -0.337, 95% CI: -0.593 to -0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (beta: 0.932, 95% CI: 0.022 1.843). Conclusions: Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women.Clinical epidemiolog