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- Title
Is there a gender difference in the associations of birthweight and adult hypothalamicpituitaryadrenal axis activity?
- Authors
Rebecca M Reynolds; Brian R Walker; Holly E Syddall; Ruth Andrew; Peter J Wood; David I W Phillips
- Abstract
OBJECTIVE: Increased hypothalamicpituitaryadrenal (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 6778 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 g) 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 6677 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.
- Subjects
HYDROCORTISONE; HYPOTHALAMIC-pituitary-adrenal axis; STATISTICAL hypothesis testing; SEX differences (Biology)
- Publication
European Journal of Endocrinology, 2005, Vol 152, Issue 2, p249
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/eje.1.01846