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

Is there a gender difference in the associations of birthweight and adult hypothalamic-pituitary-adrenal axis activity?
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.
0804-4643
249-253
Reynolds, R.M.
c58e0f89-329d-4e4e-be3f-3c53b2a847cc
Walker, B.R.
d292ba5e-9070-49a2-aa09-cf1501bc99b4
Syddall, H.E.
a0181a93-8fc3-4998-a996-7963f0128328
Andrew, R.
05cdc474-35f6-463b-b260-3d8c9af746c4
Wood, P.J.
f0dfe718-fa0f-43b1-9b2d-4bdc9c41320a
Phillips, D.I.
29b73be7-2ff9-4fff-ae42-d59842df4cc6
Reynolds, R.M.
c58e0f89-329d-4e4e-be3f-3c53b2a847cc
Walker, B.R.
d292ba5e-9070-49a2-aa09-cf1501bc99b4
Syddall, H.E.
a0181a93-8fc3-4998-a996-7963f0128328
Andrew, R.
05cdc474-35f6-463b-b260-3d8c9af746c4
Wood, P.J.
f0dfe718-fa0f-43b1-9b2d-4bdc9c41320a
Phillips, D.I.
29b73be7-2ff9-4fff-ae42-d59842df4cc6

Reynolds, R.M., Walker, B.R., Syddall, H.E., Andrew, R., Wood, P.J. and Phillips, D.I. (2005) Is there a gender difference in the associations of birthweight and adult hypothalamic-pituitary-adrenal axis activity? European journal of endocrinology, 152 (2), 249-253. (doi:10.1530/eje.1.01846).

Record type: Article

Abstract

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.

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Published date: 2005

Identifiers

Local EPrints ID: 24918
URI: http://eprints.soton.ac.uk/id/eprint/24918
ISSN: 0804-4643
PURE UUID: 0d140da9-1cfe-4cb8-8514-289832932636
ORCID for H.E. Syddall: ORCID iD orcid.org/0000-0003-0171-0306

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Date deposited: 04 Apr 2006
Last modified: 16 Mar 2024 02:59

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Contributors

Author: R.M. Reynolds
Author: B.R. Walker
Author: H.E. Syddall ORCID iD
Author: R. Andrew
Author: P.J. Wood
Author: D.I. Phillips

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