Grace Huang1, Sara Cherkerzian2, Eric B Loucks3, Stephen L Buka3, Robert J Handa4,5, Bill L Lasley6,7, Shalender Bhasin1, Jill M Goldstein2,8,9. 1. Research Program in Men's Health: Aging and Metabolism, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts. 2. Division of Women's Health, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts. 3. Department of Epidemiology, Brown University School of Public Health, Providence, Rhode Island. 4. Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado. 5. Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, Arizona. 6. Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, California. 7. Department of Obstetrics and Gynecology, School of Medicine, Center for Health and the Environment, University of California, Davis, Davis, California. 8. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 9. Department of Obstetrics & Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Abstract
Context: Growing preclinical evidence suggests that hormonal programming by androgens in utero may contribute to cardiovascular disease risk in adult offspring. However, the effect of prenatal androgens on cardiometabolic outcomes in the human population, especially their potential differential impact on male vs female offspring, has not been well studied. Design: Adult offspring (n = 274) of mothers enrolled in the New England birth cohorts of the Collaborative Perinatal Project were assessed at ages 39 to 50. Androgen bioactivity was measured in maternal serum during the third trimester using a receptor-mediated luciferase expression bioassay. Metabolic syndrome (MetS) using Adult Treatment Panel III criteria was assessed in adult offspring. Bioactive androgens were analyzed as quartiles, with the lowest quartile (Q1) defined as the reference. Generalized estimating equations were used to evaluate the relationship of maternal bioactive androgens on offspring MetS risk overall and by sex, controlling for potential confounders and intrafamilial correlation. Results: Mean age and body mass index of adult offspring were 44.7 ± 2.6 years and 29.7 ± 6.7 kg/m2, respectively. Participants born to mothers with the highest quartile (Q4) compared with Q1 of bioactive androgens had higher risk for MetS [adjusted odds ratio (aOR): 2.53(1.07 to 6.02)]. Stratified by sex, this association was found to be significant among women [Q4 vs Q1; aOR: 4.06 (1.10 to 14.93)] but not men [Q4 vs Q1; aOR: 1.67 (0.53 to 5.26)]. Women born to mothers with the highest levels of maternal bioactive androgens also demonstrated a 4.84-fold increased odds for having hypertension [Q4 vs Q1; aOR: 4.84 (1.12 to 20.85)]. Conclusion: Higher levels of maternal androgens were associated with increased risk for incident MetS in adult offspring, an effect that was significant in women but not men.
Context: Growing preclinical evidence suggests that hormonal programming by androgens in utero may contribute to cardiovascular disease risk in adult offspring. However, the effect of prenatal androgens on cardiometabolic outcomes in the human population, especially their potential differential impact on male vs female offspring, has not been well studied. Design: Adult offspring (n = 274) of mothers enrolled in the New England birth cohorts of the Collaborative Perinatal Project were assessed at ages 39 to 50. Androgen bioactivity was measured in maternal serum during the third trimester using a receptor-mediated luciferase expression bioassay. Metabolic syndrome (MetS) using Adult Treatment Panel III criteria was assessed in adult offspring. Bioactive androgens were analyzed as quartiles, with the lowest quartile (Q1) defined as the reference. Generalized estimating equations were used to evaluate the relationship of maternal bioactive androgens on offspring MetS risk overall and by sex, controlling for potential confounders and intrafamilial correlation. Results: Mean age and body mass index of adult offspring were 44.7 ± 2.6 years and 29.7 ± 6.7 kg/m2, respectively. Participants born to mothers with the highest quartile (Q4) compared with Q1 of bioactive androgens had higher risk for MetS [adjusted odds ratio (aOR): 2.53(1.07 to 6.02)]. Stratified by sex, this association was found to be significant among women [Q4 vs Q1; aOR: 4.06 (1.10 to 14.93)] but not men [Q4 vs Q1; aOR: 1.67 (0.53 to 5.26)]. Women born to mothers with the highest levels of maternal bioactive androgens also demonstrated a 4.84-fold increased odds for having hypertension [Q4 vs Q1; aOR: 4.84 (1.12 to 20.85)]. Conclusion: Higher levels of maternal androgens were associated with increased risk for incident MetS in adult offspring, an effect that was significant in women but not men.
Authors: Laura R Stroud; Catherine Solomon; Edmond Shenassa; George Papandonatos; Raymond Niaura; Lewis P Lipsitt; Kaja Lewinn; Stephen L Buka Journal: Psychoneuroendocrinology Date: 2007-01-31 Impact factor: 4.905
Authors: M Hickey; D M Sloboda; H C Atkinson; D A Doherty; S Franks; R J Norman; J P Newnham; R Hart Journal: J Clin Endocrinol Metab Date: 2009-06-30 Impact factor: 5.958
Authors: Lauren M Ellman; Christine Dunkel Schetter; Calvin J Hobel; Aleksandra Chicz-Demet; Laura M Glynn; Curt A Sandman Journal: Dev Psychobiol Date: 2008-04 Impact factor: 3.038
Authors: Diana A Stavreva; Anuja A George; Paul Klausmeyer; Lyuba Varticovski; Daniel Sack; Ty C Voss; R Louis Schiltz; Vicki S Blazer; Luke R Iwanowicz; Gordon L Hager Journal: Sci Rep Date: 2012-12-06 Impact factor: 4.379
Authors: G Huang; S A Aroner; C P Bay; S E Gilman; A Ghassabian; E B Loucks; S L Buka; R J Handa; B L Lasley; S Bhasin; J M Goldstein Journal: J Endocrinol Invest Date: 2020-08-10 Impact factor: 5.467