Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 101, Issue 5, Pages 2069-2075Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2015-3926
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Funding
- Eunice Kennedy Shriver National Institute of Child Health and Development [P50 HD044405, K12 HD055884]
- Medical Research Council UK [G1001964]
- Wellcome Trust [092283]
- Medical Research Council [G1001964, G116/172] Funding Source: researchfish
- MRC [G116/172, G1001964] Funding Source: UKRI
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Context: Polycystic ovary syndrome (PCOS) is a heritable, complex genetic disease. Animal models suggest that androgen exposure at critical developmental stages contributes to disease pathogenesis. We hypothesized that genetic variation resulting in increased androgen production produces the phenotypic features of PCOS by programming during critical developmental periods. Although we have not found evidence for increased in utero androgen levels in cord blood in the daughters of women with PCOS (PCOS-d), target tissue androgen production may be amplified by increased 5 alpha-reductase activity analogous to findings in adult affected women. It is possible to noninvasively test this hypothesis by examining urinary steroid metabolites. Objective: We performed this study to investigate whether PCOS-d have altered androgen metabolism during early childhood. Design, Setting, and Participants: Twenty-one PCOS-d, 1-3 years old, and 36 control girls of comparable age were studied at an academic medical center. Main Outcome Measures: Urinary steroid metabolites were measured by gas chromatography/mass spectrometry. Twenty-four hour steroid excretion rates and precursor to product ratios suggestive of 5 alpha-reductase and 110-hydroxysteroid dehydrogenase activities were calculated. Results: Age did not differ but weight for length Z-scores were higher in PCOS-d compared to control girls (P =.02). PCOS-d had increased 5 alpha-tetrahydrocortisol:tetrahydrocortisol ratios (P = .04), suggesting increased global 5 alpha-reductase activity. There was no evidence for differences in 110-hydroxysteroid dehydrogenase activity. Steroid metabolite excretion was not correlated with weight. Conclusions: Our findings suggest that differences in androgen metabolism are present in early childhood in PCOS-d. Increased 5 alpha-reductase activity could contribute to the development of PCOS by amplifying target tissue androgen action.
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