Session: OR46-Hyperandrogenemia: Influences & Implications
Room 121 (Moscone Center)
We studied 20 daughters of women with PCOS aged 1-3 years and 22 healthy girls of comparable age (CON). Urinary steroid excretion was profiled by gas chromatography/mass spectrometry selected-ion-monitoring, after steroid extraction from 10-24 hour diaper collections. Steroid data were compared by unpaired two-tailed t-tests (mean ± SD).
None of the girls had early pubarche. Longitudinal analysis of growth charts from birth to 24 mon showed no differences in length or weight between the groups. FDR girls had increased 5α-tetrahydrocortisol:tetrahydrocortisol ratios (FDR 2.81±1.1 vs CON 1.96±0.5, P=0.003) and 5α-tetrahydrocorticosterone:tetrahydrocorticosterone ratios (FDR 6.15±2.56 vs CON 4.61±1.69, P=0.03) suggestive of increased 5α-reductase activity. Although weight for length z-score at diaper collection differed (FDR 0.4±0.8 vs CON -0.5±0.8, p=0.009), it did not correlate with steroid ratios. Androsterone:etiocholanolone ratios did not differ between groups, which may have been secondary to the very low concentrations of these metabolites in early childhood. Total glucocorticoid and androgen excretion rates did not differ between the groups.
These findings show for the first time increased global 5α-reductase activity in early childhood FDR girls. Increased androgen and glucocorticoid metabolite excretion and 5α-reductase activity in adult women with PCOS have been attributed to increased adrenal steroidogenesis and correlated with body weight and circulating insulin levels. In this study, body weight did not correlate with measures of 5α-reductase activity nor was there evidence for increased glucocorticoid excretion. Our findings suggest that alterations in androgen metabolism are already present in infancy in girls at risk for PCOS. Whether these findings reflect genetic alterations in steroidogenesis or epigenetic changes requires elucidation.
Disclosure: AD: Advisory Group Member, Amylin Pharmaceuticals, Speaker, Bayer Schering Pharma, Advisory Group Member, Bristol-Myers Squibb. Nothing to Disclose: LCT, JI, NRF, DMO, CHS, WA
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