Central fat drives adrenal output, androgen activation and metabolic phenotype in polycystic ovary syndrome

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 498-523-Female Reproductive Endocrinology & Case Reports
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-515
Michael William O'Reilly*1, James A Hodson1, Nicola Crabtree1, Jonathan Mark Hazlehurst2, Paul Michael Stewart1, Jeremy W Tomlinson3 and Wiebke Arlt1
1University of Birmingham, Birmingham, United Kingdom, 2Univ of Birmingham, Birmingham, United Kingdom, 3University of Birmingham, United Kingdom
Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, hyperandrogenism and insulin resistance. Patterns of fat distribution in PCOS could be associated with androgen activation, glucocorticoid secretion and insulin resistance. Here we analysed the relationship between fat distribution, steroid metabolism and insulin resistance in women with PCOS.

We compared results from 100 PCOS patients (Rotterdam criteria) with 80 sex- and body mass index (BMI)-matched controls. Subjects underwent BMI measurement, body composition assessment by dual-energy x-ray absorptiometry (DEXA), fasting glucose and insulin measurement for homeostatic model assessment-insulin resistance (HOMA-IR) calculation and 24-hour urine analysis by gas chromatography/mass spectrometry. The latter included calculation of total glucocorticoid excretion (µg/24h) and markers of 5α-reductase activity (androsterone/etiocholanolone and 5α-THF/THF ratios). Serum androgens were measured by liquid chromatography/tandem mass spectrometry (LC-MS). Linear regression analysis was used to measure the impact of fat distribution on glucocorticoid secretion, 5α-reductase activity and insulin resistance.

PCOS and control patients were matched for BMI (32.1±7.1 and 32.2±6.2kg/m² respectively). Compared to controls, PCOS women had higher urinary steroid ratios indicative of 5α-reductase activity (An/Et 1.3±0.6 v 1.0±0.5, p=0.005; 5α-THF/THF 0.9±0.5 v 0.7±0.4, p=0.004) and higher total glucocorticoid excretion (9624±4214 v 8067±4165, p=0.013). After adjustment for age and BMI, central fat distribution was highly predictive of HOMA-IR, glucocorticoid secretion and 5α-reductase activity. For each percentage increase in truncal fat, HOMA-IR values increased by 7.1% (95% CI, 4.6-9.6, p<0.001) and glucocorticoid metabolites by 2.9% (95% CI, 1.3-4.9, p<0.001). Each percentage increase in truncal fat was also associated with elevated An/et and 5α-THF/THF ratios (2.3%, 95% CI 0.8-3.9, p=0.003, and 1.9%, 95% CI 0.2-3.5, p=0.024, respectively). Total leg fat was negatively predictive of insulin resistance, with each percentage increase in leg fat associated with a 3.6% reduction in HOMA-IR (95% CI 0.11-6%, p=0.005).

Body fat distribution in PCOS is closely associated with steroid metabolism and insulin resistance. Truncal obesity is highly predictive of insulin resistance, glucocorticoid secretion and androgen activation. Leg fat may confer beneficial effects on metabolism and steroid output in women with PCOS.

Nothing to Disclose: MWO, JAH, NC, JMH, PMS, JWT, WA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm