Background: Obesity-related alterations in the circulating steroid hormone profile remain
equivocal in women. Our objective was to identify circulating steroid levels that relate to
increased adiposity and altered adipose phenotype in premenopausal women. Materials and
methods: In a sample of 42 premenopausal women (age 46±3 years; BMI 27.1±4.2 kg/m2
), 19
plasma steroids were quantified by ESI-LC-MS/MS. Body composition and fat distribution were
assessed by dual-energy X-ray absorptiometry and computed tomography, respectively. Markers
of adipose tissue function including adipocyte size distributions, radiological attenuation, and
macrophage infiltration were also analyzed in surgically obtained visceral and subcutaneous fat
samples. Results: Many negative correlations were observed between adiposity measurements
such as BMI, body fat percentage or total abdominal adipose tissue area and plasma levels of
androstenedione (r=-0.33 to -0.39, p≤0.04), androsterone (r=-0.30 to -0.38, p≤0.05) and plasma
levels of steroid precursor pregnenolone (r=-0.36 to -0.46, p≤0.02). Visceral adipocyte
hypertrophy was observed in patients with low pregnenolone concentrations (p<0.05). Visceral
adipose tissue radiologic attenuation, a potential marker of adipocyte size, was also positively
correlated with pregnenolone levels (r=0.33, p<0.05). Low levels of pregnenolone were related to
increased number of macrophages infiltrating visceral and subcutaneous adipose tissue (p<0.05).
Conclusion: Plasma levels of androgens and their precursors are lower in women with increased
adiposity and visceral adipocyte hypertrophy. Low circulating pregnenolone concentration may
represent a marker of adipose tissue dysfunction
