Endocrine Abstracts

The excess androgen levels in women with PCOS may be ovarian and/or adrenal in origin and one proposed contributing mechanism is an alteration in cortisol metabolism. Increased peripheral cortisol metabolism, either by enhanced inactivation of cortisol by 5alpha-reductase or impaired reactivation of cortisol by 11b-hydroxysteroid dehydrogenase (11bHSD type 1), results in decreased negative feedback suppression of ACTH secretion maintaining normal plasma cortisol concentrations at the expense of androgen excess. We have tested whether these enzyme abnormalities are related to insulin levels in women with PCOS.

We measured 24-hour urinary excretion of steroid metabolites by gas chromatography/mass spectrometry in 30 PCOS women [mean age: 28±6 years; mean BMI: 28±6 kg/m2; mean body surface area (BSA): 1.84 m2]. A complete fasting metabolic and hormone profile were recorded. All women were studied in the early follicular phase or on random day if oligo-amenorrhoiec. Twelve of these women with PCOS were compared with 10 healthy women of similar age and BSA.

In all 30 subjects, measures of 5alpha/5beta reduction were inversely correlated with a measure of insulin sensitivity - a-THF/THF: FG/FI (r=-0.556; p=0.003) and Androsterone/Aetiocholanolone : FG/FI (r=-0.394; p=0.05). No correlation was found between FG/FI ratio with serum androgens, BMI, or BSA. A comparison between the subgroup of 12 PCOS subjects with 10 controls showed significant excess of Androsterone (p=0.04), a-THF/THF (p=0.006) a-cortolone (p=0.02), b-cortolone (p=0.03), cortolones (p=0.002), E metabolites (p=0.001), Total C19 (p=0.001), Total C21 (p=0.008) and Total cortisol metabolites (p=0.005).

Our findings suggest that the previous reported increase activity of 5alpha-reductase in women with PCOS may be secondary phenomenon due to hyperinsulinaemia often reported in this condition. Interestingly, no correlation was found between serum androgen levels or urinary excretion of androgens with either a-THF/THF ratio or Androsterone/Aetiocholanolone ratio excluding hyperandrogaenism as major regulating factor of 5alpha-reductase activity in PCOS women.