Endocrine Abstracts

Background: Glitazones (GZ) influence androgen biosynthesis in PCO syndrome. At present it is unknown whether a) steroid hormone metabolism is influenced by GZ in patients with type 2 diabetes b) there is a differential effect of RGZ and PGZ on steroid hormone metabolism c) this effect is sex-specific and d) this effect is mediated by changes in insulin sensitivity. Therefore, urinary steroid profiles and serum total testosterone and DHEA levels were analysed before and after therapy with RGZ and PGZ in patients with type 2 diabetes.

Methods: 17 patients with type 2 diabetes (7 women, 10 men, age: 60.8±9.6, years, mean±SD; BMI: 29.2±4.7, kg/m²; HbA1_c: 7.6±0.6%) were included in the study and assigned to RGZ or PGZ in a randomised cross-over study design for 12 weeks with an eight-week wash-out period in-between. Identical investigations (24-h-urinary steroid profile, plasma glucose (FPG), insulin (FI), HbA1_C, serum total testosterone and DHEA concentrations) were performed before and after each treatment period.

Results: RGZ and PGZ therapy resulted in a similar decrease in HbA1_C, FPG and FI concentrations without sex-specific differences. In men, RGZ resulted in a significant increase in serum testosterone levels compared to PGZ (RGZ: +2.5±2.1; nmol/L; mean±SD; PGZ: +0.5±3.3; P<0.04), whereas DHEA concentrations remained unchanged. In men changes of urinary androstentriol, an androgen precursor, were significantly different after RGZ compared to PGZ (RGZ: +45.7±158.1; mcg/24 h; PGZ: −119±161.1; P<0.05). In women, RGZ therapy resulted in a significant decrease in serum testosterone concentrations after RGZ compared to PGZ (RGZ: −0.3±0.3; nmol/L; PGZ: +0.3±0.4; P<0.05). Serum DHEA levels were unaffected by PGZ and RGZ. In women, there were similar effects of PGZ and RGZ on urinary androgen metabolites.

Conclusion: These data suggest that 1. GZ impact on steroid hormone synthesis, 2. there is a differential effect of RGZ and PGZ 3. this effect is sex-specific and 4. this effect is not mediated by a differential effect of RGZ