Serum levels of inhibins are differentially altered in patients with polycystic ovary syndrome: effects of being overweight and relevance to hyperandrogenism

Objective: To explore the abnormalities of serum inhibin isoform concentrat ions in a large group of patients with polycystic ovary syndrome (PCOS) and to evaluate the influence of body mass index (BMI), age, LH, and androgens on serum inhibin levels. Design: Prospective study. Setting: Reproductive endocrinology unit of an academic medical center. Patient(s): Forty-one women with PCOS were compared with 24 healthy women. Intervention(s): Blood sampling was performed in the early follicular phase in patients and in control women. Main Outcome Measure(s): Serum levels of inhibin A, inhibin B, or-inhibin, pro-alpha C (alpha-inhibin precursor proteins), LH, FSH, E-2, T, and andros tenedione (A) were assessed in all subjects. Result(s): Serum alpha-inhibin levels together with LH, T, and A levels wer e significantly increased in women with PCOS. Serum inhibin A levels were l ower in patients with PCOS than controls (median +/- SD: 7.35 +/- 2.9 vs. 9 .4 +/- 4.7 pg/mL), pro-alpha C levels were higher (265 +/- 136.7 vs. 127 +/ - 81.5 pg/mL), and inhibin B levels did not differ between the groups (110. 5 +/- 515 vs. 108 +/- 47.5 pg/mL). Simple regression analysis showed that i nhibin A and B levels were negatively correlated with BMI in patients: with PCOS (r = -0.43 and r = -0.47). Indeed, obese patients with PCOS (BMI >27 kg/m(2)) displayed significantly lower inhibin A and inhibin B levels and a higher pro-alpha C-inhibin A ratio than nonobese patients with PCOS (BMI l ess than or equal to 27 kg/m(2)). In this last subgroup, the mean inhibin B level was significantly higher than in controls (median +/- SD: 144 +/- 53 .5 vs. 108 +/- 47.5 pg/mL). Partial regression analysis, after controlling for age and BMI, demonstrated that in patients with PCOS, pro-alpha C level s were positively and independently correlated with LH and A levels. Conclusion(s): Among women with PCOS, the trend toward an excess serum inhi bin B level is observed exclusively in nonobese patients. The higher pro-al pha C levels and the lower inhibin A levels might reflect a defect in the p rocessing of inhibins specific to polycystic ovaries. In addition, our data suggest that pro-alpha C originates from the theca-interstitial cells and could participate in control of the androgen production by these cells. (Fe rtil Steril(R) 2000;73:972-7. (C) 2000 by American Society for Reproductive Medicine).