Low 11‐deoxycortisol to cortisol conversion reflects extra‐adrenal factors in the majority of women with normo‐gonadotrophic normo‐estrogenic infertility

BACKGROUND: Women with normogonadotrophic normo-estrogenic oligomenorrhoea often disclose a variety of clinical symptoms. Many of these individuals are obese with features of pseudo-hypercortisolism. In the current study, 11-deoxycortisol and cortisol concentrations were determined in this group and compared with ovulatory controls. METHODS AND RESULTS: Twenty-six women with clomiphene citrate-resistant infertility, 12 lean and 11 obese ovulatory controls were studied. Women with infertility had the highest 11-deoxycortisol concentrations (mean +/- SD: 4.1 +/- 1.5 ng/ml) compared with obese and lean controls (3.1 +/- 1.4 and 2.4 +/- 0.9 ng/ml) (P 90th percentile of ovulatory controls) were elevated in 23/26 infertile women (88%), and in 3/26 women (12%) after adrenocorticotrophic hormone (ACTH) stimulation. Three out of six lean infertile women had elevated baseline 11-deoxycortisol/cortisol ratios, but none of these women had elevated ratios after ACTH stimulation. Stepwise regression analysis, after exclusion of testosterone, revealed significant correlations between the groups (lean controls, obese controls, infertility) and ACTH-stimulated 11-deoxycortisol/cortisol ratio (P <0.05), but not with fasting glucose, insulin, cortisol, 11-deoxycortisol and baseline 11-deoxycortisol/cortisol ratios. CONCLUSIONS: Congenital adrenal hyperplasia was not observed in the majority of infertile women. The data indicate that extra-adrenal factors were involved in most of the infertility syndromes that were studied.