Non-classical 21-hydroxylase deficiency: prevalence in males with unexplained abnormal sperm analysis

Objective To evaluate the prevalence of nonclassical 21-hydroxylase deficiency (NC-21OHD) in men with abnormal sperm parameters of unexplained etiology compared with males with normal sperm analysis. Design Case control study. Setting Major tertiary medical center. Patient(s) Of 484 healthy men being followed at a fertility clinic, 222 (mean age 33.8 ± 6.1 [±SD] years) presented with abnormal findings on sperm analysis (1999 WHO criteria) of unknown cause and 262 (mean age 34.8 ± 6.5 [±SD] years) with a normal sperm analysis. Intervention(s) Random mid-morning blood sampling to test for 17-hydroxyprogesterone (17-OHP) levels. Subjects with levels of ≥ 6 nmol/L underwent a standard adrenocorticotropic hormone (ACTH) stimulation test. Main Outcome Measure(s) NC-21-OHD, defined as a stimulated ACTH level of ≥45 nmol/L. Result(s) A serum 17-OHP level of ≥6 nmol/L was detected in 11 study patients (5.0%) and 14 control subjects (5.3%). Seven study patients and 8 controls subsequently underwent ACTH stimulation test, and none had levels compatible with a diagnosis of NC-21OHD. Mean 17-OHP levels were similar in the two groups (3.3 ± 1.4 [±SD] nmol/L and 3.3 ± 1.5 [±SD] nmol/L, respectively). There was no correlation between sperm parameters and serum 17-OHP levels. Conclusion(s) Until larger studies are performed, the routine measurement of 17-OHP in the evaluation of male infertility is not recommended.