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

21-Hydroxylase Deficiency Associated with Male Infertility: Report of 2 Cases with Gene Analyses

“…Regarding the underlying mechanism of male infertility in 21-hydroxylase deficient patients, suppression of gonadotropin secretion by increased adrenal steroids due to the untreated deficiency is considered to be the cause of spermatogenesis failure (16), while it has also been suggested that the main cause of infertility in such patients is the presence of testicular adrenal rest tumors, thought to originate from aberrant adrenal tissue (17), which compress the seminiferous tubules, causing obstructive azoospermia (18). In the present two cases, though low serum concentrations of LH and FSH were observed, neither steno-sis nor compression of seminiferous tubules by a testicular tumor was identified, which supports the speculation that the suppression of gonadotropin by increased adrenal androgens due to untreated 21-hydroxylase deficiency may result in sperm dysfunction (19).…”

The spectrum of clinical, hormonal and molecular findings in 280 individuals with nonclassical congenital adrenal hyperplasia caused by mutations of the CYP21A2 gene

“…This figure must represent an underestimate, considering the fact that our referrals primarily come from paediatric endocrine units. Of particular interest is the fact that in one couple, both partners with NC‐CAH presented only with subfertility . Hence, the physician should be aware of this possibility in subjects with subfertility, especially males.…”

“…Of particular interest is the fact that in one couple, both partners with NC-CAH presented only with subfertility. 30 Hence, the physician should be aware of this possibility in subjects with subfertility, especially males.…”

The Impact of Genetic Steroid Disorders on Human Fertility

“…In males with NC-CAH, gonadal dysfunction, oligospermia, and precocious puberty have been reported [98,99]. While screening for CAH is not recommended for all men with abnormal semen analyses, measurement of 17-OHP should be assessed in men with unexplained abnormal semen parameters associated with hypogonadotropism [101]. In a Finnish study examining the child rate of adult male patients with 21-hydroxylase deficiency, the rate of paternity compared with the age-matched general Finnish male population was markedly diminished (0.07 versus 0.34) [100].…”

“…Both undertreatment and overtreatment can affect semen production in males [111]. Inadequately controlled adrenal androgens are peripherally converted to estrogens, which subsequently suppress gonadotropin secretion and leads to Leydig cell impairment [101,112,113]. On the other hand, overtreatment with exogenous corticosteroids has been shown to be associated with hypogonadotropic hypogonadism [111].…”