Fertility, sexuality and testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia

Abstract

Objective: Fertility in males with congenital adrenal hyperplasia (CAH) is reported from normal to severely impaired. Therefore, we investigated fertility/fecundity, social/sexual situation, and pituitary-gonadal function in CAH males.

Subjects and methods: The patient cohort comprised 30 males, aged 19-67 years, with 21-hydroxylase deficiency. Their fertility was compared with age-matched national population data. For the evaluation of social/sexual factors and hormone status, age-matched controls were recruited (n = 32). Subgroups of different ages (<30 years and older) and CYP21A2 genotypes (null (severe salt-wasting (SW)), I2splice (milder SW), and I172N (simple virilizing)) were also studied. Patients underwent testicular ultrasound examination (n = 21) and semen analysis (n = 14).

Results: Fertility was impaired in CAH males compared with national data (0.9 ± 1.3 vs 1.8 ± 0.5 children/father, P<0.001). There were no major differences in social and sexual factors between patients and controls apart from more fecundity problems, particularly in the I172N group. The patients had lower testosterone/estradiol (E(2)) ratio and inhibin B, and higher FSH. The semen samples were pathological in 43% (6/14) of patients and sperm concentration correlated with inhibin B and FSH. Testicular adrenal rest tumors (TARTs) were found in 86% (18/21). Functional testicular volume correlated positively with the testosterone/E(2) ratio, sperm concentration, and inhibin B. Patients with pathological semen had increased fat mass and indications of increased cardiometabolic risk.

Conclusions: Fertility/fecundity was impaired in CAH males. The frequent occurrence of TARTs resulting in testicular insufficiency appears to be the major cause, but other factors such as elevated fat mass may contribute to a low semen quality.

Figure 1

Illustration of the steps in the 3D inversion rendering process of right testicle of a 30-year-old male with CAH (genotype null/null) with two children. Acquisition in the three orthogonal planes and the rendered volume in the bottom right box. By eliminating the surrounding non-pertinent structures with the electronic scalpel, the structures of interest were left as the final inverted and rendered volume. In this case, it could be seen that the tumor was calcified and had a cystic structure (right bottom corner, the tumor marked with an arrow). In the left upper box, the tumor is marked with arrows (the size of the tumor was measured to be: 2.6×1.1×0.9 cm, corresponding to a volume of 1.4 cm³). Full colour version of this figure available via http://dx.doi.org/10.1530/EJE-11-0828.

Figure 2

Correlation between inhibin B (upper panel), total functional testicular volume (lower panel) and sperm concentration, and total functional testicular volume and inhibin (middle panel) in adult males with CAH due to 21-hydroxylase deficiency.