Fertility Issues for Men with CAH

The two main fertility issues for men with CAH are testicular abnormalities and low testosterone. Both of these conditions can occur as a result of inadequate treatment or limited intake of glucocorticoid and mineralcorticoid replacements and cause reduced sperm production. In the past, glucocorticoid (steroid) treatment for men with non salt-wasting CAH was often stopped after final height had been achieved (under the assumption that all other issues were primarily ‘cosmetic’). However, the most recent studies indicate the need for ongoing treatment of salt-wasters and simple-virilizers to maintain fertility and reduce possible testicular abnormalities.

Testicular Abnormalities
The testicles and adrenal glands are made of similar tissue. Within the testicles there is a normal amount of adrenal cells that do not typically affect fertility. However, without adequate medication or treatment, men with Classic CAH may develop testicular masses (usually benign) called adrenal rests and, in rare cases, enlarged testes.

When treatment is inadequate or sporadic in a male with CAH, the adrenal cells may grow into masses that release hormones hindering sperm production. This happens when cortisol levels are too low and there is over secretion of ACTH by the pituitary. Just as ACTH stimulates the adrenal glands and causes them to enlarge (hyperplasia) it also stimulates the adrenal cells in the testicles.

It is important to note that in patients with known CAH, adrenal rest tissue is not usually malignant and can be clinically differentiated from Leydig cell tumors by virtue of the fact that it is usually bilateral and common in men who show other evidence of poor adrenal suppression. Also, if the mass is located near the mid-center line of the testes and does not distort the contour of the testes it is likely an adrenal rest and not a malignancy.

Fortunately, adrenal rest tissue usually regresses with increased glucocorticoid treatment to reestablish optimal cortisol levels and suppress ACTH secretion. Once the correct cortisol levels have been restored, the body may be able to return to normal levels of sperm production. It may take several months to achieve normal sperm production after the increased glucocorticoid dosages have been initiated.

Enlarged testes in men with CAH are generally a result of inadequate treatment over the course of many years. The enlargement normally recedes once the cortisol levels are increased, through aggressive glucocorticoid therapy. The doctor may recommend to perform a biopsy of the enlarged testicle to ensure that there is no cancer present. CAH does not cause cancer, but it is good practice ensure that there are not other reasons for the enlargement.

Low Testosterone
It may seem counterintuitive to experience low testosterone in a disorder where the primary symptoms occur as a result of androgen excess, but this can be a frequent cause of infertility in men with uncontrolled CAH.

Men with Classic CAH who are not well suppressed will have uncontrolled adrenal androgen secretion. When too much testosterone is made by the adrenal glands over a long period of time, the body aromatizes (converts) the androgens to estrogen. The estrogen then feeds back to the pituitary which, sensing the body has enough testosterone, stops secreting the hormones that stimulate the testicles to make testosterone. This is called hypogonadotrophic hypogonadism, where the testes “shut down,” stop producing sperm and even shrink. As with adrenal rests, this condition can also (usually) be reversed with aggressive glucocorticoid therapy.

Long-term Care
Men with CAH who are interested in fertility should pay special attention to their endocrine care. Compliance (taking medicine as prescribed) is essential in avoiding adrenal rests and fertility problems. It is a good idea to establish a baseline picture of the testes after puberty with a testicular ultrasound. If no problems are found, the endocrinologist may recommend follow-up ultrasounds every few years. Men with adrenal rests that do not respond to glucocorticoid suppression can consider testis-sparing surgery with malignancy being ruled out.