Gonadal function in men with chronic illness

Normal testicular hormonal and spermatogenic function depend not only on the testis itself, but also on the integrity of the hypothalamus and anterior pituitary, which form a closed loop functional axis with negative feedback. Systemic disease has been shown to influence male gonadal function in a variety of ways, leading to reduced libido and erectile impotence, infertility, osteoporosis and decreased physical stamina and muscle mass. The effects of systemic disease may occur directly at the testicular level: reduced Leydig cell function will lead to androgen deficiency, while diseases affecting spermatogenesis may lead to male infertility. Alternatively, acute and chronic illness may interfere with the hypothalamic-pituitary axis and so lead to reduced testicular function. Hypogonadism may be defined as reduction in the functional activity of the testis, and may be primary (due to testicular disease) or secondary (due to hypothalamic-pituitary disease). Biochemical criteria in terms of testosterone levels are difficult to specify because there is a wide range of normality in the general population. Primary hypogonadism is easier to define biochemically as in general there will be lowered testosterone levels associated with elevations in gonadotrophins, however, secondary hypogonadism is more difficult to define as testosterone levels may be at the lower end of the normal range and associated with normal levels of gonadotrophins. While there may be an evolutionary or biological advantage of a low testosterone level in chronic illness as reduced sex drive and fertility will enable conservation of energy for recovery from illness and might also prevent ill males from reproducing, there are situations where low testosterone levels may not be ideal; for example leading to reduced muscle bulk in neurological conditions or respiratory failure. Severe illness of any kind may produce hypogonadotrophic hypogonadism. In a group of 30 male in-patients on a general medical ward, mean testosterone levels were found to be reduced to 49% of control values ( P<0.001) (Sempleet al., 1987). Duration of illness and whether it was acute or chronic did not significantly influence the actual level of testosterone, although testosterone values were slightly but nonsignificantly lower in those with chronic illness compared with those who were acutely ill. Follicle stimulating hormone (FSH), luteinising hormone (LH) and prolactin levels were not significantly different between the two groups. Changes in thyroid hormone levels with illness are common – ‘sick euthyroidism’, although many suggest this to be a misnomer and that the term nonthyroidal illness syndrome would be more appropriate (Chopra, 1997). In the Semple study, tri-iodothyronine (T3) and testosterone levels showed some correlation ( r 1⁄4 0.423, P< 0.05) but there was no correlation between testosterone and T4 (Semple t al., 1987). Unlike the thyroid abnormalities associated with chronic illness, neither changes in binding proteins nor abnormalities of peripheral conversion are seen in male hypogonadism associated with illness. Altered LH secretion or LH biological activity have been implicated as important in pathogenesis (Semple et al., 1987). This review will consider ageing and critical illness in addition to specific chronic illnesses, but will not consider diseases specific to the testis which affect gonadal function.