To the Editor: I appreciated the recent comprehensive review of androgen deficiency and replacement therapy in men by Handelsman and Zajac.1 I ask their opinion of the importance of obstructive sleep apnoea as a cause of secondary hypogonadism, and also of the safety of androgen replacement in men with hypogonadism who have obstructive sleep apnoea but are intolerant of continuous positive airway pressure (CPAP) treatment.

In my practice, obstructive sleep apnoea is one of the most common associations, if not indeed causes, of hypogonadotropic hypogonadism. Several studies have shown that obstructive sleep apnoea is associated with secondary hypogonadism, which is partly or completely reversed by both CPAP treatment and uvulopalatopharyngoplasty.2-4 Secondary hypogonadism is also a feature of several conditions in which there is a high prevalence of obstructive sleep apnoea, including chronic spinal cord injury and cardiac failure. Of concern, studies have shown that androgen replacement may precipitate or worsen obstructive sleep apnoea.5,6

Similarly, a study of women with endogenous androgen excess caused by polycystic ovary syndrome found they were 30 times more likely to suffer from sleep-disordered breathing than control women.7 A single case report describes resolution of obstructive sleep apnoea in a non-obese woman after removal of a benign testosterone-producing ovarian tumour.8

Thus, I would value Handelsman and Zajac’s comments as to whether they consider obstructive sleep apnoea to be an important cause of secondary hypogonadism, and whether symptoms of this condition should be sought before initiating androgen replacement therapy.

In reply: We thank Morton for his thoughtful comment that, in addition to monitoring for obstructive sleep apnoea precipitated by testosterone therapy, it may be worthwhile screening for this condition before starting treatment. Symptoms to be sought include daytime sleepiness and partner reports of loud and irregular snoring, especially among overweight men with large collar size.

Obstructive sleep apnoea rises steeply in prevalence with age and causes mild hypogonadotropic hypogonadism, which is rectified by effective continuous positive airway pressure (CPAP) treatment.1 Obesity, depression, cardiovascular disease and other conditions that become more common with age have similar effects. Together, they contribute to the lower blood testosterone levels found in unselected older men, in whom testosterone remains an unproven treatment.2 This condition differs from classical hypogonadotropic hypogonadism caused by hypothalamic or pituitary disorders, which routinely requires lifelong testosterone replacement, and (occurring in a younger population) is rarely associated with obstructive sleep apnoea.

The prevalence of obstructive sleep apnoea precipitated by testosterone treatment remains unclear. A case precipitated by injectable testosterone has been reported,3 while testosterone has potential adverse effects on sleep in older men.4 Clinical experience suggests that, among younger hypogonadal men, obstructive sleep apnoea is a rare idiosyncratic reaction to testosterone, which, like polycythaemia, may be particularly related to supraphysiological blood testosterone levels. However, the prevalence may be higher among older men. Hence, we agree that pretreatment screening is wise (rather than proven) for older men starting testosterone treatment, but is not routinely necessary for young men with classical hypogonadism.