New insights into androgen treatment of erectile dysfunction

Erectile response in mammals is centrally and peripherally regulated by androgens. Severe hypogonadism in men usually results in loss of libido and potency which can be restored by androgen administration. The original insights into the mechanisms of action of androgens on sexual function indicated that androgens particularly exert effects on libido and that sleep-related erections were androgen-sensitive but erections in response to erotic stimuli were relatively androgen-independent.

There are a number of recent developments which shed new light on testosterone treatment of erectile dysfunction in aging men.

There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological/biochemical substrate of erectile capacity, reversible upon androgen treatment. Several studies have indicated that the administration of PDE-5-inhibitors is not always sufficient to restore erectile potency in men and that administration of testosterone improves the therapeutical response to PDE-5-inhibitors considerably.

There is increasing insight not to view erectile dysfunction (ED) as a single entity but as part of the aging process. Circulating levels of testosterone are closely related to manifestations of other etiological factors in ED, such as atherosclerotic disease and diabetes mellitus. The latter are correlated with lower-than-normal testosterone levels.

This contribution will focus on the role of testosterone in erectile dysfunction (ED). Systematic observations became possible when testosterone became pharmaceutically available in the middle of the last century. The first studies pointed to a prominent role of testosterone in sexual interest while the effects of testosterone on erectile function were less apparent from these investigations In the view of many practitioners, treatment of ED with testosterone was not very efficacious. Then, in 1999 a class of new drugs, the phosphodiesterase Type 5 inhibitors (PDE-5 inhibitors) were introduced. The introduction of these highly efficacious and relatively safe compounds has had a profound impact on the diagnosis and treatment of ED. Once mainly the domain of the urologist attempting to define its precise etiology, ED is now largely treated by first-line physicians, usually without much of a diagnostic work-up, but with a degree of success. Despite the simplicity and safety of the present therapy of ED with PDE-5 inhibitors, approximately 50% of patients discontinue treatment. The reasons for discontinuation lie for a large part in an incomplete evaluation of the sexual problem. Hypogonadism, ejaculatory dysfunction, lower urinary tract symptoms, depression and last but not least, partner issues may all be components of the sexual dysfunction of the patient and should have been part of the diagnostic work-up of the patient.

Over the last years there is a renewed interest in the role testosterone in male (patho) physiology and more particular in a better definition of the place of testosterone in ED. Recent studies provide convincing evidence that there is powerful effect of testosterone on the anatomical and physiological substrate of penile erection. Furthermore, it has become clear that testosterone is not simply one of the many factors playing a role in erectile (dys) function. Circulating levels of testosterone are closely related to manifestations of other etiological factors in ED, such as atherosclerotic disease and diabetes mellitus. The latter are correlated with lower-than-normal testosterone levels. Therefore, the role of testosterone in erectile (dys) function is increasingly recognized.