Introduction

The menopause in women is fairly easily defined, as it corresponds to a manifest change in reproductive function that is relatively sudden. The existence of a corresponding change in men has not been generally accepted. However, in 1944 an important paper described the symptoms of a condition in men associated with a decline in testosterone concentrations, which could be reversed by hormone replacement treatment but not by placebo.¹ The term "male menopause" was applied by others, and has unfortunately stuck, although the authors used the much more suitable term "male climacteric syndrome". The British Medical Journal has just reopened a discussion about the existence off the male menopause, in a debate-style article.

In favor of the entity "male menopause"

Blood testosterone concentrations critical for sexual functioning lie around 11 nmol/L (320 ng/dL) and above - such levels are found in 99% of healthy men aged 20 - 40. As men age there is a natural decrease in the total mass of Leydig cells and some dysfunction of hypothalamic-pituitary homeostatic control, both of which contribute to low luteinising hormone levels, and hence reduced testosterone production. The decline in testosterone production starts in early middle age and progresses linearly. In parallel, there is an increase in plasma concentrations of sex hormone-binding globulin, resulting in a more pronounced decline in the amount of bioavailable or "active" testosterone. Concentrations of bioavailable testosterone decrease by as much as 50% between the ages of 25 and 75, and it has been estimated that as many as 50% of men over 50 have relevant hypotestosteronemia. The age-related reduction in hypothalamic-pituitary circadian rhythm can result in exaggerated falls in testosterone levels in the evening hours.

Heredity plays a role in the development of hypotestosteronemia, as it has been shown that most of the variability in testosterone concentrations and a third of the sex hormone-binding globulin decline depend on genetic factors. Other risk factors for early or exaggerated falls in testosterone are a history of orchitis, trauma to the testes, obesity, and impaired insulin utilization. Excess alcohol intake is often associated with lowered testosterone levels, whereas the influence of physical and psychological stress is still debatable.

The fact that both a decline in sexual interest and potency and a fall in testosterone levels occur with aging obviously suggests that sexual behavior is largely dependent on testosterone levels. This is not however not necessarily the case - there are many other causes of impotence in elderly man, e.g. vascular changes, pharmaceutical drug effects, neuropathies, etc.

The reported symptoms of the male climacteric syndrome include: depression and nervousness, flushes and sweats, decreased libido, erectile dysfunction, fatigue, poor concentration and poor memory. These have all been associated in clinical studies with lowered blood levels of testosterone. In several prospective studies symptoms are significantly improved by androgen supplementation, with recurrence during its withdrawal.

Additional changes associated with aging include increased central and upper body fat deposition and reduced muscle mass. This can be explained by the age-associated reduction in growth hormone, which is associated with an increase in sex hormone-binding globulin and therefore a reduction in bioavailable testosterone. There is no doubt that testosterone supplementation in such men improves fat-free mass, muscle bulk and muscle strength.

Changes in bioavailable testosterone levels are correlated with altered bone mineral density measurements at various sites, and men with low testosterone levels are at an increased risk of hip fracture. Again, testosterone replacement therapy is beneficial. The vasomotor disturbances reported (flushes and sweats), along with visual spatial ability deficiencies, can be reversed with testosterone. An association between low testosterone levels and risk factors for coronary artery disease in men has also been reported, and these can be improved by testosterone administration.²

Against the entity "male menopause"

The principal argument against the concept of a male menopause is that, unlike the female menopause, it must be a gradual change, in which the symptoms cannot be definitely ascribed to testosterone deficiency. Mere association between variables is not the same as causation - to obtain evidence of causation one requires results from intervention studies (this is discussed in our Introduction to Risk Factors paper). Although supplemental testosterone has been reported to improve many of the symptoms seen in the male climacteric, the doses used are hardly physiological. When physiologically appropriate doses of testosterone were given to elderly man sufficient to raise their serum testosterone levels into the range suitable for 20-year-olds, there were no beneficial effects on bone mineral density or muscle strength, although lean body mass increased and there was a fall in fat mass.³

In particular, the role of testosterone in declining sexual activity in elderly man is not well defined. As many as 80% of cases of erectile dysfunction are thought to have a medical cause, such as diabetes, cardiovascular disease, neurological disorders (e.g. multiple sclerosis, spinal injury), surgery (prostatectomy) and trauma. Indeed, some have claimed that erectile dysfunction should be regarded as a "sentinel of disease" and lead the physician to search diligently for its cause.

The availability of Viagra ® (sildenafil citrate) has allowed the successful treatment of erectile dysfunction of multiple etiology, and, in the absence of hypogonadism, it is clearly safer from a risk/benefit viewpoint than injections of testosterone - reduced plasma HDL-cholesterol, increased erythropoiesis and stimulated growth of an existing prostate carcinoma are known adverse effects of androgen treatment.

The other symptoms of the male climacteric can equally well be ascribed to endocrine changes associated with age other than testosterone decline. Thus the "adrenopause" (fall in dihydroepiandrosterone) or "somatopause" (decline in secretion of growth hormone and insulin-like growth factor) in old people require further study - particularly as they result in diseases (diabetes, hypothyroidism) that are more readily treatable, and with greater success, than those associated with the male climacteric.

Comment

This debate is in fact unnecessary. Whatever the term employed, men with age-related decline in their well-being, including sexual interest and ability, can be helped by their physician. Abnormally low testosterone levels will benefit from hormone supplementation, whereas men with erectile dysfunction can usually be satisfactorily treated with silendafil or other specific therapy.