The male menopause—does it exist?

British Medical Journal, March 25, 2000 by Duncan C Gould, Richard Petty, Howard S Jacobs

For and against

Be it "andropause" or "climacteric," do men undergo some kind of hormonal change akin to the female menopause? Adding to the growing debate about men's health, Duncan Gould and Richard Petty argue that some patients need investigation and treatment with testosterone. Howard Jacobs, however, is not convinced.

FOR

The term "male menopause" is inappropriate as it suggests a sudden drop in sex hormones such as occurs in women in the perimenopausal state. It is not an inevitability but may occur mainly in middle aged and elderly men when testosterone production and plasma concentrations fall. There seems to be a threshold plasma concentration below which symptoms may become apparent. Testosterone concentrations found to be critical for sexual functioning in men lie around 10.4 nmol/l (300 ng/dl), though there is variation between individuals.[1] While some have found that differences in plasma testosterone concentrations within the normal range in young healthy men do not correlate with differences in sexual activity and interest, others have shown that differences in the concentrations of the potent metabolite, dihydrotestosterone, do.[2 3]

Earlier this century the term "male climacteric" (from the Greek klimacter--the rung of a ladder) was used and is more appropriate as it suggests a decline and not a precipitous drop in hormones concentrations.[4 5] A landmark paper of 1944 accurately described symptoms, reversed by testosterone replacement but not by placebo, seen in men suffering from an age associated decline in testosterone concentrations.[5] Owing to the similarity between most of the symptoms in men and women the term "menopause" gained popularity and has unfortunately stuck.

An abnormally low concentration of testosterone (hypotestosteronaemia) may occur because of testicular dysfunction (primary hypogonadism) or hypothalamic-pituitary dysfunction (secondary hypogonadism) and may be congenital or acquired.

Endocrinology

In the ageing man reduction in testosterone concentration is due mainly to a decline in Leydig cell mass in the testicles or a dysfunction in hypothalamic-pituitary homeostatic control, or both, leading to abnormally low secretion of luteinising hormone with resultant low testosterone production. It is well recognised that with normal male ageing mean plasma testosterone concentrations decline, albeit with considerable variability between individuals and with a broad range in age related values.

Cross sectional and prospective studies show a decline that starts in early middle age and then progresses in a linear fashion.[6-11] Mirroring this decline in plasma testosterone concentration is an age associated increase in plasma concentration of sex hormone binding globulin, resulting in a more pronounced decline in the active or bioavailable testosterone moiety.[12-14] Concentrations of bioavailable testosterone decrease by as much as 50% between the ages of 25 and 75 years,[15] and it has been proposed that with respect to bioavailable concentrations as many as 50% of men over the age of 50 are hypotestosteronaemic when compared with peak early morning concentrations in young men.[16] With age there is a loss of hypothalamopituitary circadian rhythm, which may result in exaggerated falls in plasma testosterone concentrations by evening.

Effects of hypotestosteronaemia

A quantitative definition of hypotestosteronaemia has generally been accepted as 11 nmol/l (320 ng/dl) as only 1% of healthy men aged 20-40 will have a concentration below this limit.[17] Development of hypotestosteronaemia may be related to heredity as 60% of the variability of testosterone concentrations and 30% of sex hormone binding globulin may be due to genetic factors.[18] A history of orchitis, testicular trauma, or other pathology may be contributory. The presence of obesity is associated with lower concentrations of bioavailable testosterone,[19] and insulin concentrations have been found to be indirectly correlated with sex hormone binding globulin and testosterone concentrations.[20] With respect to lifestyle, excess intake of alcohol and physical and psychological stress are all associated with lowered testosterone concentrations.[21 22]

Ageing is usually associated with a decline in sexual interest and potency.[23] This suggests such changes in sexual behaviour are androgen dependent but does not prove the case. Although erectile dysfunction in elderly men is often of non-hormonal aetiology, testosterone deficiency accounts for 6-45% of all cases.[24]

Affective symptoms have long been associated with hypotestosteronaemia: depressed mood is significantly correlated with low concentrations of bioavailable testosterone in older men.[14] Some longitudinal uncontrolled studies of hypotestosteronaemic men have shown that symptoms of depression, anger, irritability, sadness, nervousness, friendliness, sense of wellbeing, and energy levels significantly improved with androgen treatment.[25 26] There is evidence for mood disturbance being linked to hypotestosteronaemia and for testosterone replacement therapy being beneficial, but placebo controlled trials are needed to confirm these issues. Fatigue may occur with hypotestosteronaemia. During one prospective study symptoms significantly improved with supplementation and decreased during androgen withdrawal, another showed significant improvements in energy levels and tiredness.[26]