By Johen E. Morley, MB, BCh

It is now been clearly demonstrated both in cross-sectional and longitudinal studies that testosterone levels decrease over the lifespan in males. Because of the increase in sex hormone binding globulin in aging, the decline in testosterone levels is even greater when a measurement of free of bioavailable testosterone (free testosterone together with that weakly bound to albumin) is made. It has been estimated that 5% of men aged 40 years and 70% of men aged 70 years have bioavailable testosterone levels below the normal value of young men; in other words, they are hypogondal. This translates into 20 million to 25 million men in the United States who have undergone the equivalent of the male menopause

Because the decline in testosterone levels is gradual – approximately 10% per decade after the age of 40 years – it has drawn less attention that the dramatic change that occurs in females at the time of the menopause. In addition, female menopause occurs because of failure of the ovaries, leading to an increase lutenizing hormone (LH) to accompany the fall in estrogens, whereas the male menopause is predominantly due to a failure of the hypothalamic-pituary unit (i.e., secondary hypogonadism) and thus is not associated with an increase in LH. Thus diagnostic difficulties, such as a need for a more sophisticated (can’t understand the word) and the failure for an increase in LH, have obscured the clear development of a male equivalent of the female menopause.

The male menopause is often referred to as the andropause, or androgen deficiency in aging males (ADAM), or viropause (when coupled with the onset of erectile dysfunction). The acceptance of male menopause has had a checkered past, with the first recognition occurring in ancient Roman times and later in the early Chinese medical literature. It was first scientifically explored toward the end of the 19^th century, when Charles Edouard Brown-Sequard, then in his 70s, injected himself with a testicular extract to enhance his function. This led to the era of rejuvenation by testicular extract injections followed by chimpanzee testicle transplants, which were pioneered by Serge Voronoff. With the isolation and manufacture of testosterone in the 1940s, a number of studies appeared suggesting that testosterone may alleviate the symptoms of the male climacteric.

It has not been until the past decade, however, that the publication of a number of controlled studies has led to the scientific validation that some of the symptoms of male menopause can be alleviated by testosterone replacement. A cross-sectional study found a strong correlation between free androgen index and the decline in appendicular muscle mass and muscle strength in older persons. Subsequent testosterone replacement studies have shown that in older hypogondal men testosterone increases muscle mass and upper limb strength. It is well recognized that aging is associated with a decline in muscle mass and strength. This melting away of muscle with aging has been termed sarcopenia, and it appears that it is in part due to age-associated testosterone deficiency.

Testosterone deficiency also has been shown to by associated with a decline in function in the aging male. Recently, it has been shown that testosterone administration improves function when administered to older males undergoing rehabilitation. Testosterone decline has been clearly associated with the decrease in libido that occurs at middle age and beyond in older males; testosterone replacement reverses this problem. In addition, testosterone is necessary for the elaboration of nitric oxide plays an important role in vasodilation necessary for penile erection, and lack of testosterone results in relatively soft erection.

Numerous other positive effects of testosterone now have been demonstrated in the older male. These include an increase in bone mineral density, which should lead to a decrease in hip fractures. Although hip fractures occur lately in males than in females, they are associated with a greater mortality rate. In older males, the fat hormone leptin increases in the circulation, and the levels of leptin are decreased by testosterone. This increase in leptin levels has been associated with the physiological anorexia of aging and the subsequent weight loss that occurs in older men.

Hematocrit levels fall with aging these levels are restored to normal by testosterone. There is decline in cognitive ability with aging that is strongly associated with the decline in bioavailable testosterone. Testosterone replacement improves age-related cognitive decline, and in an animal model of Alzheimer’s disease testosterone replacement reversed the memory defects. Low testosterone levels are associated with coronary artery disease, and testosterone replacement improves myocardinal function.

At this stage, the existence of a series of symptoms associated with the age-associated fall in testosterone levels can no longer be argued. In addition, these symptoms are reversed by testosterone replacements. Thus, the existence of the male menopause, or ADAM, is incontrovertible. The availability in the United States of new forms of testosterone gel, now make it unconscionable for the physician not to screen and to treat hypogondism in older males.