Hypogonadism of ageing - does low testosterone in ageing men require treatment?

In the healthy ageing male, a number of studies have shown that blood levels of the male hormone, testosterone, falls by a modest 1-2% annually from the age of 40 onwards. The rate and extent of this fall in testosterone varies between individuals and usually brings the levels to around the lower part of the normal range for young men eg 8-11nmol/l, in whom the reference testosterone range for blood sampled at 09.00am is 10-30nmol/l. The clinical significance of this downward trend is unclear.

Ageing is associated with increased fat (particularly abdominal fat), decreased muscle bulk, muscle strength and restricted physical activity, a decrease in bone mineral density, and a greater fracture risk, and diminished / poorer quality sexual function. Although these non-specific clinical features can occur in many chronic illnesses, they do share an uncanny resemblance to some of the key symptoms of hypogonadism - testosterone deficiency resulting from diseases in the testis or pituitary gland. There has been an assumption by many physicians that these symptoms must be caused by testosterone deficiency, and the term ‘andropause’ (or ‘male menopause’ in the popular media) has been used in this context. However, a cause and effect relationship has not been established by any means and, at present, it is uncertain how many of the symptoms and changes encountered in the ageing male might be reversed by restoration of blood testosterone levels to those seen in younger men. In some relatively small studies, testosterone administration to middle-aged and elderly men with muscle weakness and poor bone density and low or low normal testosterone, testosterone supplementation has been shown to increase bone density and muscle mass with a slight reduction in fat mass.

Whether these physiological changes also lead to physical and psychological improvements and enhanced quality of life is still uncertain. Furthermore, there may also be significant side effects to testosterone supplementation in elderly men, which may lead to an increase in sleep related problems (eg sleep apnoea: a situation where normal breathing during sleep is interrupted by pauses leading to lack of oxygenation of the blood, a rise in blood pressure etc), prostate enlargement, progression of previously undiagnosed prostate cancer, and an inappropriate increase in circulating red cell numbers (this can thicken the blood and make a patient more prone to thrombosis).

While patients with symptomatic and unequivocal biochemical deficiency of testosterone due to hypogonadism will clearly benefit from testosterone replacement, the potential benefits and risks of treating low testosterone in ageing men are currently unknown. To resolve the growing uncertainties, there is an urgent need for large properly designed studies to investigate the risk to benefit effects of testosterone supplementation in symptomatic ageing men with low normal testosterone levels. There are several such studies underway, and results are likely to become available in 2006/2007.

Until the results of such studies become available, testosterone supplementation should be withheld from healthy ageing men and administered to symptomatic ageing men only where there is clinical and biochemical evidence of androgen deficiency according to criteria established in the management of younger patients with hypogonadism. In the interim, patients concerned about potential symptoms of hypogonadism should consult their GP, who will be best positioned to make the initial assessment and, where appropriate, carry out the necessary blood tests. An onward referral to an endocrinologist is occasionally required. Some patients experiencing the symptoms described above may benefit from a change in lifestyle – for example increasing exercise, weight loss – or from diagnosis and treatment of mild depression.

PMGB 21.1.05.