Andropause

 

The menopause is a condition with proven pathophysiology leading in some women to unpleasant symptoms and bone loss over the years. Although there is no analogous process in male, the term "andropause" is being increasingly used to describe symptoms including lack of energy, depression decreased libido and erectile dysfunction occurring in middle aged or elderly men with a testosterone level at the lower end of normal range. Andropause, therefore, may imply a state of hormonal deficiency secondary to gonadal failure.

Androgens (male sex hormones) are secreted by Leydig cells of the testis in the form of Testosterone (0.24mmol/day) and by the adrenal cortex in the form of androstenedione (0.002mmol/day). Testosterone is the main male sex hormone metabolizing to the biologically active dihydrotestosterone (DHT) by 5-alpha-reductase and aromatizing to the female hormone estradiol.

Testosterone is mainly bound to sex-hormone binding globulin, albumin and cortisol-binding globulin with only 2% remaining free. This free portion is thought to be biologically active. Although the testosterone level is progressively decreased with age, it remains within normal range. Free testosterone level declines considerably between ages 40 and 70. These changes are statistically significant but always in the normal range.

The level of dihydrotestosterone is fairly stable.

Dehydroepiandrosterone (DHEA), an adrenal androgen at highest concentration in the blood of men and women, and its metabolite DHEA sulfate (DHEAS) declined 3% per year and failing by age 70 to 30% of its serum concentration at age 40.

The pituitary gonadotropins( follicle stimulating and luteinizing hormones) increase with age while prolactin level declines.

The elderly men was found to have progressive, but not total decrease in number of Leydig cells, impaired function of Sertoli cells, impaired testicular perfusion which may be a cause of overall lower androgen levels.

It is not known presently how clinically significant is the decline of androgen levels. Sexual dysfunction, the most common complaint, cannot be predicted based on serum testosterone level. Since in most aging men the level of serum testosterone is still within normal range, it may not be a significant factor in erectile dysfunction.

The loss of fertility potential is not a typical finding in the elderly, although sperm count is reduced and some decrease in motility reported. However, there are considerable inter-individual variations in fertility status.

The hormone replacement therapy has been attempted to prevent aging effects in males. Some studies found an increase in lean body mass and muscle strength with testosterone supplementation. It was also investigated the correlation of low testosterone levels and coronary artery disease in men.

The risk of androgen supplementation in older men mainly concerns the prostate and cardiovascular system. It is well established that androgens stimulate growth of prostate cancer. Limited studies showed that PSA level increased in 92% of patients receiving testosterone supplementation and failed to return to normal in 30% after cessation of the treatment.

Androgens were described to have atherogenic effect on blood-lipid profiles although an effect of supplement treatment is not well studied.Other side effects include sleep apnea and increased erythropoiesis and fibrinolysis.

At this time, hormonal replacement therapy cannot be recommended without restriction. Only small- scaled clinical studies were undertaken. The anticipated risk of cardiovascular and prostate complications is not well established.

Large double blind and placebo control studies should be performed to clarify this issue and document risk and benefit of androgen supplementation in preventing aging effect in men.

 

 

Selected Bibliography

  1. Matsumoto AM. "Andropause"-are reduced androgen level in aging Men physiologically Important.West J Med 1993;159(5):618-20
  2. Swerdloff RS, Wang C. Androgen deficiency and Aging in Men. West.J Med 1993;159:579-585
  3. Tserotas K., Merino G. Andropause and the Aging Male. Archives Androl 1998;40:87-93
  4. Merino G., Garranza-Lira Semen characteristics, endocrine profiles, and testicular biopsies of infertile male of different ages. Archives Androl 1995;35:219-224
  5. Baulieu E-E. Editorial: Dehydroepiandrosterone(DHEA): A Fountain of Youth? J Clin Endocrin Metab 1996;81(9):3147-3151
  6. Gooren LJG. The age-related decline of androgen level in men; clinically significant? Brit J Urol 1996;78:763-768
  7. Mastragiacomo I., Feghali G.,Foresta C.,Ruzza G. Andropause: incidence and pathogenesis. Arch androl 1982;9(4):29296

 

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