Male reproductive ageing human fertility androgens and hormone dependent disease

David J. Handelsman

ANZAC Research Institute, Department of Andrology, Concord Hospital, University of Sydney, Sydney, NSW2139, Australia

A bstract. The waning of male virility with age, in all its ambiguities, has always intrigued humans, prompting innumerable approaches to staving it off. In modern terms, advancing age impacts on all aspects of male reproductive health — sexuality, fertility and androgenization — with differing extents and tempo. With ageing, male sexual function declines predominantly due to vasculogenic defects in cavernosal haemodynamics, whereas libido and ejaculation are less affected. This raises the potential for prevention and treatment of erectile dysfunction as an early clinical manifestation of atherosclerosis. After maturity, male fertility persists throughout life but decreases modestly with age presumably due to concomitant decline in sexual activity rather than in sperm output or function, although systematic population studies of the latter are difficult. Male ageing is associated with a progressive, partial and variable degree of androgen deficiency, but the clinical and public health significance remain to be established. Available evidence suggests that androgen supplementation is unlikely to prolong life expectancy but might improve quality of life through prevention of apparently age-related declines in androgen-sensitive tissues. The appropriate target population, treatment modality and objectives remain to be established by further controlled clinical studies.

2002 Endocrine facets of ageing. Wiley, Chichester (Novartis Foundation Symposium 242) p 66-81

Over 50 years ago WHO defined health as 'A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity'. Analogously, male reproductive health can be considered as having three dimensions — sexuality, fertility and androgenization — each affected by ageing.

This review highlights two historical themes. The first is the importance of the great contributions of 20th century statistics to medicine—randomization and placebo controls —as the fundamentals of prospective or experimental studies. These features control not only known, but crucially unknown covariables, that influence outcomes. By contrast, retrospective or observational studies even if based on the counsel of perfection —valid population-based sampling frames and objective validation of study measures — only control for known variables. This unique power gives salience to experimental over observational designs thereby creating a distinction between strong and weak inference in biomedical science. These ideas lie at the root of evidence-based medicine, a welcome modern trend in medical science even if somewhat misnamed. Its focus is not so much on evidence per se (as subjective or anecdotal experience constitute evidence), as on the quality of evidence. Ironically, the rigour of evidence-based medicine rests upon subjective judgement of the qualities of evidence. Nonetheless, the robustness of the criteria of randomization and placebo controls are themselves ultimately susceptible to objective judgement.

The second historical theme is the ramifications of Santayana's aphorism that those not familiar with their history are condemned to repeat it. This has particular resonance for male reproductive ageing research as medical history over the last two centuries has experienced repeated colourful episodes of rejuvenation quackery, including doctors, masquerading as science. Preying on the profound and endlessly resurgent but unattainable human desire for rejuvenation will always be fertile territory for the plausible quack to harvest rich pickings — and the crop is flowering once again.

0 0

Post a comment