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I. Introduction

Charles R. Drew University of Medicine and Science and University of California Los Angeles School of Medicine Los Angeles, California 90059

	Introduction

Top Introduction References

 
OF THE one thousand generations of humans that have lived on this planet, only the men of the last two generations could have hoped to live past the age of 50! Since 1900, the number of Americans 65 yr of age or older has increased 11-fold, from 3.1 million to 33.9 million (1). By 2030, this number will have doubled again to 70 million. The older population is also getting older: while the 65–74 age group is eight times larger now than it was in 1900, the 85+ group is 31 times larger (1). Because of these powerful demographic trends brought about by increasing life expectancy, frailty, impaired sense of well-being, and sexual dysfunction have emerged as important quality-of-life issues for aging men.

Ancient Indians, Greeks, and Egyptians were aware that extracts of animal testis could promote virility, potency, and vigor in men. In modern times, the castration and testis-transplantation experiments in roosters, conducted initially by John Hunter (2) and later by Adolf Berthold (3), established the link between secretions of the testis and some of the sexually dimorphic features in the rooster. Brown- Sequard (4) recognized the association between changes in testicular function and the loss of vigor in older men; he claimed to have rejuvenated himself by injecting the extracts of guinea pig testis. In the 1930s, Butenandt (5) and Ruzicka shared the Nobel Prize for the chemical synthesis of testosterone. Although testosterone was the first hormone to be discovered and one of the first hormones to be chemically synthesized, it is ironic that we are just beginning to learn about its role in the aging process in men.

There is agreement that testosterone levels decrease with advancing age in men; however, the significance of this decrease remains unclear. We do not know whether testosterone replacement therapy in older men would have beneficial effects on muscle function, sexual function, sense of well being, and quality of life, or whether this could be done safely. There is uncertainty about the long-term effects of testosterone administration on the prostate and on the cardiovascular system. Recognizing the relative paucity of definitive data, the increasing public interest, and the controversial nature of this issue, The Journal of Clinical Endocrinology & Metabolism invited several experts to present their opinions on unresolved questions related to androgen replacement in older men. Are older men hypogonadal? How should we define hypogonadism in older men? What testosterone assay has the best discriminating ability in older men? When should free testosterone levels be measured and by what method? Can testosterone supplementation produce clinically meaningful changes in body composition and muscle function in older men? Should testosterone be given to older men with sexual dysfunction and low normal testosterone levels? What are the long-term risks of testosterone replacement in older men? How should a clinician manage an older man presenting with low testosterone levels, or with sexual dysfunction and other symptoms of hypogonadism? How should testosterone replacement be administered and monitored in older men? What are the methodological and research design problems in the conduct and interpretation of studies of testosterone replacement in older men?

It is well to remember that the debate over the relative risks and benefits of estrogen therapy in women has raged for 30 yr, and clarity has only recently begun to emerge in that field. In contrast, the debate over testosterone replacement in older men has just started; the ponderous issues of risks and benefits are unlikely to be resolved anytime soon.

	Footnotes

 
Address all correspondence regarding these controversies and requests for reprints to: Shalender Bhasin, Chief, Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, and Professor of Medicine, University of California Los Angeles School of Medicine, Los Angeles, California 90059. Reprints of the Therapeutic Controversies will include all authors and all pages, as they appear in the journal.

Accepted May 19, 1998.

	References

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1. Fowles DG. 1997 A profile of older Americans: 1997. U.S. Department of Health and Human Services; Washington, DC: American Association of Retired Persons and the Administration on Aging.
2. Irvine W. 1928 John Hunter’s experiments: evidence of an eyewitness. Letter to Professor Thomas Hamilton, University of Glasgow, June 17, 1771. Lancet. 359–360.
3. Berthold AA. 1849 Transplantation der Hoden. Arch Anat Physiol Wiss Med. 42–46.
4. Brown-Sequard CE. 1889 Des effects produits chez Phomme par des injections souscutanées d’un liquide retire des testicules frais de cobaye et de chien. CR Seanc Soc Biol. 1:420–430.
5. Butenandt A. 1931 Uber die chemische Unterschung der sexual hormones. Z. Angew Chem. 44:905–908.

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