Testosterone for older men

This past weekend I have read two widely conflicting articles about the benefits of testosterone therapy in older men. The first was published in the Journal of Clinical Endocrinology and Metabolism (who reads journals over the holidays!) and reports on the effects of anastrozole (Arimidex), an aromatase inhibitor, on BMD in men aged 60 years and older. This drug, used predominantly in the management of breast cancer in women, blocks the aromatization of testosterone to estrogen. This decrease in estrogen in turn increases production of gonadotropin-releasing hormone (GnRH) in the hypothalamus. To complete the picture, GnRH stimulates gonadotropin release from the pituitary, which stimulates testosterone production in the testes.

Sounds straightforward, but the results did not live up to the expectations. Not quite true – the same group of researchers had previously demonstrated that this approach had no beneficial effect on body composition. I presume that they were not overly surprised by the results.

What did they find? Testosterone does significantly increase in men with low testosterone by about 50% within three-months of therapy. Study participants assigned to placebo had little change in serum testosterone levels. The endpoint of the study was the effect on BMD and the data demonstrated a small but significant decrease in the patients assigned to anastrozole, but not the placebo group.

The editorial that accompanied this article provided a very compelling and readable summary of what went wrong. Men need estrogen to maintain skeletal health, and possibly other important aspects of overall health! There is abundant literature support for this concept which is not unique to men. In Europe and elsewhere testosterone therapy is available for women because controlled clinical trials demonstrated clear benefits that far outweigh the side effects. The FDA turned down an application (possibly more than one) to approve similar therapy for U.S. women.

In my clinic, I see a lot of men with low testosterone levels, most of them with type 2 diabetes. They respond well to testosterone provided as an IM injection or as a self applied skin cream. In younger patients who are still considering fathering children, clomiphene citrate is an oral alternate but only in those who demonstrate low levels of gonadotropins.

A major difference between my practice and the article discussed above is that the mean level of testosterone pre-treatment with anastrozole was still >300 ng/dL, while the patients I see are struggling to get to 200 ng/dL.

To complete the story I must alert you to an article in the New York Times magazine: “Vigor quest” by Tom Dunkel. It relates the story of a 51 year-old man who spends $10,000 or so each year on therapies to prevent the tribulations of aging (no request for insurance coverage for this hobby). He and his treating endocrinologist provide a compelling argument for the role of hormones in slowing down the aging process – a hypothesis that makes sense since both men and women demonstrate an age-related decline with a number of hormones. The article was well balanced with comments from those both pro-and-con GH replacement therapy as an anti-aging therapy.

What caught my attention was the reference to the late Dan Rudman who had an article on the effects of GH on the aging process published in the New England Journal of Medicine. To say that Rudman’s publication created a stir and a plethora of grant applications would not do it justice. To me it has a far more compelling memory – at the time of his death we, along with several others, were co-investigators on an National Institutes of Aging funded project to look further into this issue. I knew Dan and interacted with him for only a short time, but what a gem of a person! Now two decades later we are still arguing about the issues he studied and worked so hard on. Dan, give it time – answers will be forthcoming!