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
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
“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!