I thank Drs. Kaplan and Crawford (1) for their kind remarks on our article (2) on the relationship between testosterone levels and insulin sensitivity in men and for their thoughtful comments on the optimal form of androgen replacement for older men.

While the standard form of androgen replacement for hypogonadal men is testosterone, the authors express concern about its use in older men, given that it results in an increase in levels of dihydrotestosterone (DHT), which, in as-yet-unpublished data, has been identified as a risk factor for prostate cancer (3). On this basis, Drs. Kaplan and Crawford recommend that a regimen comprising coadministration of testosterone with the 5α-reductase inhibitor finasteride be considered for androgen replacemement in older men.

Preliminary evidence suggests that this may indeed be a reasonable strategy. In a carefully conducted three-arm study (testosterone alone, testosterone plus 5 mg/day finasteride, and placebo) of 70 men aged ≥65 years with testosterone levels <350 ng/dl, Tenover and colleagues (4,5) demonstrated that testosterone therapy both alone and in combination with finasteride improved body composition, physical performance, bone mineral density, and total cholesterol. However, concomitant treatment with finasteride appeared to attenuate the negative effect of testosterone on the prostate in that subjects who received the dual regimen had no increase in prostate-specific antigen levels and had a significantly lower increase in prostate volume than those treated with testosterone alone (5). While these data are encouraging, they are based on small patient numbers, and the favorable effects on prostate-specific antigen levels may not necessarily translate to a reduction in prostate cancer risk. In addition, while finasteride was shown to reduce the development of prostate cancer in middle-aged men, the incidence of high-grade prostate tumors and sexual side effects was increased (6).

Therefore, I believe that further research is still needed to identify the androgen regimen that confers optimal benefit to older men without compromising prostate health and overall patient safety.

Kaplan SA, Crawford ED: Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men (Letter).
Diabetes Care
Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, Tripathy D, Yialamas M, Groop L, Elahi D, Hayes FJ: Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men.
Diabetes Care
Thompson IM: New insights and developments from the Prostate Cancer Prevention Trial: the promise of SELECT [presentation online],
. Available from http:// webcasts.prous.com/aua2005/article.asp?AID=22&CID=YY&CLID=2. Accessed 26 September 2005
Page ST, Amory JK, Bowman FD, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL: Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T.
J Clin Endocrinol Metab
Amory JK, Watts NB, Easley KA, Sutton PR, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL: Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone.
J Clin Endocrinol Metab
Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr: The influence of finasteride on the development of prostate cancer.
N Engl J Med

F.H. has been an advisory board member for Auxilium and has received honoraria from Solvay.