This Article Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Palusinski, R. Articles by Barud, W. Search for Related Content PubMed PubMed Citation Articles by Palusinski, R. Articles by Barud, W.

Proscar and Propecia—A Therapeutic Perspective

Robert Palusiski and Wojciech Barud

University School of Medicine in Lublin, 20-081 Lublin, Poland

Address correspondence to: Robert Palusiski, M.D., Department of Medicine, University School of Medicine in Lublin, 20-081 Lublin, Poland. E-mail: robert.p.palusinski{at}uth.tmc.edu.

The article by Dr. Rosner (1) points out an important problem of long-term side effects of finasteride treatment brought about by the surprising results of the Prostate Cancer Prevention Trial (PCPT) (2). In this study, chronic inhibition of 5-reductase was associated not only with sexual dysfunction and gynecomastia, but also with a worrisome increased risk of high-grade prostate cancer. Keeping in mind a higher incidence of breast cancer reported by the other group (3), it seems reasonable to believe that long-term treatment with finasteride may disturb androgen-estrogen balance to the extent that may result in carcinogenesis.

Many epidemiological and experimental studies have shown that prostate hyperplasia and cancer develop more frequently in a hormonal milieu where estrogens predominate over androgens, as it happens in aging males. The inhibition of 5-reductase further shifts the hormonal imbalance associated with aging by decreasing 5-dihydrotestosterone and increasing testosterone, which in turn may be locally aromatized to estrogens. The aberrant up-regulation of aromatase expression in benign prostate hypertrophy and prostate cancer (4) makes this scenario even more probable.

The other possible mechanism by which hormonal changes may affect prostate cancer development is the capacity of sex hormones to modulate immune response. Androgen and estrogen receptors are present on most immune competent cells, and sex hormones are known to affect T helper 1 (Th1)/Th2 cell balance (5, 6). Th1 response is associated with cell-mediated immunity, e.g. elimination of cancerous cells, whereas Th2 response is credited with immune tolerance such as fetus survival during pregnancy. Therefore, finasteride could potentially be involved in alteration of immune surveillance against cancer in aging males.

In this context, the alternative method of prostate cancer prevention in elderly men could paradoxically be a substitutive treatment with 5-dihydrotestosterone. In many studies, this nonaromatizing androgen restored estrogen/androgen balance by decreasing plasma levels of estradiol and testosterone. Dihydrotestosterone supplementation appears to have favorable effects on sexual function and cardiovascular system, with no adverse effects on the prostate as measured by symptoms, prostate-specific antigen levels, or prostate volume (7). Therefore, it would be of great clinical importance if the rigorous assessment of the prevalence of prostate cancer, such as in PCPT, were accommodated in long-term studies employing treatment with non-5-reducible androgens (e.g. dihydrotestosterone).

Footnotes

A response to this letter was invited, but the authors of the original article chose not to provide one.

Received September 14, 2004.

References

1. Rosner W 2004 Proscar and propecia—a therapeutic perspective. J Clin Endocrinol Metab 89:3096–3098[Free Full Text]
2. 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 Jr CA 2003 The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224[Abstract/Free Full Text]
3. McConnell JD, Roehrborn CG, Bautista OM, Andriole Jr GL, Dixon CM, Kusek JW, Lepor H, McVary KT, Nyberg Jr LM, Clarke HS, Crawford ED, Diokno A, Foley JP, Foster HE, Jacobs SC, Kaplan SA, Kreder KJ, Lieber MM, Lucia MS, Miller GJ, Menon M, Milam DF, Ramsdell JW, Schenkman NS, Slawin KM, Smith JA; Medical Therapy of Prostatic Symptoms (MTOPS) Research Group 2003 The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 349:2387–2398[Abstract/Free Full Text]
4. Ellem SJ, Schmitt JF, Pedersen JS, Frydenberg M, Risbridger GP 2004 Local aromatase expression in human prostate is altered in malignancy. J Clin Endocrinol Metab 89:2434–2441[Abstract/Free Full Text]
5. Huber SA, Kupperman J, Newell MK 1999 Estradiol prevents and testosterone promotes Fas-dependent apoptosis in CD4+ Th2 cells by altering Bcl 2 expression. Lupus 8:384–387[Abstract/Free Full Text]
6. Giron-Gonzalez JA, Moral FJ, Elvira J, Garcia-Gil D, Guerrero F, Gavilan I, Escobar L 2000 Consistent production of a higher TH1:TH2 cytokine ratio by stimulated T cells in men compared with women. Eur J Endocrinol 143:31–36[Abstract]
7. Barud W, Palusiski R, Makaruk B, Hanzlik J 2003 Dihydrotestosterone treatment in men with coronary artery disease. Influence on sex hormones, lipid profile, insulin resistance and fibrynogen. Annales UMCS Sectio D 58:241–246

This Article Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Palusinski, R. Articles by Barud, W. Search for Related Content PubMed PubMed Citation Articles by Palusinski, R. Articles by Barud, W.