Endocrinologist against use of Fin in young men, cancer

Science Other Studies
#1

CLINICAL PERSPECTIVE: Proscar and Propecia—A Therapeutic Perspective
PDF: jcem.endojournals.org/cgi/reprint/89/7/3096.pdf

The Journal of Clinical Endocrinology & Metabolism 89(7):3096–3098
Printed in U.S.A. Copyright © 2004 by The Endocrine Society

Short article by WILLIAM ROSNER, Department of Medicine, St. Luke’s Roosevelt Hospital Center, New York / Columbia University College of Physicians and Surgeons, New York

*** He notes the possible increases in high-grade prostate cancer as a result of Finasteride, that the medical community has not come to conclusions about whether Finasteride should be used to prevent prostate cancer, and finally, shares his opinion on why he is against Finasteride use in young men for cosmetic (hairloss) purposes.

Selected bits:

… "Two years after (1994) the approval of Proscar for BPH, a trial began to determine whether it could decrease the incidence of prostate cancer; the subjects were men 55 yr of age and older.

The major result of the trial, a decrease in the incidence of low-grade prostate cancers accompanied by an absolute and relative increase in high-grade prostate cancers (Table 1), was surprising and led to discontinuation of the trial before its planned ending.

… “Although the issue of using Proscar to treat BPH has been addressed, there remains the question of how to advise patients who take Propecia (finasteride, 1 mg) for the treatment of baldness.”

… "Although the steroidal surrogates correctly predicted the efficacy of Proscar in BPH, its action on the prevention of prostate cancer appears mixed. This issue is now unsettled, but raises concern for those in whom finasteride is used for a cosmetic rather than a moderately severe medical problem (BPH)."

… "Second, and more problematic, is the fact that there has been no open discussion of the potential danger in the long-term use of Propecia."

… "We need to think seriously about the large group of men, younger by far than those with prostate disease, who use finasteride for hair loss and not for symptoms arising from BPH. Bear in mind that the treatment of alopecia with finasteride is a lifelong commitment and that “lifelong’” means a long time for young men.

Will these patients be protected from prostate cancer, or are they at greater risk of serious disease? Whatever the answer, because of the prospect of many years of use, there should be a sense of urgency in sorting out this dilemma.’

… “In the interim, physicians and their patients should at least be aware of the potential risks and together should evaluate the use of Propecia for baldness. For mypart, I will stay with the tried and true, “first do no harm.””

#2

Followup response to Rosner’s article, further highlighting the issues of Finasteride usage, by Robert Palusiski and Wojciech Barud – University School of Medicine in Lublin, Poland

PDF: jcem.endojournals.org/cgi/reprint/89/12/6359

[b]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 /b (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).