In the New England Journal Prostate Cancer Prevention Trial, 18,882 men over the age of 55 years with normal DRE and PSA’s below 3.0 were randomly assigned placebo or Finasteride (1). This cohort was followed for 7 years. The results were highly unexpected.
Finasteride Group:
- Cancer 18.4%
- 37% of these more aggressive types
Placebo Group:
- Cancer 24.4%
- Of these 22.3% more aggressive types
The group receiving Finasteride, a 5-alpha reductase inhibitor, had lower incidence of prostate cancer but a greater incidence of high grade (worse) prostate cancers than placebo. The researchers concluded “Finasteride prevents or delays the appearance of prostate cancer, but this possible benefit and a reduced risk of urinary problems must be weighed against sexual side effects and the increased risk of high-grade prostate cancer.”
Is there such a thing as age-related Finasteride deficiency? Is the reason men get prostate cancer because they’re deficient in Finasteride? No and no, on both counts. Elevated levels of DHT may increase your male patient’s risk of developing prostate cancer but the metabolites of DHT may actually help prevent and reduce the grade of prostate cancers.
Testosterone is converted to DHT via the 5-alpha reductase enzyme. DHT is the most potent androgen and along with T causes proliferation and secretion (dedifferentiating) by activating androgen receptors. BUT then DHT is converted to androstanediol via a 3-beta HSD reaction (2). Androstanediol is a differentiation (redifferentiating) agent that activates estrogen beta receptors (2). The process of cancer development is primarily a dedifferentiation process.
There is considerable debate about the outcomes of the NEJM Prostate Cancer Prevention Trial (3).
- Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 349(3):215–24, 2003.
- O. Imamov, G.-J. Shim, M. Warner, and J.-A. Gustafsson “Estrogen Receptor beta in Health and Disease” Biol Reprod, November 1, 2005; 73(5): 866 – 871.
- Prostate Cancer Prevention Trial (PCPT). National Cancer Institute http://www.cancer.gov/cancertopics/factsheet/prevention/pcpt
