Finasteride & Prostate Cancer

Finasteride (trade name, Proscar) is a medication that is approved by the FDA for the treatment of benign enlargement of the prostate gland (benign prostatic hypertrophy, or BPH).  As men age, their prostate glands gradually enlarge.  The prostate gland is situated at the base of the bladder, and essentially wraps around the proximal urethra.  As the prostate enlarges, the urethra can become progressively more compressed, resulting in difficulty with urination.  Finasteride works by inhibiting an enzyme (5-alpha reductase) that converts testosterone into dihydrotestosterone (DHT).  The prostate gland is stimulated to enlarge by DHT, and so finasteride can be helpful in nonsurgically reducing BPH-related symptoms.  Analogous to many breast cancers, which appear to be stimulated by the female sex hormone estrogen, many prostate cancers are known to be stimulated to grow by DHT.  Therefore, some researchers have proposed using finasteride as a potential prostate cancer prevention drug.  A large-scale prospective study of finasteride appears in the current issue of the New England Journal of Medicine.

Over the 7-year study period, a total of 18,882 men, all 55 years old or older, and all with normal prostate-specific antigen (PSA) levels, were observed for evidence of new prostate cancers.  The study volunteers were randomized to take either 5 mg per day of finasteride or a placebo (sugar pill).  Annual PSA levels and digital rectal exams were performed on all patients.  Any abnormalities in either of these tests were followed-up with biopsy of the prostate gland. 

A total of 9,060 volunteers completed the study.  Prostate cancer was subsequently diagnosed in 803 of the 4,368 (18.4%) men who were taking finasteride, while 1,147 of the 4,692 (24.4%) men in the placebo group developed prostate cancer during the course of this study.  This outcome was consistent with a 24.8% reduction in the relative risk of developing prostate cancer in the group of men taking finasteride for 7 years.  However, the news was not all good for the finasteride group.  The tumors in the finasteride group tended to appear more aggressive under the microscope when compared to the tumors in the placebo group, and the men taking finasteride also experienced a significant increase in sexual function complaints.  Not surprisingly, however, the incidence of urinary tract obstructive symptoms were less common among the men taking finasteride.

Prostate cancer is, on many levels, the male analogue of breast cancer (although breast cancer does occasionally afflict males as well as females).  In the majority of cases, both types of cancer appear to be fueled, at least in part, by sex hormones.  As has been shown with drugs like Tamoxifen, blocking the stimulation of sex hormone receptors can significantly reduce the risk of developing estrogen-sensitive breast cancer, or of developing a recurrence of a previous breast cancer.  At the same time, breast cancers that do arise while patients are taking estrogen blockers tend to be more aggressive in their microscopic appearance, and are far more likely to grow independent of sex hormone stimulation (i.e., they tend to be hormone resistant).  So, the results of this finasteride study are hardly surprising. 

In addition, there are some important differences between the biology of breast cancer and prostate cancer, and in patient response to antihormonal therapy for each disease.  Women who take estrogen blockers will inevitably develop symptoms of menopause, including, to varying degrees, hot flashes and vaginal dryness.  While prostate cancer tends to be rather indolent in the majority of cases, often progressing slowly over a period of many years, breast cancer is almost uniformly fatal once it spreads to distant sites in the body.  In the case of finasteride, urinary obstructive symptoms often improve, as expected, but the incidence of sexual dysfunction is, also as expected, quite high.  Also, Tamoxifen, when taken for 5 years, has been shown to reduce the risk of developing breast cancer by nearly 50%, as opposed to the more modest 25% prostate cancer risk reduction noted in this study following 7 years of finasteride therapy.  Based upon these factors, the use of finasteride for prostate cancer prevention should probably be limited to those men with a strong family history of prostate cancer and concomitant BPH.

Autism & Overgrowth of the Brain in Early Life

Autism is a syndrome (or more realistically, a spectrum of syndromes) that is usually diagnosed within the first 2 or 3 years of life.  An unusual finding that has been associated with autism is a propensity for overgrowth of portions of the brain at the time of diagnosis.  The timing of brain overgrowth in relation to the actual onset of autism has not been clear, however.  It is probable, though, that the process of brain overgrowth begins before the clinical symptoms of autism become obvious.  A new study in the current issue of the Journal of the American Medical Association was designed to explore this issue in further detail.

A total of 48 children with a history of autism spectrum disorder (ASD) were included in this study.  The children were 2 to 5 years of age at the time they entered the study, and all children had previously undergone routine head circumference measurements, and other body measurements, during their first year of life. 

When the 48 children with ASD were compared with children without ASD, the kids with ASD were determined to have been born with significantly smaller head circumferences (HC) than the children without ASD.  However, at both 1 to 2 months and 6 to 14 months after birth, babies who were later diagnosed with ASD had markedly increased HC, indicating a surge in brain size.  Only 6% of infants without ASD developed abnormal brain enlargement, while 59% of the children who were later diagnosed with ASD had significant acceleration of brain growth between birth and 6 to 14 months.  The authors of this study concluded that ASD may be heralded by measurable changes in brain growth, and long before the clinical symptoms of ASD become evident.  The precise mechanism of the abnormal brain growth seen in children with ASD, and its relationship to the symptoms of ASD, are the subjects of intense study at this time.

Dr. Robert A. Wascher