What do these three things have in common?
- Benign prostatic hyperplasia or BPH (non-cancerous prostate enlargement)
- Male pattern baldness
- Aggressive prostate cancer that is potentially lethal.
The first—and most obvious—answer is that they are all risks that men face with aging. The second less obvious answer is a class of medication called 5-alpha reductase inhibitors. In men’s health, these drugs are better known by their trade names: Avodart (dutasteride) for BPH, Proscar (finasteride) for BPH, and Propecia (finasteride) for male hair loss. In at least two large-scale studies, it was found that men who use these medications have a lower risk of prostate cancer (PCa). However, if they do develop PCa, they have a higher risk of aggressive, potentially lethal disease.
Prescribing Avodart or Proscar for BPH
The prostate gland is part of the male reproductive system. It produces the prostate fluid that forms semen. It needs the male hormone, testosterone, to develop and function. As men age, it’s normal for the prostate to enlarge (BPH). However, since the urethra (passage for urine) runs from the bladder through the center of the prostate, BPH can eventually narrow the urethra. Avodart or Proscar is then frequently prescribed because both drugs can reduce BPH.
How do these drugs work?
The way in which the drugs work is by making testosterone less available to prostate cells. The form of testosterone that prostate cells most readily take up is called dihydrotestosterone, or DHT. It is 10 times more potent than testosterone.[i] DHT is a converted form of testosterone, and an enzyme called 5-alpha reductase is needed for this conversion. Then, when there is an abundance of DHT, prostate growth is stimulated; when DHT is scarce, prostate growth is limited. This is where the drugs come into play.
Remember the term 5-alpha reductase inhibitors? As “inhibitor” suggests, the drugs block the chemical interaction from occurring, without affecting the production of testosterone needed for overall male health. Thus, they prevent testosterone from converting to DHT, and over time, the prostate gland reduces closer to its pre-BPH size. Urine can now flow freely through the prostate and out of the body. Note that Propecia (finasteride) is often prescribed to correct for male pattern baldness, which is androgen-dependent. While Propecia helps maintain hair growth, it is also affecting the prostate gland.
What about prostate cancer risk?
Concern about the safety of long-term 5-alpha reductase inhibitors use came about as the result of a large-scale seven year observational study (Prostate Cancer Prevention Trial or PCPT) of 18,880 men randomized into two groups: finasteride and placebo.[ii] According to Hirshburg, et al. (2016), “In the patient population diagnosed with prostate cancer that was taking finasteride, there was a 27-percent increase in ‘high grade’ Gleason scores of 7 to 10.”[iii] Another study that performed 18 years’ follow up with the same patients confirmed the findings of the first. The finasteride group had fewer cases of biopsy-proven PCa than the placebo group (10.5% vs. 14.9%) but a greater risk of Gleason grade 7-10 PCa in the finasteride vs. placebo group (3.5% risk vs. 3.0%).[iv] Clearly, such results would lead to worry, even though the increased risk was quite small.
On the other hand, The Health Professionals Follow-Up Study (38,058 men, 1996-2010) found no significant difference in Gleason scores between men who used finasteride and those who did not. In addition, a critical review of the PCPT results and one other large study suggested biases that may have led to the discovery of greater aggression risk among 5-alpha reductase inhibitor users.[v] Using a different mathematical model to analyze the data, the authors likewise found no significant Gleason grade differences.
What should we believe?
It is confusing when researchers draw different conclusions using a large data pool. One important point is that all studies point to an average reduced risk of developing prostate cancer when these drugs are used long-term. It makes sense. By reducing BPH, the risk of chronic prostate inflammation is also reduced – and chronic inflammation is a potential PCa precursor. Also, there is no reported survival difference among finasteride users who developed low-grade vs. high-grade PCa.
Another important point is that long-term use of 5-alpha reductase inhibitors has other side effects: erectile dysfunction, reduced libido, less ejaculate, and depression (reported in several small studies).
Focal laser ablation for BPH
Urinary dysfunction due to BPH can have a harsh effect on quality of life. It is no wonder that many men seek relief from pharmaceuticals. But, for those who want relief without being on medication, the Sperling Prostate Center offers focal laser ablation (FLA), a minimally invasive MRI-guided procedure that safely reduces prostate volume and relieves urethral blockage with no side effects. For more information, visit our webpage on BPH.
[i] Roehrborn, C. 5-?-Reductase Inhibitors Prevent the Progression of Benign Prostatic Hyperplasia. Rev Urol. 2003; 5(Suppl 5): S12–S21.
[ii] Thompson IM, Goodman PJ, Tangen CM, Lucia MS et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003 Jul 17;349(3):215-24. Epub 2003 Jun 24.
[iii] Hirshburg J, Kelsey P, Therrien C, Gayino AC, Reichenberg J. Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review. J Clin Aesthet Dermatol. 2016 Jul; 9(7): 56–62.
[v] Lacy JM, Kyprianou N. A tale of two trials: The impact of 5?-reductase inhibition on prostate cancer (Review). Oncol Lett. 2014 Oct;8(4):1391-1396.