NEWS FLASH : 7/22/2022
This just in! A May 19, 2022 issue of JAMA Online carried a Swedish study on whether the drugs commonly used to treat BPH and male pattern baldness increase the risk of dying from PCa. The controversy over this is described in our original blog below. The new study, based on a large cohort of both 5-ARI users and nonusers, found no association between 5-ARI use and increased PCa mortality. However, similarly to our recent update, the authors write, “Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.”[i] These testing differences stem from a broad recommendation that men who take these drugs for BPH or baldness should be more rigorously monitored (PSA and biopsy) for early PCa detection. While we believe it’s good news that 5-ARIs are not linked with more risk of PCa-specific death, we stand by our recommendation to integrate multiparametric MRI before biopsy into the monitoring protocol for 5-ARI users.
UPDATE: 10/26/2021
If you read the blog below when we posted it in early 2018, you’ll be interested in this update. It starts with a 2019 retrospective study[ii] published in the Journal of the American Medical Society (JAMA). The study posed the question whether a class of drugs commonly prescribed to reduce urinary symptoms of BPH (benign prostatic hyperplasia) puts men at risk of a more serious disease, prostate cancer (PCa). The drugs are 5-alpha reductase inhibitors (5-ARI) with brand names Avodart and Proscar. Do these drugs lead to delayed diagnosis of prostate cancer (PCa)? The problem is linked with PSA screening, since using the medications decreases the amount of PSA detected in a blood test. When PSA appears low, men are unlikely to be referred for a biopsy. If no one’s looking for PCa, it may progress undetected for months, even years, until it is large and aggressive—at which point, treatment is more likely to fail. Thus, does taking these drugs raise the risk of dying from PCa?
More recently, at the September 2021 American Urological Association’s Virtual Experience, a team from the Levine Cancer Institute (Charlotte, NC) presented their data suggesting that use of 5-ARI drugs is a reason to perform a prostate biopsy.[iii] In an interview, lead investigator Dr. James T. Kearns remarked, “While not emphasized in common risk calculators, pre-diagnostic use of 5-ARI should be considered when deciding to biopsy.”[iv] This conclusion was based on a comparison of 842 PCa patients at their own institution, 5-ARI users vs. non-users. At the time of PCa diagnosis, users were significantly more likely to have later-stage disease than non-users.
At the Sperling Prostate Center, we find this very concerning. However, for BPH patients using 5-ARI drugs, we recommend having a prostate scan using 3T multiparametric MRI before moving on to a biopsy. Such as scan is highly accurate at detecting the kind of PCa that may require treatment; if such suspicious activity is observed, an in-bore (real time) MRI-guided targeted biopsy uses the fewest needles yet gains the most accurate diagnosis.
Post originally published 5/12/2018
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.[v] 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.[vi] 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.”[vii] 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%).[viii] 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.[ix] 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 minimal side effects. For more information, visit our webpage on BPH.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
References
[i] Björnebo L, Nordström T, Discacciati A, et al. Association of 5?-Reductase Inhibitors With Prostate Cancer Mortality. JAMA Oncol. 2022;8(7):1019–1026.
[ii] Sarkar RR, Parsons JK, Bryant AK, Ryan ST et al. Association of Treatment With 5?-Reductase Inhibitors With Time to Diagnosis and Mortality in Prostate Cancer. JAMA Intern Med. 2019 Jun 1;179(6):812-819.
[iii] Roebuck E, Sha W, Lu C, Miller C et al. 5-ARI Usage Associated with More Advanced Prostate Cancer at Diagnosis. Poster presentation MP30-14 at 2021 AUA Virtual Experience. https://www.auajournals.org/doi/abs/10.1097/JU.0000000000002027.14
[iv] Persaud, Natasha. “Investigators: Consider 5-ARI Use When Deciding on Prostate Biopsy.” Renal & Urology News, Sep. 12, 2021. https://www.renalandurologynews.com/home/conference-highlights/aua-2021/5-alpha-reductase-inhibitors-are-a-risk-factor-for-prostate-cancer-biopsy/
[v] Roehrborn, C. 5-?-Reductase Inhibitors Prevent the Progression of Benign Prostatic Hyperplasia. Rev Urol. 2003; 5(Suppl 5): S12–S21.
[vi] 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.
[vii] 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.
[viii] Ibid.
[ix] 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.
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
