Finasteride and Dutasteride are 5-alpha reductase inhibitors, which many scientists believe have the potential to reduce prostate cancer risks and progression and increase prostate cancer survival significantly
Here we touch on a really controversial subject: that two drugs Dutasteride and Finasteride might be able to reduce prostate cancer aggression and increase survival times without the need for ADT and all the negatives they bring to men (writes Chris Woollams, Oxford University Biochemist and a founder of CANCERactive).
What is 5-alpha Reductase, and why men should know about it?
As men age past 50, they start to make lowered levels of testosterone. They become less lean, have more fat stores and this encourages more oestrogen production which decreases testosterone further. Like me, Charles Myers, a scientist who formed the Prostate Forum in the USA after beating his own prostate cancer, believes that limiting saturated fat in the body is crucial to increasing survival times. As testosterone falls, higher levels of 5-alpha reductase are produced. Research shows that 5-alpha reductase is present in higher levels in malignant prostate tissue than it is in benign (1), and that 5-alpha reductase encourages testosterone to develop into Dihydrotestosterone, or DHT, its biologically active form (2).
What are the two drugs Dutasteride and Finasteride
According to Drugs.com:
‘Dutasteride is used to treat benign prostatic hyperplasia (BPH) in men with an enlarged prostate. Dutasteride helps improve urinary flow and may also reduce your need for prostate surgery later on.’
‘Finasteride (Proscar) is used alone or with other medication to treat symptoms of benign prostatic hyperplasia (BPH) in men with enlarged prostate.’
Research: Dutasteride lowers the risk of Prostate cancer
A 4-year study (3) amongst men at high risk of developing prostate cancer showed that Dutasteride reduced the risk of prostate cancer by more than 22.8%. The research involved 6729 men in a multicenter, randomised, double-blind, placebo-controlled, parallel-group study. All the men were between 50 and 75 years of age, had a PSA of 2.5 to 10.0 ng per ml, and had had at least one negative prostate biopsy in the six months before enrollment.
Among the 6729 men who underwent a biopsy, or a prostate surgery, cancer was detected in 659 of the 3305 men in the dutasteride group, as compared with 858 of the 3424 men in the placebo group. There was a slightly higher risk of cardiac failure in the Dutasteride group when compared to the placebo group. The best results were obtained in men who had a Gleason score of 5, or 6.
The dose of Dutasteride used in the research was 0.5 mg per day.
Finasteride - research with prostate cancer
As early as 2003, University of Texas researchers had studied (4) the effects of Finasteride against a commonly used drug which reduced benign prostatic hyperplasia, Doxazosin, and a placebo. In a long-term trial involving 3047 men, Finasteride reduced the risk of acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection by 34% compared to the placebo. The Doxazosin reduced risk by 39%. Their actions were different though. Doxazosin is an alpha-blocker, whereas Finasteride, as in the first study above using Dutasteride, blocks 5-alpha reductase.
When combined, the two drugs reduced risk by 66%.
In 2009 there was a systematic review (5) of 15 randomised trials involving 5-alpha reductase inhibitors (5-ARIs) Finasteride (Proscar) and Dutasteride. This stated, ‘A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI’.
For your information, Finasteride is available in two different strengths: Proscar 5 mg tablets and Propecia 1 mg tablets.
Drug Warnings for Finasteride and Dutasteride
The FDA has now stepped in and issued a warning in several parts. The FDA website states:
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Be aware that treatment with 5-ARIs causes an approximate 50% reduction in prostate-specific antigen (PSA) values by 6 months; however, individual patients receiving 5-ARIs may experience varying decreases in PSA values. Therefore, any confirmed increase in PSA while on a 5-ARI may signal the presence of prostate cancer and should be evaluated, even if that PSA is in the normal range of men not taking a 5-ARI.
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Know that 5-ARIs are not approved for the prevention of prostate cancer.
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Be aware that 5-ARIs may increase the risk of high-grade prostate cancer.
The FDA came to this conclusion because of two trials - the Prostate Cancer Prevention Trial (PCPT), and the Reduction by Dutasteride of Prostate Cancer Events trial (REDUCE).
In the PCPT study, 7 years of Finasteride therapy reduced the risk of prostate cancer by 24.8% and in the REDUCE trial, Dutasteride treatment was associated with a relative risk reduction of 22.8% over 4 years.
The FDA however felt both trials demonstrated an increased risk of high-grade disease and after a pathological reassessment of the trial data, detected an absolute increase of 0.7% and 0.5% in the incidence of high-grade cancers (Gleason score 8–10) with finasteride and dutasteride, respectively. The FDA ordered that warnings should be put on the labels of both drugs.
What the UK Nice Website has to say on 5-alpha reductase inhibitors is here (7)
Are the Warnings correct?
In a National Cancer Institute 2018 review of the data from the PCPT and REDUCE trials, ‘Revisiting 5α-reductase inhibitors and the risk of prostate cancer’ (8) the two researchers concluded that they were not, and had unfortunately had a significant effect on clinical prostate cancer treatment. The researchers concluded that, ‘published data contradict this (FDA) argument and suggest that 5-ARIs are safe in terms of prostate cancer risk and mortality, and the new research findings from Unger and colleagues (9) (who looked at 17 years data) and Wallerstadt (a 2018 much larger population study from the Karolinska) suggest there might be true long-term benefits of 5-ARIs in preventing prostate cancer.’
The Wallerstadt study in the National Institutes of Cancer Journal found tha 5-alpha reductase inhibitors ‘did not statistically significantly affect the long-term risk of being diagnosed with a high grade prostate cancer’ (10)
This view was confirmed by the 2022 study mentioned above (2). They conclude ‘Men using 5-ARIs were less likely to be diagnosed with low-risk prostate cancer, without increasing long-term risk of lethal prostate cancer or cancer-specific death after diagnosis’. And ‘Our results provide evidence that 5-ARI use is safe with respect to prostate cancer mortality in the context of regular healthcare access.’
And it is also not the case according to a later study (11) from the Karolinska Institute in Sweden reported in 2022. They concluded that there was no association between treatment with 5-alpha reductase inhibitors and increased mortality; having followed 349,152 men for an average of 8.2 years.
5-alpha reductase and prostate cancer
I needed to study this subject because when I started CANCERactive 22 years ago, we interviewed the Professor at the Royal Marsden in London who was adamant that prostate cancer was caused by high testosterone. We now know that’s not true. Professor Robert Thomas, on my Sunday Show, told viewers that his team were finding lowered levels of testosterone in patients. I also knew about the potential benefits of Finasteride and Dutasteride from 2002 Australian research I came across.
So this review article was in part a quest to explain to readers what this was all about.
In the USA many men with prostate cancer have heard of Charles (snuffy) Myers. He regularly uses Dutasteride in his protocols and has YouTube videos on this. With one of the UK men I am trying to help, he used Dutasteride and Low Dose Naltrexone.
You might like to read this review (12) on Myers (how to beat prostate cancer without spending a penny). It talks of the crucial importance of fat control through diet and a vigorous exercise programme too, just as I do.
Myers himself refers to research showing that after just one year of Dutasteride, serum levels of DHT had reduced by 94%; and a 0.5 mg dose increases testosterone serum levels by 19-26% (as would lifting weights in the gym).
Go to: 12 Natural Compounds that fight Prostate cancer
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You can find a video featuring Myers here - https://www.youtube.com/watch?v=kkak51haCPo.
There are other articles from him on the Web. For example - https://grandroundsinurology.com/durable-complete-remission-prostate-cancer/.
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References
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Type 1 and type 2 5alpha-reductase expression in the development and progression of prostate cancer; Lynn N Thomas et al; Eur Urol; 2008 Feb;53(2):244-52.
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5-alpha reductase inhibitors and prostate cancer mortality among men with regular access to screening and health care; Jane B. Vaselkiv et al; Cancer Epidemiol Biomarkers Prev. 2022 Jul 1; 31(7): 1460–1465
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Effect of Dutasteride on the Risk of Prostate Cancer; Gerald L. Andriole et al; N Engl J Med, April 2010; 362:1192-1202.
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The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. McConnell JD et al; N Engl J Med 2003;349:2387-2398
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Use of 5alpha-reductase inhibitors for prostate cancer chemoprevention: Barnett S. Kramer et al; J Urol; 2009 Apr;181(4):1642-57.
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FDA Website - 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer; https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-5-alpha-reductase-inhibitors-5-aris-may-increase-risk-more-serious
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NICE - 5-alpha Reductase Inhibitors - https://cks.nice.org.uk/topics/luts-in-men/prescribing-information/5-alpha-reductase-inhibitors/
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Revisiting 5α-reductase inhibitors and the risk of prostate cancer
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Using Medicare Claims to Examine Long-term Prostate Cancer Risk of Finasteride in the Prostate Cancer Prevention Trial; Joseph M Unger et al; J Natl Cancer Inst; 2018 Nov 1;110(11):1208-1215.
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Risk of Prostate Cancer in Men Treated With 5α-Reductase Inhibitors-A Large Population-Based Prospective Study; Anna Wallerstedt et al; J Natl Cancer Inst; 2018 Nov 1;110(11):1216-1221.
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Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality; Lars Björnebo, MD; Tobias Nordström; Andrea Discacciati et al; May 19, 2022 JAMA Oncology
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A review on Charles Myers - https://sperlingprostatecenter.com/defeating-prostate-cancer-without-spending-a-penny-on-drugs/