Finasteride and Dutasteride are 5-alpha reductase inhibitors, which many scientists believe have the potential to restrict prostate cancer growth, reduce progression and increase prostate cancer survival significantly; we also cover natural alternatives to these two off-label drugs.
Here we touch on two controversial subjects:
* Firstly that testosterone isn't actually the prime food for prostate cancer cells. That honour goes to DiHydroTestosterone or DHT
* Secondly that two drugs Dutasteride and Finasteride which block the formation of DHT when used 'off-label', might be able to reduce prostate cancer aggression and increase survival times with or without using ADT drugs and all their negatives that these hormone blockers 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 lowers 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 fat (especially saturated fat) in the body is crucial to increasing survival times. But the downward spiral of higher oestrogen and lowered testosterone is only part of the picture.
As testosterone falls, higher levels of an enzyme, 5-alpha reductase, are produced. Research shows that 5-alpha reductase is present in much higher levels in malignant prostate tissue than it is in benign (1), and that 5-alpha reductase encourages what little testosterone remains to convert into Dihydrotestosterone, or DHT, the biologically more active form (2). DHT is known to drive prostate cancer cell growth and is central to prostate cancer development, progression, and drug resistance. 5.alpha reductase inhibitors (5ARIs) might well be of significant benefit.
DHT, not testosterone, drives prostate cancer,
DHT is the most potent androgen and a critical fuel for prostate cancer growth.
Testosterone actually helps healthy prostate cells grow, and not surprisingly, it is found in the prostate and about10% in circulating blood. One study described this as follows: Testosterone, the most abundant circulating androgen in males, is synthesised by the Leydig cells of the testes under the control of hypothalamus and anterior pituitary gland, and can further be converted to more potent form Dihydrotestosterone (DHT) by the action of enzyme 5αR”. While testosterone can bind to the Androgen Receptor (AR), DHT has a much stronger binding ability, even changing the way genes are transcribed (13).
When men take Androgen Deprivation Therapy (ADT) and testosterone blocking drugs, DHT can simply be produced in other ways. In fact, a study from Duke Medical School showed that while testosterone lowering drugs could help in the early stages of prostate cancer, testosterone supplementation might help in advanced cancer, because it would suppress 5-alpha reductase levels that could drive DHT production from other sources independent of testosterone.
With low testosterone following ADT use, you can have a more aggressive cancer because DHT starts to be produced from other sources. Even after testicular testosterone is suppressed, the adrenal glands continue to produce DHT precursors such as DHEA and androstenedione. Several enzymes are involved including 5-alpha reductase in turning these into DHT.
What are the two drugs Dutasteride and Finasteride?
According to Drugs.com:
‘Dutasteride is used to treat hair loss, and 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 prostates.’
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 (BPH), 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 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 actually 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.’
Moreover, the Wallerstadt study in the National Institutes of Cancer Journal found that 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 exactly 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. First, though, are there natural alternatives?
Natural foods blocking 5-alpha reductase
1. LYCOPENE - A significant number of studies has shown that tomatoes and, in particular, lycopene (an alpha-carotene in tomatoes) when consumed are inversely linked to prostate cancer risk and instead cause a reduction in PSA levels. Strictly Lycopene is a carotenoid. A polyphenol.
Importantly, tomato and lycopene interact with the Androgen Receptor and alter signaling, reducing the risk of advanced prostate cancer. There are actually two forms of 5-alpha Reductase - SRD5A1 and SRDA52. Consumption of tomato and lycopene lowers SRD5A2, alters gene expression and lowers a protein DJ1 which causes heightened expression of the AR. As prostate cancer progresses DNA hyper methylation occurs. Lycopene blocks this (14). Lycopene can also block the conversion of glutamine to glutamate - but that's another issue found here (Foods that starve cancer of glutamate).
2. CURCUMIN a polyphenol found found in turmeric that acts as a 5-alpha reductase inhibitor. Preclinical studies demonstrate that curcumin inhibits both 5-alpha reductase type 1 (SRD5A1) and type 2 (SRD5A2) enzymes, both of which are key in DHT production.
3. POMEGRANATE contains polyphenols like punicalagin and ellagic acid, that exhibit anti-5-alpha-reductase activity. Studies show that pomegranate extract (POMx) and pomegranate juice (PJ) significantly suppress the expression of SRD5A1, reducing DHT levels, even after ADT has failed.
4. EGCG (GREEN TEA) - while this shows potent inhibition of 5-alpha reductase in cell-free assays, particularly targeting the type1 isozyme, it doesn't cross cell membranes well according to research.
5. ORGANIC GINGER ROOT (ZINGIBER) - contains bioactive compounds, particularly gingerol and zingerone, that have been shown to inhibit 5α-reductase and DHT. Also has anti-inflammatory and anti-microbial benefits.
6. QUERCETIN - again it inhibits 5-alpha reductase and lowers DHT. It also exhibits anti-androgen effects by suppressing androgen receptor (AR) activity. Also an anti-oxidant and anti-inflammatory.
7. OLEIC ACID (olive oil) - present in Saw Palmeto where its presence contributes to the dual inhibition of both 5αR1 and 5αR2,
8. CRANBERRY - A 2020 in vivo study with rats demonstrated that cranberry powder significantly reduced prostate weight by 33%, lowered DHT levels by up to 28% in the prostate, and decreased both type 1 and type 2 5-alpha reductase activity—by 18% and 35%, respectively. Contains proanthocyanidins, flavonoids, and other polyphenols that support urinary tract health, and stop E coli sticking to tissues in UTIs.
9. ZINC - is a potent inhibitor of 5α-reductase, particularly types 1 and 2, reducing DHT production. Studies show it can inhibit the enzyme by up to 98% in vitro, with complete inhibition observed at concentrations of 3–9 mmol/L - the inhibition occurs through non-competitive binding.
Charles Myers, prostate cancer and Dutasteride
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).
Dutasteride and Finasteride have reports that they reduces libido and have several other androgen deprivation signs; for that reason, readers might be interested to note that effective dosage of Lycopene is 60 mg to 400 mg depending upon the research study.
Other natural compounds such as polyphenols, phytosterols and fatty acids also have researched (15) benefits with 5-alpha Reductase an/or gene alterations in the androgen receptor system. The main natural compounds are listed above but others include Genistein, Kaemferol, Fisetin and lauric acid (in Coconut oil).
Go to: 12 Natural Compounds that fight Prostate cancer
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/
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Intratumoral androgen biosynthesis in prostate cancer; Cai C., Balk S.P;.Endocr. Relat. Cancer. 2011;18:R175–R182.
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Can Lycopene Impact the Androgen Axis in Prostate Cancer? Catherine C Applegate et al; Nutrients. 2019 Mar;11(3): 633.
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Phytochemicals With Anti 5-alpha-reductase Activity; Version 3, Published online July 6 2021
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'Study Solves Testosterone’s Paradoxical Effects in Prostate Cancer' Duke Health September 04 2024