The criminal treatment of chemical castration is the go-to for prostate cancer.
But before someone gets cancer, an enlarged prostate is treated with a 5-alpha reductase inhibitor like finasteride or dutasteride, which has a host of other side effects. More on that later.
The prostate is a walnut-sized gland located between the bladder and the penis and it’s just in front of the rectum. The prostate regulates its hormone levels very well. In hypogonadism, when serum testosterone is low, the prostate will often have normal levels of testosterone and DHT (10 times greater than normal serum levels). On the flip side, injecting massive amounts of testosterone will increase testosterone and DHT in the blood, but not in the prostate (R).
In this article, I’ll show you that testosterone and DHT are actually protective against prostate cancer.
Testosterone, DHT and prostate health
The initial relationship between prostate cancer and testosterone was first investigated by Huggins and Hodge in the 1940s (R).
They found that androgens enlarged the prostate. This is because androgens are the initial signal for DNA synthesis, which in theory can lead to excessive growth, such as cancer growth.
Why they were wrong
Prostate growth is much more complex and extends beyond androgens binding to their receptors. Instead, growth response is due to combined effects from epigenetic factors, growth factors, and negative feedback receptor downregulation, highlighting that serum androgen concentration is a single factor in the multifaceted pathophysiology of prostate cancer development (R).
So androgen might still play a part some might say, but I’ll soon show you the opposite evidence. Plus, no conclusive data have been demonstrated that testosterone therapy increases prostate cancer risk (R).
This brings us to the saturation model hypothesis.
The saturation model hypothesis explains that there are only so many androgen receptors that androgens can bind to. Once all the receptors are occupied, it cannot further promote growth. Meaning there is a limit to how much growth androgens can induce growth. Beyond this receptor saturation point, any cellular prostatic growth exists independent of serum androgen levels. (R)
Low T doesn’t prevent prostate growth/cancer
Prostate cancer growth still occurs at near castrate levels and the addition of exogenous testosterone does not further stimulate prostate cancer growth (R).
And testosterone levels near castration levels actually worsen prostate health. Testosterone below 346 ng/dl is associated with higher PSA, higher clinical staging, worse D’Amico progression risk, increased risk of bilateral disease involvement, along with greater tumor burden (R, R). More on that later.
Put in other words, DNA proliferation/secretory activity showed the steepest rise in response to androgen exposure at lower levels of testosterone when compared with higher levels of testosterone (R). The more androgens there were, the less it induced DNA proliferation/secretory.
This phenomenon was demonstrated in vivo when prostatic cell activity was no longer dependent on androgen levels as early as 1968 by Dr. Coffey et al (R).
TRT among patients with low-risk prostate cancer did not:
- Increase PSA. Testosterone only modulated PSA levels when T was under 250ng/dl. Over that, there was no longer a correlation between PSA and testosterone, and thus PSA was a parameter independent of testosterone levels (R)
- lead to higher systemic progression.
- result in a change in prostate size/secretory activity (R).
Human evidence that low testosterone increases the risk of prostate cancer
Testosterone and risk of prostate cancer
The common theory is that testosterone promotes prostate growth and increases the risk of getting prostate cancer.
However, this does not take into consideration that as testosterone drops with age, the incidence of prostate cancer increases. You’d expect every 20-year-old to have the highest risk of prostate cancer and every 80-year-old, the lowest.
Let’s look at a few studies that show that low testosterone predisposes to prostate cancer.
In 2006, Morgentaler et al (R) found prostate cancer in:
- 21% of men with testosterone <250 ng/dl compared to only
- 12% of men with testosterone level >250 ng/dl.
In 2013, Rastrelli et al, found that low serum testosterone (defined as <240 ng/dL) was an independent predictor for prostate cancer.
Shin et al (R) found prostate cancer in:
- 38.9% of men with testosterone less than 385ng/dl compared to
- 29.5% of men with testosterone >385ng/dl.
This study found no difference between prostate volumes or incidences of prostate cancer diagnosis among hypogonadal men and men on TRT compared to that of eugonadal men (R).
Ultimately, a 2009 close review of the existing literature in this meta-analysis concluded that the incidence of PCa detection and overall prevalence was no different between hypogonadal men on supplemental androgen therapy and the general public (R).
Two very large studies found that TRT doesn’t increase the risk of prostate cancer, but is actually protective.
- Wallis et al found that in a cohort of >10,000 patients treated with TRT (compared to 28,000 non-treated), patients on TRT had a significantly lower risk of developing prostate cancer. This study shows that patients who were on TRT the longest saw the greatest protection. This suggests that long-term TRT is not only safe but may also have protective effects against the development of prostate cancer (R).
- Loeb et al compared 38,570 men with prostate cancer with 192,838 without prostate cancer and found that there was no overall increase in the risk of prostate cancer in men who received TRT (R). In addition, the patients who did receive TRT had lower incidents of prostate cancer in general, as well as aggressive prostate cancers, noted as early as the first year of starting (R).
The testosterone to PSA ratio was strongly associated with prostate cancer risk, with 80% sensitivity, and 60% specificity (R). Meaning, a low testosterone to PSA ratio (e.g. 200ng/dl testosterone to 4ng/ml PSA) meant a higher risk of getting prostate cancer.
In summary, men with low testosterone, especially in conjunction with elevated PSA, had the highest risk of getting prostate cancer.
Testosterone and risk of aggressive higher-grade prostate cancer
Prostate cancer is graded into different groups, each having its own score, based on how aggressive it is. Below 6 is low risk. 7 is moderate risk and 8+ is high risk.
In 2000, Hoffman and Morgentaler found that men with testosterone ≤300 ng/dl had a greater percentage of Gleason 8 or higher prostate cancer.
This study found that men on TRT vs non-TRT had lower positive prostate biopsy rates (16% vs 51%). Of that 16% in the TRT group, 71% were in milder stages (Gleason Grade Group (GG) 3 pattern) vs of the 51% of the non-TRT group, 40.5% had primary GG3 pattern, and 60% with greater than GG3 pattern (R).
The findings of the article suggest that not only does TRT not have an increased risk of prostate cancer development, but it also demonstrates a protective effect against the development of high risk locally aggressive prostate cancer (R).
Free T and prostate cancer
Men who progressed to more severe forms of prostate cancer had significantly lower free testosterone levels, independent of PSA (R, R). Furthermore, free testosterone level <0.45 ng/dL was associated with a sevenfold increase in the risk of disease progression (R).
DHT and prostate cancer risk
“Ok, ok, ok, but if testosterone is good, then DHT must be the criminal, right?“
DHT is created from testosterone, and as mentioned above, DHT is 10 times higher in the prostate than in the serum. Why would the prostate concentrate/accumulate a hormone that is supposedly so bad for it?
Low vs normal DHT
Recent papers have found that men with lower intraprostatic DHT had a higher risk of aggressive prostate cancer (Gleason score of >7) compared to those with high intraprostatic DHT (R).
Topical DHT treatment didn’t increase PSA or prostate size (R).
This is because of this saturation point. Excess DHT may result in the suppression of androgenic-induced growth of prostate cells (R).
Here is 1 study showing that chronic DHT treatment shrunk the prostate (R).
Finsteride and dutasteride
Finasteride is a 5AR type 1 inhibitor and dutasteride is a type 1 and 2 inhibitors.
Both are used to “treat” prostate hypertrophy and prevent the risk of prostate cancer.
But is it helpful?
Although finasteride and dutasteride significantly lower intraprostatic DHT, they do not have an inhibitory effect on human castration-resistant prostate cancer (R).
Plus, they increase the risk of getting aggressive prostate cancer. As you’ve seen previously, low total and free testosterone increase the risk of aggressive prostate cancer, and so does low DHT.
“PCa (prostate cancer) detected in patients treated with finasteride were of a higher grade than those in patients administered a placebo. High Gleason scores between 7 and 10 were found in 6.4% of the tumors in the finasteride group, compared with only 5.1% of those in the placebo group.” (R)
“The REDUCE trial revealed an overall reduction in the number of PCa patients with a low Gleason score of 5–6 in those receiving dutasteride versus those given a placebo (19.9% compared to 25.1%, respectively). However, during 4-year periods, PCa with high Gleason score of 8–10 were more continual in the dutasteride-treated group than in the placebo group. The FDA analyzed these trials and cited the fact that the obligate increased incidence of tumors with Gleason scores between 8 and 10 by 0.7% with finasteride and by 0.5% with dutasteride.” (R)
Additionally, finasteride didn’t prevent the increase in PSA over time for those at risk (R).
Although the increased risk of aggressive prostate cancer is relatively small compared to the placebo groups, these 5AR inhibitors have many other side effects as well, such as sexual dysfunction (ED, watery semen, loss of penile sensitivity, etc.), depression, etc. Read up on post-finasteride syndrome (PFS) if in doubt. There are many studies proving that it exists and is very prevalent among those using 5AR blockers.
- Post-finasteride syndrome: How to resolve it…
- The truth about DHT: what the science shows
- The easiest way to optimize DHT
- Toxic DHT: can DHT ever be too high
- How to increase DHT
Estrogen and prostate cancer
It turns out that it’s not testosterone or even DHT that promotes prostate cancer, but rather estrogen.
In rats, DHT, which cannot be converted to estradiol or testosterone, did not cause a significant prostate cancer incidence compared to testosterone (R). On the contrary, estrogen speeds up prostate cancer risk (R).
Mice never get prostate cancer if they lack estrogen receptor-α or aromatase (R).
Men as they age develop an increased estrogen-to-androgen ratio, which coincides with the development of benign prostatic hyperplasia (R).
The development of BPH/LUTS (lower urinary tract symptoms) is associated with an increased ratio of estrogen to androgen levels, and this ratio, when mimicked in a variety of animals, induces BPH and lower urinary tract dysfunction (LUTD) (R).
Additionally, an imbalance in the estrogen/androgen ratio may affect prostate fibrosis. Estradiol may activate the degree of prostate fibrosis. In contrast to the effect of estradiol, DHT may inhibit the degree of prostate fibrosis (R).
Typically with age, you’ll see testosterone drop, but estradiol remains the same or even increase. This shifts the estrogen-to-androgen ratio negatively.
Why is that?
It’s due to a variety of reasons, such as a decrease in thyroid function, nutritional deficiencies, oxidative stress and inflammation, insulin resistance, high stress, poor sleep, etc.
- Optimize your testosterone-to-estrogen ratio with thyroid
- How to inhibit aromatase
- Foods that lower aromatase
The plethora of existing data investigating TRT and prostate cancer suggests that:
- The risk is comparable with that of eugonadal males who do not receive TRT
- TRT has shown protective effects with overall lower rates of higher-risk aggressive prostate cancer subtypes.
Low total and free testosterone as well as low DHT increase the risk of prostate cancer, especially the aggressive kind. Plot twist!
>1000ng/dl Testosterone: My Step-by-Step Guide on How I Do It Naturally!