What is the link between testosterone and prostate cancer?
One of the biggest myths about testosterone therapy is that it causes prostate cancer. There are a number of "low power studies" based on completely flawed theories around the claim that testosterone causes prostate cancer. This misinformation stems way back to the 1940s when doctors knew very little about prostate cancer. In particular, one study where doctors discovered when castrating people with prostate cancer, they lived a bit longer.
The Link Between Testosterone and Prostate Cancer is Based on Flawed Studies
In their hugely flawed study, they noticed that one guy, yes, one, lived longer after castrating him. So, of course, they assumed that lowering testosterone by castration was the answer. For generations after, it was and still is, accepted that testosterone causes prostate cancer.
Dr. Abraham Morgentaler, the leading expert on testosterone replacement therapy and its effects on prostate cancer, states in his article published in JAMA that.
".....the limited clinical trials to date have shown risk of prostate cancer in men undergoing TRT of approximately 1%, a rate not different from untreated men not being treated with testosterone."
Dr. Abraham Morgentaler
The Study that Started the Myth
The basis of this opinion is all because of one study by 4 Dr. Huggins and Dr. Hodges in 1941. The study looked at treating men who already had prostate cancer by:
1. Castrating them (lowering testosterone)
2. Chemically castrating them (declining testosterone)
3. Giving them estradiol (estrogen)
Importantly this study did not look at men without prostate cancer and did not look at what happens when you GIVE testosterone. There have been several studies since. Two notable ones looked at what happens when you give testosterone to men with advanced prostate cancer. One study used biopsy as a litmus test of whether the disease burden increased or decreased. The other study looked at disease progression.
- In the Harvard study by Dr. Morgantaler (April 2011), 100% of the 12 patient biopsies at the beginning of the study had prostate cancer. During this study, the participants received testosterone weekly. Afterward, 50% of the biopsies were negative.
- In the Johns Hopkins Study (December 2017), 47 men received pulse therapy with testosterone. One man was disease-free by the end of the study, and, in the rest of the men, the disease did not progress.
It's Low Testosterone That Causes Cancer, Not High!
New research (1) (2) now shows that it is not high testosterone levels that can cause prostate cancer; it is low testosterone, which causes the condition to be more aggressive. This shifting paradigm from old-school theories to the correct new way of thinking is excellent news for prostate cancer patients and those worried about testosterone replacement therapy.
There are only a certain number of androgen receptors in the human body that bind with testosterone to 'activate it.' That is why testosterone only increases prostate cancer incidence in men who have extremely low testosterone levels of up to 200 ng/dl. After this level, a curious thing happens. The rate of prostate cancer starts to decline over time, and if you achieve high enough levels, you will see the decline drop at or below what is the considered baseline risk for prostate cancer for men who do not take testosterone.
This model describes the saturation effect. It is likened to you pouring water on a sponge. After a while, the sponge can only hold so much water. After that, the water just seeps away from the sponge. Think of the prostate as having a finite number of receptors for testosterone. Up until a level of 200 ng/dl, the testosterone will attach to these receptors and stimulate the prostate. After that, at higher testosterone levels, the testosterone no longer attaches to these receptors to stimulate the prostate.
It doesn't matter how much testosterone is circulating in our blood. Once all the receptors are full, they, too, can take no more. This saturation point explains why high testosterone levels do not affect prostate cancer risk, but low levels certainly can. In fact, men with low testosterone levels tend to develop a more aggressive form of prostate cancer.
The Importance of Estradiol
Now you may wonder if testosterone doesn't cause prostate cancer at optimal levels and drops the risk of prostate cancer; what causes this drop in prostate cancer? Believe it or not, it is ESTRADIOL (i.e., estrogen). Wait. "I thought estrogen was bad for men." That is a falsehood that was started by weightlifters and then propagated by misinformed doctors to help boost testosterone production. No, estrogen, particularly the form of estrogen called estradiol, which comes directly from testosterone, does not make you cry when you watch kittens on TV or make you have breasts (gynecomastia).
This falsehood was a ploy propagated by the book from the 1980s. called the "Underground Steroid Book." This book deceived doctors into prescribing estrogen blockers such as aromatase inhibitors to increase testosterone by blocking one of the pathways testosterone goes down. If you block one of the pathways, it causes a backup. Therefore, you force testosterone into the more "desirable" path of boosting testosterone levels and DHT (dihydrotestosterone), which men want to build muscle. Incidentally, DHT is 10-100 times more active than testosterone.
So How Does Estradiol Reduce Prostate Cancer Risk in Men?
There are two things estradiol does to reduce and even treat prostate cancer. It causes apoptosis (suicide) of the prostate cancer cells and reduces the blood supply to prostate cancer cells. In fact, before the advent of the drugs Casodex and Lupron, which are androgen deprivation drugs, men with prostate cancer were treated with a synthetic estrogen called DES (Diethylstilbestrol). Incidentally, there are two reasons why they stopped using DES. The first is that Casodex and Lupron were the new, more expensive drugs, and thus they were favored to be prescribed. The second is that DES increases the risk of heart disease (by increasing matrix metalloprotease).
The funny thing is Casodex and Lupron (the drugs of choice for treating prostate cancer) cause heart disease, depression, diabetes, sexual dysfunction, gynecomastia, dementia, hot flashes, and osteoporosis. Estradiol does not increase these diseases and symptoms. It decreases the risk of heart disease, osteoporosis, dementia, PROSTATE CANCER, sexual dysfunction, and visceral fat (which causes diabetes, high cholesterol, and high blood pressure).
Latest Research Shows TRT Does Not Aggravate Prostate Cancer
The latest research shows that TRT may not make prostate cancer more aggressive. There are even studies saying the opposite - that, in some instances, TRT can help. One study of 2500,00 men in Sweden found that men prescribed TRT for longer than a year had no increase in prostate cancer risk. In fact, their risk of aggressive disease fell by 50 percent.
Even so, we always err on the side of caution and don't prescribe testosterone to patients with prostate cancer or a recent history of it. We insist on checking the PSA levels of all new patients to assess their cancer risk and monitor them throughout their treatment. Interestingly, low testosterone levels are now considered one possible cause of prostate cancer. Studies are currently ongoing to determine why this could be and why maintaining normal levels may protect against aggressive disease.
Testosterone and Prostate Summary:
- Testosterone is safe, indicated, and efficacious in prostate cancer survivors that have been treated and cured.
- Testosterone administration does not increase the risk or incidence of prostate cancer in the general population or prostate cancer survivors.
- Low levels of testosterone are associated with increased risk and higher Gleason scores.
- Higher testosterone levels portend a decreased risk of cancer.
- The "Saturation Model" explains this discrepancy where maximal stimulation of prostate cancer occurs at a very low level of testosterone.
- Estradiol produces an effective tumor response along with improvement in function and symptomatic quality of life indices.
- Estradiol has a direct apoptotic effect in addition to an androgen-suppressive effect.
- Estradiol provides androgen deprivation without estrogen deprivation.
