Bombshell: Explosive Medical Secrets That Will Redefine Aging (19 page)

But I saw firsthand how well men were doing on testosterone, not just with sex but a general all-over improvement in their health, vigor, well-being, and mood. Some years later, a training fellow and I went through all the published literature on T and prostate cancer for a review paper on the risks of testosterone for the
New England Journal of Medicine
. We looked at several hundred articles from medical journals to investigate the association between high testosterone and prostate cancer. In the end we couldn’t find a single article that showed any compelling evidence that high T, or raising T with treatment, was a risk for prostate cancer. Not one.

SS:
So the theory of low testosterone being protective from getting prostate cancer was totally inaccurate? That’s an amazing story. Think of all the men who suffered as a result of this inaccuracy.

AM:
Right. The traditional idea, taught for decades, that raising T would cause prostate cancer or would make an existing small cancer grow like wildfire was based on a misunderstanding of data that went back to Huggins in 1941. All this time the medical establishment had been relying on old outdated information, and because it seemed to make sense to people, it had never been seriously questioned or challenged.

Probably the single best thing I ever did in medicine or science was going to the basement of the Countway Library of Medicine at Harvard and pulling out the original Huggins paper. I couldn’t believe my eyes when I read it. Huggins and his coauthor, Hodges, had removed the testicles in a relatively small group of men with metastatic prostate cancer and showed that a blood test called acid phosphatase dropped quickly, presumably due to lack of testosterone. This indicated that the cancer had regressed, which was very cool. This was the first successful treatment for advanced prostate cancer, and as I mentioned before, we still treat metastatic prostate cancer by lowering T, although we tend to do it now with medications rather than removing the testicles.

In addition, Huggins and Hodges wrote that they had also administered T injections to men with prostate cancer, and the acid phosphatase went up in all of them. That sounded bad when I first was reading it. But when I looked more closely, they only gave testosterone to three men. In the Results section they only gave results for two men. One of these men had already been castrated, which put him in a different category altogether. In the end, the theory that prostate cancer will grow like wildfire if an otherwise normal man receives testosterone was based on a single man! And the actual data provided for that one man was not particularly convincing. That blood test, acid phosphatase, is no longer used because it’s so erratic. And in the one individual who supposedly showed a definite increase in acid phosphatase during testosterone administration, his levels were bouncing all over the place.

I found a few additional stimulating articles among the old literature. Prior to 1982, there were several studies where investigators had actually treated men with testosterone even though they had metastatic prostate cancer. At the time, the idea that the prostate was hormonally sensitive was new, and they were trying to figure out what happened when they gave T and when they took it away. Although no one really was prepared to say it at the time, it became clear to me
from these various studies that if T was given to men with prostate cancer after their own T had been reduced to zero (by testosterone-lowering drugs), their cancers grew rapidly. However, when T was administered to men without any prior hormonal treatment, if they had just been left alone before receiving T, then nothing happened to them.

SS:
So your conclusion is …

AM:
Prostate cancer needs some testosterone in order to grow. But it can only use a little. Adding more doesn’t seem to do anything bad.

SS:
We are talking about active cancer.

AM:
Yes.

SS:
Well, that makes sense. Men are individualized just as women; everybody needs what they need.

AM:
I like to use the analogy of a houseplant. If I go away and don’t water a houseplant, when I come back it’s going to be dry and shriveled up. If I come home in time and water it, the plant will grow and gain mass again. Once it’s had enough water it doesn’t matter if I let a garden hose run into that plant night and day, it will never grow to the size of a tree.

SS:
Are you saying that excess testosterone won’t make prostate cancer metastasize?

AM:
That’s right. In multiple research studies, there is no evidence that men with higher T are at any greater risk of metastatic or aggressive disease than men with lower T. Like the plant and water, prostate cancer can only accommodate, or use, a certain amount of its nutrient, testosterone. My colleague, Abdul Traish, Ph.D., and I have written this concept up and called this the
saturation model
. At some point that plant is saturated, like a sponge that’s full of water.

On a biochemical level, the way hormones usually work is that they bind to a receptor molecule. If you don’t have the receptor to recognize and bind to, the hormone doesn’t do anything. Each cell has a limited number of copies of the receptor molecule. Once all the copies of the receptor are filled with androgen (testosterone), additional testosterone has nothing to bind to. It turns out that human prostates have their androgen receptors completely filled (we say the receptors are “saturated”) at extremely low T concentrations, about 120 nanograms per deciliter. That’s why men with advanced prostate cancer in those old studies who received T did fine if they hadn’t yet been treated to lower their testosterone. And it also explains why
men in those studies who had undergone castration did poorly with T administration—because the androgen receptors weren’t filled yet with T, so there was still opportunity for T to bind to the receptor and thereby influence the cells to grow or divide more rapidly. We think of a normal level of testosterone to be above 350 ng/dL. If you drop a man’s testosterone severely by administering medicines like Lupron, the prostate actually becomes “thirsty,” if you will, for testosterone, and now the prostate is deficient and that allows the low testosterone to cause trouble, which wouldn’t happen if levels were normal or even modestly reduced.

Testosterone makes men feel better. However, the fear that T will necessarily cause prostate cancer to appear, or grow if already present, has been the number one reason physicians have shied away from offering this to more men. And until very recently, it was believed that T was contraindicated in any man with a diagnosis of prostate cancer, even if he appeared to be cured of his cancer.

In the May 2011 issue of the
Journal of Urology
, my colleagues at Baylor Medical College and I published a study that seriously challenges that old taboo, in which we gave T to men with untreated prostate cancer. I got started with this project about five years ago when an eighty-four-year-old man walked into my office with some sexual complaints. He couldn’t have an adequate erection, he couldn’t have an orgasm, and he felt tired all the time. He was a lawyer, in great shape, with a beautiful shock of white hair on his head, and he still went to work every day. We tested his blood and he did have low T, as I suspected, but he also had a very high PSA. His value was 8.5, and anything above 4.0 ng/mL is considered abnormal and a risk for prostate cancer. I don’t do a lot of biopsies in men in their eighties, but he wanted to know if he had cancer, so I did a biopsy on him. The biopsy showed he had relatively low-grade prostate cancer in both sides of his prostate. He said he really didn’t want to treat the cancer, which I thought was reasonable given his age and the likelihood that this low-grade cancer wouldn’t cause him any trouble for many years, if ever. But then he told me he wanted to try the testosterone treatment we’d discussed before his biopsy! I told him I had never given testosterone to a man with active prostate cancer.

SS:
What did you do?

AM:
I told him conventional wisdom is that his cancer will get worse. I also told him I do a lot of lecturing and research on this topic, and I wasn’t sure that it was true. He asked, “If you give me
testosterone and the cancer gets worse, will you be able to know?” I said, “Most likely because your PSA will go up.” He’s a lawyer, very smart, intelligent, and logical. He said to me, “Listen, I’m eighty-four years old. What have I got to lose?”

SS:
Did you give it to him?

AM:
Yes. You know what happened? Over two years, his PSA dropped from 8.5 to the sevens, into the sixes, into the fives, and then stabilized in the low sixes. After two years of testosterone treatment, I published his results as the first case of long-term T administration in a man with untreated prostate cancer, revealing no progression of disease.

SS:
That’s fantastic, one man, one case, two years of testosterone therapy in a man with untreated prostate cancer. How is he today?

AM:
He’s fine! He still comes to see me a couple times a year. He’s eighty-nine, he’s been on testosterone the whole time, and there’s no evidence of cancer progression. His case gave me the courage to start giving T to other men in the same situation. The paper we published in May 2011 gave the results of testosterone therapy in a small group of men, thirteen of them, all with active, untreated prostate cancer. They were rigorously monitored, and all of them had follow-up biopsies—an average of two sets of follow-up biopsies per individual. The average time of T therapy was two and a half years. Amazingly, none of these men had any progression of their cancer. Their PSA did not rise, and the size of the prostate measured by ultrasound when we did the biopsies did not go up. In fact, 54 percent of all the biopsies we did in these men showed no cancer at all.

I had another patient fifty-nine years old, more money than God, flies everywhere in his private jet. He was diagnosed with prostate cancer and had his prostate removed surgically.

SS:
Didn’t he do any research?

AM:
This guy is smart, but when you are diagnosed, even the smartest get scared. He’d been on testosterone for a year and had done very well with it. But when his cancer was diagnosed, all his doctors were telling him, “You gotta get off testosterone, it’s making the cancer grow.” So he did, stopped cold turkey. While recuperating from surgery in one of his homes in the Bahamas or somewhere, a place he loves, he became suicidal. He told me he was watching a show on assisted suicide and he was taking notes on how to do it. He had only been off testosterone for a few months. So he decides, screw it, I’m going back on testosterone. Within a week he felt like himself again.
But his wife was worried and said, “You can’t do that or it will wake up those sleeping cells.”

SS:
But … he wanted to kill himself when he was off it.

AM:
Right. So he finds me and explains how great he feels on testosterone and is it safe for him to take? He asks, “If you told me that I would live three years with testosterone versus ten years without it, I would take the three years.” He went back on testosterone and his cancer numbers have gone down.

SS:
The testosterone theories have never made sense. If high testosterone were the problem, then every young man would have cancer.

AM:
That is absolutely correct.

SS:
I believe this research deserves the Nobel Prize. When you consider all the men who have been castrated, had prostates removed, been put on useless drugs, and destroyed their quality of life, to find that it might be as simple as T replacement is revolutionary.

AM:
Thank you, Suzanne. You are so good for my ego! You know, I’ve been doing this for twenty-plus years and it’s been a serious challenge to get the message out there. There is such resistance to this information. Historically we’ve been depriving men of androgen and in so many cases been wrong! I hope I’m not getting too technical. Do you know the difference between androgen and testosterone?

SS:
No, I don’t.

AM:
“Androgen” is a general term for chemicals similar to testosterone. I mentioned earlier that there are receptors that hormones bind to; anything that’s in a class like testosterone and binds to the androgen receptor is called an androgen. As a rule, androgens have positive effects on muscle and bone. There are several fairly well-known androgens. The best known, and most plentiful in the body, is testosterone itself. Others include DHT (dihydrotestosterone) and androstenedione.

SS:
Isn’t too much DHT dangerous?

AM:
No, I don’t think there’s any reason to believe it is. Some people have raised concerns about DHT because most testosterone is converted to DHT within the prostate cells, and DHT binds more tightly to the androgen receptor. So some have believed that higher levels of DHT are risky for prostate cancer. However, as we’ve discussed, whether it’s T or DHT in the prostate, the theoretical evidence as well as my own research shows that excess androgen is exactly that, a mere excess.

DHT appears to be responsible for some good things for men, such as erections. DHT is involved in the signaling pathway that allows cells in the penis to release the chemical that causes erections.

Testosterone creams tend to increase DHT because there’s an enzyme in the skin called 5-alpha-reductase that converts testosterone to DHT. So it’s fairly common to get higher DHT levels with T gels or creams. I am not aware of any evidence that high levels of DHT are a problem, and in fact there have now been several studies in which men were treated with DHT gels. Their blood levels of DHT increased quite dramatically, but those men experienced no significant problems. I don’t worry about high DHT levels at all.

SS:
This is new information. I thought high DHT levels were worrisome, just like overly high estrogen levels in men.