Prostate Cancer and Testosterone
Dr. John Lee, a Norwegian practicing in California, has written the following for treatment of Prostate Cancer.
In 1941, Dr. Huggins showed that castration slowed the progression of prostate cancer. The cancer benefit was assumed to be due to testosterone reduction. Since that time, physicians have relied on suppression of testosterone production in their treatment of the disease. However, the benefit does not last and eventually prostate cancer progresses, presumably a result of an androgen-insensitive state of the cancer cells. Despite this fact, metastatic prostate cancer patients continue to be treated with androgen blockade. Castration and/or synthetic analogs of gonadotropin releasing hormone (e.g. Lupron) eliminate testicular testosterone but do not diminish androgens of adrenal origin. Total androgen blockade can be achieved by a combination of castration or gonadotropin-releasing hormone with an anti-androgen that blocks cell nucleus uptake of all androgens. One such anti-androgen drug is flutamide. A recent (8 Oct 1998 NEJM) study reported that, in patients with metastatic prostate cancer, the combination of orchiectomy plus flutamide conferred nosurvival advantage over orchiectomy alone. In fact, the only observed effect of flutamide was a reduction in quality of life, particularly more diarrhea and worse emotional functioning. Brain cells, as we know need some testosterone.
This finding raises several interesting points. One is that medicine has made no real progress in treating prostate cancer by androgen reduction since 1941. Second, flutamide has been under study since at least 1989, and recommended for prostate cancer treatment for over five years. Conventional medicine claims superiority over alternative practice by reason of being "evidence based." Why did it take five years for conventional medicine to discover that it had embraced a worthless drug? Perhaps this recent study will stimulate a re-examination of the conventional hypothesis concerning the role of testicular hormones.
Orchiectomy removes not only testicular testosterone production but also its production of estradiol. Why chose testosterone as the cause of prostate cancer? Is it not clear that the time of life when testosterone is at its highest level (around age 18) is the same time of life when prostate cancer is least likely? Why does prostate cancer occur so often in aging men? Testosterone supplementation prevents survival of prostate cancer cells transplanted to test mammals. Testosterone given to test mammals after transplantation of prostate cancer tissue will slow tumor growth. In prostate cancer cell culture, testosterone kills the cancer cells. It is time for a new hypothesis.
Consider three changes in testicular hormone production as men age. Progesterone production falls and since progesterone is a potent inhibitor of 5 alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT), this decline of progesterone causes increased testosterone conversion to DHT. Since testosterone is a direct antagonist of estradiol (and DHT isn't), relative estradiol effect increases. Could this be the cause of prostate cancer?
Embryology teaches us that the prostate is the male equivalent of the female uterus. They differentiate from the same embryonic cells and they share many of the same genes such as the oncogene, Bcl-2, and the cancer protector gene, p53. It is, therefore, no surprise that the hormonal relationships in endometrial cancer will be the SAME in prostate cancer. Researchers TS Wiley and Prof. Bent Formby, using prostate cancer cell cultures, have clarified much of the relationships between hormones, gene effects, and prostate cancer cell growth. Their in vitro test show the following:
Estradiol increases Bcl-2 product that leads to cell proliferation and delay in apoptosis, both of which increase cancer risk. Progesterone suppresses Bcl-2 action and increases p53 product that slows cell proliferation and restores proper apoptosis, both of which decrease cancer risk. Testosterone (but not the DHT) stops cancer cell growth. Insulin increases cancer cell growth.
It should be recalled that adult male's estradiol levels are equivalent to or greater than that of post menopausal females. Estradiol's effects, however, are suppressed (antagonized) by the male's greater production of testosterone. As noted above, progesterone is a potent inhibitor of 5 alpha-reductase and, as males age, the decline of progesterone increases the conversion rate of testosterone to DHT. Thus, in aging males, testosterone levels fall not only because of less production of but also by its increased conversion to DHT. In this situation, estradiol effect rises. Just as estradiol is a known endometrial carcinogen, so also is estradiol a likely prostate cancer carcinogen in aging males.
Lastly, it is recognized that chronic inflammation may also be carcinogenic. It is wise therefore, to maintain one's intake of anti-oxidants such as vitamin C, selenium, and the fat soluble anti-oxidant vitamins, A, E, D, and K.
It is time to revamp the prostate cancer hypothesis. Orchiectomy provided a prostate cancer benefit not because it removed testicular testosterone but it lowered estradiol levels. The course of prostate cancer growth is not a linear progression of cancer cells multiplying from one rogue cell; it is due to continued change of normal prostate cells to cancer cells because of the continued presence of an underlying metabolic imbalance. The most likely underlying metabolic imbalance in all hormone dependent cancers is estrogen dominance (too much estrogen). Prevent the estrogen dominance and you will prevent the cancer. If the cancer is already underway, correcting the estrogen dominance will slow the cancer growth and prolong life.
In the case of prostate cancer, the new treatment plan would include the following:
- Diet should avoid sugar, refined starches, and other glycemic (insulin-raising) foods as well as high estrogen foods such as feedlot meat and milk.
- Maintain a good intake of anti-oxidants.
- Monitor saliva hormone levels of progesterone and testosterone in males over 50.
- Supplement progesterone and testosterone by transdermal cream to maintain saliva levels consistent with that of healthy mature males. When supplemented in this manner, the doses required are quite small: I suspect that appropriate doses will be in the range of 8-10 mg/day of progesterone and 2-3 mg/day of testosterone.
From my clinical experience, it would not surprise that exercise and an active sex life are also protective factors against prostate cancer.
Male castration's prostate cancer benefit stemmed from estradiol reduction, not testosterone reduction. Given the choice, I would choose testosterone and progesterone supplementation over castration.
John Lee, M.D.
January 1999
Three other books of note to buy are:
What Your Doctor May Not Tell You About Menopause by John Lee, M.D.
Our Stolen Future by Theo Colborn
Healthy Living in a Toxic World by Cynthia Fincher, Ph.D.
This is not intended to provide personal medical advice which should be obtained directly from a physician.
