LEF recently ran an
article on testosterone and prostate cancer. Testosterone saturates the prostate at very low blood levels, so replacing testosterone only makes the cancer grow faster if you're starting from castrate levels. The idea that testosterone replacement will make prostate cancer grow is called "the Huggins myth" in two journal articles. LEF's conclusions:
Low blood levels of testosterone do not protect against prostate cancer and, indeed, may increase the risk.
High blood levels of testosterone do not increase the risk of prostate cancer.
Treatment with testosterone does not increase the risk of prostate cancer, even among men who are already at high risk for it.
My third reference reports that if a prostate cancer cell has a zinc-sensing receptor, then zinc will improve its growth and survival. Zinc citrate desensitizes this receptor!!! More validation for my
choice.
Urologe A. 2009 Mar 20.
[Testosterone replacement therapy and prostate cancer : The current position 67 years after the Huggins myth.]
Rinnab L, Gust K, Hautmann RE, Küfer R.
Abteilung Urologie und Kinderurologie, Universitätsklinikum, Prittwitzstrasse 43, 89075, Ulm, Deutschland, ludwig.rinnab@uniklinik-ulm.de.
Hypogonadism is highly prevalent in the elderly and in men with prostate cancer. Symptoms of hypogonadism, such as depression, lack of libido, and decreased bone mineral density, can significantly impair quality of life. In addition, testosterone plays an important role in erectile preservation and in growth and function of the cavernosal and penile nerves. There are compelling data showing that testosterone replacement therapy (TRT) does not increase the risk of prostate cancer. The literature (four published studies) concerning men treated with TRT after definitive therapy for prostate cancer reports only one biochemical recurrence. Based on these data, physicians cannot really justify withholding TRT from symptomatic patients after they have been successful treated for prostate cancer. This review gives the practising urologist an overview of the latest literature and useful advice on this controversial topic.
PMID: 19296069
Eur Urol. 2006 Nov;50(5):935-9.
Testosterone and prostate cancer: an historical perspective on a modern myth.
Morgentaler A.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. amorgent@bidmc.harvard.edu
OBJECTIVES: To review the historical origins and current evidence for the belief that testosterone (T) causes prostate cancer (pCA) growth. METHODS: Review of the historical literature regarding T administration and pCA, as well as more recent studies investigating the relationship of T and pCA. RESULTS: In 1941 Huggins and Hodges reported that marked reductions in T by castration or estrogen treatment caused metastatic pCA to regress, and administration of exogenous T caused pCA to grow. Remarkably, this latter conclusion was based on results from only one patient. Multiple subsequent reports revealed no pCA progression with T administration, and some men even experienced subjective improvement, such as resolution of bone pain. More recent data have shown no apparent increase in pCA rates in clinical trials of T supplementation in normal men or men at increased risk for pCA, no relationship of pCA risk with serum T levels in multiple longitudinal studies, and no reduced risk of pCA in men with low T. The apparent paradox in which castration causes pCA to regress yet higher T fails to cause pCA to grow is resolved by a saturation model, in which maximal stimulation of pCA is reached at relatively low levels of T. CONCLUSIONS: This historical perspective reveals that there is not now-nor has there ever been-a scientific basis for the belief that T causes pCA to grow. Discarding this modern myth will allow exploration of alternative hypotheses regarding the relationship of T and pCA that may be clinically and scientifically rewarding.
PMID: 16875775
Carcinogenesis. 2008 Sep;29(9):1692-700.
Extracellular zinc and zinc-citrate, acting through a putative zinc-sensing receptor, regulate growth and survival of prostate cancer cells.
Dubi N, Gheber L, Fishman D, Sekler I, Hershfinkel M.
Department of Morphology, Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University, PO Box 653, Beer Sheva 84105, Israel.
Prostate Zn(2+) concentrations are among the highest in the body, and a marked decrease in the level of this ion is observed in prostate cancer. Extracellular Zn(2+) is known to regulate cell survival and proliferation in numerous tissues. In spite of this, a signaling role for extracellular Zn(2+) in prostate cancer has not been established. In the present study, we demonstrate that prostate metastatic cells are impermeable to Zn(2+), but extracellular Zn(2+) triggers a metabotropic Ca(2+) rise that is also apparent in the presence of citrate. Employing fluorescent imaging, we measured this activity in androgen-insensitive metastatic human cell lines, PC-3 and DU-145, and in mouse prostate tumor TRAMP-1 cells but not in androgen-sensitive LNCaP cells. The Ca(2+) response was inhibited by Galphaq and phospholipase C (PLC) inhibitors as well as by intracellular Ca(2+) store depletion, indicating that it is mediated by a Gq-coupled receptor that activates the inositol phosphate (IP(3)) pathway consistent with the previously identified zinc-sensing receptor (ZnR). Zn(2+)-dependent extracellular signal-regulated kinase and AKT activation, as well as enhanced Zn(2+)-dependent cell growth and survival, were observed in PC-3 cells that exhibit ZnR activity, but not in a ZnR activity-deficient PC-3 subline. Interestingly, application of Zn(2+)-citrate (Zn(2+)Cit), at physiological concentrations, was followed by a profound functional desensitization of extracellular Zn(2+)-dependent signaling and attenuation of Zn(2+)-dependent cell growth. Our results indicate that extracellular Zn(2+) and Zn(2+)Cit, by triggering or desensitizing ZnR activity, distinctly regulate prostate cancer cell growth. Thus, therapeutic strategies based either on Zn(2+) chelation or administration of Zn(2+)Cit may be effective in attenuating prostate tumor growth.
PMID: 18310092
