New study below.
The BAT concept is that supraphisiological testosterone [T] is required for therapeutic effect. My own use of T has aimed to raise levels to ~1,000 ng/dL.
Men in the PCa years have lower T ("naturally"), but men with PCa seem to have less. To some extent, the cancer seems able to lower T. Men with the lowest T have a poorer prognosis.
From the few studies available 13 years ago, it seemed to me that T had a biphasic effect on proliferation - permissive at low levels & resistant at high-normal levels. My feeling was that the emergence of the pro-growth alpha estrogen receptor [ERalpha] in PCa cells was the impetus for growth, & that estrogen-dominance was to be avoided.
In the new mouse study:
"... results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth."
In terms of Morgentaler's Saturation theory, T saturation of androgen receptors occurs at 150–200 ng/dL. Reducing T below that level will slow proliferation. What is missing from the theory is that increasing T might also reduce proliferation.
"Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed ..."
"Mice that had low serum T levels had the shortest tumor volume doubling time ... This doubling time was significantly shorter than that in the high dose 5 mg T arm ... and in the orchiectomy arm "
-Patrick
ncbi.nlm.nih.gov/pubmed/288...
BMC Cancer. 2017 Sep 7;17(1):635. doi: 10.1186/s12885-017-3569-x.
Testosterone inhibits the growth of prostate cancer xenografts in nude mice.
Song W1, Soni V1, Soni S1, Khera M2.
Author information
1
Scott Department of Urology, Baylor College of Medicine, Jones Building 506C, One Baylor Plaza, Houston, TX, 77030, USA.
2
Scott Department of Urology, Baylor College of Medicine, Jones Building 506C, One Baylor Plaza, Houston, TX, 77030, USA. mkhera@bcm.edu.
Abstract
BACKGROUND:
Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice.
METHODS:
Different serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested.
RESULTS:
The data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001).
CONCLUSION:
These results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.
KEYWORDS:
Androgen; Prostate cancer; Testosterone
PMID: 28877700 DOI: 10.1186/s12885-017-3569-x
