Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth

Morgentaler, Abraham; Traish, Abdulmaged M.

doi:10.1016/j.eururo.2008.09.024

Cited by 392 publications

(333 citation statements)

References 46 publications

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“…This finding is consistent with the proposed androgen saturation model, which posits the existence of a certain threshold level of maximal androgenic stimulation, above which there is no further increase in risk of prostatic carcinogenesis [7]. However, a level of androgenic stimulation below this threshold would, consequently, entail a reduced risk of prostate cancer.…”

Section: Introductionsupporting

confidence: 90%

“…We suggest that this protective effect may be a result of the frequently associated hypogonadism [9;10], resulting in a reduction in the level of androgenic stimulation to below the proposed androgen saturation threshold [7]. In "the Prostate Cancer Prevention Trial" (PCPT), men treated with the 5α-reductase inhibitor finasteride, which prevents the conversion of testosterone to 5α-dihydrotestosterone, exhibited a 25% reduction in the overall rate of prostate cancer diagnosis [30].…”

Section: Discussionmentioning

confidence: 99%

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Male infertility and prostate cancer risk: a nested case–control study

Ruhayel

Giwercman

Ulmert

et al. 2010

Cancer Causes Control

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The pathogenesis of prostate cancer is unclear, although experimental evidence implicates androgens as playing an important role. Infertile men frequently suffer from some degree of hypogonadism and may hence be hypothesized to be at lower risk of developing prostate cancer than fertile men. To test this hypothesis, we conducted a case-control study nested within "the Malmö Diet and Cancer Study" cohort in Sweden, inviting 661 prostate cancer cases, and 661 age-matched controls to participate.Of the 975 (74%) respondents, we excluded 84 childless men with unknown fertility status.Thus, 891 men were included, providing 445 prostate cancer cases and 446 controls. Of these, 841 (94%) men were biological fathers and 50 (6%) men were infertile. Logistic regression showed that the infertile men were at significantly lower risk of being diagnosed with prostate cancer than the fertile men (odds ratio, 0.45; 95% confidence interval, 0.25-0.83). Conditional and unconditional multivariate models, adjusting for socioeconomic, anthropometric, and health-status-related factors, provided similar estimates.We conclude that enduring male infertility is associated with a reduced prostate cancer risk, thus corroborating the theory that normal testicular function, and hence most probably sufficient steroidogenesis, is an important contributing factor to the later development of this malignancy.

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Section: Introductionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Male infertility and prostate cancer risk: a nested case–control study

Ruhayel

Giwercman

Ulmert

et al. 2010

Cancer Causes Control

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“…16 According to this theory, PCa is testosterone-sensitive at low testosterone levels, but after androgen receptors are fully occupied, further testosterone increments have modest or no effect on the prostate or PCa dynamics. This hypothesis is supported by studies in men on TRT showing modest or no PSA increase after initiating testosterone injections, as well as no increased risk for cancer.…”

Section: Discussionmentioning

confidence: 99%

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer

Albuquerque

Guglielmetti

Barbosa³

et al. 2017

Rev. Assoc. Med. Bras.

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Objective: To evaluate the relation between serum total testosterone (TT) and prostate cancer (PCa) grade and the effect of race and demographic characteristics on such association. Method: We analyzed 695 patients undergoing radical prostatectomy (RP), of whom 423 had serum TT collected. Patients were classified as having hypogonadism or eugonadism based on two thresholds of testosterone: threshold 1 (300 ng/dL) and threshold 2 (250 ng/dL). We evaluated the relation between TT levels and a Gleason score (GS) ≥ 7 in RP specimens. Outcomes were evaluated using univariate and multivariate analyses, accounting for race and other demographic predictors. Results: Out of 423 patients, 37.8% had hypogonadism based on the threshold 1 and 23.9% based on the threshold 2. Patients with hypogonadism, in both thresholds, had a higher chance of GS ≥ 7 (OR 1.79, p=0.02 and OR 2.08, p=0.012, respectively). In the multivariate analysis, adjusted for age, TT, body mass index (BMI) and race, low TT (p=0.023) and age (p=0.002) were found to be independent risk factors for GS ≥ 7. Among Black individuals, low serum TT was a stronger predictor of high-grade disease compared to White men (p=0.02). Conclusion: Hypogonadism is independently associated to higher GS in localized PCa. The effect of this association is significantly more pronounced among Black men and could partly explain aggressive characteristics of PCa found in this race.

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“…As a result, in the poor prognosis group (>5 sites of bone metastasis, hydronephrosis, pain requiring analgesics, alkaline phosphatase >2 times the upper limit of the normal range), bilateral orchiectomy should be performed for a better survival benefi t. The reason why surgical castration is superior to medical castration with LHRH is not clear. According to Morgentaler's saturation model, prostate carcinoma requires a fairly low testosterone concentration for the carcinoma to fl ourish [32] . There are some studies indicating that LHRH therapy does not achieve as low of a testosterone level as does bilateral orchiectomy [33][34][35][36] .…”

Section: Wwwchinapharcom Lin Yh Et Almentioning

confidence: 99%

A comparison of androgen deprivation therapy versus surgical castration for patients with advanced prostatic carcinoma

Lin¹,

Chen²,

Hou³

et al. 2011

Acta Pharmacol Sin

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Aim: To examine the outcomes of patients with advanced prostate carcinoma who underwent medical or surgical castration. Methods: A hundred twenty one consecutive cases of patients with advanced prostate carcinoma who underwent medical or surgical castration between 2001 and 2006 were retrospectively reviewed. Associations between clinical outcomes and prognostic scoring factors were determined based on the Reijke study. In the surgical and medical castration groups, the impact on the prostate-specifi c antigen (PSA) normalization rate, the rebound rate and the disease-free survival rate were evaluated. The mean follow-up was 36.1 months. Results: In the initial 12 months, there were no statistical differences in the PSA normalization rate and the PSA rebound rate between the two groups. However, the PSA rebound rate after the 12th month (20.90% vs 40.74%, P=0.0175) and the 18th month PSA normalization rate (59.70% vs 37.04%, P=0.0217) differed signifi cantly between the two groups, and these differences were maintained to the end of the study. When comparing patients grouped according to Reijke prognosis scores, there was no difference between medical and surgical castration for the good prognosis group. However, among the patients given a poor prognosis, surgical castration was superior in terms of the PSA normalization rate, the PSA rebound rate, the tumor progression-free survival rate (P<0.001) and the overall survival rate (P<0.001). Conclusion: Advanced prostate carcinoma patients with poor pretreatment prognosis scores should undergo surgical castration rather than medical castration for better PSA rebound rates and overall survival.Keywords: androgen; surgical castration; prostate neoplasm; metastasis; prognosis; medical castration; prostate-specifi c antigen; luteinizing hormone-releasing hormone (LHRH) Acta Pharmacologica Sinica (2011) 32: 537-542; doi: 10.1038/aps.2010 published online 14 Mar 2011 Original Article # The two authors contributed equally to this work. * To whom correspondence should be addressed. In this study, we compared the clinical effectiveness of surgical and medical castration with respect to patient outcomes. We also identifi ed clinical outcomes and PSA response features that predicted favorable treatment outcomes for prostate carcinoma after ADT. Materials and methods Patient selectionAfter obtaining institutional review board approval for a retrospective study of the medical records from January 2001 to March 2006, we identified all patients who had advanced prostate carcinoma. Patients with localized prostate carcinoma received definitive therapy, such as radical surgery or radiotherapy. Patients whose clinical staging was greater than tumor stage T3, T4, or metastatic disease, received hormone therapy. In this study, we included these patients receiving hormone therapy but excluded patients on radiotherapy or chemotherapy for prostate carcinoma. However, there were some patients on palliative radiotherapy for spinal or other bone metastases.The exclusion criteria for this...

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Shifting the Paradigm of Testosterone and Prostate Cancer: The Saturation Model and the Limits of Androgen-Dependent Growth

Cited by 392 publications

References 46 publications

Male infertility and prostate cancer risk: a nested case–control study

Male infertility and prostate cancer risk: a nested case–control study

Low serum testosterone is a predictor of high-grade disease in patients with prostate cancer

A comparison of androgen deprivation therapy versus surgical castration for patients with advanced prostatic carcinoma

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