The Effect of Testosterone Replacement Therapy on Prostate-Specific Antigen (PSA) Levels in Men Being Treated for Hypogonadism

Kang, Deying; Li, Hongjun

doi:10.1097/md.0000000000000410

Cited by 43 publications

(23 citation statements)

References 35 publications

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“…These findings are similar to what is seen in literature currently, and are explained by the saturation model proposed by Morgentaler & Traish 18,28 . While our rates of BCR were lower than clinical norms, our trial design doesn’t allow comment on causative factors.…”

Section: Resultssupporting

confidence: 93%

Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes

et al. 2016

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Purpose Both testosterone deficiency (TD) and prostate cancer (CaP) have increasing prevalence with age. However, because of the relationship between CaP and androgen receptor activation, testosterone therapy (TT) among patients with known CaP has been approached with caution. Materials and Methods We identified a cohort of 82 hypogonadal men with CaP who were treated with TT. These included 50 men treated with Radiation Therapy (XRT), 22 with Radical Prostatectomy (RP), 8 managed with Active Surveillance (AS), 1 with Cryotherapy and 1 with High-Intensity Focused Ultrasound. We monitored prostate specific antigen (PSA), testosterone, hemoglobin, biochemical recurrence (BCR) and PSA Velocity (PSAV). Results Median patient age was 75.5 years and median follow up was 41 months. We found an increase in both testosterone (p<0.001) and PSA (p=0.001) levels in the entire cohort. PSA increased in the AS patients, however no patients were upgraded to higher Gleason Score on subsequent biopsies, and none have yet gone on to definitive treatment. We did not have any cases of BCR amongst RP patients, but 3 XRT patients (6%) experienced BCR. It is unclear whether these were related to TT or reflected the natural biology of their disease. We calculated the mean PSAV to be 0.001, 0.12, and 1.1 ug/L/yr for the RP, XRT, and AS groups, respectively. Conclusions In the absence of randomized placebo controlled trials, our study supports the hypothesis that TT may be oncologically safe in hypogonadal men following definitive treatment or active surveillance for CaP.

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Section: Resultssupporting

confidence: 93%

Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes

et al. 2016

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“…A downregulation of serum SHBG also occurs in healthy men following Te administration [29]. We speculate that, in pathological conditions where serum SHBG is reduced, for example, in overweight and obese men [30–33], Te uptake, glucuronidation, and efflux would be increased potentially exacerbating Te deficiency.…”

Section: Discussionmentioning

confidence: 99%

Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells

Pham

McWhinney

et al. 2016

International Journal of Endocrinology

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Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line. Internalisation of SHBG and testosterone, the effects of SHBG on testosterone uptake, metabolism, regulation of androgen responsive genes, and cell growth were assessed. LNCaP cells internalised SHBG by a testosterone independent process. Testosterone was rapidly taken up and effluxed as testosterone-glucuronide; however this effect was reduced by the presence of SHBG. Addition of SHBG, rather than reducing testosterone bioavailability, further increased testosterone-induced expression of prostate specific antigen and enhanced testosterone-induced reduction of androgen receptor mRNA expression. Following 38 hours of testosterone treatment cell morphology changed and growth declined; however, cotreatment with SHBG abrogated these inhibitory effects. These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease.

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“…The AR activation increases until reaches a threshold and, when all receptors are saturated, the testosterone increasing will not have an effect (Warburton et al, 2015). Support for this theory comes from studies such as those by Khera et al (2011) and Kang and Li (2015) where hypogonadal men did not show difference in PSA levels after testosterone therapy.…”

Section: Discussionmentioning

confidence: 99%

Modulation of inflammatory and hormonal parameters in response to testosterone therapy: Effects on the ventral prostate of adult rats

Mendes

Castilho

Pinho

et al. 2018

Cell Biology International

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Testosterone is often recommended in the treatment of several aging-related conditions. However, there are still questions about the consequences of this therapy in terms of hormonal and inflammatory parameters that are crucial for prostate homeostasis. Thus, we investigate if the testosterone therapy (TT) modulates the hormone receptors and inflammatory cytokines in the ventral prostate of adult rats. Wistar rats aging 150 days were divided into two experimental groups (n = 10/group): T: received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks; and C: received corn oil as vehicle. Animals were euthanized at 180 days old by decapitation. Blood was collected to obtain hormone and cytokines concentrations. The ventral prostate was dissected and processed for light microscope and molecular analyses. Relative ventral prostate weight and epithelial compartment were increased after TT. The number of intact and degranulated mast cells was reduced in the T group. Plasma testosterone, DHT and intraprostatic testosterone concentrations were higher in the T group. TT leads to an increase in cell proliferation and up-regulation of AR, ERβ, PAR-4, and NRF2. Importantly, plasma concentration and tissue expression of IL-10 and TNF-α were higher after TT. In summary, these results indicate that TT can regulate inflammatory response, with impacts in cytokines and mast cell population, and modulates steroids receptors, important parameters for prostatic homeostasis.

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The Effect of Testosterone Replacement Therapy on Prostate-Specific Antigen (PSA) Levels in Men Being Treated for Hypogonadism

Abstract: Supplemental Digital Content is available in the text

Cited by 43 publications

References 35 publications

Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes

Testosterone Therapy in Patients with Treated and Untreated Prostate Cancer: Impact on Oncologic Outcomes

Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells

Modulation of inflammatory and hormonal parameters in response to testosterone therapy: Effects on the ventral prostate of adult rats

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