madman
Super Moderator
ABSTRACT
Introduction: Although testosterone therapy (TTh) is the standard practice in otherwise healthy hypogonadal men, this therapy has historically been contraindicated in men with a history of prostate cancer. Recent evidence suggests that there is minimal or no prostate cancer growth in the setting of TTh administration in men definitively treated for non-metastatic prostate cancer.
Objective: To review the evidence supporting the safety and efficacy of TTh in patients previously treated for localized prostate cancer.
Methods: A literature review of the PubMed database was performed to identify studies evaluating the safety and efficacy of TTh in patients with a history of prostate cancer. Search terms included Testosterone Therapy, Testosterone Replacement Therapy, and Radical Prostatectomy, Radiotherapy, External Beam Radiation Therapy, EBRT, Brachytherapy; Prostate Cancer, and Hypogonadism, Low Testosterone; Bipolar Androgen Therapy.
Results: Available literature provides evidence for the safe application of TTh in patients previously treated for prostate cancer with either radical prostatectomy or radiotherapy. Furthermore, there exists evidence that severely hypogonadal levels of testosterone may lead to worse oncological outcomes. More recent research has begun to elucidate the effectiveness of bipolar androgen deprivation therapy in the treatment of prostate cancer. This mechanism of action increases the level of evidence indicating that the traditional management of maintaining testosterone levels at low levels may no longer be standard of care. TTh likely has a role in improved erectile function and other quality-of-life concerns in patients developing testosterone deficiency after being treated for prostate cancer.
Conclusions: TTh should be offered to select hypogonadal patients who have a history of definitively treated prostate cancer. Adequately designed randomized controlled trials are necessary to confirm the safety and efficacy of TTh in this population.
INTRODUCTION
Testosterone deficiency is a clinical syndrome that can include diminished libido, osteoporosis, and cognitive impairment, which results from a deficiency in the production of testosterone.1 Although testosterone therapy (TTh) is the standard practice in otherwise healthy hypogonadal men, a history of prostate cancer was previously considered a contraindication to TTh.2 Restriction of TTh from men with prostate cancer was largely practiced because of historical tradition.3 The prevalence of evidence confirming that TTh benefitted the quality of life led to a paradigm shift in the treatment of testosterone deficiency in men with prostate cancer, as well as the manner in which exogenous androgens affect the prostate.3
Since the early 1950s, testosterone was thought to cause prostate cancer or, if the man had prostate cancer, to result in increased growth of cancer. In 1941 Huggins and Hodges established the hormonal responsiveness of prostate cancer. Huggins would later go on to receive the Nobel Prize for his research on androgens and prostate cancer. They reported that the marked reductions in testosterone by castration or estrogen treatment caused metastatic prostate cancer to regress, and also that administration of exogenous testosterone caused prostate cancer to grow.4 To this day, androgen ablation remains a mainstay of treatment for advanced prostate cancer.5
In response to literature describing no prostate cancer growth or progression in men receiving TTh, the validity of the androgen-responsiveness model was called into question.6 On review of previous literature, Morgentaler and Traish found that reports of testosterone causing rapid growth of prostate cancer occurred in men who already had extremely low testosterone levels due to castration or estrogen treatment.7 They concluded that the maximal androgenic stimulation of prostate tissue was reached at relatively low concentrations. This is known as the saturation model. Marks et al further described that raising serum testosterone levels did not raise testosterone levels within the prostate.8 Experimental studies report that the concentration at which this saturation occurs is quite low.9 Reports of men treated with TTh after treatment for localized prostate cancer have shown low to absent recurrence rates2 ; however, concern remains among practitioners that testosterone may promote recurrence.1
RESULTS
Evidence synthesis for this review
*Treatment of Testosterone Deficiency With TTh After Radical Prostatectomy
*Treatment of Testosterone Deficiency With TTh After Radiotherapy
*Treatment of Testosterone Deficiency With TTh After Brachytherapy
*Treatment of Testosterone Deficiency With TTh After External Beam Radiation Therapy.
*Testosterone Deficiency and Prostate Cancer Outcomes
*Testosterone Deficiency and Bipolar Androgen Therapy
*Role of TTh in Erectile Function Recovery After Prostate Cancer
CONCLUSION
Available evidence suggests that administration of TTh for the treatment of testosterone deficiency appears to be safe in patients previously treated with definitive local therapy for prostate cancer. This review validates this finding in patients treated either with surgical therapy or single or multimodal radiotherapy. Owing to the limited availability of randomized controlled trials, clinicians should remain vigilant when selecting appropriate patients to administer TTh in secondary hypogonadal men with a history of prostate cancer.
Introduction: Although testosterone therapy (TTh) is the standard practice in otherwise healthy hypogonadal men, this therapy has historically been contraindicated in men with a history of prostate cancer. Recent evidence suggests that there is minimal or no prostate cancer growth in the setting of TTh administration in men definitively treated for non-metastatic prostate cancer.
Objective: To review the evidence supporting the safety and efficacy of TTh in patients previously treated for localized prostate cancer.
Methods: A literature review of the PubMed database was performed to identify studies evaluating the safety and efficacy of TTh in patients with a history of prostate cancer. Search terms included Testosterone Therapy, Testosterone Replacement Therapy, and Radical Prostatectomy, Radiotherapy, External Beam Radiation Therapy, EBRT, Brachytherapy; Prostate Cancer, and Hypogonadism, Low Testosterone; Bipolar Androgen Therapy.
Results: Available literature provides evidence for the safe application of TTh in patients previously treated for prostate cancer with either radical prostatectomy or radiotherapy. Furthermore, there exists evidence that severely hypogonadal levels of testosterone may lead to worse oncological outcomes. More recent research has begun to elucidate the effectiveness of bipolar androgen deprivation therapy in the treatment of prostate cancer. This mechanism of action increases the level of evidence indicating that the traditional management of maintaining testosterone levels at low levels may no longer be standard of care. TTh likely has a role in improved erectile function and other quality-of-life concerns in patients developing testosterone deficiency after being treated for prostate cancer.
Conclusions: TTh should be offered to select hypogonadal patients who have a history of definitively treated prostate cancer. Adequately designed randomized controlled trials are necessary to confirm the safety and efficacy of TTh in this population.
INTRODUCTION
Testosterone deficiency is a clinical syndrome that can include diminished libido, osteoporosis, and cognitive impairment, which results from a deficiency in the production of testosterone.1 Although testosterone therapy (TTh) is the standard practice in otherwise healthy hypogonadal men, a history of prostate cancer was previously considered a contraindication to TTh.2 Restriction of TTh from men with prostate cancer was largely practiced because of historical tradition.3 The prevalence of evidence confirming that TTh benefitted the quality of life led to a paradigm shift in the treatment of testosterone deficiency in men with prostate cancer, as well as the manner in which exogenous androgens affect the prostate.3
Since the early 1950s, testosterone was thought to cause prostate cancer or, if the man had prostate cancer, to result in increased growth of cancer. In 1941 Huggins and Hodges established the hormonal responsiveness of prostate cancer. Huggins would later go on to receive the Nobel Prize for his research on androgens and prostate cancer. They reported that the marked reductions in testosterone by castration or estrogen treatment caused metastatic prostate cancer to regress, and also that administration of exogenous testosterone caused prostate cancer to grow.4 To this day, androgen ablation remains a mainstay of treatment for advanced prostate cancer.5
In response to literature describing no prostate cancer growth or progression in men receiving TTh, the validity of the androgen-responsiveness model was called into question.6 On review of previous literature, Morgentaler and Traish found that reports of testosterone causing rapid growth of prostate cancer occurred in men who already had extremely low testosterone levels due to castration or estrogen treatment.7 They concluded that the maximal androgenic stimulation of prostate tissue was reached at relatively low concentrations. This is known as the saturation model. Marks et al further described that raising serum testosterone levels did not raise testosterone levels within the prostate.8 Experimental studies report that the concentration at which this saturation occurs is quite low.9 Reports of men treated with TTh after treatment for localized prostate cancer have shown low to absent recurrence rates2 ; however, concern remains among practitioners that testosterone may promote recurrence.1
RESULTS
Evidence synthesis for this review
*Treatment of Testosterone Deficiency With TTh After Radical Prostatectomy
*Treatment of Testosterone Deficiency With TTh After Radiotherapy
*Treatment of Testosterone Deficiency With TTh After Brachytherapy
*Treatment of Testosterone Deficiency With TTh After External Beam Radiation Therapy.
*Testosterone Deficiency and Prostate Cancer Outcomes
*Testosterone Deficiency and Bipolar Androgen Therapy
*Role of TTh in Erectile Function Recovery After Prostate Cancer
CONCLUSION
Available evidence suggests that administration of TTh for the treatment of testosterone deficiency appears to be safe in patients previously treated with definitive local therapy for prostate cancer. This review validates this finding in patients treated either with surgical therapy or single or multimodal radiotherapy. Owing to the limited availability of randomized controlled trials, clinicians should remain vigilant when selecting appropriate patients to administer TTh in secondary hypogonadal men with a history of prostate cancer.
