An Approach to Testosterone Therapy in Men After Treatment for Localized Prostate Cancer

Testosterone Therapy in Men With Prostate Cancer

The use of testosterone in men with a history of prostate cancer remains controversial in light of established findings linking androgens to prostate cancer growth. However, hypogonadism significantly affects quality of life and has negative sequelae, and the risks and benefits of testosterone therapy might be worthwhile to consider in all men, even those with a history of high-risk prostate cancer. To discuss the effects of testosterone on the prostate and the use of testosterone therapy in hypogonadal men with a history of prostate cancer. Review of the literature examining the effects of testosterone on the prostate and the efficacy and safety of exogenous testosterone in men with a history of prostate cancer. Summary of effects of exogenous and endogenous testosterone on prostate tissue invitro and invivo, with a focus on effects in men with a history of prostate cancer. Testosterone therapy ameliorates the symptoms of hypogonadism, decreases the risk for its negative sequelae, and can significantly improve quality of life. Recent studies do not support an increased risk for de novo prostate cancer, progression of the disease, or biochemical recurrence in hypogonadal men with a history of non-high-risk prostate cancer treated with testosterone therapy. Evidence supporting the use of testosterone in the setting of high-risk prostate cancer is less clear. Despite the historical reluctance toward the use of testosterone therapy in men with a history of prostate cancer, modern evidence suggests that testosterone replacement is a safe and effective treatment option for hypogonadal men with non-high-risk prostate cancer. Additional work to definitively demonstrate the efficacy and safety of testosterone therapy in men with prostate cancer is needed, and persistent vigilance and surveillance of treated men remains necessary.

Purpose of ReviewPreviously considered an absolute contraindication, the use of testosterone therapy in men with prostate cancer has undergone an important paradigm shift. Recent data has changed the way we approach the treatment of testosterone deficiency in men with prostate cancer. In the current review, we summarize and analyze the literature surrounding effects of testosterone therapy on patients being treated in an active surveillance protocol as well as following definitive treatment for prostate cancer.Recent FindingsThe conventional notion that defined the relationship between increasing testosterone and prostate cancer growth was based on limited studies and anecdotal case reports. Contemporary evidence suggests testosterone therapy in men with testosterone deficiency does not increase prostate cancer risk or the chances of more aggressive disease at prostate cancer diagnosis. Although the studies are limited, men who received testosterone therapy for localized disease did not have higher rates of recurrences or worse clinical outcomes. Current review of the literature has not identified adverse progression events for patients receiving testosterone therapy while on active surveillance/watchful waiting or definitive therapies.SummaryThe importance of negative effects of testosterone deficiency on health and health-related quality of life measures has pushed urologists to re-evaluate the role testosterone plays in prostate cancer. This led to a paradigm shift that testosterone therapy might in fact be a viable option for a select group of men with testosterone deficiency and a concurrent diagnosis of prostate cancer.

37-Year-Old Man With Fatigue and Erectile Dysfunction

ABSTRACTIntroduction: The use of testosterone therapy (TTh) in men with prostate cancer (PCa) is relatively new, and controversial, due to the longstanding maxim that TTh is contraindicated in men with PCa. Scientific advances have prompted a reevaluation of the potential role for TTh in men with PCa, particularly as TTh has been shown to provide important symptomatic and general health benefits to men with testosterone deficiency (TD), including many men with PCa who may expect to live 30–50 years after diagnosis.Areas covered: This review outlines the historical underpinnings of the historical belief that TTh ‘fuels’ PCa and the experimental and clinical studies that have radically altered this view, including description of the saturation model. The authors review studies of TTh in men with PCa following radical prostatectomy and radiation therapy, in men on active surveillance, and in men with advanced or metastatic PCa.Expert opinion: TTh provides important symptomatic and overall health benefits for men with PCa who have TD. Although more safety studies are needed, TTh is a reasonable therapeutic option for men with low-risk PCa after surgery or radiation. Data in men on active surveillance are limited, but initial reports are reassuring.

Purpose of reviewThe purpose of this article is to examine the contemporary data linking testosterone therapy in overweight and obese men with testosterone deficiency to increased lean body mass, decreased fat mass, improvement in overall body composition and sustained weight loss. This is of paramount importance because testosterone therapy in obese men with testosterone deficiency represents a novel and a timely therapeutic strategy for managing obesity in men with testosterone deficiency.Recent findingsLong-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, marked reduction in waist circumference and BMI and improvement in body composition. Further, testosterone therapy ameliorates components of the metabolic syndrome. The aforementioned improvements are attributed to improved mitochondrial function, increased energy utilization, increased motivation and vigor resulting in improved cardio-metabolic function and enhanced physical activity.SummaryThe implication of testosterone therapy in management of obesity in men with testosterone deficiency is of paramount clinical significance, as it produces sustained weight loss without recidivism. On the contrary, alternative therapeutic approaches other than bariatric surgery failed to produce significant and sustained outcome and exhibit a high rate of recidivism. These findings represent strong foundations for testosterone therapy in obese men with testosterone deficiency and should spur clinical research for better understanding of usefulness of testosterone therapy in treatment of underlying pathophysiological conditions of obesity.

Research in brief

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer

A New Era of Testosterone and Prostate Cancer: From Physiology to Clinical Implications

MP48-08 SAFETY OF TESTOSTERONE THERAPY IN MEN WITH PROSTATE CANCER

Changes in Prostate Specific Antigen in Hypogonadal Men After 12 Months of Testosterone Replacement Therapy: Support for the Prostate Saturation Theory

Trends in Testosterone Therapy use in Prostate Cancer Survivors in the United States

Purpose: To investigate prostate-specific antigen (PSA) and clinical responses to a variety of treatment strategies involving testosterone therapy (TTh) in men with metastatic prostate cancer (mPCa). Materials and Methods: Case records were reviewed for three men with advanced PCa treated with TTh for improved quality of life. Two had bone metastases and nephrostomies at baseline. The third had biochemical recurrence, and continued TTh after developing bone metastases. All rejected androgen deprivation therapy, desired improved quality of life with TTh, and accepted the risk of rapid PCa progression and death. Results: All men experienced substantial symptomatic and health benefits during TTh, including improved strength, vigor, and sexuality. Two reversed substantial weight loss. A 94-year-old man with baseline PSA of 546 ng/mL survived 11 months with continuous TTh, with last PSA of 2493 ng/mL. Two men in their 60s received some form of TTh for 3.5 and 8 years, respectively, and are still alive. None experienced sudden major adverse events. Continuous TTh resulted in progressive rise in PSA to high values. The combination of TTh and enzalutamide provided moderate protection against weakness and fatigue with PSA <10ng/mL for 6 months. PSA values fluctuated from <1.0 to >100 ng/mL within 1–2 months depending on recent androgen status. The most promising strategy appears to be a modified bipolar androgen therapy consisting of repeating cycles of 8 weeks of high-dose TTh followed by 4 weeks of enzalutamide, allowing for prolonged periods of vigor while maintaining PSA control. Conclusions: These pilot results support explorations of new hormonal strategies involving TTh for men with mPCa.

Testosterone deficiency has been reported in patients with Parkinson disease (PD), Alzheimer disease, and Huntington disease. It is not known whether testosterone therapy (TT) in men with borderline hypogonadism and neurodegenerative diseases will be of substantial benefit. Previously, we reported that testosterone deficiency is more common in patients with PD compared with age-matched control subjects, and we also reported in 2 small open-label studies that some nonmotor symptoms responded favorably to TT. To define the effects of TT on nonmotor and motor symptoms in men with PD and probable testosterone deficiency. Double-masked, placebo-controlled, parallel-group, single-center trial. Two experimental groups: patients with PD who were receiving either TT or placebo. Participants received either the study drug by intramuscular injection (200 mg/mL of testosterone enanthate every 2 weeks for 8 weeks) or placebo (isotonic sodium chloride solution injections). In patients in each group, the testosterone serum concentration was obtained at each study visit. During 2 study visits, testosterone levels were blindly evaluated and the intramuscular testosterone dose was increased by 200 mg/mL if the free testosterone value failed to double from the baseline value. The primary outcome variable was the St Louis Testosterone Deficiency Questionnaire, and secondary outcome measures included measures of mood, cognition, fatigue, motor function, and frequency of adverse events. At the end of the double-blind phase, all patients were offered open-label TT and were followed up after 3 and 6 months. Fifteen patients in the placebo group (mean age, 69.9 years), receiving a mean total levodopa equivalent dose of 924 mg/d, had a baseline free testosterone level of 47.91 pg/mL, compared with 15 patients in the TT group (mean age, 66.7 years), receiving an average total levodopa equivalent dose of 734 mg/d, who had a baseline free testosterone level of 63.49 pg/mL. Testosterone was generally well tolerated. More subjects in the TT group experienced lower extremity edema (40% vs 20%). In 2 patients, 1 in each group, prostate-specific antigen levels were elevated from baseline. The improvement in the TT group compared with the placebo group (1.7 vs 1.1) on the St Louis Testosterone Deficiency Scale was not statistically significant. In addition, there were no significant differences in motor and nonmotor features of PD between the 2 groups, although a few subscales showed improvements (Hopkins Verbal Learning Test, P<.04; and Backward Visual Span subtrial, P<.03). However, long-term open-label TT resulted in delayed but sustained improvement in subjects in the TT group who continued to receive treatment (n = 6) compared with subjects in the placebo group who elected not to receive TT (n = 3). Testosterone therapy was generally well tolerated in elderly men with PD and probable testosterone deficiency. While there was no significant difference in the motor and nonmotor scales between the TT and placebo groups at the end of 8 weeks compared with baseline, this may be due to several study limitations, including small sample size, a strong placebo effect with intramuscular therapy, and short follow-up that did not allow measurement of delayed effects of TT in some subjects. Until more definitive studies are reported, practitioners should be particularly cautious in treatment of low testosterone concentrations in men with PD and borderline testosterone deficiency, and careful consideration should be given to the risks vs the benefits of TT.

Introduction The role of testosterone therapy (TTH) in men with prostate cancer (PC) is debated, especially in men on active surveillance (AS). Objective This study aimed to review our data on TTH in this population. Methods The study population consisted of (i) men with PC on active surveillance (ii) with two total T (TT) levels &amp;lt;300 ng/dL (iii) associated with symptoms (iii) performed using LCMS (v) conducted in an early morning fashion who (vi) pursued T therapy (TTH). TTH included exogenous (transdermal, intramuscular) and clomiphene citrate (CC) in the setting of low/low-normal LH levels. T lab work including PSA levels, were checked within 4 weeks of TTH initiation, every three months in the first year and every six months after that. Target TT level was the middle tertile of the normal reference range at our institution. We report on T and PSA levels in this group. Results 82 patients are included. Mean age = 64 ± 9 years. Median pre-TTH PSA levels were 4.6 [3.4, 6.7] ng/mL. Mean baseline TT levels were 305 ± 145 ng/dL. 19% of these men had a TT level &amp;lt;200 ng/dL. Median Gleason score (GS) was 6 with 90% 3+3, 9% 3+4 and 1% 4+3. Median duration on AS before TTH was 14 [1, 43] months. 45% received transdermal T, 19% intramuscular T and 36% CC. Post-TTH TT = 553 ± 268 ng/dL, PSA = 4.9 [3.2, 9.2] Median duration of TTH at last follow-up was 14 [1, 39] months. Median PSA change per patient was 0.3 [-0.9, 2.6] ng/mL, representing a median of 14 (-24, 70) % change in PSA per patient (p= 0.045). 42% had a decrease in PSA, 58% an increase. In 88% of men who experienced a rise in PSA, the PSA rose ≥10%. 50% of men on TTH who had a PSA level below 4 ng/dL rose above 4. 28% of men experienced a PSA level increase ≥1 ng/mL per year. In 18% of these men, TTH was stopped and definitive PC treatment was instituted. In men with ≤1 ng/mL per year increase in PSA, another 18% opted for definitive PC treatment. The most common reason for this was PSA anxiety. Conclusions In men with PC on AS treated with TTH, minimal changes in PSA were seen, with equal numbers of men experiencing a rise and a drop in PSA. About fifth of men ceased AS and proceeded to definitive therapy for their PC. Disclosure No