3rd Annual Jefferson Urology Symposium: Men’s Health Forum

© The Canadian Journal of Urology TM : International Supplement, August 2020 Khera greater increase in PSAor a significantly increased risk of cancer thanmenwithout HGPIN. In 2003, this article was considered controversial as there were concerns of giving TTh to men with HGPIN. Over the next 15 years, thereweremany studies assessing the use of TTh in men following radical prostatectomy and radiation therapy for prostate cancer. 9-11 While these studies were predominately retrospective in nature and selected for lowrisk patients, they did not demonstrate an increased risk of prostate cancer recurrencewithTTh in thesemen. Further studies during this time also assessed the use of TTh in men on active surveillance with no increased risk of cancer progression. 11,12 More recently, there have been studies assessing the use of TTh to treat men with castrate resistant prostate cancer or with low metastatic prostate cancer burden or biochemical PSA recurrence. In 2015, Schweizer et al published a series of 14 men with castrate resistant prostate cancer who were treated with high doses of TTh. 13 These patients received testosterone enanthate 400 mg IMeverymonth for 3months. Androgendeprivation therapy (ADT)was also continuedat this time to suppress endogenous testosterone production, allowing for rapid cycling from supraphysiologic serum T levels to near castrate serum T levels. This rapid cycling was termed bipolar androgen therapy (BAT). The investigators found that BATwaswell tolerated and that 50%of patients had a reduction in their PSA, and 50% of patients also had improved radiographic responses. All patients (10 of 10) demonstrated a reduction in PSA after receiving BAT, suggesting that BATmay also restore androgen receptor sensitivity. In a subsequent study by Schweizer et al, the effects of BAT in 29 men with androgen ablation naïve prostate cancerwas evaluated. 14 These 29 asymptomatic hormone sensitive prostate cancer patients had either lowmetastatic prostate cancer burden or non-metastatic disease with a biochemical PSA recurrence. These men received 6 moths of ADT followed by 400 mg of testosterone cypionate IM every 4 weeks for 3 months. The investigators found that 59% of men had a PSA < 4 ng/dl after 18 months (primary endpoint) and that many of these men had significant improvements in quality of life and erectile function. In light of these new publications over the past 15 years, it is not surprising that many clinicians are not as concerned with giving TTh to men with a history of prostate cancer. A study by Millar et al in 2016 sent a survey to urologists regarding their opinion and prescribing patterns on TTh in men on active surveillance for low risk prostate cancer. 15 This survey found that 96% and 84% of urologists believed that it was safe to give TTh to men with a history of a radical prostatectomy and radiation therapy, respectively. In fact, 63% of urologists believed it was safe to give TTh to men on active surveillance. It is important to note that the AUA T guidelines recommend that patients with testosterone deficiency and a history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy. 6 However, theAUAT Guidelines do recommend that clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer. Many urologists are still concerned that TTh will worsen lower urinary symptoms (LUTS). This concern is also fueled by the fact that current package inserts of testosterone products state “Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH.” However, currently there is no convincing data to support this claim. In fact, a review article by Delay and Kohler found that long term TTh either had no effect on LUTS or actually improved LUTS over time. 16 Other studies have also found improvements in voided volumes and post-void residuals in men taking TTh. 16 Thus, patients should be counseled appropriately regarding the use of TTh in men with BPH and LUTS. Testosterone and lifestyle modification Initial treatment options for many medical conditions include lifestyle modifications. For example, patients presentingwithhypertension, hyperlipidemia, or obesity are first encouraged to try lifestyle modification before considering medical therapy. Lifestyle modification as well as varicocelectomyhave alsobeen shown to improve serum T levels in hypogonadal men. Camacho et al conducted a longitudinal study of 2736 men assessing changes in weight and testosterone levels. 17 These investigators demonstrated that there is a bi-directional relationship between weight and serum T levels. In this study, men who lost ≥ 15% of their body weight demonstrated a significant increase in free testosterone (FT) (51.8; 95% CI 1.7, 101.9 pmol/l). In addition, those men whose weight increased by ≥ 15% demonstrated a greater decline in FT (-47.1; 95% CI -136.9, 42.7  pmol). In a meta-analysis of 22 studies assessing the effects of weight loss (diet or surgery) on T levels, weight loss through both diet and bariatric surgery were both effective in significantly increasing serum total and free testosterone. 18 Alowcaloriediet resulted ina 9.8%weight losswitha 83ng/dLincrease in serumT levels. However, bariatric surgery resulted in a 32%weight losswith a 250 ng/dL increase in serum T values. Thus, weight loss seems to be an effective strategy to increasing serum T levels especially if the weight loss can be sustained. 22