Acute primary testicular failure due to radiotherapy increases risk of severe postoperative adverse events in rectal cancer patients.

AIM: The aim of this study is to analyze postoperative adverse events (AE) in relation to acute primary testicular failure after radiotherapy (RT) for rectal cancer. METHOD: This relation was assessed in 104 men, included in a previous prospective cohort study of men treated with surgical resection of the rectum for rectal cancer stage I-III. Postoperative AE were graded according to Clavien-Dindo (2004). Grade 3 or more was set as cut-off for severe postoperative AE. The impact of primary testicular failure on postoperative AE was related to the cumulative mean testicular dose (TD) and the change in Testosterone (T) and Luteinizing hormone (LH) sampled at baseline and after RT. RESULTS: Twenty-six study participants (25%) had severe postoperative AE. Baseline characteristics and endocrine testicular function did not differ significantly between groups with (AE+) and without severe postoperative AE (AE-). After RT, the LH/T-ratio was higher in AE+, 0.603 (0.2-2.5) vs 0.452 (0.127-5.926) (p = 0.035). The longitudinal regression analysis showed that preoperative change in T (OR 0.844, 95% CI 0.720-0.990, p = 0.034), LH/T-ratio (OR 2.020, 95% CI 1.010-4.039, p = 0.047) and low T (<8 nmol/L, OR 2.605, 95 CI 0.951-7.139, p = 0.063) were related to severe postoperative AE. CONCLUSION: Preoperative decline in T due to primary testicular failure induced by preoperative RT could be a risk factor regarding short-term outcome of surgery in men with rectal cancer.

The effects of testosterone administration on muscle areas of the trunk and pelvic floor in hysterectomized women with low testosterone levels: proof-of-concept study.

OBJECTIVE: The aim of this study was to determine the effect of testosterone administration on trunk and pelvic floor muscle area in women with low testosterone levels. METHODS: Participants were hysterectomized women with total testosterone<31 ng/dL and/or free testosterone<3.5 pg/mL; participating in the Testosterone Dose Response in Surgically Menopausal Women (TDSM) trial. All participants received a standardized transdermal estradiol regimen during the 12-week run-in period, and were then randomized to receive weekly intramuscular injections of placebo, or 3, 6.25, 12.5, or 25 mg testosterone enanthate for 24 weeks. Muscle areas of the trunk and pelvis were measured at baseline and end of treatment using 1.5 Tesla magnetic resonance imaging. Total and free testosterone levels were measured by liquid chromatography-tandem mass spectrometry and equilibrium dialysis, respectively. Testosterone effect on muscle areas was analyzed using linear regression models. RESULTS: A total of 24 women who had available baseline and posttreatment magnetic resonance imaging were included in the analysis. Increased cross-sectional areas of the paraspinal, psoas, and abdominal wall muscles were seen after testosterone administration. The estimated mean change (95% CI; P value) between treatment groups was 4.07 cm (1.26-6.88; P = 0.007) for paraspinal, 1.60 cm (0.10-3.09; P = 0.038) for psoas major, and 7.49 cm (1.96-13.02; P = 0.011) for abdominal wall muscles. Increases in psoas muscle area were significantly associated with changes in free testosterone concentrations. No significant changes in obturator internus and pelvic floor muscle areas were observed. CONCLUSION: Short-term testosterone administration in women with low testosterone levels was associated with increased trunk muscle area.

Effects of Testosterone Replacement on Electrocardiographic Parameters in Men: Findings From Two Randomized Trials.

Context: Endogenous testosterone levels have been negatively associated with QTc interval in small case series; the effects of testosterone therapy on electrocardiographic parameters have not been evaluated in randomized trials. Objective: To evaluate the effects of testosterone replacement on corrected QT interval (QTcF) in two randomized controlled trials. Participants: Men with pre- and postrandomization electrocardiograms (ECGs) from the Testosterone and Pain (TAP) and the Testosterone Effects on Atherosclerosis in Aging Men (TEAAM) Trials. Interventions: Participants were randomized to either placebo or testosterone gel for 14 weeks (TAP) or 36 months (TEAAM). ECGs were performed at baseline and at the end of interventions in both trials; in the TEAAM trial ECGs were also obtained at 12 and 24 months. Outcomes: Difference in change in the QTcF between testosterone and placebo groups was assessed in each trial. Association of changes in testosterone levels with changes in QTcF was analyzed in men assigned to the testosterone group of each trial. Results: Mean total testosterone levels increased in the testosterone group of both trials. In the TAP trial, there was a nonsignificant reduction in mean QTcF in the testosterone group compared with placebo (effect size = -4.72 ms; P = 0.228) and the changes in QTcF were negatively associated to changes in circulating testosterone (P = 0.036). In the TEAAM trial, testosterone attenuated the age-related increase in QTcF seen in the placebo group (effect size= -6.30 ms; P < 0.001). Conclusion: Testosterone replacement attenuated the age-related increase in QTcF duration in men. The clinical implications of these findings require further investigation.

Testosterone and body composition in men after treatment for rectal cancer.

INTRODUCTION: Preoperative radiotherapy for rectal cancer may affect Leydig cell function. However, the diagnosis of posttreatment hypogonadism is complicated as sexual symptoms associated to hypogonadism can rely on adverse events of pelvic radiation and surgery. AIM: The objective of this study was to investigate the association of testosterone levels and body composition. The clinical value of such an association is tested subsequently in the study population. METHODS: This was a longitudinal study with prospective registration during 2010-2012 and 1-year follow up. Men with rectal cancer stage I-III, treated with radiotherapy and surgery, were eligible, and 40 of 53 men were available for analysis. MAIN OUTCOME MEASURES: The areas of skeletal muscle and adipose tissue were assessed on a defined section of a computed tomography at baseline and after 1 year. Androgen levels were recorded from morning blood samples. RESULTS: The area of skeletal muscle was related to the level of bioavailable testosterone (P = 0.01) but not to the level of serum testosterone (P = 0.36). The subcutaneous adipose tissue was not related to testosterone levels. Men with posttreatment serum testosterone levels of 8-12 nmol/L and longitudinal loss of psoas muscle area had a significantly increased luteinizing hormone-testosterone ratio compared with those with longitudinal gain of psoas muscle. CONCLUSIONS: The area of psoas muscle is related to the unbound fraction of circulating testosterone in men treated for rectal cancer. The longitudinal loss of psoas muscle in men with borderline levels of serum testosterone seems to be an androgen-related symptom associated with compensatory activation of the pituitary-gonadal axis indicating a testicular failure in this group of patients.