Quality of Life and Sexual Function Benefits of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME).

BACKGROUND: The benefits and risks of long-term testosterone administration have been a topic of much scientific and regulatory interest in recent years. AIM: To assess long-term quality of life (QOL) and sexual function benefits of testosterone replacement therapy (TRT) prospectively in a diverse, multinational cohort of men with hypogonadism. METHODS: A multinational patient registry was used to assess long-term changes associated with TRT in middle-age and older men with hypogonadism. Comprehensive evaluations were conducted at 6, 12, 24, and 36 months after enrollment into the registry. OUTCOMES: QOL and sexual function were evaluated by validated measures, including the Aging Males' Symptom (AMS) Scale and the International Index of Erectile Function (IIEF). RESULTS: A total of 999 previously untreated men with hypogonadism were enrolled at 25 European centers, 750 of whom received TRT at at least one visit during the period of observation. Patients on TRT reported rapid and sustained improvements in QOL, with fewer sexual, psychological, and somatic symptoms. Modest improvements in QOL and sexual function, including erectile function, also were noted in RHYME patients not on TRT, although treated patients showed consistently greater benefit over time in all symptom domains compared with untreated patients. AMS total scores for patients on TRT were 32.8 (95% confidence interval = 31.3-34.4) compared with 36.6 (95% confidence interval = 34.8-38.5) for untreated patients (P < .001). Small but significant improvements in IIEF scores over time also were noted with TRT. Approximately 25% of treated and untreated men also used phosphodiesterase type 5 inhibitors, with notable differences in the frequency of phosphodiesterase type 5 inhibitor prescription use according to physician specialty and geographic site location. CLINICAL IMPLICATIONS: TRT-related benefits in QOL and sexual function are well maintained for up to 36 months after initiation of treatment. STRENGTHS AND LIMITATIONS: The major strengths are the large, diverse patient population being treated in multidisciplinary clinical settings. The major limitation is the frequency of switching from one formulation to another. CONCLUSION: Overall, we confirmed the broad and sustained benefits of TRT across major QOL dimensions, including sexual, somatic, and psychological health, which were sustained over 36 months in our treatment cohort. Rosen RC, Wu F, Behre H, et al. Quality of Life and Sexual Function Benefits Effects of Long-Term Testosterone Treatment: Longitudinal Results From the Registry of Hypogonadism in Men (RHYME). J Sex Med 2017;14:1104-1115.

Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men.

OBJECTIVES: To evaluate the effects of testosterone-replacement therapy (TRT) on prostate health indicators in hypogonadal men, including rates of prostate cancer diagnoses, changes in prostate-specific antigen (PSA) levels and lower urinary tract symptoms (LUTS) over time. PATIENTS AND METHODS: The Registry of Hypogonadism in Men (RHYME) is a multi-national patient registry of treated and untreated, newly-diagnosed hypogonadal men (n = 999). Follow-up assessments were performed at 3-6, 12, 24, and 36 months. Baseline and follow-up data collection included medical history, physical examination, blood sampling, and patient questionnaires. Prostate biopsies underwent blinded independent adjudication for the presence and severity of prostate cancer; PSA and testosterone levels were measured via local and central laboratory assays; and LUTS severity was assessed via the International Prostate Symptom Score (IPSS). Incidence rates per 100 000 person-years were calculated. Longitudinal mixed models were used to assess effects of testosterone on PSA levels and IPSS. RESULTS: Of the 999 men with clinically diagnosed hypogonadism (HG), 750 (75%) initiated TRT, contributing 23 900 person-months of exposure. The mean testosterone levels increased from 8.3 to 15.4 nmol/L in treated men, compared to only a slight increase from 9.4 to 11.3 nmol/L in untreated men. In all, 55 biopsies were performed for suspected prostate cancer, and 12 non-cancer related biopsies were performed for other reasons. Overall, the proportion of positive biopsies was nearly identical in men on TRT (37.5%) compared to those not on TRT (37.0%) over the course of the study. There were no differences in PSA levels, total IPSS, or the IPSS obstructive sub-scale score by TRT status. Lower IPSS irritative sub-scale scores were reported in treated compared to untreated men. CONCLUSIONS: Results support prostate safety of TRT in newly diagnosed men with HG.

Testosterone treatment is not associated with increased risk of adverse cardiovascular events: results from the Registry of Hypogonadism in Men (RHYME).

AIMS: The aim of this study was to assess cardiovascular (CV) safety of testosterone replacement therapy (TRT) in a large, diverse cohort of European men with hypogonadism (HG). METHODS: The Registry of Hypogonadism in Men (RHYME) was designed as a multi-national, longitudinal disease registry of men diagnosed with hypogonadism (HG) at 25 clinical sites in six European countries. Data collection included a complete medical history, physical examination, blood sampling and patient questionnaires at multiple study visits over 2-3 years. Independent adjudication was performed on all mortalities and CV outcomes. RESULTS: Of 999 patients enrolled with clinically diagnosed HG, 750 (75%) initiated some form of TRT. Registry participants, including both treated and untreated patients, contributed 23 900 person-months (99.6% of the targeted) follow-up time. A total of 55 reported CV events occurred in 41 patients. Overall, five patients died of CV-related causes (3 on TRT, 2 untreated) and none of the deaths were adjudicated as treatment-related. The overall CV incidence rate was 1522 per 100 000 person-years. CV event rates for men receiving TRT were not statistically different from untreated men (P=.70). Regardless of treatment assignment, CV event rates were higher in older men and in those with increased CV risk factors or a prior history of CV events. CONCLUSIONS: Age and prior CV history, not TRT use, were predictors of new-onset CV events in this multi-national, prospective hypogonadism registry.