Dany-Jan Yassin

Long‐Term Testosterone Treatment in Elderly Men with Hypogonadism and Erectile Dysfunction Reduces Obesity Parameters and Improves Metabolic Syndrome and Health‐Related Quality of Life

INTRODUCTION Late-onset hypogonadism (LOH) is diagnosed when declining testosterone concentrations in the aging male cause unwanted symptoms such as erectile dysfunction (ED), reduced bone density and muscle strength, and increased visceral obesity. Testosterone deficiency is also associated with insulin resistance and the metabolic syndrome (MetS). Restoring testosterone to physiological concentrations has beneficial effects on many of these symptoms; however, it is not known whether these effects can be sustained in the long term. AIMS To investigate whether treatment with testosterone undecanoate (TU) has a long-term and sustained effect on parameters affected by the MetS in men with LOH and ED, to determine whether long-term testosterone treatment can improve the overall health-related quality of life in these men, and to establish the safety of long-term testosterone treatment. METHODS Two hundred sixty-one patients (mean age 59.5 ± 8.4 years) diagnosed with LOH and ED were treated with long-acting TU in a prospective, observational, and longitudinal registry study. Men received intramuscular injections of 1,000 mg TU at day 1, at week 6, and every 3 months thereafter. MAIN OUTCOME MEASURES Parameters affected by the MetS, including obesity parameters (body weight, waist circumference, and body mass index [BMI]), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, HbA1c (glycated hemoglobin), and blood pressure, as well as total testosterone levels and health-related quality of life, were assessed. RESULTS We found TU significantly improved obesity parameters (body weight, waist circumference, and BMI) and lowered total cholesterol, LDL cholesterol, triglycerides, fasting blood glucose, HbA1c , and blood pressure over the 5-year study. HDL cholesterol was increased. TU treatment resulted in a sustained improvement in erectile function and muscle and joint pain, which contributed to an improvement in long-term health-related quality of life. Furthermore, we found a relationship between health-related quality of life and waist circumference. Finally, we found no evidence that long-term treatment with TU increases the risk of prostate carcinoma. CONCLUSION Long-term TU in men with LOH and ED reduces obesity parameters and improves metabolic syndrome and health-related quality of life.

Erectile dysfunction is a prognostic indicator of comorbidities in men with late onset hypogonadism

Abstract Introduction: The role of testosterone deficiency in erectile dysfunction (ED) is increasingly recognized; however, there is a need to clarify the nature of the relationship between ED and late onset hypogonadism (LOH). Aim: In this study, we sought to determine the correlators of ED severity amongst men with LOH. Methods: 130 patients diagnosed with LOH fulfilling the criteria of total testosterone ≤3.5 ng/ml (<12 nmol/l) and with an erectile function domain score <21 on the International Index of Erectile Function questionnaire (IIEF questions 1–5) were enrolled for a subsequent trial of Testosterone Undecanoate. Demographic data were recorded at baseline. Main outcome measures: Subjects completed three standardised questionnaires to assess sexual health including International Prostate Symptom Score (IPSS), Aging Males Symptoms (AMS) and IIEF Sexual Health Inventory for Men (SHIM). Patients were stratified by ED severity with SHIM scores of 1–7 considered severe ED, 8–11 moderate ED and 12–16 mild to moderate. Serum testosterone, sex hormone binding globulin (SHBG) and lipids (total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein) were assessed along with plasma fasting glucose and HbA1c. Weight, BMI and waist circumference were also recorded. Results: A significant association was observed between severity of ED and mean weight (p = 0.000), waist circumference (p = 0.000), triglycerides (p = 0.009), total cholesterol (p = 0.027), HbA1c (p = 0.000), fasting glucose (p = 0.003) and AMS scores (p = 0.043). No significant differences were seen in testosterone fractions and SHBG levels between ED subgroups. A positive correlation existed between the prevalence of diabetes mellitus (type 1 and type 2) and ED severity in this cohort (p = 0.018). Conclusions: The descriptive data of our cohort show that increased severity of ED within LOH patients correlated with an increased waist circumference, hyperglycemia, hypertriglyceridemia, hyperlipidemia and a history of diabetes mellitus. Severe ED functions as a prognostic indicator of co-morbidities in men with LOH.

Vitamin D treatment improves levels of sexual hormones, metabolic parameters and erectile function in middle-aged vitamin D deficient men.

Abstract Background: The associations between serum vitamin D (VD), serum testosterone (TT) and metabolic syndrome are complex and with limited published research, particularly on the effects of VD treatment on sexual hormones, erectile function and the metabolic syndrome. Objectives: This study assessed whether a monthly high dose VD treatment for 12 months in VD deficient middle-aged men was associated with: changes in levels of sexual hormones, improvement of diabetes control and metabolic syndrome components, better erectile function [International Index of Erectile Function (IIEF)-5 questionnaire]; and changes in a prostate marker. Materials and methods: Descriptive research of a prospective study, conducted between October 2014 and September 2015, 102 male patients ≥35 [(±SD: 53.2 ± 10.5), (range 35–64)] years with deficient serum VD level (<30 ng/mL) were included in the study. Participants were followed up for one year, with monitoring at 3-, 6-, 9- and 12-months. At the initial baseline visit, a complete medical examination was conducted, and blood was drawn for laboratory tests for above biochemical and hormonal variables under examination. Participants received an initial VD (Ergocalciferol; oral solution 600 000 IU/1.5 ml), and followed a VD treatment regime thereafter. At the four follow up visits (3, 6, 9 and 12 months), blood was collected, and patients’ erectile function was evaluated by IIEF-5 questionnaire. Main outcome measures: During the follow up visits, all the biochemical and hormonal (TT, estradiol and luteinizing hormones, HbA1c, serum lipids profile) were assessed, and patients’ erectile function was evaluated by IIEF-5 questionnaire. Results: Patients’ mean age was 53.2 ± 10.4 years. Serum VD exhibited significant increments (p <0.001) from baseline (15.16 ± 4.64 ng/mL), to 3 (31.90 ± 15.99 ng/mL), 6 (37.23 ± 12.42 ng/mL), 9 (44.88 ± 14.49 ng/mL) and 12 months (48.54 ± 11.62 ng/mL), and there was significant stepladder increases in both serum TT level (12.46 ± 3.30 to 15.99 ± 1.84 nmol/L) and erectile function scores (13.88 ± 3.96 to 20.25 ± 3.24) (p <0.001 for both). We also observed significant stepladder decreases in estradiol (87.90 ± 27.16 to 69.85 ± 14.80 pmol/L, p = 0.001), PTH (from 58.52 ± 28.99 to 38.33 ± 19.44 pg/mL, p <0.001) and HbA1c levels (7.41 ± 2.85 to 6.66 ± 1.67%, p = 0.001). Mean BMI significantly decreased from 33.91 ± 6.67 to 33.14 ± 6.35 kg/m2 (p = 0.001); and PSA values significantly increased from 0.59 ± 0.30 to 0.82 ± 0.39 ng/mL (p <0.001) at the end of the 12 months’ follow-up. There were no changes in LH levels. Conclusion: This study demonstrated that VD treatment improves testosterone levels, metabolic syndrome and erectile function in middle-aged men. More randomized placebo-controlled interventional trials of VD treatment in patients with the metabolic syndrome and low TT could assist in uncovering the putative roles of VD.

Early weight loss predicts the reduction of obesity in men with erectile dysfunction and hypogonadism undergoing long-term testosterone replacement therapy

Abstract We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA1C), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102 cm. Age was not a predictor of weight loss.

Is there a protective role of testosterone against high-grade prostate cancer? Incidence and severity of prostate cancer in 553 patients who underwent prostate biopsy: a prospective data register

Abstract This study investigated the role of testosterone replacement therapy (TRT) in prostate safety and cancer progression. A cohort of 553 patients, 42 treated and 162 untreated hypogonadal men, and 349 eugonadal men were included. Pathological analysis of prostate biopsies examining the incidence and severity of PCa revealed that: 16.7% of treated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 71.4% and >6 in 28.6% of men, a predominant score of 3 and tumour staging of II in 85.7% men; 51.9% of untreated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 40.5% and >6 in 59.5% men, a predominant score of 3 (77.4%) and tumour staging of II (41.7%) or III (40.5%); 37.8% of eugonadal men had a positive biopsy, a Gleason score of ≤6 in 42.4% and >6 in 57.6% of men, a predominant score of 3 (82.6%) and tumour staging of II (44.7%) or III (47.7%). The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT, with significantly lower severity of PCa in terms of staging and grading in the same group. These results suggest that TRT might have a protective effect against high-grade PCa.

Is there a relationship between the severity of erectile dysfunction and the comorbidity profile in men with late onset hypogonadism

Abstract Objective: To determine whether the severity of erectile dysfunction (ED) in a man diagnosed with late-onset hypogonadism (LOH) gives information about his metabolic syndrome state, as patients with LOH often have sexual symptoms and associated cardiovascular and metabolic comorbidities, but the role of ED in predicting the prevalence of comorbid disease in men with low levels of testosterone is currently unknown. Patients and methods: Men (130) diagnosed with LOH and fulfilling the criteria of a total testosterone level of <3.5 ng/mL (<12 nmol/L), and with an erectile function domain score of <21 on the International Index of Erectile Function questionnaire (IIEF, questions 1–5), were enrolled for a subsequent trial of supplementation with testosterone undecanoate. Demographic data were recorded at baseline. The men completed three standardised questionnaires to assess sexual health, including the International Prostate Symptom Score, Ageing Males Symptoms (AMS) and IIEF Sexual Health Inventory for Men (SHIM). Patients were stratified by the severity of ED, with SHIM scores of 1–7 considered severe, 8–11 moderate, and 12–16 mild to moderate. Levels of serum testosterone, sex hormone binding globulin (SHBG) and lipids (total cholesterol, triglycerides, high-density and low-density lipoprotein) were assessed, along with plasma fasting glucose and glycated haemoglobin (HbA1c) levels. Body weight, body mass index and waist circumference were also recorded. Results: There was a significant association between the severity of ED and mean weight (P < 0.001), waist circumference (P < 0.001), triglycerides (P = 0.009), total cholesterol (P = 0.027), HbA1c (P < 0.001), fasting glucose (P = 0.003) and AMS scores (P = 0.043). There were no significant differences in testosterone fractions and SHBG levels between the ED subgroups. There was a positive correlation between the prevalence of diabetes mellitus (type 1 and type 2) and the severity of ED in these men (P = 0.018). Conclusions: The descriptive data showed that a greater severity of ED in men with LOH correlated with an increased waist circumference, hyperglycaemia, hypertriglyceridaemia, hyperlipidaemia, and a history of diabetes mellitus. Severe ED is a prognostic indicator of comorbidities in men with LOH.

Testosterone therapy has positive effects on anthropometric measures, metabolic syndrome components (obesity, lipid profile, Diabetes Mellitus control), blood indices, liver enzymes, and prostate health indicators in elderly hypogonadal men

To alleviate late‐onset hypogonadism, testosterone treatment is offered to suitable patients. Although testosterone treatment is commonly given to late‐onset hypogonadism patients, there remains uncertainty about the metabolic effects during follow‐ups. We assessed the associations between testosterone treatment and wide range of characteristics that included hormonal, anthropometric, biochemical features. Patients received intramuscular 1,000 mg testosterone undecanoate for 1 year. Patient anthropometric measurements were undertaken at baseline and at each visit, and blood samples were drawn at each visit, prior to the next testosterone undecanoate. Eighty‐eight patients (51.1 ± 13.0 years) completed the follow‐up period. Testosterone treatment was associated with significant increase in serum testosterone levels and significant stepladder decrease in body mass index, total cholesterol, triglycerides and glycated haemoglobin from baseline values among all patients. There was no significant increase in liver enzymes. There was an increase in haemoglobin and haematocrit, as well as in prostate‐specific antigen and prostate volume, but no prostate biopsy intervention was needed for study patients during 1‐year testosterone treatment follow‐up. Testosterone treatment with long‐acting testosterone undecanoate improved the constituents of metabolic syndrome and improved glycated haemoglobin in a stepladder fashion, with no adverse effects.

MP91-11 POSITIVE EFFECTS OF LONG-TERM TREATMENT WITH TESTOSTERONE UNDECANOATE INJECTIONS (TU) ON RENAL FUNCTION IN HYPOGONADAL MEN: REAL-LIFE DATA FROM A PROSPECTIVE CONTROLLED REGISTRY STUDY

Serum early morning total T (TT) levels were measured at baseline and periodically after ADT cessation. Multivariable time-to-event analysis (Cox proportional hazards) was performed to determine predictors of TT recovery after ADT cessation and included the following variables: patient age, baseline T level, and duration of ADT. RESULTS: 1641 men with a mean age of 66 (43-94) years were included. Primary treatment for PCa was RP in 36%, while the remainder had either RT or primary ADT. The majority received a GnRH agonist as mainstay for ADT. Mean duration of ADT was 28.8 39 months [0.5 to 324]. Distribution of ADT exposure was: <6 months (m) 33%, 6-12m 19%, 12-24m 16%,>24m 33%. Median follow-up was 47.5 45 months. Mean TT values were: baseline 358 ng/dl, 6-12m post ADT cessation 96 ng/dl, 12-18 174 ng/dl, 18-24m 228 ng/dl, >24m 273 ng/dl. At last follow-up: 77% men had TT level above castrate level, 45% had TT >300ng/dl and 39% returned to pre-treatment TT level. Age over 65 years, ADT duration of 6 months or greater, and baseline T of less than 400 ng/dl were all significantly associated with a slower recovery time. Multivariable analysis data are presented in the Table. CONCLUSIONS: Approximately one third of patients undergoing ADT for prostate cancer at our center had return of TT level back to pre-treatment level with 23% maintaining castrate TT levels at 24 months after ADT cessation.

MP91-14 CARDIOVASCULAR DISEASE (CVD), HYPOGONADISM & ED: POSITIVE EFFECTS UNDER LONG-TERM TREATMENT WITH TESTOSTERONE UNDECANOATE INJECTIONS (TU)

INTRODUCTION AND OBJECTIVES:ED is a predictive risk factor for CVD. We monitored effectiveness and safety of long-term Testosterone Therapy (TTh) in hypogonadal men with a history of CVD.METHODS:Two observational registry studies of 622 hypogonadal men from two urological centers: 77 men with a previous diagnosis of coronary artery disease (CAD; n=48) and/or a myocardial infarction (MI; n=40) and/or stroke (n=7) received TU for up to 14 years.RESULTS:Mean age was 60.65 ± 4.98 years, mean follow-up time was 7.29 ± 1.20 years. Testosterone (T) levels rose from 9.78 ± 1.56 nmol/L to trough levels (measured prior to the following injection) between 16 and 18 nmol/L. IIEF-EF (maximum score: 30) increased from 19.64 ± 6.34 to 24.49 ± 4.69 with a change from baseline of 5.37±0.36, this improvement was statistically significant for the first three years and remained statistically significant vs baseline throughout the observation time and stable compared to previous years.Weight decreased progressively from 114.4...

PD45-01 CHANGE OF CATEGORIES OF THE INTERNATIONAL PROSTATE SYMPTOM SCORE (IPSS) IN HYPOGONADAL PATIENTS WITH AND WITHOUT TESTOSTERONE THERAPY FOR UP TO 12 YEARS: REAL-WORLD DATA FROM TWO POOLED CONTROLLED REGISTRY STUDIES

INTRODUCTION AND OBJECTIVES: Sexual dysfunction has a significant impact on quality of life. The use of pornography among females and its impact on sexual dysfunction is poorly described. As an exploratory outcome of a study primarily investigating the relationship between pornography and erectile dysfunction, we attempt to better define pornography use and any contribution to sexual dysfunction in women. METHODS: After IRB approval, all patients presenting to a urology clinic of ages 20-40 years between February and August, 2016 were offered an anonymous survey consisting of self-reported medical history and demographic questions, validated questionnaires and novel questions addressing sexual function, pornography use and addictive behavior. Accrual continues, and we report a planned interim analysis. Descriptive data was compiled, and strength of correlation between subdomains of female sexual function, obsessive or craving behaviors and pornography use were examined. All variables were analyzed with linear regression. RESULTS: Of the first 48 females who agreed to take the survey included in the analysis, the mean age was 28 years. The subjects reported minimal medical comorbidities or risk factors with the most common being depression (16%), PTSD (12%) and smoking (31%). The sample was primarily white (62%), married (60%), heterosexual (81%), and active duty military (58%). The majority of respondents denied pornography use (61%) and 25% used less than weekly. Of those that used pornography, 72% reported duration of 15 minutes or less. The primary access was internet (68%) and phone (55%). The mean Female Sexual Function Inventory total score was 64. There was no observed correlation between female sexual function and pornography use. CONCLUSIONS: Interim results better describe pornography use among females. In a sample of women ages 20-40, pornography use is not uncommon with the main access being through internet or phone. There does not appear to be any correlation between its use and sexual dysfunction as determined by self-reported questionnaire. Further study may better elucidate any relationship between pornography and female sexual dysfunction.