SUMMARYThe aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 lg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol/mol)] and a significant reduction in body weight (p < 0.01), but also a further increase in SHBG (p < 0.05) and T (p < 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p < 0.05) and weight (p < 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED.

Background: Functional hypogonadism is a common disorder among patients with obesity and type 2 diabetes mellitus and could be managed by first treating the underlying causes.Objective: The present study was undertaken to investigate the contribution of body weight and glycemic control to the reversibility of hypogonadism to eugonadism in a real-life setting. Materials and methods:Adult obese male patients with uncontrolled type 2 diabetes mellitus, complaining of mild to moderate erectile dysfunction and suspected of functional hypogonadism evaluated at our institution from 2015 to 2017, were retrospectively included. The gonadal status 3 and 12 months after the glucose-lowering medication prescription was assessed.Results: Seventy-one consecutive patients were enrolled, with 24 (34%) of them achieving total testosterone ≥300 ng/dL (10.4 nM/L) at the end of the study. When they were stratified according to HbA1c and body weight loss, a direct correlation was found for the latter only. Particularly, 94% of patients achieving a body weight loss >10% presented with total testosterone ≥300 ng/dL. An inverse correlation was found for HbA1c, with no higher prevalence of total testosterone ≥300 ng/dL in patients with HbA1c <6.5%. Discussion:The findings are strengthened by the rigorous study design. However, a limited number of patients and glucose-lowering medications could be included. Conclusions:The present study supports the hypothesis that in obese patients with uncontrolled type 2 diabetes mellitus losing weight may have a greater impact on androgens compared to improving glycemic control. Further prospective studies are needed to corroborate this finding. K E Y W O R D Sfunctional hypogonadism, erectile dysfunction, type 2 diabetes mellitus, obesity | 655 GIAGULLI et AL.

Background Erectile function depends on a complex interaction between demographic, metabolic, vascular, hormonal, and psychological factors that trigger erectile dysfunction (ED). In the present study we carried out a cross-sectional study assessing the impact of non-communicable chronic diseases (NCDs), male hypogonadism, and demographic factors in characterizing men with ED. Four hundred thirty-three consecutive outpatients with ED were extracted from the electronic database from January 2017 to December 2019. The International Index of Erectile Function (IIEF) 5 score was used to diagnose ED and stratify its severity, standardized values of serum testosterone (10.5 nM/L) and luteinizing hormone (LH 9.4 IU/L) to diagnose and classify male hypogonadism and the Charlson Comorbidity Index (CCI) to weigh the role of each NCD on ED. Results Forty-six percent of participants were eugonadal (EuG), 13% had organic hypogonadism (OrH), and the remaining 41% had functional hypogonadism (FuH). Hypogonadal men had a significantly lower IIEF 5 score (p < .0001) than EuG. FuH had a higher CCI than OrH and EuG (all p < .0001). In a multivariable model, only free T (FT) and Sex Hormone Binding Globulin (SHBG) showed a direct correlation with the IIEF 5 score (all p < .0001). Age and CCI had an inverse correlation with IIEF 5 score (all p < .0001). Conclusion Serum FT, SHBG, and CCI are the leading determinants of ED severity. Besides overt hypogonadism, a relevant burden of severe NTCDs in middle-aged or older adults features the patient’s characteristics who will suffer from severe ED. Appropriate clinical approaches and, when necessary, treatments are required in these clusters of patients.

Introduction. The prevalence of erectile dysfunction (ED) increases along with the burden of chronic diseases. This retrospective study aimed to assess the prevalence and severity of ED according to the levels of chronic comorbidities.Material and Methods. Two hundred twenty-two outpatients referred to the Outpatients Clinic of Endocrinology and Metabolic Disease of Conversano Hospital (Italy) with ED complaints from January 2018 to December 2019 were retrospectively eligible for this cross-sectional study. The ED severity and comorbidities burden were assessed by the 5-item International Index of Erectile Function questionnaire (IIEF-5) and Charlson comorbidity index (CCI). A modified index (mCCI) was developed to integrate other common risk factors for ED and was compared to the original tool. The primary outcome was to assess the prevalence of ED according to the severity of CCI. The secondary outcomes included the correlation between 1) IIEF-5 and total testosterone (TT); 2) CCI and TT; 3) IIEF-5 and CCI. Finally, the performance of the CCI and mCCI were compared.Results. The overall prevalence of ED increased along with the CCI score: 45% (5 on 11) for CCI=0; 95% (19 on 20) for CCI=1; 91% (29 on 32) for CCI=2; 99% (158 on 160) for CCI≥3 (p<.0001) Moreover, IIEF-5 score was directly correlated with TT levels (r=0.67; p<.0001). CCI correlated with both TT levels and IIEF-5 score (r=-0.34 and -0.44; p<.0001, respectively). Finally, a lower IIEF-5 score was significantly and independently associated with higher age and CCI as well as lower TT and SHBG. Compared to the CCI, an equal performance was also found with the mCCI.Discussion. Our results showed that CCI and mCCI are reliable tools to assess the presence and severity of ED among outpatients referred to the endocrine center. However, some limitations should be considered, including the number of participants, which appeared underpowered; the single-center experience; possible underestimation of CCI referred to a diagnostic delay of included comorbidities; arbitrary assignment of burden-points to hypertension dyslipidemia and cigarette smoking.Conclusion. The present study found that CCI, a validated tool to assess the burden of comorbidities, correlates with both the prevalence and severity of ED. This confirms that ED is a reliable proxy of overall male health, but further studies are needed to confirm this potential application.

Background: The prevalence of erectile dysfunction (ED) rises with the number and severity of chronic diseases. Study aims. This cross-sectional study assessed the frequency and severity of ED in patients with multiple chronic conditions. Study aims: This cross-sectional study assessed the frequency and severity of ED in patients with multiple chronic conditions. Methods: The 5-item International Index of Erectile Function questionnaire (IIEF-5) to diagnose and classify ED. The Charlson Comorbidity Index (CCI) was used to assess the burden of chronic comorbidity. The primary outcome was to assess the ED frequency according to CCI severity. The secondary outcomes included the assessment of correlation between 1) IIEF-5 and total testosterone (TT), 2) CCI and TT, 3) IIEF-5 and CCI. Lastly, the CCI and modified CCI (mCCI) performance were compared with each other. Results: The overall frequency of ED increased along with the CCI score severity: 45% for CCI=0; 95% for CCI=1; 91% for CCI=2; 99% for CCI≥3 (p<.0001). CCI correlated negatively with TT levels and IIEF-5 score (r=-0.34 and -0.44; p<.0001). Compared to the CCI, a novel proposed mCCI performs well. Discussion: The frequency and severity of ED are relevant in outpatients with sexual complaints and those with chronic comorbidities. Despite limitations, mCCI may be considered a reliable tool to assess the overall burden of multiple chronic conditions in patients with comorbidities. Conclusion: ED is a reliable proxy of overall male health. Further studies are needed to confirm this potential application.