Erectile Dysfunction in Patients with Multiple Chronic Conditions: A Cross- Sectional Study.

BACKGROUND: The prevalence of erectile dysfunction (ED) rises with the number and severity of chronic diseases. 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) was used 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 the correlation between 1) IIEF-5 and total testosterone (TT), 2) CCI and TT, and 3) IIEF-5 and CCI. Lastly, the CCI and modified CCI (mCCI) performances 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.

Weight loss more than glycemic control may improve testosterone in obese type 2 diabetes mellitus men with hypogonadism.

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.

Effect of clomiphene citrate treatment on the Sertoli cells of dysmetabolic obese men with low testosterone levels.

BACKGROUND: Clomiphene citrate (CC) has been shown to restore the hypothalamic-pituitary-gonadal (HPG) axis by increasing testosterone (T) levels to physiological levels in patients with dysmetabolic conditions such as obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM). However, the data are unclear regarding the effects on Sertoli cell (SC) function. AIM: To study SC function by assessing Inhibin B (IB) and anti-Mullerian hormone (AMH) levels at baseline and after 3 months of CC treatment. MATERIALS AND METHODS: This is an ancillary study of a cross-over, randomised, double-blind, placebo-controlled trial performed to evaluate androgen response to CC treatment in dysmetabolic obese subjects with low T levels treated with metformin. We evaluated SC function by assessing IB and AMH levels at baseline and after 3 months of each treatment in ten dysmetabolic obese subjects with low T levels. In all subjects, the influence of the clinical characteristics, metabolic and hormonal baseline parameters on SC and Leydig (LC) function, evaluated respectively with AMH, IB, follicle-stimulating hormone (FSH) and T levels, was tested. RESULTS: No significant changes were observed for IB and AMH concentrations after each treatment period. Whereas T and oestradiol (E2) levels were shown to be significantly higher in the CC plus metformin phase (CC/Met) only. No clinical, metabolic or hormonal parameters showed significant effects on serum AMH at baseline or after treatments. However, baseline T, dihydrotestosterone (DHT) and E2 positively affected IB levels during CC/Met therapy (P = .003, P = .038 and P = .049, respectively). Baseline leptin and FSH had a negative (P = 031) and positive (P = .048) respectively role on T levels during CC/Met, as they were statistically significant compared to the placebo period (Plac/Met). CONCLUSION: Unlike the LC activity, CC was unable to influence SC function, as shown by the lack of IB and AMH serum modifications, thus suggesting an intrinsic nonreversible defect of SC cells in patients with dysmetabolic conditions.

Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.

CONTEXT: Low testosterone (T) levels are often found in obese men with impaired glucose tolerance (IGT) and overt type 2 diabetes (T2DM); however, the mechanisms underlying this condition and its correct therapy are still under debate. OBJECTIVE: To evaluate the effectiveness of clomiphene citrate (CC) in increasing endogenous T levels in obese men with low serum T and with IGT or T2DM treated with metformin (MET). DESIGN: Cross-over, randomized, double-blind, placebo-controlled study. METHODS: 24 obese men, aged 47.3 ±. 6.3 (range 35-55 years), with low T level (≤3 ng/mL) and naïve diagnosis of IGT or T2DM were included. Subjects were randomized to CC 25 mg/day or placebo (Plac) with MET 2 g/day for 3 months. After a 6-week wash-out period, subjects were moved to the alternative arm for additional 3 months. Clinical evaluation and blood exams performed prior to and at the end of treatment. RESULTS: Of 24 randomized, 21 were evaluable, classified as IGT (n = 11) or T2DM (n = 10). Compared to baseline levels, T levels increased significantly after 3 months of CC treatment (3.03±0.80 to 5.99±1.67 ng/mL P<0.001) but not after the Plac treatment (2.87±0.78 to 3.09±0.84 ng/mL P<0.001 between the treatments). T changes were similar in IGT and T2DM subjects. Gonadotropins as well raised significantly after CC treatment (LH 3.83±1.45 to 8.53±6.40 mU/mL; FSH 4.84±1.67 to 10.15±5.08 mU/mL P<0.001 respectively), whereas no changes for LH (3.51±1.59 to 3.63±1.39 mU/mL) but a smooth increased for FSH (4.61±2.49 to 5.39±2.65 mU/mL; P = 0.004) were shown after Plac treatment (LH P = 0.001 and FSH P = 0.002 between treatments). Furthermore, fasting glucose (106.8±23.2 to 101.1±25.7 mg/dL; P = 0.004), insulin (19.3±12.1 to 15.6±10.1 µU/mL; P = 0.010) and HOMA-IR (4.94±2.89 to 3.69±2.12; P = 0.001) decreased significantly during the CC treatment period, whereas no significant changes were observed in any of these parameters in the Plac treatment. CONCLUSIONS: A low dose of CC therapy was able to significantly increase serum T levels in all participants with mild modifications of clinical and metabolic parameters. TRIAL REGISTRATION: EudraCT 2011-000439-10.