Male subclinical hypogonadism and late-onset hypergonadotrophic hypogonadism: mechanisms, endothelial function, and interplay between reproductive hormones, undercarboxylated osteocalcin, and endothelial dysfunction.

BACKGROUND: Pathogenesis and endothelial function in subclinical hypogonadism (SCH) remain unclear. Undercarboxylated osteocalcin (ucOC) participates in atherosclerosis and reproduction. We explored the underlying mechanisms and interplay of endothelial dysfunction, unOC and reproductive hormones in SCH and primary late-onset hypogonadism (LOH). METHODS: In the SCH, LOH, and healthy eugonadal male groups, we measured serum unOC, calculated luteinizing hormone/testosterone (LH/T), LH.T product, and estradiol/T (E/T) as indicators of impaired Leydig cells, androgen sensitivity index (ASI), and aromatase activity, respectively (LH set-point regulators), and assessed flow-mediated dilation of the brachial artery (FMD%), carotid-intima media thickness (CIMT), and aortic stiffness (AS). RESULTS: ↑LH/T, ↑ASI, ↓aromatase activity, normal T, follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels, ↑unOC, and enhanced atherosclerotic markers (↓FMD%, ↑CIMT, ↑AS) are characteristics of SCH. Testosterone was positively correlated with FMD% in SCH. The independent predictors were: SHBG and LH for FMD% and CIMT, respectively, and LH/T, ucOC, FSH, estradiol, and E/T ratio for AS in the LOH group; and LH for FMD% & AS and LH and LH/T for CIMT in all study subjects. CONCLUSIONS: SCH is a distinct clinical entity characterized by impaired androgen sensitivity and aromatase activity, compensatory elevated unOC, endothelial dysfunction, and anti-atherogenic role of testosterone.

Usefulness of routine assessment of free testosterone for the diagnosis of functional male hypogonadism.

OBJECTIVE: To investigate whether routine assessment of free testosterone improves the diagnostic accuracy of functional hypogonadism. METHODS: Total and free testosterone (calculated on SHBG levels) were determined in 188 patients with sexual symptoms and 184 with infertility. RESULTS: Hypogonadism (calculated free testosterone <63 pg/ml) was found in 47/188 (25.0%) patients with sexual symptoms and in 21/184 (11.4%) with infertility. Total testosterone determination misdiagnosed hypogonadism in 8.4% (12/143) of men with sexual symptoms and in 2% (3/152) with infertility. In subjects with borderline total testosterone, only 24.7% (19/77) had hypogonadism confirmed by free testosterone levels. Free testosterone levels significantly correlated with age, haematocrit, gonadotropins, gynecomastia, BMI, and number of co-morbidities, whereas total testosterone associated only with the latter two. Furthermore, age, haematocrit, BMI, and the presence of erectile dysfunction and of low libido were significantly different between men with normal and low free testosterone, whereas only BMI and low libido were significantly different between patients with normal and low total testosterone. CONCLUSION: Routine assessment of free testosterone allows a more accurate diagnosis of functional hypogonadism, especially in men with sexual symptoms. Free testosterone levels associate with clinical and biochemical parameters of androgen deficiency better than total testosterone levels.

Oncological safety and functional outcomes of testosterone replacement therapy in symptomatic adult-onset hypogonadal prostate cancer patients following robot-assisted radical prostatectomy.

PURPOSE: Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP). METHODS: We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006-2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression. RESULTS: Among the forty-seven men who received TRT, the mean age was 60.83 years with a median follow-up of 48 months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p = 0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p = 0.043), higher International Society of Urological Pathology score (p < 0.001), seminal vesical invasion (p = 0.018) and positive surgical margin (p < 0.001) were predictors of BCR. However, TRT was not (p = 0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p = 0.022), and serum testosterone level (p < 0.001) before and 6 months after initiation of TRT. CONCLUSION: Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.

Biochemical predictors of structural hypothalamus-pituitary abnormalities detected by magnetic resonance imaging in men with secondary hypogonadism.

PURPOSE: Organic conditions underlying secondary hypogonadism (SH) may be ascertained by magnetic resonance imaging (MRI) of the hypothalamic-pituitary region that could not be systematically proposed to each patient. Based upon limited evidence, the Endocrine Society (ES) guidelines suggest total testosterone (T) < 5.2 nmol/L to identify patients eligible for MRI. The study aims to identify markers and their best threshold value predicting pathological MRI findings in men with SH. METHODS: A consecutive series of 609 men seeking medical care for sexual dysfunction and with SH (total T < 10.5 nmol/L and LH ≤ 9.4 U/L) was retrospectively evaluated. An independent cohort of 50 men with SH was used as validation sample. 126 men in the exploratory sample and the whole validation sample underwent MRI. RESULTS: In the exploratory sample, patients with pathological MRI findings (n = 46) had significantly lower total T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate specific antigen (PSA) than men with normal MRI (n = 80). Receiver Operating Characteristics analysis showed that total T, LH, FSH and PSA are accurate in identifying men with pathologic MRI (accuracy: 0.62-0.68, all p < 0.05). The Youden index was used to detect the value with the best performance, corresponding to total T 6.1 nmol/L, LH 1.9 U/L, FSH 4.2 U/L and PSA 0.58 ng/mL. In the validation cohort, only total T ≤ 6.1 nmol/L and LH ≤ 1.9 U/L were confirmed as significant predictors of pathologic MRI. CONCLUSION: In men with SH, total T ≤ 6.1 nmol/L or LH ≤ 1.9 U/L should arise the suspect of hypothalamus/pituitary structural abnormalities, deserving MRI evaluation.

Hormone-related diseases and prostate cancer: An English national record linkage study.

Insulin-like growth factor-I (IGF-I) and testosterone may be related to prostate cancer risk. Acromegaly is associated with clinically high IGF-I concentrations. Klinefelter's syndrome, testicular hypofunction and hypopituitarism are associated with clinically low testosterone concentrations. We aimed to investigate whether diagnosis with these conditions was associated with subsequent prostate cancer diagnosis and mortality. We used linked English national Hospital Episode Statistics and mortality data from 1999 to 2017 to construct and follow-up cohorts of men aged ≥35 years diagnosed with (i) acromegaly (n = 2,495) and (ii) hypogonadal-associated diseases (n = 18,763): Klinefelter's syndrome (n = 1,992), testicular hypofunction (n = 8,086) and hypopituitarism (n = 10,331). We estimated adjusted hazard ratios (HRs) and confidence intervals (CIs) for prostate cancer diagnosis and death using Cox regression in comparison with an unexposed reference cohort of 4.3 million men, who were admitted to hospital for a range of minor surgeries and conditions (n observed cases = 130,000, n prostate cancer deaths = 30,000). For men diagnosed with acromegaly, HR for prostate cancer diagnosis was 1.33 (95% CI 1.09-1.63; p = 0.005; n observed cases = 96), HR for prostate cancer death was 1.44 (95% CI 0.92-2.26; p = 0.11; n deaths = 19). Diagnosis with Klinefelter's syndrome was associated with a lower prostate cancer risk (HR = 0.58, 95% CI 0.37-0.91; p = 0.02; n observed cases = 19) and hypopituitarism was associated with a reduction in prostate cancer death (HR = 0.53, 95% CI 0.35-0.79; p = 0.002; n deaths = 23). These results support the hypothesised roles of IGF-I and testosterone in prostate cancer development and/or progression. These findings are important because they provide insight into prostate cancer aetiology.

Self-esteem among eunuchs of Hazara Division, Pakistan.

Self-esteem among eunuchs is highly influenced by a variety of factors. The aim of the current study was to investigate the differences in self-esteem of eunuchs on the basis of education, income, age and marital status. The study was conducted at the University of Haripur, Pakistan, from December 2015 to November 2016. A sample of 140 eunuchs was collected from different areas of Hazara division, through purposive and snowball sampling technique. A self-esteem scale with four sub-scales was used to measure the self-esteem of eunuchs. One-way analysis of variance was used to determine education level differences. The t-test was applied to find out the impact of demographics differences such as marital status, income level, and age on self-esteem of eunuchs. The scale used was found to be quite reliable with alpha coefficient of 0.85. The outcomes are significant and showed that educated, higher income, younger and unmarried eunuchs had higher self-esteem (p<0.05).

[Chronobiological features of different regimens of testosterone gel therapy in men with androgen deficiency].

INTRODUCTION: Androgens play a key role in the male development. All the physiological processes in the body, including the production of testosterone, have their chronobiological features. Aging is accompanied by a disruption in the regulation of chronobiological processes. With androgen deficiency, these changes occur at any age. In recent years, transdermal forms of testosterone have become very popular in the treatment of this condition. AIM: To evaluate the effectiveness and chronobiological features of various regimens of testosterone gel therapy for external use in men with androgen deficiency. MATERIALS AND METHODS: The study comprised 90 men aged 45 to 60 years with testosterone deficiency. Patients were randomized into three groups of 30 people each. In group I (control) patients received basic therapy, including exercise, diet, and multivitamins. In group II, patients received basic therapy concurrently with testosterone gel for external use (Androgel) at a daily dose of 5 g (1 sachet). Patients in group III were administered basic therapy in combination with 10 g testosterone (2 sachets). The effectiveness of treatment was assessed at 3 (visit 2) and 6 (visit 3) months. Depending on the results of visit 2, a correction of therapy was carried out, if necessary. During each visit, the patients underwent evaluation, including hematocrit, levels of FSH, LH, prolactin, total testosterone, blood SHBG, waist circumference, and body weight. Patients completed the ICEF-5 questionnaire, the Hamilton scale (HDRS, HARS), and the SF-36 questionnaire. We also tested the patients for the chronobiological status and desynchronosis. RESULTS: During the visit I, the homogeneity of the study population was confirmed. At three months, the patients of groups II and III showed a more pronounced increase in testosterone, a decrease in body weight and waist circumference, as well as an improvement in the psycho-emotional status and quality of life according to the questionnaires. Desynchronosis persisted in 25 (83.3%), 9 (30%), and 4 (13.3%) patients in groups I, II, and III, respectively. Given the findings, the treatment was adjusted. The patients in the groups were divided into subgroups A and B. In subgroups A, patients continued to receive initial therapy, and in subgroups B, the treatment was adjusted. At six months, the level of GT increased to normal values in all subgroups except subgroup IA. The most marked reduction in body weight and waist circumference was noted in subgroups IA, IIA, and IIIB. A significant decrease in the average scores on the HDRS and HARS scales and an improvement in the SF-36 scale were observed in the subgroups IA, IIA, IIIB. Desynchronosis persisted in 3, 2, and one patient in subgroups IB, IIB, and IIIA. CONCLUSION: The testosterone gel therapy in patients with androgen deficiency can effectively reverse the manifestations of the disease and normalize the chronorhythm. Transdermal testosterone gel at a daily dose of 5 g in the morning can be recommended to alleviate clinical manifestations of the disease and eliminate desynchronosis in this category of patients. In patients with low baseline testosterone levels, it is advisable to administer the drug at a daily dose of 10 g.

Synthesis and biological evaluation of novel selective androgen receptor modulators (SARMs). Part II: Optimization of 4-(pyrrolidin-1-yl)benzonitrile derivatives.

We recently reported a class of novel tissue-selective androgen receptor modulators (SARMs), represented by a naphthalene derivative A. However, their pharmacokinetic (PK) profiles were poor due to low metabolic stability. To improve the PK profiles, we modified the hydroxypyrrolidine and benzonitrile substituents of 4-(pyrrolidin-1-yl)benzonitrile derivative B, which had a comparable potency as that of compound A. This optimization led us to further modifications, which improved metabolic stability while maintaining potent androgen agonistic activity. Among the synthesized compounds, (2S,3S)-2,3-dimethyl-3-hydroxylpyrrolidine derivative 1c exhibited a suitable PK profile and improved metabolic stability. Compound 1c demonstrated significant efficacy in levator ani muscle without increasing the weight of the prostate in an in vivo study. In addition, compound 1c showed agonistic activity in the CNS, which was detected using sexual behavior induction assay.

The presence of symptoms of testosterone deficiency in the exercise-hypogonadal male condition and the role of nutrition.

PURPOSE: High volumes of aerobic exercise have been associated with reduced testosterone (T), known as the exercise-hypogonadal male condition (EHMC). Although the presence of low T has been identified, few studies have assessed the presence of androgen-deficient symptoms. The purpose of this investigation is to assess men exhibiting EHMC and evaluate their hypothalamic-pituitary-gonadal axis, the presence of hypogonadal symptoms, and also investigate a possible contribution of inadequate nutrition to the condition. METHODS: A cross-sectional design compared 9 long-distance runners exhibiting EHMC to 8 non-active controls. Comparisons included serum T, luteinizing hormone (LH), follicle-stimulating hormone, and cortisol, the Aging Male Symptoms (AMS) questionnaire score, bone mineral density (BMD), and a food frequency questionnaire. RESULTS: Mean T was significantly reduced in the EHMC group (EHMC 9.2 nmol L-1 vs. CONT 16.2 nmol L-1). The EHMC group demonstrated significantly higher AMS scores (EHMC 27.1 ± 7.3 vs. CONT 19.7 ± 2.5). There were no differences in bone density, although 3 cases of osteopenia were noted for EHMC in the lumbar spine, 1 in the right femur, and 1 in the radius. Energy availability was significantly reduced in EHMC (EHMC 27.2 ± 12.7 vs. CONT 45.4 ± 18.2 kcal d FFM-1). CONCLUSIONS: Men exhibiting EHMC do appear to present with symptoms associated with androgen deficiency. For the most part, these symptoms are limited to those reported on the AMS questionnaire, although there are also some cases of clinically low BMD. It is possible that inadequate energy intake is contributing to this condition.

Characterization of Prostate Cancer in a Functional Eunuch.

BACKGROUND: Eunuchs rarely, if ever, develop prostate cancer (CaP). This article reports on a 62-year-old functional eunuch from prepubertal mumps orchitis who developed clinically localized CaP. METHODS: Serum and CaP and benign prostate tissue androgen levels were measured using a validated liquid chromatography-tandem mass spectrometry assay. The assay measures testosterone; dihydrotestosterone (DHT); the adrenal androgens, androstenedione and dehydroepiandrosterone; and the androgen metabolites, androsterone and androstanedione. Gene and protein expression levels of androgen metabolism enzymes, and androgen receptor and androgen-regulated genes were measured using quantitative reverse-transcription polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Intracrine androgen metabolism produced tissue DHT when serum and tissue testosterone levels were castrate and undetectable, respectively. Androgen receptor, androgen-regulated, and androgen metabolism enzyme genes were expressed but at lower levels in CaP than benign tissues. CONCLUSIONS: DHT was synthesized using the primary backdoor androgen metabolism pathway and not using androstenedione or dehydroepiandrosterone via the frontdoor or secondary backdoor pathways.

Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy.

AIMS: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole-body dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (ß) represent the placebo-controlled mean effect of intervention. RESULTS: LBM (ß = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (ß = -1.3 kg, p = 0.009), fat mass trunk (ß = -0.7 kg, p = 0.043), fat mass legs (ß = -0.7 kg, p = 0.025), fat mass arms (ß = -0.3 kg, p = 0.001), and HDL cholesterol (ß = -0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin-stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin-stimulated rates of EGP, lipid- and glucose-oxidation were unaltered after TRT. CONCLUSION: TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.

Effects of tadalafil treatment combined with physical activity in patients with low onset hypogonadism: results from a not-randomized single arm phase 2 study.

PURPOSE: To investigate a possible relation between penile Doppler ultrasound examination (PDUE) parameters and efficacy of chronic therapy with tadalafil (TAD) combined with a protocol of aerobic physical activity (PA) in patients with late onset hypogonadism (LOH). METHODS: The study evaluated 30 patients consecutively enrolled with LOH and erectile dysfunction which present contraindication to hormonal replacement therapy for concomitant prostate disease. These patients were subjected to a combined protocol with phosphodiesterase V selective inhibitors (TAD 5 mg daily) and aerobic PA. RESULTS: After three months, we observed significant improvements in erectile function [IIEF-5, median (IQR) = 13.0 (7.0-18.0) versus 6.0 (5.0-6.75); p < 0.01] and of the main metabolic [homeostatic model assessment index, median (IQR) = 2.5 (1.62-3.37) versus 3.0 (2.0-3.75); p < 0.01; body mass index, median (IQR) = 27.0 (24.0-28.75) versus 27.5 (24.0-29.5)] and vascular parameters [peak systolic velocity, median (IQR) = 29.5 (24.25-31.0) versus 28.0 (23.0-24.25); acceleration time, median (IQR) = 114 (105.25-134.0) versus 115.0 (106.5-134.0)], assessed by PDUE. CONCLUSION: PA in association with phosphodiesterase V inhibitors could compensate the effects of hypogonadism on erectile function and facilitate the clinical response to these drugs even in the absence of adequate serum concentrations of total testosterone.

The correlation between highly sensitive C-reactive protein levels and erectile function among men with late-onset hypogonadism.

We investigated the correlation between highly sensitive C-reactive protein (hs-CRP) levels and erectile function, and assessed the clinical role of hs-CRP levels in men with late-onset hypogonadism (LOH) syndrome. For 77 participants, we assessed Sexual Health Inventory for men (SHIM) score, Aging Male Symptoms (AMS) score and International Prostate Symptom Score (IPSS). We also evaluated free testosterone (FT), hs-CRP, total cholesterol, triglyceride levels, high density lipoprotein cholesterol, hemoglobin A1c, body mass index, waist size and blood pressure. We attempted to identify parameters correlated with SHIM score and to determine the factors affecting cardiovascular risk based on hs-CRP levels. A Spearman rank correlation test revealed that age, AMS score, IPSS and hs-CRP levels were significantly correlated with SHIM score. Age-adjusted analysis revealed that hs-CRP and IPSS were the independent factors affecting SHIM score (r= -0.304 and -0.322, respectively). Seventeen patients belonged to the moderate to high risk group for cardiovascular disease, whereas the remaining 60 belonged to the low risk group. Age, FT value and SHIM score showed significant differences between the two groups. A multivariate regression analysis demonstrated that SHIM score was an independent factor affecting cardiovascular risk (OR: 0.796; 95%CI: 0.637-0.995).

Could gonadal and adrenal androgen deficiencies contribute to the depressive symptoms in men with systolic heart failure?

BACKGROUND: Testosterone (TT) and dehydroepiandrosterone sulphate (DHEAS) are neurosteroids and their deficiencies constitute the hormone risk factors promoting the development of depression in elderly otherwise healthy men. We investigated the link between hypogonadism and depression in accordance with age and concomitant diseases in men with systolic HF using the novel scale previously dedicated for elderly population. METHODS: We analysed the prevalence of depression and severity of depressive symptoms in population of 226 men with systolic HF (40-80 years) compared to 379 healthy peers. The severity of depression was assessed using the Polish long version of Geriatric Depression Scale (GDS). RESULTS: In men aged 40-59 years the severity of depressive symptoms was greater in NYHA classes III-IV compared to NYHA classes I-II and reference group. In men aged 60-80 years depressive symptoms were more severe in NYHA class III-IV compared to controls (all p ≤ 0.001). In multivariate logistic regression model in men aged 40-59 years advanced NYHA class was associated with higher prevalence of mild depression (OR = 2.14, 95%CI: 1.07-4.29) and chronic obstructive pulmonary disease (COPD) with higher prevalence of severe depression (OR = 69.1, 95%CI: 2.11-2264.3). In men aged 60-80 years advanced NYHA class and TT deficiency were related to higher prevalence of mild depression (respectively: OR = 2.9, 95%CI: 1.3-6.4; OR = 3.6, 95%CI: 1.2-10.63). CONCLUSION: TT deficiency, COPD and advanced NYHA class were associated with higher prevalence of depression in men with systolic HF.

The effect of testosterone treatment on prostate histology and apoptosis in men with late-onset hypogonadism.

OBJECTIVES: To investigate the effect of testosterone replacement therapy (TRT) on prostate histology and apoptosis in men with late-onset hypogonadism (LOH). METHODS: The study included 25 men, having LOH with prostate-specific antigen (PSA) level of 4 ng/ml or less. All patients underwent transrectal ultrasound guided prostate biopsy at baseline, and received testosterone undecanoate treatment for 1 year. Prostate biopsy was repeated at the end of 1 year of testosterone therapy. In addition to clinical and biochemical parameters, prostate histology and apoptotic index (AI) were compared before and after the TRT. RESULTS: The mean serum total testosterone significantly increased from 178.04 ± 51.92 to 496.28 ± 103.73 ng/dl (p = 0.001). No significant differences were observed in serum total and free PSA level, prostate volume and maximal urinary flow rate. There were also no significant differences in AI, stroma/epithelial cells ratio, Ki-67 positive cells and atrophy score of prostate tissue before and after the TRT. CONCLUSIONS: This study demonstrated that TRT did not affect serum PSA level, prostate volume and maximal urinary flow rate. This study also suggests that TRT does not cause the risk for prostate cancer development, because of no significant differences in prostate histology after TRT.

Factors that may be influencing the rise in prescription testosterone replacement therapy in adult men: a qualitative study.

OBJECTIVE: To explore and describe the factors that may be influencing the rise of prescribing and use of testosterone replacement therapy (TRT) in adult men. DESIGN: A rapid qualitative research design using semi-structured interviews with providers and patients. SETTING: Ontario, Canada. PARTICIPANTS: Nine men who have used TRT (referred to as "patients"), and six primary care clinicians and seven specialists (collectively referred to as "providers") who prescribed or administered TRT. METHOD: Patients' and providers' perspectives were investigated through semi-structured interviews. A purposive sampling approach was used to recruit all participants. We conducted qualitative analysis using the framework approach for applied health research. MAIN FINDINGS: Participants perceived the following factors to have influenced TRT prescriptions and use in adult men: provider factors (diagnostic ambiguity of age-related hypogonadism and beliefs about appropriateness of TRT) and patient factors (access to information on TRT and drug seeking behavior). They perceived that these factors have perpetuated a rise in prescription in the absence of clear clinical guidelines and unclear research evidence on the safety and efficacy of TRT. CONCLUSION: The findings of this study highlight that much work still needs to be done to improve diagnostic accuracy and encourage appropriate TRT prescription in adult men. In addition, both patients and providers need more information about the risks and long-term effects of TRT in men.

Erectile dysfunction, loss of libido and low sexual frequency increase the risk of cardiovascular disease in men with low testosterone.

INTRODUCTION: Testosterone deficiency increases the cardiovascular disease (CVD) risk. AIM: To evaluate the effect of erectile dysfunction (ED), sexual frequency and hypogonadal symptoms on CVD risk. METHODS: A total of 395 hypogonadal men aged 45-74 years were surveyed using the Androgen Deficiency in the Aging Male and the International Index of Erectile Function. MAIN OUTCOME MEASURES: The 10-year CVD risk was measured with the Framingham Risk Score. Logistic regression was performed to obtain the odds ratios of sexual function and hypogonadal symptoms for a 10-year CVD risk ≥20% (high risk). RESULTS: The mean age was 56.1 ± 6.7 years. The mean 10-year CVD risk of the whole cohort was 18.1% ± 11.4%, while 131 subjects (33.2%) were classified as high risk. Logistic regression revealed that ED severity was associated with CVD risk [OR = 2.37 (CI 1.24-4.51) for mild-to-moderate ED, OR = 4.39 (1.78-8.43) for moderate ED and OR = 12.81 (4.65-26.11) for severe ED]. Compared to sexual frequency <1 per month, sexual frequency ≥4 decreased the risk of high CVD risk [OR = 0.35 (0.23-0.780)]. Loss of libido [OR = 2.95 (1.91-4.12)] and less strong erection [OR = 3.87 (CI 2.11-4.95)] increased the risk of high CVD risk. All remained significant after adjustment for age and testosterone. CONCLUSIONS: ED, decreased sexual frequency and loss of libido predict a high 10-year CVD risk in hypogonadal men.

RigiScan data under long-term testosterone therapy: improving long-term blood circulation of penile arteries, penile length and girth, erectile function, and nocturnal penile tumescence and duration.

BACKGROUND: Late-onset hypogonadism (LOH) presents with low serum testosterone (TT) levels and sexual and nonsexual symptoms. Erectile dysfunction affects a man's self-esteem and as a result partner relationship and quality of life. OBJECTIVES: To investigate the andrological clinical profile outcomes of testosterone therapy (TTh) in men (n = 88) with symptomatic LOH complaints and symptoms. MAIN OUTCOME MEASURES: Erectile function was assessed using the International Index of Erectile Function-5 questionnaire at baseline and at 6 and 12 months of TTh. In addition, penile length was measured at baseline and 12 months. We also evaluated nocturnal penile tumescence (NPT, using RigiScan) and blood flow of cavernous arteries (penile Doppler ultrasonography) at baseline and 12 months of TT. MATERIALS AND METHODS: Eighty-eight LOH men (Mage 51.1 years) with erectile dysfunction, all with serum TT <10.4 nmol/L before TTh. Patients received intramuscular long-acting testosterone undecanoate for 12 months. RESULTS: Following TTh, in all patients, serum TT levels were restored within 3 months to normal levels. Compared with baseline values, erectile function significantly improved at 6 (mean score increase 1.95) and 12 months (mean score increase 2.16). No significant changes in penile length were observed. NPT significantly improved at 12 months in terms of both the frequency (mean increase 1.27 times) and duration of rigidity (mean increase 5.12 min). As regards the blood flow of the cavernous arteries, we observed a significant improvement (decrease of 1.16 cm/s) and end diastolic velocity of the penile arteries. CONCLUSION: TTh in men with LOH resulted in improvement of the erectile function, NPT, and to some extent the blood flow of the cavernous arteries.

The reproductive health indices and sex hormone levels in middle-aged and elderly Chinese men.

OBJECTIVE: The aim of this study was to analyze the age-related recession trajectory of reproductive health indices in middle-aged and elderly Chinese men. METHODS: A population-based cross-sectional study was conducted in Jiashan County, Zhejiang in 2012. Healthy men between 40 and 80 years of age were considered eligible for the study. Physical examination and the sex hormones were measured. The subjects were assessed based on the 5-item version of the International Index of Erectile Function (IIEF-5) for Erectile Dysfunction (ED), and Aging Males' Symptoms (AMS) scale for Symptomatic Late-Onset Hypogonadism (SLOH). RESULTS: TG showed a decrease at age 60 years. Testis volume and TT did not show significant difference among the four age groups; cFT began to decrease at age 50 years and Bio-T decreased faster at age 50 years. SHBG and LH increased faster at age 50 and 70 years, respectively. IIEF5 score decrease faster at age 60 years. AMS scores increased faster at age 70 years. With the increase in age, the symptoms of ED and SLOH became severer. CONCLUSION: Different indices on reproductive health of men showed turning points at different ages. At first, androgenic sex hormones decreased faster, and then erectile dysfunction got severer, and the last overall male syndromes declined.

Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomised clinical study.

This study examined the effect of Testofen, a specialised Trigonella foenum-graecum seed extract on the symptoms of possible androgen deficiency, sexual function and serum androgen concentrations in healthy aging males. This was a double-blind, randomised, placebo-controlled trial involving 120 healthy men aged between 43 and 70 years of age. The active treatment was standardised Trigonella foenum-graecum seed extract at a dose of 600 mg/day for 12 weeks. The primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms; secondary outcome measures were sexual function and serum testosterone. There was a significant decrease in AMS score over time and between the active and placebo groups. Sexual function improved, including number of morning erections and frequency of sexual activity. Both total serum testosterone and free testosterone increased compared to placebo after 12 weeks of active treatment. Trigonella foenum-graecum seed extract is a safe and effective treatment for reducing symptoms of possible androgen deficiency, improves sexual function and increases serum testosterone in healthy middle-aged and older men.