Association between life's essential 8 and testosterone deficiency in men: NHANES 2011-2016.

Background: Serum testosterone is intrinsically associated to cardiovascular disease. Our aim is to explore the relationship between the recently updated cardiovascular health measurement, known as Life's Essential 8 (LE8), and the prevalence of testosterone deficiency (TD) in adult males in the United States. Methods: Study data was obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. A weighted multivariate logistic regression model was applied to evaluate the correlation between LE8 and testosterone deficiency. Restricted Cubic Spline (RCS) was employed to explore its non-linear relationship. In addition, a stratified analysis was conducted. Results: The final analysis included 2332 participants from NHANES from 2011 to 2016. After adjusting for confounding factors, the odds ratios (ORs) and 95% confidence intervals (CIs) for testosterone deficiency in participants with moderate and higher LE8 scores compared to the lowest LE8 scores were 0.59 (0.38-0.92) and 0.38 (0.19-0.76), respectively. The results of subgroup analysis showed that LE8 score was significantly associated with TD among young and middle-aged participants. Conclusion: A lower LE8 score is related to a higher incidence of testosterone deficiency, especially in young and middle-aged men. Further research is necessary to explore the potential mechanisms between them.

[Hypogonadism in men with inflammatory joint diseases: Frequency and clinical characteristics].

AIM: To study the frequency of hypogonadism (HG) in men with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to evaluate the impact of HG on the course of RA and and concomitant diseases. MATERIALS AND METHODS: A single-stage continuous study included 170 men with RA, 57 men with AS and 85 men with PsA, who were hospitalized at the Nasonova Research Institute of Rheumatology. Patients were assessed for total testosterone (ТS) levels and subsequently divided into subgroups with normal (>12 nmol/l) and reduced levels. An intergroup comparison was carried out on the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of rheumatic disease, as well as on concomitant conditions. The second stage of the study involved a pairwise intergroup comparison among patients with HG with RA, AS and PsA. RESULTS: The incidence of ТS deficiency among patients with RA was 24.1%, among patients with AS - 17.5%, and with PsA - 31.8%. In patients with RA, HG was associated with a significantly higher mean body mass index, higher fasting blood glucose and uric acid, higher erythrocyte sedimentation rate and anemia. Patients with AS with HG had significantly lower hemoglobin levels and more frequent anemia, as well as higher levels of C-reactive protein and erythrocyte sedimentation rate. In PsA, older age was observed in the androgen deficiency group, as well as higher body mass index and fasting glucose levels; obesity was more common. An intergroup comparison of quantitative and qualitative indicators between patients with androgen deficiency in all three rheumatic diseases (RDs) did not reveal significant differences in the average concentrations of ТS, luteinizing hormone, sex hormone binding globulin, experience of RD, laboratory markers of inflammatory activity, as well as glucose and uric acid. A similar incidence of diabetes mellitus, obesity and anemia was noted for all three nosologies. CONCLUSION: ТS levels and the presence of HG were not associated with the stage and activity of RD, but ТS deficiency was accompanied by higher laboratory indicators of inflammatory activity, lower hemoglobin values, and metabolic disorders. Patients with HG, regardless of nosology, had similar levels of sex hormones and indicators reflecting RD and concomitant conditions.

Androgen Deficiency in Aging Males (ADAM) Score as a Predictor of Total Testosterone Levels in Type 2 Diabetes Mellitus: A Prospective, Cross-sectional Study.

OBJECTIVE: Assessment of Androgen Deficiency in Aging Males (ADAM) questionnaire in predicting serum testosterone levels in type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: A single centre, prospective, cross-sectional epidemiological study in 250 male individuals with T2DM. ADAM questionnaire and serum total testosterone (TT) levels were analyzed for correlation using a Chi-squared test. Jaccard analysis to evaluate the concordance and dissimilarity between ADAM score and TT levels, providing insights into ADAM's predictive ability for testosterone levels. RESULTS: The mean age of the study population was 49.1 ± 7.8 years. The mean duration of diabetes was 6.2 ± 5.1 years. 27.6% were diagnosed with hypogonadism, while 72.4% were eugonadal. The mean age was 51.1 and 48.4 years in the hypogonadal and eugonadal cohorts, respectively (p < 0.02). The mean TT in the hypogonadal cohort was 220.6 ± 61.3 ng/dL, and in the eugonadal cohort was 475.4 ± 152.9 ng/dL (p < 0.001). The mean body mass index (BMI) in the hypogonadal cohort was 26.5 ± 4.0 kg/m2, and in the eugonadal group was 25.2 ± 3.6 kg/m2 (p < 0.02). Chi-square analysis established a strong positive correlation between the positive ADAM score and hypogonadism (p < 0.011). Of the 69 hypogonadal subjects, 84.05% had a positive ADAM score, yielding a sensitivity of 84.05% in detecting hypogonadism with a specificity of 32.04%. CONCLUSION: The ADAM questionnaire is a practical and cost-effective initial screening tool for identifying symptoms suggestive of testosterone deficiency. It has high sensitivity in identifying men with hypogonadism, while caution must be in place as it has a very low specificity. In resource-poor settings, ADAM score could be a clinical marker of hypogonadism.

Hypogonadism, frailty, and postoperative outcomes among men undergoing radical nephrectomy.

BACKGROUND AND OBJECTIVE: Hypogonadism and frailty may impact postoperative outcomes for men undergoing radical nephrectomy (RN). We aimed to determine the prevalence of hypogonadism in men undergoing RN and whether hypogonadism and frailty are associated with adverse postoperative outcomes. METHODS: We identified men undergoing RN between 2012 and 2021 using the IBM Marketscan database. Frailty was determined using the Hospital Frailty Risk Score (HFRS). Patients were considered to have hypogonadism if diagnosed <5 years before RN. Length of stay (LOS), complications, emergency department (ED) visits, and readmissions were evaluated between men with and without hypogonadism at the time of surgery. Subgroup analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 13 598 men who underwent RN, 972 (7.1%) had hypogonadism. Men with hypogonadism were more frail compared to men without hypogonadism (HFRS: median: 8.2, interquartile range [IQR]: 5.2-11.7 vs. median: 7.0, IQR: 4.3-10.7, p < 0.001) and had increased incidence of postoperative ileus (13.0% vs. 10.8%, p = 0.045), acute kidney injury (25.5% vs. 21.6% p = 0.005), and cardiac arrest (1.2% vs. 0.6%, p = 0.034). Hypogonadism was not associated with LOS, 90-day ED visit or readmission. However, high-risk frailty was associated with increased risk of 90-day ED visit (hazard ratio [HR]: 2.1, 95% confidence interval [95% CI]: 1.9-2.4, p < 0.001) and 90-day inpatient readmission (HR: 2.6, 95% CI: 2.2-3.1, p < 0.001), compared to low-risk frailty patients. Among men with hypogonadism, TRT was not associated with any postoperative outcomes. CONCLUSIONS: Hypogonadism and frailty should be considered in the preoperative evaluation for men undergoing RN as risk factors for adverse postoperative outcomes.

The Role of Hypogonadism in the Body Composition of Obese Men in the Preoperative Period of Bariatric Surgery.

OBJECTIVE: To describe clinical characteristics, hormonal profile and body composition of obese men in preoperative of bariatric surgery. METHODS: Cross-sectional, population-based study. Patients evaluated from June 2019 to December 2021 in 2 obesity referral centers. Patients underwent clinical evaluation, androgen deficiency screening using Androgen Deficiency in the Aging Male questionnaire, hormonal profile and body composition assessment through body mass index (BMI), body fat percentage (FM-%) and mass (FM-kg) measured by electrical bioimpedance and dual energy x-ray absorptiometry. To characterize hypogonadism, 2 cut-off points were considered: TT <264 ng/dL and TT <164 ng/dL. RESULTS: Thirty patients were included, mean age 35.6 ± 8.8 years, mean weight 129.4 ± 14.0 kg and mean BMI 42.3 ± 4.7 kg/m2. Dyslipidemia was the most prevalent comorbidity. Considering TT <264 ng/dL, 22 patients (73%) had hypogonadism. The mean TT in hypogonadal men was 198.9 + 68.7 ng/dL and in eugonadal men 357.0 + 59.5 ng/dl (P < .001). Using TT <164 ng/dL, 7 patients (23%) had hypogonadism. The mean TT in hypogonadal patients was 116.6 + 28.9 ng/dL and in eugonadal patients 279.0 + 75.0 ng/dL (P < .001). In Androgen Deficiency in the Aging Male questionnaire, 93.3% had positive screening, with no significant difference between groups. There was no statistically significant difference in body composition between groups when using TT <264 ng/dL as the hypogonadism cutoff. Considering hypogonadism TT <164 ng/dL, hypogonadal patients had significantly higher values of weight (139.0 × 126.5 kg P = .036), BMI (46.1 × 41.2 kg/m2P = .014), FM-% (48.0 × 42.8% P = .010) and FM-kg (66.3 × 53.9 kg P = .007) than eugonadal patients. CONCLUSION: Hypogonadism was identified in at least 23% of patients. Considering TT below the lower limit of normality for characterization of hypogonadism, we identified a significant worsening in body composition parameters.

Serum gonadal hormones levels and hypogonadism in ART naïve newly diagnosed HIV infected adult males in Mwanza, Tanzania.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is an endemic chronic disease which is characterized with progressive depletion of CD4 T cells and increased susceptibility to opportunistic infections. Previous studies have associated HIV infection with increased hypogonadism. However, the prevalence of hypogonadism remained poorly defined and widely ranging in various studies. This study aims to evaluate the serum gonadal hormonal levels and hypogonadism in antiretroviral therapy (ART) naïve newly diagnosed HIV infected-males in Mwanza, Tanzania. METHODS: This was a comparison study involving 81 ART naïve newly diagnosed HIV-infected adult males as study group and 81 apparently healthy HIV-negative males as comparison group. The participants in the study group and comparison group were matched by body mass index and age. Serum hormones [Total testosterone (TT), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) were estimated. Serum testosterone < 300 ng/dl, or testosterone > 300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers of hypogonadism. Data were analyzed using STATA version 15. RESULTS: The median serum testosterone level among ART naïve newly diagnosed HIV-infected adult males was significantly lower as compared to their comparison group (447 [259-534] versus 517 [396-605]; p = 0.0074) and shown to decrease with decreasing CD4 level. The median [IQR] serum FSH level among ART naïve newly diagnosed HIV-infected adult males was significantly higher than among their comparison group (3.8 [2.1-6.5] versus 2.6 [1.8-4.2]; p = 0.0086). The differences in serum LH and Estradiol were not statistically significant. Furthermore, the proportion of hypogonadism was significantly higher among ART naïve newly diagnosed HIV-infected adult males than in their comparison group (37.0% [30/81] versus 14.8% [12/81]; p = 0.0006). Out of these 30, 24 HIV-infected males had secondary hypogonadism, one had primary, and the remaining five had compensatory hypogonadism. CONCLUSION: Serum testosterone was lower and follicle stimulating hormone was higher among ART naïve HIV-infected males as compared to the HIV negative controls. Hypogonadism, mainly secondary, is common endocrine abnormality among ART naïve HIV-infected male patients in this study. HIV is associated with variations in gonadal hormones which may lead to sexual dysfunction in infected individuals.

Cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage I seminoma treated with a risk-adapted strategy: a Spanish single-centre retrospective analysis.

PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.

Testosterone therapy and the risk of cardiovascular disease in older, hypogonadal men.

The debate over the cardiovascular (CV) implications of testosterone therapy (TT) have resulted in diverging safety recommendations and clinical guidelines worldwide. This narrative review synthesizes and critically evaluates long-term studies examining the effects of TT within the context of aging, obesity, and endogenous sex hormones on CV disease (CVD) risk to support informed clinical decision-making. Observational studies have variably linked low endogenous testosterone with increased CVD risk, while randomized controlled trials (RCTs) demonstrate that TT yields cardiometabolic benefits without increasing short-term CV risk. The TRAVERSE trial, as the first RCT powered to assess CVD events, did not show increased major adverse cardiac events (MACE) incidence; however, its limitations - specifically the maintenance of testosterone at low-normal levels, a high participant discontinuation rate, and short follow-up - warrant a careful interpretation of its results. Furthermore, findings from the TTrials cardiovascular sub-study, which showed an increase in non-calcified plaque, indicate the need for ongoing research into the long-term CV impact of TT. The decision to initiate TT should consider the current evidence gaps, particularly for older men with known CVD. The CV effects of maintaining physiological testosterone levels through exogenous means remain to be fully explored. Until more definitive evidence is available, clinical practice should prioritize individualized care and informed discussions on the potential CV implications of TT.

Evaluation of the Incidence of Low Testosterone Levels in Young Male Adults with Moderate to Severe Obesity-Single-Centre Study from India.

PURPOSE: With the increase in obesity epidemic among Asians, it is necessary to evaluate the impact of obesity on this population. Low testosterone levels are known to be associated with obesity. This is the 1st study from Asia to evaluate incidence and magnitude of hypotestosteronemia in young adults with BMI more than 32.5 kg/m2 defined as moderate to severe obesity in Asians. MATERIALS AND METHODS: One hundred thirty-four male patients with BMI more than 32.5 kg/m2, between 18 and 30 years old who visited a single bariatric facility between 2017 and 2020, were evaluated with BMI, total and free testosterone levels and clinical features of gynecomastia, hypogonadism, and thinning of pubic and armpit hair. Statistical analysis was performed using SPSS, Spearman's correlation coefficient, and ANOVA test. RESULTS: 60.4% of patients (84/134) had low testosterone levels (< 300 ng/dl) and 23.9% (32/134) had levels between 300 and 400 ng/dl. 89.6% patients (120/134 had gynecomastia, 60.4% (81/134) had thinning of pubic and arm pit hair, and 62.7% (84/134) had hypogonadism. Testosterone levels showed a decreasing trend with increasing BMI, but it was not statistically significant. CONCLUSION: Obesity is one of the important etiologies of hypotestosteronemia and its manifestations in young adults. The actual incidence may be significantly higher than what is reported in the literature. High-quality research is required to address questions of diagnosis and best treatment options.

Erectile function and androgen and estrogen beta receptor gene polymorphisms in acromegalic men.

PURPOSE: Sexual dysfunctions are often experienced by male patients with acromegaly, due to a combination of hypogonadism and other comorbidities, but are a scarcely investigated complication. Erectile dysfunction is also closely related to cardiovascular diseases through endothelial dysfunction. Therefore, this project aimed to assess the prevalence of erectile dysfunction in a population of acromegalic men and evaluate its association with cardio-metabolic disorders, also exploring associations with androgen and estrogen receptor gene polymorphisms. METHODS: Sexually active men aged 18-65 with previous diagnosis of acromegaly were recruited. Clinical and laboratory data were retrospectively collected. Each patient also provided a blood sample for AR and ERß gene polymorphisms analyses and filled out the IIEF-15 questionnaire. RESULTS: Twenty men with previous diagnosis of acromegaly (mean age 48.4 ± 10.0 years) were recruited. 13/20 subjects (65%) had erectile dysfunction, but only four had a concurrent biochemical hypogonadism, with no significant correlation with IIEF-15 scores. Total testosterone negatively correlated with sexual intercourse satisfaction domain (ρ = - 0.595; p = 0.019) and general satisfaction domain (ρ = - 0.651; p = 0.009). IGF-1 levels negatively correlated with biochemical hypogonadism (ρ = - 0.585; p = 0.028). The number of CAG and CA repeats in AR and ERß receptors genes was not significantly associated with IIEF-15 scores or with GH/IGF-1 levels, but a negative correlation between CA repeats and the presence of cardiomyopathy (ρ = - 0.846; p = 0.002) was present. CONCLUSIONS: Men with acromegaly have a high prevalence of erectile dysfunction, but it does not appear to be correlated with treatments, testosterone levels and AR/ER-beta signaling. Nonetheless, a shorter CA polymorphic trait (ERbeta) is associated with the presence of cardiomyopathy. If confirmed, these data may suggest an association between an incorrect hormonal balance and increased cardiovascular risk in acromegaly subjects.

Male Hypogonadism After Recovery from Acute COVID-19 Infection: A Prospective Observational Study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 can affect the hypothalamic-pituitary-gonadal axis (HPG) due to the expression of the angiotensin-converting enzyme 2 receptor. OBJECTIVES: To assess the prevalence of hypogonadism and Sertoli cell dysfunction in coronavirus disease 2019 (COVID-19) male survivors. METHOD: Male subjects recovered from acute COVID-19 infection were prospectively observed. The primary outcomes included the proportion of hypogonadism, defined biochemically as serum testosterone<230 ng/dL or CFT of<6.4 ng/mL if the total testosterone is between 230-320 ng/m. Sertoli cell dysfunction was defined as inhibin-B level<54.5 pg/mL. Subjects with hypogonadism were followed up at 12 months to assess the recovery of the HPG axis. RESULTS: Eighty-three subjects aged≥18 years were evaluated at a median of 120 (±35) days post-recovery. Their mean age was 49.50±12.73 years, and the mean BMI was 26.84±5.62 kg/m2. Low testosterone was detected in 21 (24.71%) and low inhibin-B was detected in 14 (19.71%) out of 71 subjects at 3 months. Subjects with low testosterone were younger, with a mean age of 43.29±12.03 years (P-0.08) and higher BMI (P-0.012). The severity of COVID-19 infection, duration of hospitalization, and other factors were not significantly associated with low testosterone. At 12 months, 18 out of 21 subjects came for follow-up, of which 9 (50%) showed persistently low testosterone, suggestive of hypogonadism. CONCLUSION: Following COVID-19 infection, testosterone levels recovered over time; however, a significant proportion of subjects had low levels at 12-month follow-up. These findings have long-term implications for the management of COVID-19 subjects.

Noninvasive Indices of MASLD Are Associated With Hypogonadism in Male Patients With Type 2 Diabetes Mellitus.

CONTEXT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, affecting one-fourth of the adult population worldwide. Recent data found an association between MASLD and hypogonadism, but this relation in patients with type 2 diabetes mellitus (T2DM) is still unclear. OBJECTIVE: To evaluate in men with T2DM the association between total testosterone (TT) and noninvasive indices of hepatic steatosis (Fatty Liver Index [FLI], Hepatic Steatosis Index [HSI], Dallas Steatosis Index [DSI]) and fibrosis (AST to Platelet Ratio Index [APRI], Fibrosis-4 Index [FIB-4]), and their predictive cutoff values in identifying hypogonadism. METHODS: Cross-sectional study on 189 men with T2DM, without history of liver diseases and alcoholism, recruited on an outpatient basis. Interventions were andrological evaluation, metabolic parameters, TT, and liver indices. The main outcome measures were comparison of steatosis and fibrosis indices with testosterone levels and presence of hypogonadism. Receiver operating characteristic curves were used to identify cutoff values of liver indices in predicting low testosterone (<12 nmol/L). RESULTS: FLI, HSI, and DSI were negatively related with TT and were higher in the low-testosterone group than in the normal-testosterone group (FLI: 74.1 [61.4-93.5] vs 56.5 [32.1-78.2], P < .001; HSI: 41.5 [39.2-45.9] vs 40.1 [36.6-43.2], P = .005; DSI: 0.45 [-0.08-+1.04] vs -0.07 [-1.02-+0.58], P < .001). FLI and DSI also correlated with clinical symptoms of hypogonadism. No differences between groups were observed for APRI and FIB-4. FLI ≥63 was the best parameter as predictive index of low TT (sensitivity 73%, specificity 64%). CONCLUSION: We found an association between noninvasive indices of steatosis and hypogonadism in patients with T2DM. These indices could be used to direct the patients to andrological evaluation.

Hypogonadism is frequent in very old men with multimorbidity and is associated with anemia and sarcopenia.

BACKGROUND: Clinical data regarding hypogonadism in very old men with multimorbidity are rare. Hypogonadism can contribute to osteoporosis, anemia and sarcopenia and is therefore a relevant problem for geriatric patients. METHODS: A total of 167 men aged 65-96 years (mean 81 ± 7 years) admitted to an acute geriatric ward were included in a cross-sectional study. Body composition derived from dual-energy X­ray absorptiometry, bone mineral density, handgrip strength, multimorbidity, polypharmacy and laboratory values were obtained from the routine electronic clinical patient file. RESULTS: Hypogonadism was present in 62% (n = 104) of the study participants, of whom 83% showed clinical manifestation of hypogonadism (hypogonadism in combination with anemia, sarcopenia and/or low T­score). The subgroups showed a distribution of 52% primary and 48% secondary hypogonadism. Compared to the eugonadal patients, hypogonadal patients had reduced handgrip strength (p = 0.031) and lower hemoglobin levels (p = 0.043), even after adjustment for age, body mass index and glomerular filtration rate. CONCLUSION: Hypogonadism is common in geriatric patients. If chronic anemia, sarcopenia, or osteoporosis are diagnosed, testosterone levels should be determined in geriatric settings.

Genetic regulation of testosterone level in overweight males from the Kazakh population and its association with hypogonadism.

Male hypogonadism and erectile dysfunction in different populations are associated with excess body weight. A key aspect in most studies is the metabolism of sexual hormones, primarily testosterone. At the same time, the binding protein sex hormone binding globulin (SHBG) can play a large role, as it determines the ratio of total and bioavailable testosterone in blood, i.e. both the hormone content and level of its production. Recent research has identified common mutations that affect SHBG levels, such as the rs727428 polymorphic locus, which is associated with alterations in histone protein function, affecting the regulation of ribonucleic acid (RNA) protein SHBG synthesis. Similar relationships have been observed for prevalent mutations, including rs5934505 and rs10822184, in diverse populations. This study involved 300 individuals of Kazakh nationality from the Eastern Kazakhstan region, examining three polymorphic variants of the SHBG gene (rs727428, rs5934505, and rs10822184). The participants were categorized into three groups: individuals with hypogonadism and obesity (group 1, n=85), those with excess body weight but no hypogonadism (group 2, n=70), and individuals with neither excess body weight nor hypogonadism (group 3, n=145). The frequency of mutant gene alleles impacting GPS (SHBG) synthesis in the Kazakh population was notably high, comparable to European and South-East Asian populations. However, the association between excess body weight and these mutations exhibited varying patterns. Hypogonadism was linked to decreased GPS levels, strongly correlating with total testosterone but not bioavailable testosterone. The retention of sexual functions in overweight men was not always directly related to BMI levels and GPS concentrations.

Testosterone replacement therapy is not associated with increased prostate cancer incidence, prostate cancer-specific, or cardiovascular disease-specific mortality in Finnish men.

BACKGROUND: Concerns have been expressed over the safety of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH). Previous studies have shown controversial results regarding the association of TRT with the risk of cardiovascular events or prostate cancer (PCa) incidence, aggressiveness, and mortality. This study explores the overall risk of PCa and risk by tumor grade and stage, as well as mortality from PCa and cardiovascular disease (CVD), among men treated with TRT compared to men without LOH and TRT use. MATERIALS AND METHODS: The study included 78,615 men of age 55-67 years at baseline from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC). Follow-up started at randomization and ended at death, emigration, or a common closing date January 1st, 2017. Cox proportional hazards regression model with time-dependent variables and adjustment for age, trial arm, use of other medications, and Charlson comorbidity index was used. Comprehensive information on TRT purchases during 1995-2015 was obtained from the Finnish National Prescription Database. PCa cases were identified from the Finnish Cancer Registry and causes of death obtained from Statistics Finland. RESULTS: Over the course of 18 years of follow-up, 2919 men were on TRT, and 285 PCa cases were diagnosed among them. TRT users did not exhibit a higher incidence or mortality rate of PCa compared to non-users. On the contrary, men using TRT had lower PCa mortality than non-users (HR = 0.52; 95% CI 0.3-0.91). Additionally, TRT users had slightly lower CVD and all-cause mortality compared to non-users (HR = 0.87; 95% CI 0.75-1.01 and HR = 0.93; 95% CI 0.87-1.0, respectively). No time- or dose-dependency of TRT use was evident in any of the analyses. CONCLUSION: Men using TRT were not associated to increased risk for PCa and did not experience increased PCa- or CVD-specific mortality compared to non-users. Further studies considering blood testosterone levels are warranted.

Metabolic/endocrine disorders in survivors of childhood-onset and cranial radiotherapy- treated ALL/NHL: a meta-analysis.

BACKGROUND: Cranial radiotherapy (CRT) is recommended to high-risk pediatric patients with acute lymphoblastic leukemia or aggressive non-Hodgkin's lymphoma (ALL/NHL). However, effects of CRT treatment on the development of metabolic/endocrine disorders remain unclear. This meta-analysis aimed to identify metabolic and endocrine disturbances in survivors of childhood-onset and CRT-treated ALL/NHL. METHODS: Different online databases were searched using restricted search fields. Follow-up data and outcome measurements, including the prevalence of growth hormone (GH) deficiency, hypothyroidism, vitamin D deficiency, overweight/obesity, and hypogonadism were recorded. The height data was indicated by height-standard deviation score (height-SDS). Statistical estimates such as odds ratio (OR) and weighted standard mean difference (SMD) were compared between additional CRT treatment group and non-CRT treatment group. Study-to-study heterogeneity was calculated by calculating I-squared statistic, and fixed/random effect was applied to synthesize and analyze extracted data. RESULTS: Fifteen studies were included (4269 patients in total). Adult height SDS was lower in CRT-treated patients (pooled SMD = -0.581, 95% CI: -0.649--0.512), and CRT-treated patients were likely to develop short stature (pooled OR = 2.289, 95% CI:1.674-3.130). Regardless of the study year, which potentially reflects the state-of-the-art CRT technique, the prevalence of short stature and GH deficiency was time-independent. Additionally, previous CRT can increase the risk of precocious puberty (pooled OR = 2.937, 95% CI: 1.281-6.736), hypothyroidism (pooled OR = 2.057, 95% CI:1.510-2.801), and hypogonadism (pooled OR = 3.098, 95% CI:2.521-3.807). However, the risk of being overweight/obese was similar between the patients with and without CRT (pooled OR = 1.278, 95% CI: 0.675-2.421). CONCLUSION: Childhood-onset and CRT-treated ALL/NHL survivors are likely to have shorter height, precocious puberty, hypothyroidism, and hypogonadism.

Acromegaly versus hypogonadism: Bone fragility and evaluation.

INTRODUCTION: Osteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender. METHODOLOGY: We performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine. RESULTS: Vertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS. CONCLUSIONS: Vertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly.

The association of hypogonadism with depression and its treatments.

According to World Health Organization estimates, 5% of the adult population worldwide suffers from depression. In addition to the affective, psychomotor and cognitive symptoms which characterize this mood disorder, sexual dysfunction has been frequently reported among men suffering from depression. The most common sexual manifestations are decreased libido, erectile dysfunction and orgasmic disorder. In addition, epidemiological studies have documented a reduction of testosterone concentrations in men with depression and, for these reasons, depressive disorders appear as one possible cause of male functional hypogonadism. Moreover, some largely used antidepressant medications can cause or worsen sexual complaints, thus depression and its treatments rise several andrological-relevant issues. The other way round, men with hypogonadism can manifest depressed mood, anxiety, insomnia, memory impairment which, if mild, may respond to testosterone replacement therapy (TRT). However, the prevalence of functional hypogonadism in depression, and of depressive symptoms in hypogonadal men, is not known. Severe depressive symptoms do not respond to TRT, while the effect of treating major depression on functional hypogonadism, has not been investigated. Overall, the clinical relevance of each condition to the other, as well as the physiopathological underpinnings of their relationship, are still to be clarified. The present review summarizes current evidence on the influence of testosterone on mood and of depression on the hypothalamic-pituitary-testis axis; the clinical association between male hypogonadism and depression; and the reciprocal effects of respective treatments.

Update on acquired hypogonadism in men living with HIV: pathogenesis, clinic, and treatment.

Hypogonadism is a frequent finding among men living with HIV (MLWH) and it seems to occur earlier in comparison with the general male population. Although the prevalence of hypogonadism in MLWH has significantly lowered thanks to advancements in medical management, it remains high if compared with age-matched HIV-uninfected men, ranging from 13% to 40% in the age group of 20-60 years. Signs and symptoms of low serum testosterone (T) in MLWH are cause of concern since they are non-specific, of mild-to-moderate degree, and often overlapping with those of infection per se. For these reasons, hypogonadism can be underestimated in the absence of targeted laboratory blood examinations. With regard to the etiological factors involved in the T decrease, emerging evidence has suggested the functional nature of hypogonadism in MLWH, pointing out the mutual relationship between sex steroids, health status, comorbidities, and HIV-related factors. In agreement with this hypothesis, a therapeutic approach aiming at improving or reversing concomitant diseases through lifestyle changes (e.g. physical activity) rather than pharmacological T treatment should be theoretically considered. However, considering both patient's barriers to lifestyle changes to be maintained overtime and the lack of evidence-based data on the efficacy of lifestyle changes in normalizing serum T in MLWH, T therapy remains an option when other non-pharmacological interventions are ineffective as well as for all other functional forms of hypogonadism. From this perspective, the traditional therapeutic management of male hypogonadism in MLWH, especially the role of T supplementation, should be revised in the light of the probable functional nature of hypogonadism by considering a good balance between benefits and harmful. This narrative review presents an overview of current knowledge on hypogonadism in MLWH, deepening the factors driving and taking part in T decrease, providing advice for the clinical approach, and underlining the importance of individualized treatment aiming at optimizing non-gonadal comorbidities and thus avoiding over-, or even unnecessary, treatment with T.