Testosterone therapy has become a cornerstone treatment for men with hypogonadism, offering significant benefits such as improved sexual function, mood, muscle mass, and bone density. However, concerns about its cardiovascular safety have historically tempered its use. This position statement synthesizes the current evidence on the cardiovascular safety of testosterone therapy, drawing from key studies including the TRAVERSE trial, other trials, and recent meta-analyses.

Testosterone therapy aims to restore testosterone levels in men with hypogonadism, a condition associated with increased cardiovascular and metabolic risks. Early research produced mixed results, with some studies suggesting a potential increase in cardiovascular events such as myocardial infarction and stroke, while others indicated possible cardiovascular benefits, particularly in men with coexisting conditions like metabolic syndrome and type 2 diabetes.

The TRAVERSE trial, a large-scale, randomized, placebo-controlled study, provided robust evidence that testosterone therapy does not significantly increase the risk of major adverse cardiovascular events. Testosterone therapy was found to effectively mitigate anemia in hypogonadal men, highlighting a dual benefit of increasing red blood cell production while managing cardiovascular risks. The findings from the TRAVERSE trial align with those from previous meta-analyses that concluded that testosterone therapy is safe and does not increase cardiovascular risk.

There is consensus that testosterone therapy, when prescribed to appropriately selected patients and monitored regularly, is safe from a cardiovascular standpoint, with the potential benefits outweighing the risks when the therapy is used responsibly. Current guidelines recommend individualized treatment plans with careful monitoring, especially of hematocrit levels. This position statement amalgamates previous knowledge with current data and is in agreement with recent United States Food and Drug Administration label changes for testosterone products.

Secondary erythrocytosis refers to an elevation in hemoglobin or hematocrit due to elevated serum erythropoietin levels. Medications including testosterone and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are increasingly recognized as causes of secondary erythrocytosis. We conducted a systematic review to inform the clinical management of drug-induced erythrocytosis. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic literature search in MEDLINE, EMBASE, CENTRAL (all via Ovid), and Google Scholar. Of the 2036 articles screened for eligibility, 45 studies were included in our review, with 35 studies on testosterone and other androgen use, 5 studies on SGLT-2 inhibitors, 3 studies on antiangiogenic tyrosine kinase inhibitors (TKIs), 1 study on erythropoiesis-stimulating agents, and 1 study on a treatment regimen for multidrug-resistant tuberculosis. Cisgender and transgender men on prescription testosterone had erythrocytosis rates of up to 66.7%, with intramuscular formulations, higher doses, and older age associated with increased risk of erythrocytosis. Up to 2.7% of men on testosterone therapy developed thromboembolic events. Among individuals on SGLT-2 inhibitors, erythrocytosis rates ranged from 2.1% to 22%, with those who discontinued therapy demonstrating improvement or resolution of erythrocytosis. Thromboembolic events were reported in up to 10% of these individuals. Antiangiogenic TKIs were studied in patients with cancer, with erythrocytosis developing in up to 43.5% of patients. Drug-induced erythrocytosis is a heterogeneous condition for which there is no clear consensus among clinicians about its diagnosis and management. We offer recommendations for clinical practice within the scope of this systematic review, although further research is required.

Impaired sexual functioning is one of the consequences of obesity with hormonal disorders involving testosterone.

To explore the link between obesity and sexual desire, to assess how changes in body weight affect sexual desire, and to examine the role of testosterone in these changes in obese and overweight men.

The systematic review was conducted in PubMed. Studies involving obese/overweight men that reported different libido levels or changes after weight loss interventions were included. Meta-analysis and meta-regression were performed.

The search identified 2259 studies, of which 28 met the eligibility criteria. Most studies focused on weight-loss interventions (n = 21, 77%), with 13 studies investigating the effect of bariatric surgeries. Testosterone levels were reported in 14 studies. The studies encompassed a total population of 18 653 people, including 10 356 obese and overweight men. Of the 28 identified studies, 15 indicated a potential association between BMI, waist circumference, and sexual desire. Effect size meta-analysis (calculated using data from four studies presenting results before and after bariatric surgery) suggests that an increase in the International Index of Erectile Function sexual desire domain was very strongly associated with changes in a patients' weight resulting from bariatric surgery (d = 1.22, 95% CI 0.41-2.03, P = 0.003). The meta-analysis of four studies, presenting results before and after diet intervention, showed a strong impact of weight loss on an increase of the Sexual Desire Inventory (SDI), (d = 1.16, 95% CI 0.44-1.88, P = 0.002) The meta-regression revealed a significant association between the level of sexual desire on the SDI and the magnitude of BMI changes before and after dieting interventions (R2 = 77.97%; P = 0.002). The meta-analysis of plasma total testosterone levels from studies that present results before and after selected diets showed a strong impact of diet on the increase in testosterone levels after interventions (d = 1.39 95% CI 0.86-1.92; P < 0.001). There was a significant impact of the level of plasma total testosterone on the variance of sexual desire in the SDI questionnaire (R2 = 5.33%; P < 0.001).

A lack of studies that focus on sexual desire in obesity, the heterogeneity of the included population, the variability in the used questionnaires and reported statistics.

A potential association between sexual desire and body weight exists. Weight loss interventions, including dietary changes and bariatric surgery, significantly increased both sexual desire and plasma total testosterone levels. Additionally, variations in plasma total testosterone levels had a significant effect on the variability of sexual desire in obese men.

Testosterone has a pivotal role in spermatogenesis, erectile function, libido and expression of secondary sexual characteristics. The prevalence of symptomatic, laboratory-proven testosterone deficiency increases with age and is often treated with testosterone replacement therapy (TRT). Treatment with exogenous androgens suppresses gonadotropin levels, inhibits endogenous testosterone production and drastically reduces intratesticular testosterone, consequently impairing spermatogenesis. Sperm production often slowly resumes after TRT cessation. However, the rate of recovery shows highly variable kinetics that might complicate family planning. Medical therapies (including aromatase inhibitors and selective oestrogen receptor antagonists) and exogenous gonadotropins (including human chorionic gonadotropin and follicle-stimulating hormone) may be used to preserve or restore spermatogenesis in select populations receiving TRT. Exogenous testosterone is contraindicated in men trying to conceive, but new short-acting formulations, including oral testosterone undecanoate and nasal testosterone gel, might incompletely suppress the hypothalamic-pituitary-gonadal axis and partially preserve spermatogenesis.

Testicular aging commonly leads to testosterone deficiency and impaired spermatogenesis, yet the underlying mechanisms remain elusive. Here, we show that Leydig cells are particularly vulnerable to aging processes in testis. Single-cell RNA sequencing identifies the expression of Hmgcs2, the gene encoding rate-limiting enzyme of ketogenesis, decreases significantly in Leydig cells from aged mice. Additionally, the concentrations of ketone bodies β-hydroxybutyric acid and acetoacetic acid in young testes are substantially higher than that in serum, but significantly diminish in aged testes. Silencing of Hmgcs2 in young Leydig cells drives cell senescence and accelerated testicular aging. Mechanistically, β-hydroxybutyric acid upregulates the expression of Foxo3a by facilitating histone acetylation, thereby mitigating Leydig cells senescence and promoting testosterone production. Consistently, enhanced ketogenesis by genetic manipulation or oral β-hydroxybutyric acid supplementation alleviates Leydig cells senescence and ameliorates testicular aging in aged mice. These findings highlight defective ketogenesis as a pivotal factor in testicular aging, suggesting potential therapeutic avenues for addressing age-related testicular dysfunction.

Given the various roles of testosterone in men's health, we conducted a multi-ancestral genetic analysis of total testosterone, free testosterone, SHBG, and hypogonadism in men within the Million Veteran Program (MVP). Here we identified 157 significant testosterone genetic variants, of which 8 have significant ancestry-specific associations. These variants implicate several genes, including SERPINF2, PRPF8, BAIAP2L1, SHBG, PRMT6, and PPIF, related to liver function. Genetic regulators of testosterone have cell type-specific effects in the testes, liver, and adrenal gland and are associated with disease risk. We conducted a meta-analysis amongst ancestry groups to identify 188 variants significantly associated with testosterone, of which 22 are novel associations. We constructed genetic scores for total testosterone, SHBG levels, and hypogonadism and find that men with higher testosterone genetic scores have lower odds of diabetes, hyperlipidemia, gout, and cardiac disorders. These findings provide insight into androgen regulation and identify novel variants for disease risk stratification.

Recent years have brought significant development in athlete doping use detection with the implementation of the Athlete Biological Passport (ABP). The aim of this study was to explore if similar methods could also be used to detect non-medical use of anabolic androgenic steroids (AAS) among clinical patients. For this purpose, six elastic net regression models were trained in a sample of Finnish specialized health care male patients (N = 2918; no doping = 1911, AAS doping = 1007), using different approaches to longitudinal laboratory measurements as predictive variables. The laboratory data was retrieved from the Hospital District of Helsinki and Uusimaa (HUS) data lake, and doping use status was defined by patient disclosure, recorded in digital medical record free texts. Length of observation time (e.g., time between the first and last laboratory measurement) was used as weight. Model performance was tested with holdout cross-validation.

All the tested models showed promising discriminative ability. The best fit was achieved by using the existence of out-of-reference range measurements of 31 laboratory parameters as predictors of AAS doping, with test data area under the receiver operating characteristic curve (AUC) of 0.757 (95% CI 0.725-0.789).

The findings of this preliminary study suggest that AAS doping could be detected in clinical context using real-life longitudinal laboratory data. Further model development is encouraged, with added dimensions regarding the use of different AAS substances, length of doping use, and other background data that may further increase the diagnostic accuracy of these models.

Hypogonadotropic hypogonadism (HH) represents a relatively rare cause of nonobstructive azoospermia (NOA), but its knowledge is crucial for the clinical andrologists, as it represents a condition that can be corrected with medical therapy in 3 quarters of cases. There are forms of congenital HH, whether or not associated with an absent sense of smell (anosmic HH or Kallmann syndrome, and normosmic HH, respectively), and forms of acquired HH. In congenital HH, complete absence of pubertal development is characteristic. On the other hand, if the deficit occurs after the time of pubertal development, as in acquired HH patients, infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance. Gonadotropin-releasing hormone (GnRH) or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results, although a small but significant proportion of patients do not achieve sufficient responses.

This review explores the increasing use of testosterone therapy in aging men, driven by the need to address age-related symptoms like decreased libido, muscle weakness, and anemia. Studies such as the Testosterone Trials and Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy Response in Hypogonadal Men trial show that testosterone therapy can offer benefits in sexual function, physical performance, and bone density, with no significant increase in risks for cardiovascular events or prostate cancer. However, conflicting data suggest that careful, individualized treatment is necessary, especially in older men with existing health conditions.

Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.

Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.

Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations.

The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie).

In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225 mg oral testosterone undecanoate twice daily, and doses were adjusted by 75 mg/dose at weeks 4 and 8 based on average serum total testosterone concentration and maximum observed serum concentration. The primary endpoint was the proportion of patients receiving oral testosterone undecanoate with serum total testosterone concentration within the eugonadal reference range (300-1140 ng/dL). Secondary endpoints included the proportion of patients with maximum serum total testosterone concentrations within predetermined limits, safety parameters, and quality-of-life endpoints including the Short Form-36v2 Health Survey, Psychosexual Daily Questionnaire, and International Prostate Symptom Score.

Overall mean ± SD baseline testosterone was 205.7 ± 71.6 ng/dL. For patients receiving oral testosterone undecanoate, 87.4% demonstrated a 24-h average serum total testosterone concentration within the reference range following titration. Oral testosterone undecanoate demonstrated a nominal statistically significantly greater mean change from baseline than 1.62% topical testosterone gel for Short Form-36v2 Health Survey measures of mental health (2.91 vs. -0.10; p = 0.035), and mental component summary (3.82 vs. 0.55; p = 0.009); and Psychosexual Daily Questionnaire measure of weekly negative mood (-0.57 vs. -0.20; p = 0.021). Safety endpoints were comparable between therapies. No deaths or treatment-related serious adverse events were reported.

Male patients with hypogonadism receiving oral testosterone undecanoate 225 mg twice daily demonstrated improvements in libido and sexual frequency. Serum testosterone concentrations were within the reference range in 87% of patients without dose titration.

Sedentary behavior has emerged as a potential risk factor for various health issues, including hormonal imbalances like testosterone deficiency (TD). However, the relationship between sedentary time and TD remains underexplored, especially with respect to the complex biological mechanisms underlying this association. This study aimed to examine the association between sedentary time and TD in adult males.

This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey 2011-2016. A total of 6057 male participants aged 20 years and older were included. Sedentary time was categorized into quartiles, and TD was defined as serum testosterone levels below 300 ng/dL. Logistic regression models were employed to assess the association between sedentary time and TD, adjusting for demographic, lifestyle, and health-related covariates. Restricted cubic spline (RCS) analysis and segmented regression were also conducted to explore potential non-linear relationships and thresholds. Subgroup analyses were performed to examine the consistency of associations across various groups.

The analysis revealed a significant positive association between sedentary time and TD. Prolonged sedentary behaviour was consistently associated with higher odds of TD across all models (all p < 0.001). RCS analysis showed a significant non-linear relationship, particularly as sedentary time exceeded 4.5 h per day, with a marked increase in the likelihood of TD (p-non-linear = 0.027). Subgroup analysis indicated that this association was most pronounced in Non-Hispanic Whites, current smokers, and drinkers, and was weaker in individuals with diabetes, where the association lost statistical significance after full adjustment.

This study identifies a significant association between prolonged sedentary behaviour and a higher risk of TD, suggesting that sedentary behavior may play a key role in the development of TD, particularly in specific high-risk populations.

Little is known about temporal trends in the incidence of male hypogonadism and its correlation with socioeconomic status, which we examined in the present study.Data were extracted from the Maccabi Health Services computerized database between 2001-2017. The study population included 4,261 men aged 21 to 80 years with biochemically proven hypogonadism defined and classified according to the European Male Aging Study criteria. Patients on testosterone or testosterone-modifying drugs were excluded. The socioeconomic status was assessed based on verified financial data pertinent to the area of residence.The incidence of male hypogonadism increased with age in all the socioeconomic strata. Among the hypogonadal men, 75% had hypogonadotropic hypogonadism. The overall incidence of hypogonadism increased 1.4-fold between the 2001-2009 and 2010-2017 periods [from 41.7 (39.7-43.8) to 58.5 (56.4-60.8) per 100,000 person-years) (95% CI)], mainly due to an increase in hypogonadotropic hypogonadism. The temporal increase in hypogonadotropic hypogonadism occurred in all age groups and all socioeconomic strata but was notably more prominent in >51-year age groups of the more affluent socioeconomic strata. The mean body mass index remained unchanged throughout the study period.A temporal increase was observed in male hypogonadism, mainly hypogonadotropic hypogonadism, corresponding with previously observed temporal decreases in testosterone levels in men. This trend could be possibly partly attributed to an underappreciated increase in mental distress due to decreasing global happiness indices, increasing stress, and occupational burnout in specific occupations associated with more affluent populations (i.e., high-tech, finance, medical). This preliminary proposition deserves further investigation.

Testosterone is the classical male anabolic hormone, involved in sexual development, virilisation and regulation of body composition in adult men. Organic disease involving the hypothalamus, pituitary or testes may interfere with endogenous testosterone production. In such men, testosterone treatment effectively ameliorates symptoms and signs of androgen deficiency. However, non-gonadal factors including age, body mass index and medical comorbidities influence circulating testosterone, and older men have on average lower testosterone concentrations compared with younger men. In these men, testosterone treatment would be a pharmacological intervention requiring stringent justification via high-quality evidence from randomised controlled trials (RCTs). Recent RCTs show benefits of testosterone treatment to improve sexual function, anaemia and bone mineral density in older men, and to prevent or revert type 2 diabetes mellitus in men at high risk. Results from a large cardiovascular safety trial in men with or at risk of cardiovascular disease provide important reassurance as to cardiovascular and prostate safety of testosterone treatment. Key questions remain as to whether testosterone's anabolic and other effects can be used safely to counter reductions in lean mass associated with incretin-based weight loss medications in men with obesity, and whether it might prevent disabilities including frailty, osteoporotic fractures and dementia in older men generally. This last question could be answered by a new testosterone RCT, targeting men in the 65-80 years age bracket, which would necessarily be large and of extended duration. A composite endpoint could be used which integrates potential benefits and risks, such as disability-free survival.

Testosterone deficiency seriously affects male reproductive function, growth and development, and quality of life. There is a certain association between inflammation and testosterone. PIV, a novel immune-inflammatory biomarker, has emerged. However, little is known about the relationship between PIV and serum testosterone. This study aims to investigate the relationship between PIV and serum testosterone. In this cross-sectional study, we analyzed data from 7389 participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. Serum total testosterone levels were measured using precise isotope dilution liquid chromatography and tandem mass spectrometry. PIV was calculated as (neutrophil count × monocyte count × platelet count)/lymphocyte count. Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the PIV and testosterone deficiency. Using PIV Quartile 1 as the reference, in the fully adjusted model, the odds ratios (OR) and 95% confidence intervals (CI) for Quartile 2 to Quartile 4 participants were 1.14 (0.93, 1.40), 1.28 (0.99, 1.65), and 1.51 (1.18, 1.95), respectively (P for trend < 0.001), with participants in the highest quartile of PIV having a 51% increased risk of testosterone deficiency compared to those in the lowest quartile of PIV. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between PIV and testosterone deficiency, with a turning point at 565.89. The subgroup analysis results showed that, except for obesity, there was no statistically significant difference in the relationship between PIV and testosterone deficiency among different subgroups (P > 0.05). Our study results indicate a positive correlation between PIV and the risk of testosterone deficiency. This suggests that PIV may serve as a potential indicator for testosterone deficiency.

Background: Hypogonadism frequently occurs among men with chronic kidney disease (CKD) and is a highly unfavorable prognostic factor. Therefore, a simple and common screening for testosterone deficiency may be important. The measurement of testosterone in saliva appears to be an attractive alternative to serum testosterone. This study aimed to assess the usefulness of determining free testosterone concentration in saliva to detect testosterone deficiency in men with advanced CKD, including those on dialysis. Methods: A total of 77 adult, male patients (aged 41-89 years old)-30 with CKD stage G3-G4, 30 on hemodialysis (HD), and 17 on peritoneal dialysis (PD)-were evaluated. The concentration of free testosterone was determined in saliva (SalFT), while the concentration of total testosterone (TT) was determined in blood serum. Serum-free testosterone levels were calculated (cFT). Results: SalFT did not differ from cFT in the CKD (p = 0.547) and PD groups (p = 0.409). In the HD group, SalFT was higher than cFT (p = 0.009). SalFT was positively correlated with cFT (r = 0.435 in the CKD and r = 0.479 in the HD) and TT (r = 0.451 in CKD), but only in the group of patients with SalFT levels below 140 pg/mL and 120 pg/mL, respectively. A cut-off value of SalFT ≤ 60.6 pg/mL showed 73.9% sensitivity and 77.8% specificity for testosterone deficiency recognition. Conclusions: Our study supports the value of SalFT measurement as a non-invasive approach in the diagnosis of testosterone deficiency in men with advanced CKD, as well as patients on hemodialysis.

In epidemiological studies, higher leukocyte and platelet counts are associated with increased risk of cardiovascular events. Effects of testosterone replacement therapy (TRT) on leukocyte subsets and platelets in men with hypogonadism and association of circulating leukocyte subtypes and platelets during TRT with cardiovascular events remain unknown.

In the TRAVERSE Trial, 5,204 men, 45-80 years with hypogonadism and preexisting or increased risk of cardiovascular disease (CVD) were randomized to transdermal testosterone or placebo gel daily for up to 5 years. We determined the effect of TRT on neutrophils, monocytes, lymphocytes and platelets and association of changes in leukocyte subtypes and platelets with risk of major adverse cardiovascular (MACE) and venous thromboembolism (VTE) events.

TRT was associated with significantly greater increase in neutrophils and monocytes, and greater decrease in lymphocytes and platelets than placebo. Changes in neutrophil (odds ratio for 1 SD increase in cell count (OR) 1.32 [1.01, 1.73]) and monocyte (OR 1.39 [1.08, 1.79]) counts were associated with increased risk of VTE, accounting for TRT. Neutrophil and monocyte counts at baseline and on-treatment were also associated with increased risk of MACE, adjusting for treatment (baseline: neutrophils OR 1.18 [1.06,1.31], monocytes OR 1.16 [1.05,1.29]; on-treatment neutrophils: OR 1.25 [1.12, 1.40]; monocytes: OR 1.18 [1.06,1.31]).

TRT increased circulating neutrophils and monocytes and decreased lymphocytes and platelets in men with hypogonadism. Changes in monocyte and neutrophil counts were associated with increased risk of VTE. Neutrophil and monocyte counts should be considered when evaluating VTE risk in hypogonadal men treated with TRT.

URL:https://clinicaltrials.gov/study/NCT03518034. Unique identifier: NCT03518034. The study was initially registered on March 5, 2018, and the first participant was enrolled on May 23, 2018.

Testosterone replacement therapy is gaining more and more popularity among hypogonadal men. The positive effects on body composition, metabolic functions, and mental well-being can improve the quality of life of many men. However, testosterone can also trigger several side effects, including increases in hematocrit and hemoglobin levels. Exogenous testosterone tends to increase erythropoiesis. The testosterone-induced increase in red blood cells can increase performance via improved transport of oxygen to the body. However, red blood cell overproduction can cause blood clots and severe sequelae such as heart attack, stroke, or pulmonary embolism. These side effects need to be closely monitored in testosterone replacement therapy (TRT) patients. Traditionally, cessation of TRT was recommended for patients with severe polycythemia. However, cessation of TRT can lead to the recurrence of symptoms experienced before TRT. Fortunately, recent innovations in testosterone preparations allow a treatment with less side effects on hematocrit levels.

This review focuses on highlighting novel methods to treat hypogonadism while minimizing side effects related to hematocrit levels.

We identified relevant articles using PubMed and Google Scholar searching for specific terms from 2000-2024.

Elevations in hematocrit levels triggered by testosterone therapy seem to be controversial, some studies advocate noninferior effects as compared to placebo while others found adverse side effects on cardiovascular health. However, the way of administration of testosterone seems to strongly influence the extent of hematocrit increases and can therefore be minimized by choosing the right testosterone preparation.

Depending on the route of administration, testosterone replacement therapy can lead to significant increases in hematocrit and potential cardiovascular incidents. On the other hand, for hypogonadal patients with anemia, testosterone replacement therapy might be beneficial not only for restoring healthy testosterone levels but also red blood cells.

The repercussions and outcomes of the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has raised concerns about potential adverse effects on the male reproductive system. Telomeres are crucial in maintaining the integrity and stability of genomic DNA, and viral infections can induce changes in telomere biology. In this study, the repercussions of SARS-CoV-2 infection in male reproductive health were analyzed.

This case-control study enrolled subjects who donated blood and semen samples. Fifty-six men with and 56 without prior COVID-19 infection, ages 18-45 years, were included. Semen analysis and hormonal levels were evaluated. The presence of SARS-CoV-2 RNA in semen and the sperm telomere length were assessed by quantitative polymerase chain reaction and associated with clinical and laboratory data. To reduce interference factors, known variables that influence telomere length were analyzed independently.

Sperm telomere length was significantly diminished in the COVID-19 positive group with a mean difference of 0.635 compared to the negative group (p = 0.041). Most individuals in the COVID-19 positive group were clinically classified as asymptomatic/mild illness, and all samples were collected more than 90 days after recovery. No statistically significant differences were observed between the groups in terms of clinical data, semen parameters, and serum levels of follicle-stimulation hormone, estradiol, and testosterone. Persistent or subgenomic SARS-CoV-2 RNA was not detected in the semen samples.

This study revealed that SARS-CoV-2 infection reduced sperm telomere length without alterations in semen parameters or hormonal levels. These results provide further evidence that SARS-CoV-2 infection can induce genomic alterations in human sperm.

The objective is to evaluate the efficacy and safety of testosterone supplementation in testicular cancer survivors with treatment-related hypogonadism.

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and used Embase, PubMed/MEDLINE, Cochrane Central, Web of Science Core Collection, Korean Journal Index, SciELO, and Global Index Medicus to obtain data in June of 2024.

Analyses evaluating testosterone supplementation in testicular cancer survivors with treatment-induced hypogonadism were included. Any analyses not assessing supplementation in this population or deemed unretrievable were excluded.

Ten analyses were included for analysis. A total of 332 bilateral or unilateral testicular cancer survivors with treatment-influenced hypogonadism were reviewed, with 238 patients receiving testosterone replacement. Eight of the 10 analyses assessed participants without poor quality-of-life (QOL) metrics, metabolic factors, and bone mineral density (BMD) at baseline and only found a significant benefit in fat distribution metrics with testosterone supplementation. Two analyses evaluated participants with poor QOL metrics or BMD at baseline and showed improvements in QOL or BMD with testosterone supplementation.

There is robust evidence regarding the efficacy and safety of testosterone replacement in hypogonadal individuals but limited evidence specifically evaluating supplementation in testicular cancer survivors with treatment-influenced hypogonadism.

The results suggest testosterone replacement may be beneficial in patients with impaired QOL metrics, metabolic factors, and BMD at baseline; the results also suggest that routine supplementation for all individuals in this patient population lacks efficacy.

Sex is a central aspect of human life and is significantly impacted by chronic illness. Cirrhosis, due to its unique pathophysiology and the side effects of common therapies, serves as a paradigmatic example, being associated with very high rates of sexual dysfunction in both men and women. Liver transplantation can modify certain hormonal and pathophysiological aspects related to sexual dysfunction, but complete recovery occurs in only a relatively small percentage of patients. This review examines the pathophysiology, epidemiology, and management of sexual and reproductive dysfunction in patients with cirrhosis and those undergoing liver transplantation. It provides a framework for understanding the sources of dysfunction, tools for identifying it in clinical settings, and interventions to improve sexual health and functioning in these patients.

Individuals with opioid use disorder (OUD) have reduced life expectancy and inferior outcomes when treated for depression, diabetes, and fractures. Their elevated risk of testosterone deficiency may contribute to all of these relationships, however few individuals prescribed opioids are evaluated with testosterone assays. The purpose of this study is to determine whether patients with opioid use disorder are evaluated for testosterone deficiency after development of a symptom that may merit investigation, such as erectile dysfunction (ED).

We conducted a retrospective longitudinal cohort study that utilized data from a national database called TriNetX. Patients were eligible for inclusion if they were 20 to 90 years of age, male, and diagnosed with erectile dysfunction. We utilized descriptive statistics and logistic regression to address study aims.

Testosterone testing was uncommon for all patients with ED. Among 20,658 patients, it was assessed in 11.2% with OUD and 15.1% without OUD. Among those screened, 40% individuals with OUD and ED had testosterone deficiency. Odds of screening those with OUD were lower than matched controls (RR 0.74).

Individuals with OUD are at increased risk of testosterone deficiency than the general population, but nearly 90% are not evaluated for this condition even after development symptoms. That 40% of individuals assessed were classified as testosterone deficient suggests endocrine disorders may be contributing to increased fracture risk, chronic pain, and severe depression commonly encountered in patients with OUD. Addressing this care gap may reduce morbidity and mortality associated with opioid use disorder.

The association between low serum testosterone levels and all-cause mortality in male and female patients with cardiovascular disease (CVD) was investigated. This study extracted data on CVD patients from the National Health and Nutrition Examination Survey (NHANES) database (1999-2000, 2003-2004, 2011-2012, and 2013-2014). The association between low serum testosterone levels (≤ 300 ng/dL) and all-cause mortality in male and female CVD patients was evaluated using univariate and multivariate Cox regression analyses, with hazard ratios (HR) and 95% confidence intervals (CI). A total of 1,177 participants (689 males) with a mean age of 66.01 ± 12.52 years were included in the study. The median follow-up time was 55 (44, 71) months. Low serum testosterone levels occurred in 487 (70.68%) males and 394 (80.74%) females. Additionally, 202 (29.32%) male patients and 94 (19.26%) female patients with CVD were dead. After adjusting for covariates, low serum testosterone levels were associated with an increased risk of all-cause mortality in male CVD patients (HR = 1.48, 95% CI 1.08-2.02, P = 0.013), while the association was not significant in females. Low serum testosterone levels may be associated with an increased risk of all-cause mortality in male CVD patients, but not in female patients.

Erectile dysfunction (ED) is a prevalent condition affecting male sexual health, characterized by the inability to achieve or maintain satisfactory erections. ED has a multifactorial pathogenesis in which psychological, hormonal, neurologic, cardiovascular, and lifestyle factors all contribute to a progressive decline of erectile function. A critical underlying mechanism involves oxidative stress (OS), an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, which disrupts endothelial function, reduces nitric oxide (NO) bioavailability, and contributes to vascular dysfunction. This narrative review explores the interplay between OS and ED, focusing on the roles of ROS sources such as NADPH oxidase, xanthine oxidase, uncoupled nitric oxide synthase, and mitochondrial dysfunction. It examines the impact of OS on chronic conditions like hypertension, diabetes mellitus, hyperlipidemia, hypogonadism, and lifestyle factors like smoking and obesity, which exacerbate ED through endothelial and systemic effects. Emerging research underscores the potential of antioxidant therapies and lifestyle interventions to restore redox balance, improve endothelial function, and mitigate ED's progression. This review also highlights gaps in understanding the molecular pathways linking ROS to ED, emphasizing the need for further research to develop targeted therapeutic strategies.

Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived FoF1-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded FoF1-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30-40 μm vs. 15-25 μm in untreated). These results highlight the ATM's potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity.

Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism.

Lycium barbarum extracts have been shown to be effective in male reproductive protection and male infertility. However, its role in enhancing testicular function, such as testosterone synthesis, and the potential mechanism remain to be understood. To elucidate the effects of Lycium barbarum glycopeptide (LbGp) on testosterone synthesis, we isolated primary Leydig cells (LCs) from testes and performed RNA sequencing (RNA seq) on LCs treated with LbGp. In this study, we demonstrated that LbGp promoted testosterone synthesis in LCs both in vivo and in vitro. We also demonstrated that LbGp elevated adenosine 5'-triphosphate (ATP) synthesis and cell proliferation by enhancing glucose metabolism. Mechanistically, LbGp upregulated testosterone synthesis by suppressing TGF-β pathway and enhancing the expression of steroidogenic genes: Cyp11a1, Hsd3b1, Hsd17b3, Star, and Sf-1. These findings indicate that LbGp plays an important role in enhancing testicular function and promoting testosterone synthesis.

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at a higher risk of developing bone disorders. Awareness and understanding of the disease are crucial for prevention and early diagnosis. Currently, there is no research on the risk factors and knowledge of bone fragility in the population with IBD in Taiwan. This study aimed to evaluate the risk factors and self-assessed knowledge levels of bone health among patients with IBD in Taiwan. Methods: This single-center cross-sectional study included 59 adult patients. Clinical data, blood tests, bone mineral density (BMD), T-score, Z-score, and questionnaires covering self-assessed knowledge, fracture risks, and physical activity were assessed. The patients were divided into normal and low BMD groups. Results: Of all participants, eighteen (30.5%) had low BMD: six (10.2%) had BMD below the expected range, ten (16.9%) had osteopenia, and two (3.4%) had osteoporosis. Vitamin D insufficiency and deficiency were observed in 26.3% and 66.6% of the patients, respectively. According to multivariate analysis, age and sex hormone deficiency are strongly associated with low BMD. Educational interventions significantly improved the patients' self-assessed knowledge levels. Conclusions: Age and sex hormone deficiency are significant factors contributing to low BMD in IBD patients. Not only women but also men with IBD who had symptoms of hypogonadism are at high risk for low BMD. Educational interventions improve self-assessment knowledge regarding the relationship between IBD and bone health.

Increasing numbers of transgender and gender-diverse individuals are seeking initiation of gender-affirming hormone therapy. This aligns an individual's physical characteristics with their gender identity and improves psychological outcomes. Physical changes, including changes to muscle mass and body fat redistribution, can alter sex-specific laboratory reference ranges.

We review the impact of gender-affirming hormone therapy on laboratory parameters with sex-specific reference ranges, with a focus on hemoglobin/hematocrit, renal function, cardiac biomarkers, and prostate-specific antigen.

Gender-affirming hormone therapy results in changes in laboratory parameters with sex-specific reference ranges. For individuals established on gender-affirming hormone therapy, reference ranges that align with an individual's gender identity should be used for hemoglobin/hematocrit, serum creatinine, and high-sensitivity cardiac troponin and N-terminal brain natriuretic peptide. Clinicians should interpret these biomarkers according to the reference range that aligns with one's affirmed gender.

Testosterone, estradiol, and dihydrotestosterone share common ligand binding sites on sex hormone binding globulin and albumin. It is unknown whether and how changes in testosterone, dihydrotestosterone, and estradiol concentrations during testosterone replacement therapy affect free testosterone fraction.

To determine the effect of changes in testosterone, dihydrotestosterone, and estradiol concentrations on free testosterone fraction during testosterone replacement therapy of men with hypogonadism.

Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and dihydrotestosterone concentrations over 12 months of testosterone replacement therapy with changes in free testosterone fraction, measured using equilibrium dialysis. We used random forests to evaluate the associations of predicted mean changes in free testosterone fraction with changes in circulating concentrations of each hormone at low, mean, or high change in the other two hormones.

Testosterone replacement therapy not only increased total testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations, but also the percent free testosterone, even though sex hormone binding globulin levels did not change. The predicted changes in free testosterone fraction during testosterone replacement therapy exhibited a non-linear relationship with changes in each of total testosterone, dihydrotestosterone, and estradiol concentrations. Greater increases in testosterone, dihydrotestosterone, and estradiol levels during testosterone replacement therapy were each associated with higher model-predicted percent free testosterone. Substantially smaller changes in molar concentrations of estradiol and dihydrotestosterone had a greater effect on percent free testosterone than those in testosterone.

During testosterone replacement therapy of men with hypogonadism, changes in testosterone, dihydrotestosterone, and estradiol concentrations each altered percent free testosterone non-linearly. Small changes in estradiol concentrations exerted much larger effect on the free testosterone fraction than testosterone and dihydrotestosterone, suggesting complex interactions of the three hormones with the binding proteins. Assessment of changes in free testosterone during testosterone replacement therapy should include consideration of changes in all three hormones.

Low testosterone in middle-aged/older men contributes to accelerated vascular aging, including endothelial dysfunction. However, the mechanisms by which low testosterone affects endothelial dysfunction are not well understood. We sought to determine whether higher endothelin-1 (ET-1) levels are associated with reduced brachial artery flow-mediated dilation (FMD) in middle-aged/older men with low testosterone. Plasma ET-1 was quantified in 60 men categorized as young (n = 20, age = 30 ± 4 yr, testosterone = 510 ± 63 ng/dL), middle-aged/older with normal testosterone (n = 20, age = 59 ± 6 yr, testosterone = 512 ± 115 ng/dL), or middle-aged/older with low testosterone (n = 20, age = 60 ± 8 yr, testosterone = 265 ± 47 ng/dL). Endothelial function was determined via brachial artery FMD. Venous and arterial endothelial cells were harvested via endovascular biopsy in a subset of participants and stained for ET-1 expression. Middle-aged/older men with normal testosterone exhibited lower brachial artery FMD (5.7 ± 2.2%) compared with young men (7.3 ± 1.3%, P = 0.020), which was exaggerated in middle-aged/older men with low testosterone (4.0 ± 1.8%, P = 0.010 vs. middle-aged/older men with normal testosterone). Plasma ET-1 was not different between young (5.6 ± 0.9 ng/dL) and middle-aged/older men with normal testosterone (6.0 ± 1.4 ng/dL, P = 0.681) but was higher in middle-aged/older men with low testosterone (7.7 ± 2.8 ng/dL) compared with both groups (P < 0.001 vs. young men; P = 0.013 vs. middle-aged/older men with normal testosterone). There was no difference in venous (P = 0.616) or arterial (P = 0.222) endothelial cell ET-1 expression between groups. There was a significant inverse association between plasma ET-1 and FMD (r =-0.371, P = 0.004). These data suggest that the accelerated age-associated reduction in endothelial dysfunction in middle-aged/older men with low testosterone is related to higher circulating ET-1.NEW & NOTEWORTHY Middle-aged/older men with low testosterone have reduced vascular endothelial function compared with young and age-matched men with normal testosterone. In this manuscript, we demonstrate that men with low testosterone have higher plasma endothelin-1, which is associated with worse brachial artery flow-mediated dilation. The source of higher plasma endothelin-1 remains unknown; however, higher circulating endothelin-1 appears to be a mechanism contributing to reduced vascular endothelial function in men with low testosterone.

We aimed to depict the age-specific distribution of total Testosterone (tT) levels among young men presenting to a single academic centre with uro-andrological complaints. Overall, tT levels from 2593 men aged 20-44 years were analyzed. Men were grouped into 'infertile men' and 'men with sexual dysfunction (SD)' according to their primary complaints. Data was also collected from 71 same-ethnicity age-comparable fertile controls. Linear regression fitted the relationship between tT and increasing age. Distribution of tT was determined for each 5-year age-group, both for the overall population and the subgroups. tT quantiles were reported for each sample sub-group and age-group. Of 2664 men, 1913 (71.81%) were classified as infertile, 680 (25.52%) with SD and 71 as fertile men (2.67%), respectively. tT levels depicted a reduction of 0.14 nmol/L per year between 20 and 44 years of age (p < 0.001) within the overall study population. Significant reduction was also observed for the population stratified by urological complaints (all p < 0.05). This is the first study to describe tT levels as a function of baseline clinical status in a large same-ethnicity cohort of young men, uniformly assessed using a standardized laboratory method.

Genetic variation in SHBG structure may affect estimates of sex steroid exposure by altering the affinity of the protein for its ligand. Consequently, free hormone calculations assuming constant binding affinity may, for certain genetic variations, lead to incorrect diagnoses if genetic variation is not taken into consideration.

To investigate the effects of genetic variation in SHBG on calculated and measured serum free testosterone (T) in men.

Population-based sibling-pair study in 999 healthy men aged 25 to 45 (mean, 34.5) years.

Genotyping using microarray (Illumina) for single-nucleotide polymorphism (SNPs) suggested to affect binding affinity and/or concentration of SHBG or T. SHBG concentrations were measured using immunoassay and in a subset (n = 32) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total T was measured using LC-MS/MS. Free T was calculated and in a subset (n = 314) measured directly using LC-MS/MS after equilibrium dialysis.

Allelic frequencies of analyzed SNPs ranged from 0.5% to 58.2%. Compared to wild-type, SHBG concentrations were lower in rs6258 heterozygotes (-24.7%; P < .05) and higher in rs6259 heterozygotes, rs727428 homozygotes, and carriers of rs1799941 (+10.8 to 23.1%; all P < .05). Total T was higher in rs727428 homozygotes and carriers of rs5934505, rs1799941and rs6259 (+3.9 to 21.4%; all P < .05). No clear effects on measured free T were found, except for a trend toward higher values in rs6259 homozygotes, significant for calculated free T (+18.7%; P < .05) in the larger global study population.

In these men, analyzed SNPs were relatively prevalent and affected serum concentrations of total T and SHBG but not calculated or measured free T except for a higher trend in rs6259 homozygotes.

Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear.

To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism.

Secondary analysis of a randomized, double-blind, placebo-controlled trial.

Veterans Affairs Medical Center.

Eighty-three older (age ≥ 65 years) men with obesity (body mass index ≥ 30 kg/m2) and persistently low Am testosterone (< 10.4 nmol/L) associated with frailty.

LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for 6 months.

The primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, and adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure; and metabolic syndrome score.

HbA1c decreased similarly in LT + TRT and LT + Pbo groups (-0.5 ± 0.1 vs -0.6 ± 0.1%, respectively; P = 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in the LT + Pbo group vs 0.2 ± 1.1 mg/dL in the LT + TRT group, P = .01) and adiponectin levels (-408 ± 489 ng/mL in LT + TRT group vs 1832 ± 468 ng/mL in LT + Pbo group, P = .02).

In older men with obesity and hypogonadism, adding TRT for 6 months to LT does not result in further improved cardiometabolic profiles and could potentially blunt some of the metabolic benefits induced by LT.

Chronic obstructive pulmonary disease (COPD) frequently coexists with other comorbidities, including hypogonadism. However, the association between COPD severity and hypogonadism remains controversial. This study aimed to evaluate this association and compare the clinical characteristics of hypogonadal and eugonadal COPD patients.

A cross-sectional study including men with stable COPD was performed. Hypogonadism was diagnosed based on the presence of symptoms, according to the Androgen Deficiency in Aging Males questionnaire, and a total testosterone deficit (<300ng/dL). COPD severity was classified according to the Spanish COPD guideline risk classification. A multivariate logistic regression analysis was performed in order to evaluate the relationship between COPD severity and hypogonadism.

134 subjects were recruited. The prevalence of hypogonadism was higher in severe COPD than in mild COPD, with a prevalence ratio of 1.8 (p=0.007). An increased odds of hypogonadism was observed in severe COPD subjects (OR 2.60, 95% CI 1.23-5.48, p=0.012) independent of age, body mass index, cardiovascular disease, and chronic renal failure. Hypogonadal COPD patients exhibited lower percentage levels of FVC and FEV1 and a higher degree of dyspnea than compared to eugonadal COPD patients.

Patients with severe COPD had a higher prevalence of hypogonadism compared to those with mild COPD. Additionally, severe COPD was identified as an independent risk factor for hypogonadism. These findings suggest that hypogonadism should be evaluated in patients with COPD, particularly in those with severe disease.