Effect of testosterone replacement therapy on lower urinary tract symptoms: A systematic review and network meta-analysis.

OBJECTIVE: In this study, we aimed to perform a network meta-analysis (NMA) to investigate the effects of different testosterone replacement therapy (TRT) administration routes on lower urinary tract symptoms (LUTS) in aging men with late-onset hypogonadism (LOH). METHODS: A systematic search of PubMed, Embase, The Cochrane Library, CNKI, WanFang Data, and VIP was conducted to identify randomized controlled trials (RCTs) reporting data on International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) level, or prostate volume. NMA was performed, and subgroup analysis was conducted to assess the impact of TRT duration on outcomes. RESULTS: A total of 21 RCTs involving 2453 participants were included. For pairwise meta-analysis, p values for TRT delivered by transdermal, intramuscular, and oral routes were as follows: IPSS: 0.93, 0.20, and 0.76; PSA level: 0.20, 0.27, and 0.98; prostate volume: 0.18, 0.04, and 0.16. There were no significant differences in IPSS, PSA level, or prostate volume between TRT routes. In subgroup analysis, long-term intramuscular TRT significantly decreased IPSS (p = 0.03), short-term transdermal TRT increased PSA levels (p < 0.001), and short-term intramuscular TRT increased the prostate volume (p = 0.04). Other forms of TRT showed no significant change in IPSS, PSA level, and prostate volume compared with the placebo. Indirect comparison of the three administration routes demonstrated no significant differences in IPSS, PSA level, and prostate volume. Nevertheless, surface under the cumulative ranking curve analysis indicated that intramuscular TRT had an 83% probability of being the best method for decreasing IPSS. CONCLUSIONS: The results demonstrate that TRT does not worsen LUTS regardless of the administration route. Intramuscular TRT may be the preferred treatment for aging men with LOH and LUTS. Intramuscular TRT may be the preferred treatment for men with LOH and LUTS. Further research is warranted to validate these findings and optimize TRT management strategies.

Testosterone therapy for functional hypogonadism in middle-aged and elderly males: current evidence and future perspectives.

Population aging is a global phenomenon driving research focus toward preventing and managing age-related disorders. Functional hypogonadism (FH) has been defined as the combination of low testosterone levels, typically serum total testosterone below 300-350 ng/dL, together with manifestations of hypogonadism, in the absence of an intrinsic pathology of the hypothalamic-pituitary-testicular (HPT) axis. It is usually seen in middle-aged or elderly males as a product of aging and multimorbidity. This age-related decline in testosterone levels has been associated with numerous adverse outcomes. Testosterone therapy (TTh) is the mainstay of treatment for organic hypogonadism with an identifiable intrinsic pathology of the HPT axis. Current guidelines generally make weak recommendations for TTh in patients with FH, mostly in the presence of sexual dysfunction. Concerns about long-term safety have historically limited TTh use in middle-aged and elderly males with FH. However, recent randomized controlled trials and meta-analyses have demonstrated safe long-term outcomes regarding prostatic and cardiovascular health, together with decreases in all-cause mortality and improvements in various domains, including sexual function, body composition, physical strength, bone density, and hematopoiesis. Furthermore, there are numerous insightful studies suggesting additional benefits of TTh, for instance in cardio-renal-metabolic conditions. Specifically, future trials should investigate the role of TTh in improving symptoms and prognosis in various clinical contexts, including sarcopenia, frailty, dyslipidemia, arterial hypertension, diabetes mellitus, fracture risk, heart failure, stable angina, chronic kidney disease, mood disorders, and cognitive dysfunction.

MicroRNA-361-5p Alleviates Leydig Cell Apoptosis and Promotes Cell Growth by Targeting PIAS1 in Late-Onset Hypogonadism.

Late-onset hypogonadism (LOH) is an age-related syndrome characterized by deficiency of serum testosterone produced by Leydig cells. Previous evidence suggested that microRNA (miR)-361-3p can serve as a promising biomarker for LOH. Nonetheless, its detailed function and molecular mechanism in LOH remain unclarified. The 24-month-old male mice were selected as an animal LOH model, and mouse Leydig cell line TM3 was stimulated with H2O2. ELISA was employed for testosterone level evaluation. Hematoxylin-eosin staining was implemented for histologic analysis of mouse testicular tissues. Western blotting and RT-qPCR were utilized for evaluating molecular protein and RNA expression, respectively. Functional experiments were conducted to test miR-361-5p roles. Luciferase reporter assay was for verifying the interaction between miR-361-5p and protein inhibitor of activated STAT 1 (PIAS1). miR-361-5p displayed a decreased level in the testes of LOH mice. Overexpressing miR-361-5p attenuated Leydig cell loss in the testis and elevated serum and intratesticular testosterone levels in LOH mice. H2O2 stimulation impaired TM3 cell viability, proliferation and intracellular testosterone production and enhanced cell apoptosis. miR-361-5p targeted PIAS1 in TM3 cell. PIAS1 upregulation counteracted miR-361-5p overexpression-mediated alleviation of cell apoptosis and elevation of testosterone synthesis in H2O2-stimualetd TM3 cells. miR-361-5p ameliorates LOH progression by increasing testosterone production and alleviate Leydig cell apoptosis via downregulation of PIAS1.

Pharmacological management of testosterone deficiency in men current advances and future directions.

INTRODUCTION: Testosterone deficiency (TD) is relatively common in aging men, affecting around 2% of the general population. Testosterone replacement therapy (TRT) represents the most common medical approach for subjects who are not interested in fathering. AREAS COVERED: This review summarizes advances in TRT, including approved or non-approved pharmacological options to overcome TD. When possible, a meta-analytic approach was applied to minimize subjective and biased interpretations of the available data. EXPERT OPINION: During the last decade, several new TRT formulations have been introduced on the market, including oral, transdermal, and parenteral formulations. Possible advantages and limitations have been discussed appropriately. Anti-estrogens, including selective estrogen modulators or aromatase inhibitors still represent further possible off-label options. However, long-term side effects on sexual function and bone parameters constitute major limitations. Glucagon-like peptide 1 analogues can be an alternative option in particular for massive obesity-associated TD. Weight loss obtained through lifestyle modifications including diet and physical exercise should be encouraged in all overweight and obese patients. A combination of TRT and lifestyle changes can be considered in those subjects in whom a reversal of the condition cannot be expected in a reasonable time frame.

Association of salivary testosterone levels during the post-awakening period with age and symptoms suggestive of late-onset hypogonadism in men.

BACKGROUND: The lack of association between serum testosterone levels and symptoms suggestive of hypogonadism is a significant barrier in the determination of late-onset hypogonadism (LOH) in men. This study explored whether testosterone levels increase after morning awakening, likewise the cortisol awakening response (CAR) in the hypothalamic-pituitary-adrenal (HPA) axis, and whether testosterone levels during the post-awakening period are associated with age and symptoms suggestive of late-onset hypogonadism (LOH) in men. METHODS: Testosterone and cortisol levels were determined in saliva samples collected immediately upon awakening and 30 and 60 min after awakening, and scores of the Aging Males' Symptoms (AMS) questionnaire were obtained from 225 healthy adult men. RESULTS: A typical CAR (an increase in cortisol level ≥ 2.5 nmol/L above individual baseline) was observed in 155 participants (the subgroup exhibiting typical CAR). In the subgroup exhibiting CAR, testosterone levels sharply increased during the post-awakening period, showing a significant negative correlation with age, total AMS score, and the scores of 11 items on the somatic, psychological, and sexual AMS subscales. Of these items, three sexual items (AMS items #15-17) were correlated with age. Meanwhile, there was no notable increase in testosterone levels and no significant correlation of testosterone levels with age and AMS score in the subgroup exhibiting no typical CAR (n = 70). CONCLUSIONS: The results indicate that the hypothalamus-pituitary-gonad (HPG) axis responds to morning awakening, and determining testosterone levels during the post-awakening period in men with typical CAR may be useful for assessing HPG axis function and LOH.

The present study found that the HPG axis in healthy adult men responds to the morning awakening, characterized by increased salivary testosterone levels after the awakening period.The levels of salivary testosterone during the first hour after awakening are negatively associated with age and the severity of symptoms suggestive of LOH in adult men with typical CAR.

Testosterone Therapy for Late-Onset Hypogonadism: A Clinical, Biological, and Analytical Approach Using Compounded Testosterone 0.5-20% Topical Gels.

Testosterone is integral to men's sexual and overall health, but there is a gradual decline in the ageing male. The topical administration of testosterone is a valuable option as a supplement (replacement) therapy to alleviate hypogonadal symptoms. The clinical efficacy of a compounded testosterone 5% topical gel was assessed retrospectively in a male patient in his seventies by evaluating the laboratory testing of the serum total testosterone and the results of a validated androgen deficiency questionnaire. After treatment, the patient's hypogonadal symptoms improved and the serum total testosterone level achieved was considered clinically optimal. The skin permeation of the testosterone topical gel (biological testing) was evaluated in vitro using the Franz finite dose model and human cadaver skin, and it is shown that testosterone can penetrate into and through ex vivo human skin. Testosterone therapy is often prescribed for extended periods, and consequently, it is crucial to determine the beyond-use date of the compounded formulations. The analytical testing involved a valid, stability-indicating assay method for compounded testosterone 0.5% and 20% topical gels. This multidisciplinary study shows evidence supporting topically applied testosterone's clinical efficacy and the compounded formulations' extended stability. Personalized, topical testosterone therapy is a promising alternative in current therapeutics for hypogonadal patients.

Gonadal efficacy of Thymus quinquecostatus Celakovski: Regulation of testosterone levels in aging mouse models.

Late-onset hypogonadism (LOH) is an age-related disease in men characterized by decreased testosterone levels with symptoms such as decreased libido, erectile dysfunction, and depression. Thymus quinquecostatus Celakovski (TQC) is a plant used as a volatile oil in traditional medicine, and its bioactive compounds have anti-inflammatory potential. Based on this knowledge, the present study aimed to investigate the effects of TQC extract (TE) on LOH in TM3 Leydig cells and in an in vivo aging mouse model. The aqueous extract of T. quinquecostatus Celakovski (12.5, 25, and 50 µg/mL concentrations) was used to measure parameters such as cell viability, testosterone level, body weight, and gene expression, via in vivo studies. Interestingly, TE increased testosterone levels in TM3 cells in a dose-dependent manner without affecting cell viability. Furthermore, TE significantly increased the expression of genes involved in the cytochrome P450 family (Cyp11a1, Cyp17a1, Cyp19a1, and Srd5a2), which regulate testosterone biosynthesis. In aging mouse models, TE increased testosterone levels without affecting body weight and testicular tissue weight tissue of an aging animal group. In addition, the high-dose TE-treated group (50 mg/kg) showed significantly increased expression of the cytochrome p450 enzymes, similar to the in vitro results. Furthermore, HPLC-MS analysis confirmed the presence of caffeic acid and rosmarinic acid as bioactive compounds in TE. Thus, the results obtained in the present study confirmed that TQC and its bioactive compounds can be used for LOH treatment to enhance testosterone production.

From couplepause to doublepause: the impact of midlife physical, psychological, and social changes on the sexual life of aging couples.

INTRODUCTION: Midlife men and women are facing frequent sexual problems that affect not only individuals' sexual health but also the sexual health of aging couples. OBJECTIVES: To review the main sexual life challenges faced by midlife couples, to present the concepts of couplepause and doublepause as 2 new paradigms to address the sexual health needs of aging couples, and to discuss key aspects in couple-focused care. METHODS: An online meeting attended by 5 European experts in sexual health was carried out in June 2023 to discuss the topic. The conversation centered on their clinical experience and expert opinion. Additionally, the indexed literature was reviewed to endorse and complement the expert opinions obtained in the aforementioned meeting. RESULTS: Midlife men and women face physical, psychological, and sociocultural changes that affect their sexual activity. These changes may be experienced differently between genders. Both members of a couple may experience age-related changes concurrently or in an unsynchronized manner affecting their sexual health. Communication, sharing expectations, defining sexual dynamics, and couple goals are determinant for the sexual health of a midlife couple. Couplepause and doublepause are 2 new complementary paradigms that effectively address the sexual health needs of aging couples as a unit, considering physical, psychological, cultural, social, and dyadic-related factors. Couple-centered strategies should promote open communication about couple intimacy issues, understanding the diverse expectations according to gender and orientation, communication styles, and goals. The following are identified as crucial aspects to promote couple-focused care: education and training of health care professionals, the provision of information to aging couples, physician involvement in addressing sexual problems, the need for collaboration across medical specialties, and the development of effective tools and strategies. CONCLUSIONS: The sexual problems of aging couples should be managed following couple-centered strategies that effectively address their sexual health needs as a couple.

Long noncoding RNA XIST inhibition promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-145a-5p that targets SIRT1 in late-onset hypogonadism.

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300 µM H2O2 for 8 h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.

An updated systematic review and meta-analysis of the effects of testosterone replacement therapy on erectile function and prostate.

Introduction: Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT remain controversial. An updated systematic review and meta-analysis aimed to determine the effectiveness and security of TRT treating for LOH. Methods: Randomized controlled trials (RCTs) of TRT for LOH were searched in the databases of Pubmed, Embase, Clinicaltrials.gov and Cochrane from 1990 to 2023 and an updated meta-analysis was conducted. Results: The results of 28 RCTs involving 3461 patients were included and scrutinized in this analysis. Among these, 11 RCTs were of long-term duration (≥12 months), while 18 RCTs were short-term studies (<12 months) comparing TRT with a placebo. TRT modalities comprised injection, oral administration, and transdermal administration. International Index of Erectile Function (IIEF) (Weighted Mean difference (WMD) 3.26; 95%; 95% confidence interval (CI) 1.65-4.88; P<0.0001) was obviously improved in the TRT group. International Prostate Symptom Score (IPSS) (WMD 0.00; 95% CI -0.45-0.45; P=1.0), Prostate Volume (PV) (WMD 0.38; 95% CI -0.64-1.41; P=0.46), Maximum Flow Rate (Qmax) (WMD 1.86; 95% CI -0.98-4.69; P=0.20), Postvoid Residual Urine Volume (PVR) (WMD 3.20; 95% CI -5.87-12.28; P=0.49) and Prostate-Specific Antigen (PSA) (WMD 0.08; 95% CI -0.00-0.17; P=0.06) were not significantly statistical between two groups. Conclusion: This meta-analysis reveals that TRT could improve the IIEF score of hypogonadal men without detriment to the IPSS score, PV, Qmax, PVR and PSA regardless of the administration method or duration of treatment.The meta-analysis was registered at PROSPERO (CRD42023413434).

A narrative review on inflammaging and late-onset hypogonadism.

The increasing life expectancy observed in recent years has resulted in a higher prevalence of late-onset hypogonadism (LOH) in older men. LOH is characterized by the decline in testosterone levels and can have significant impacts on physical and mental health. While the underlying causes of LOH are not fully understood, there is a growing interest in exploring the role of inflammaging in its development. Inflammaging is a concept that describes the chronic, low-grade, systemic inflammation that occurs as a result of aging. This inflammatory state has been implicated in the development of various age-related diseases. Several cellular and molecular mechanisms have been identified as contributors to inflammaging, including immune senescence, cellular senescence, autophagy defects, and mitochondrial dysfunction. Despite the extensive research on inflammaging, its relationship with LOH has not yet been thoroughly reviewed in the literature. To address this gap, we aim to review the latest findings related to inflammaging and its impact on the development of LOH. Additionally, we will explore interventions that target inflammaging as potential treatments for LOH.

α-Tocotrienol in rice bran enhances steroidogenesis in mouse Leydig cell via increased gene expression of steroidogenic acute regulatory protein and induction of its mitochondrial translocation.

Rice is a staple food in the Asian region and one of the world's major energy sources. Testosterone is a steroid hormone that maintains physical, sexual, and cognitive ability, and its decline causes health problems like late-onset hypogonadism. Evaluation of various grain extracts showed rice bran to stimulate testosterone secretion from Leydig model cells. α-Tocotrienol was found as a bioactive compound in rice bran, and mechanistic analysis showed the stimulation of steroid hormone synthesis through enhanced gene expression of steroidogenic acute regulatory protein as well as inducing mitochondrial localization of the protein. Preliminary study showed an increasing trend in serum testosterone levels in mice by oral intake of α-tocotrienol. These results suggest that α-tocotrienol intake may be effective in preventing symptoms caused by low testosterone levels.

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.

[Xiongcan Yishen Formula up-regulates the clock gene expressions in the testis tissue of the rats with late-onset hypogonadism].

OBJECTIVE: To investigate the effect of Xiongcan Yishen Formula (XYF) on the expressions of the clock genes in the testis tissue of the rats with late-onset hypogonadism (LOH). METHODS: Forty-eight 8-week-old male SD rats were randomly divided into 6 groups, normal control, model control, testosterone propionate (TP), and low-, medium- and high-dose XYF. The LOH model was made in the later 5 groups of rats by intraperitoneal injection of D-galactose at 480 mg/kg/d for 56 successive days, while the normal controls were injected with the same volume of normal saline. After modeling, the rats in the low-, medium- and high-dose XYF groups were treated intragastrically with XYF at 10.4, 20.8 and 41.6 g/kg/d, bid, respectively, those in the normal and model control groups with the same volume of distilled water, and those in the TP group intramuscularly with TP at 5.21 mg/kg/d, qd alt, all for 28 days. After treatment, the supernatant was obtained for measurement of the serum T level by ELISA, and the testis tissue collected for determination of the mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the LOH model control group showed significantly decreased serum T and mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 (P < 0.05). In comparison with the findings in the model controls, the T level was remarkably increased in the TP and XYF groups (P < 0.05), the expressions of StAR mRNA and CYP11A1 mRNA and protein markedly up-regulated in the high-dose XYF group (P < 0.05), and so was the expression of the StAR protein in the XYF and TP groups (P < 0.05), those of BMAL1 and NR1D1 proteins and PER2 mRNA and protein in the high-dose XYF group (P < 0.05), those of BMAL1 mRNA and CRY1 protein in the medium- and high-dose XYF groups (P < 0.05), that of NR1D1 mRNA in the XYF and TP groups (P < 0.05), and that of CRY1 mRNA in the medium- and high-dose XYF and TP groups (P < 0.05). CONCLUSION: Xiongcan Yishen Formula could up-regulate the expressions of the clock genes in the testis tissue of the LOH rats and increase the serum T level as well, which may underlie the mechanisms of Xiongcan Yishen Formula acting on LOH.

New perspectives in functional hypogonadotropic hypogonadism: beyond late onset hypogonadism.

Functional hypogonadotropic hypogonadism (FHH) is an increasingly frequent condition, whose pathological mechanisms are not yet fully clarified. The concept of FHH has now completely replaced that of late onset hypogonadism, that only concerned the ageing man. FHH is the result of an impairment of the hypothalamic-pituitary gonadal axis (HPG-A) function, resulting in decreased testosterone concentrations associated with low or inappropriately normal gonadotropin levels and infertility; it can be diagnosed once organic causes of hypogonadism are excluded. The growing occurrence of FHH derives from its association with widespread conditions, such as obesity and diabetes mellitus, but also to the increasing ease and frequency of use of several drugs, such as opioids, glucocorticoids, and sex steroids. Moreover, given the tendency of many subjects to excessive physical activity and drastic reduction in caloric intake, FHH may also be secondary to low energy availability. Finally, the association with HIV infection should not be overlooked. Therefore, there is an important variability in the diseases that can lead to FHH. Despite the heterogeneity of the underlying pathologies, the mechanisms leading to FHH would seem quite similar, with the initial event represented by the impairment at the HPG-A level. Nevertheless, many different biological pathways are involved in the pathogenesis of FHH, therefore the aim of the current paper is to provide an overview of the main relevant mechanisms, through a detailed analysis of the literature, focusing specifically on pathogenesis and clinical, diagnostic and therapeutic aspects.

Efficacy of testosterone replacement treatment for patients with symptoms of late-onset hypogonadism based on real-world patient satisfaction.

Late-onset hypogonadism is generally treated with testosterone replacement treatment. However, the efficacy rate of treatment for patients with low testosterone is not clear because patients without low testosterone are also treated in real-world clinical settings. This study comprised 110 men with low testosterone concentration of <3.0 ng/mL who underwent testosterone replacement treatment. Physical factors, laboratory and endocrinologic profiles, and scores of several questionnaires were assessed. Testosterone replacement treatment was performed with intramuscular injection of 250 mg of testosterone esters every 2-4 weeks, and efficacy was judged by patient satisfaction. After confirming efficacy, changes in several factors by the treatment were evaluated. Finally, the comparison between evaluation by patient satisfaction and by that with the questionnaires was assessed. Among the 110 patients, 77 (70.0%) were satisfied with the treatment, which was effective in 65.7%, 71.4%, and 73.1% of patients with mental, physical, and sexual dysfunction, respectively. The questionnaire scores including the Aging Males Symptoms rating scale were significantly improved in both the satisfaction and non-satisfaction group. However, no significant differences in the amount of change in questionnaire scores were found for all questionnaire scores improved by testosterone replacement treatment between the groups. Patient satisfaction was not associated with improvement of the Aging Males Symptoms score. Although testosterone replacement treatment was effective for 70.0% of the hypogonadal patients, patient satisfaction did not correlate with improvement of questionnaire scores. We concluded that not only questionnaire results but also patient satisfaction is important when evaluating efficacy in patients undergoing testosterone replacement treatment.

The impact of testosterone in men's health.

Testosterone plays a key role in the maintenance of physical and mental functions in men. Age-related testosterone decline is closely associated with sarcopenia and muscle deterioration, while testosterone decline is linked with the etiology and prevention of diseases such as angina pectoris, arteriosclerosis, obesity, metabolic syndrome, and dementia. Late-onset hypogonadism (LOH) is defined as a disease characterized by age-related testosterone decline and associated clinical symptoms. Testosterone replacement therapy improves health-related QOL in patients with LOH.

Male Reproduction and Aging.

Recent publications of well-conducted population studies have informed us that the syndromic prevalence of age-related low testosterone, also known as late-onset hypogonadism, is quite low. Several well-conducted trials in middle-aged and older men with age-related decline in testosterone levels have revealed that efficacy of testosterone therapy is modest with improvement in sexual function, mood, volumetric bone density, and anemia. Although select older men might benefit from testosterone therapy, its effect on prostate cancer risk and major adverse cardiovascular events remains unclear. The results of the ongoing TRAVERSE trial will likely provide important insights into these risks.

Summary of the clinical practice manual for late-onset hypogonadism.

Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.