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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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The association between the use of testosterone replacement therapy (TRT) and prostate cancer remains uncertain. Thus, we investigated whether TRT is associated with an increased risk of prostate cancer in men with late-onset hypogonadism. We used the UK Clinical Practice Research Datalink to assemble a cohort of 12,779 men who were newly diagnosed with hypogonadism between January 1, 1995, and August 31, 2016, with follow-up until August 31, 2017. Exposure to TRT was treated as a time-varying variable and lagged by 1 year to account for cancer latency, with nonuse as the reference category. During 58,224 person-years of follow-up, a total of 215 patients were newly diagnosed with prostate cancer, generating an incidence rate of 3.7 per 1,000 person-years. In time-dependent Cox proportional hazards models, use of TRT was not associated with an overall increased risk of prostate cancer (hazard ratio = 0.97; 95% confidence interval: 0.71, 1.32) compared with nonuse. Results remained consistent in secondary and sensitivity analyses, as well as in a propensity score-matched cohort analysis that further assessed the impact of residual confounding. Overall, the use of TRT was not associated with an increased risk of prostate cancer in men with late-onset hypogonadism., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The relationship between endogenous testosterone (T) levels and cardiovascular (CV) risk in men is conflicting., Aim: To verify whether endogenous T levels represent a possible risk factor for CV morbidity and mortality., Methods: We conducted a random effect meta-analysis considering all the available data from prospective observational studies comparing subjects with baseline reduced endogenous T levels to those with higher T levels as derived from an extensive MEDLINE, Embase, and Cochrane search. The identification of relevant studies was performed independently by 2 of the authors (G.R. and G.C.), and conflicts resolved by the third investigator (M.M.)., Main Outcome Measures: CV mortality and morbidity were investigated., Results: After screening, 37 observational studies, published between 1988 and 2017 including 43,041 subjects with a mean age of 63.5 years and mean follow-up of 333 weeks, were considered. Low endogenous T at enrollment predicted overall and CV mortality, as well as CV morbidity, when both unadjusted and fully adjusted models were considered (odds ratio = 1.26 [CI, 1.17; 1.36], 1.54 [CI, 1.25; 1.89], and 1.17 [CI, 1.01; 1.36]; all P < .05 when overall mortality, CV mortality, and CV incidence and fully adjusted models were considered, respectively). The data were confirmed even when nonpopulation-based studies were excluded from the analysis. Metaregression analysis applied to the fully adjusted model showed that the risk of CV mortality was inversely related to mean age at enrollment (S = -0.014 [-0.017;-0.010] and I = 1.073 [0.806;1.339]; both P < .0001) and directly related to the prevalence of diabetes and to the proportion of active smokers., Clinical Implications: Low endogenous T levels in aging men can represent a possible CV risk factor., Strengths & Limitations: The present data demonstrated, for the first time, that low T predicts not only CV mortality but also CV morbidity. Data derived from studies reporting information on CV mortality suggested major publication bias although they were confirmed applying Duval and Tweedie trim and fill method. However, observational studies should be considered with caution due to the lack of complete follow-ups and due to the poor management of missing data., Conclusion: The present meta-analysis shows that low T in aging men is a marker of CV risk. The possible benefits of T treatment in reducing this risk should be examined in longer-term, specifically designed trials. Corona G, Rastrelli G, Di Pasquale G, et al. Endogenous Testosterone Levels and Cardiovascular Risk: Meta-Analysis of Observational Studies. J Sex Med 2018;15:1260-1271., (Copyright © 2018. Published by Elsevier Inc.)

Background: Testosterone action is mediated through the androgen receptor (AR), whose sensitivity is influenced by the AR CAG repeat polymorphism. However, the relation between late-onset hypogonadism (LOH) and AR CAG repeat length is unclear and studies of Asian populations are limited., Aim: To investigate the relation between AR CAG repeat length and LOH in Korean men., Methods: 263 Korean men (mean age = 63.43 ± 10.9 years) were enrolled from 2014 to 2015. LOH diagnosis was based on a serum testosterone level lower than 3.5 ng/mL and positive androgen deficiency according to the Aging Males' Symptom Scale (AMS). Total testosterone levels and answers to the LOH-related questionnaire were analyzed., Outcomes: The relation between AR CAG repeat length and LOH was determined., Results: Mean CAG repeat length was 22.1 ± 4.6 and mean serum testosterone levels were 2.6 ± 0.7 and 6.0 ± 2.0 ng/mL in men with and without LOH, respectively. Men with LOH showed significantly longer AR CAG repeat lengths than men without LOH (26.1 vs 21.6, P < .001). Longer CAG repeat lengths were correlated with higher AMS total scores (r = 0.454, P = .001) and AMS psychotic, somatic, and sexual sub-scores (r = 0.276, 0.246, and 0.571, P = .006, .007, .001, respectively) and significantly lower 5-item International Index of Erectile Function scores (r = -0.261, P = .001). Multivariate analysis showed that patient age and CAG repeat length were independently associated with LOH (odds ratio = 1.05 and 1.29, P = .041 and <.001, respectively)., Clinical Implications: A longer CAG repeat length is associated with LOH symptoms and LOH., Strengths and Limitations: Associations between CAG repeats and LOH were verified in Korean patients. Moreover, a longer CAG repeat length was shown to be an independent risk factor for LOH. Limitations included the small number of LOH patients studied and that other sex hormone-associated factors were not measured., Conclusions: AR CAG repeat length was associated with LOH prevalence and clinical symptoms in this Korean male population. Thus, it is important to measure CAG repeat length for patients with LOH symptoms with normal testosterone levels. Kim JW, Bae YD, Ahn ST, et al. Androgen Receptor CAG Repeat Length as a Risk Factor of Late-Onset Hypogonadism in a Korean Male Population. Sex Med 2018;6:203-209., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between testosterone (T) and cardiovascular (CV) risk in men is conflicting., Aim: To verify whether T therapy (TTh) represents a possible risk factor for CV morbidity and mortality., Methods: We conducted a random effect meta-analysis considering all available data from pharmaco-epidemiological studies as well as randomized placebo-controlled trials (RCTs)., Outcomes: CV mortality and morbidity were investigated., Results: After screening, 15 pharmaco-epidemiological and 93 RCT studies were considered. The analysis of pharmaco-epidemiological studies documented that TTh reduces overall mortality and CV morbidity. Conversely, in RCTs, TTh had no clear effect, either beneficial or detrimental, on the incidence of CV events. However, a protective role of TTh on CV morbidity was observed when studies enrolling obese (body mass index >30 kg/m 2 ) patients were scrutinized (Mantel-Haenszel odds ratio 0.51 [95% CI 0.27-0.96]; P = .04), although this association disappeared when only high-quality RCTs were considered (Mantel-Haenszel odds ratio 0.64 [95% CI 0.22-1.88]; P = .42). Finally, an increased risk of CV diseases was observed in RCTs when T preparations were prescribed at dosages above those normally recommended, or when frail men were considered., Clinical Implications: Pharmaco-epidemiological studies showed that TTh might reduce CV risk, but this effect was not confirmed when RCTs were considered., Strengths & Limitations: Meta-analysis of pharmaco-epidemiological studies indicates that TTh reduces overall mortality and CV morbidity. In addition, even in RCTs, a protective role of TTh on CV morbidity was envisaged when studies enrolling obese (body mass index >30 kg/m 2 ) patients were considered. Pharmaco-epidemiological studies should be considered with caution due to the lack of completeness of follow-up and of the management of missing data. In addition, properly powered placebo-controlled RCTs with a primary CV end point, in men with late-onset hypo-gonadism, are not yet available. Finally, the duration of all studies evaluated in the present meta-analysis is relatively short, reaching a maximum of 3 years., Conclusions: Data from RCTs suggest that treatment with T is not effective in reducing CV risk, however, when TTh is correctly applied, it is not associated with an increase in CV risk and it may have a beneficial effect in some sub-populations. Corona G, Rastrelli G, Di Pasquale G, et al. Testosterone and Cardiovascular Risk: Meta-Analysis of Interventional Studies. J Sex Med 2018;15:820-838., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as 'late-onset hypogonadism (LOH)'. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment. However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy). Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising. Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment. Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment. This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported., Aim: To analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH., Methods: We reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed., Main Outcome Measures: The main outcome measure was dynamic parameter changes during testosterone supplementation., Results: TU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements., Conclusion: Long-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters., (Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Testosterone replacement therapy (TRT) is a common treatment for hypogonadism in aging males. Men with low to low-normal levels of testosterone have documented benefit from hormone replacement. Recent meta-analyses have revealed that increases in hemoglobin (Hb) and hematocrit (Hct) are the variants most commonly encountered. Clinically, this response is described as erythrocytosis or polycythemia secondary to TRT. However, the recent Food and Drug Administration warning regarding the risk for venothromboembolism (VTE) has made the increases in Hb and Hct of more pertinent concern. The risks associated with androgen replacement need further examination., Aim: To review the available literature on erythrocytosis and polycythemia secondary to TRT. To discuss potential etiologies for this response, the role it plays in risk for VTE, and recommendations for considering treatment in at-risk populations., Methods: A literature review was performed through PubMed regarding TRT and erythrocytosis and polycythemia., Main Outcome Measures: To assess the mechanisms of TRT-induced erythrocytosis and polycythemia with regard to basic science, pharmacologic preparation, and route of delivery. To review Hct and risk for thrombotic events. To offer clinical suggestions for therapy in patients at risk for veno-thrombotic events., Results: Men undergoing TRT have a 315% greater risk for developing erythrocytosis (defined as Hct > 0.52) when compared with control. Mechanisms involving iron bioavailability, erythropoietin production, and bone marrow stimulation have been postulated to explain the erythrogenic effect of TRT. The association between TRT-induced erythrocytosis and subsequent risk for VTE remains inconclusive., Conclusions: All TRT formulations cause increases in Hb and Hct, but injectables tend to produce the greatest effect. The evidence regarding the risk for VTE with increased Hct is inconclusive. For patients with risk factors for veno-thrombotic events, formulations that provide the smallest effect on blood parameters hypothetically provide the safest option. Further trials are needed to fully evaluate the hematological side effects associated with TRT. Jones SD Jr, Dukovac T, Sangkum P, Yafi FA, and Hellstrom WJG. Erythrocytosis and polycythemia secondary to testosterone replacement therapy in the aging male. Sex Med Rev 2015;3:101-112., (Copyright © 2015 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The use of testosterone replacement therapy (TRT) in men with prostate cancer is controversial given concerns of androgen-related cancer progression. Although emerging evidence suggests that TRT may be safe in this setting, no study has investigated dose-related effects., Aim: We used time-varying analysis to determine whether increasing TRT exposure is associated with worse outcomes., Methods: Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1991 to 2007. Subjects treated with TRT were stratified by duration of treatment. Weighted propensity score methods were used to adjust for differences between groups. A Cox proportional hazards model was constructed to assess the effect of injectable TRT exposure on outcomes., Main Outcome Measure: Overall mortality (OM), prostate cancer-specific mortality (PCSM), and use of salvage androgen deprivation therapy (ADT)., Results: Men treated with TRT, regardless of duration, did not experience higher OM or PCSM (all hazard ratio [HR] <1.0, all P ≤ 0.002). We found no difference in use of salvage ADT in the ≤ 30-day and 31-60 day groups compared with no-TRT (HR 1.23 and 1.05, P=0.06 and 0.81, respectively), whereas it was lower for men on long-term TRT (HR 0.70, P=0.04)., Conclusions: TRT following prostate cancer diagnosis and treatment does not increase mortality or the use of salvage ADT. Using time-varying analysis, we demonstrate that longer duration of TRT is not associated with adverse mortality or greater need for ADT., (© 2014 International Society for Sexual Medicine.)

Introduction: Androgen receptor (AR) CAG polymorphism has been found to influence sexual function. However, no study has evaluated its potential to condition sexual function recovery after testosterone replacement therapy (TRT) in a large cohort of hypogonadic subjects., Aim: To evaluate the role of this polymorphism in sexual function improvement after TRT in late-onset hypogonadism (LOH)., Methods: Seventy-three men affected by LOH were retrospectively considered. Evaluations were performed before TRT started (time 0) and before the sixth undecanoate testosterone injection., Main Outcome Measures: International Index of Erectile Function (IIEF) questionnaire (erectile function [EF], orgasmic function [OF], sexual desire [SD], intercourse satisfaction [IS], overall satisfaction [OS], and total IIEF-15 score); total and free testosterone and estradiol; AR gene CAG repeat number., Results: TRT induced a significant increase in total and free testosterone and estradiol. All IIEF domains significantly improved after TRT. AR CAG repeats negatively and significantly correlated with all the variations (Δ-) of sexual function domains, except for Δ-OS. Conversely, Δ-total testosterone was found to be positively and significantly correlated with sexual function domain variations, except for Δ-IS and Δ-OS. Δ-estradiol did not correlate significantly with any of the variations of sexual function domains. After inclusion in generalized linear models, the number of AR gene CAG triplets was found to be independently and negatively associated with Δ-EF, Δ-SD, Δ-IS, and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated with Δ-EF, Δ-OF, Δ-SD, and Δ-Total IIEF-15 score. However, after including time 0 total testosterone in the model, AR gene CAG triplets remained independently and negatively associated only with Δ-EF and Δ-Total IIEF-15 score, whereas Δ-total testosterone was independently and positively associated only with Δ-EF., Conclusions: Longer length of AR gene CAG repeat tract seems to lower TRT-induced improvement of sexual function in LOH., (© 2014 International Society for Sexual Medicine.)

Introduction: Late-onset hypogonadism, lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), and prostate cancer commonly coexist in the aging male. Due to a better understanding of the physiology and impact of testosterone on benign and malignant diseases of the prostate, the view toward testosterone replacement therapy (TRT) in these individuals has changed dramatically over time., Aim: This communication evaluates the effects of testosterone on benign prostatic growth and prostate cancer and reviews the evidence for TRT for men with BPE and prostate cancer., Methods: A literature review was performed with regards to TRT in men with prostate cancer as well as the effect of testosterone on the growth of benign prostate tissue and prostate cancer carcinogenesis., Main Outcome Measure: To evaluate the evidence for an effect of testosterone on the growth of benign prostate tissue and the development of prostate cancer and TRT in men with prostate cancer., Results: TRT does not exacerbate LUTS. Current evidence is lacking but suggests that TRT may not increase the risk of subsequent diagnosis of prostate cancer, and is unlikely to impact recurrence or progression for men with treated prostate cancer, but longer follow-up is needed., Conclusions: There is no evidence to suggest that TRT is contraindicated in men with BPE or effectively treated prostate cancer. Tan RBW, Silberstein JL, and Hellstrom WJG. Testosterone and the prostate. Sex Med Rev 2014;2:112-120., (Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Late-onset hypogonadism (LOH) is diagnosed when declining testosterone concentrations in the aging male cause unwanted symptoms such as erectile dysfunction (ED), reduced bone density and muscle strength, and increased visceral obesity. Testosterone deficiency is also associated with insulin resistance and the metabolic syndrome (MetS). Restoring testosterone to physiological concentrations has beneficial effects on many of these symptoms; however, it is not known whether these effects can be sustained in the long term., Aims: To investigate whether treatment with testosterone undecanoate (TU) has a long-term and sustained effect on parameters affected by the MetS in men with LOH and ED, to determine whether long-term testosterone treatment can improve the overall health-related quality of life in these men, and to establish the safety of long-term testosterone treatment., Methods: Two hundred sixty-one patients (mean age 59.5 ± 8.4 years) diagnosed with LOH and ED were treated with long-acting TU in a prospective, observational, and longitudinal registry study. Men received intramuscular injections of 1,000 mg TU at day 1, at week 6, and every 3 months thereafter., Main Outcome Measures: Parameters affected by the MetS, including obesity parameters (body weight, waist circumference, and body mass index [BMI]), total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, HbA1c (glycated hemoglobin), and blood pressure, as well as total testosterone levels and health-related quality of life, were assessed., Results: We found TU significantly improved obesity parameters (body weight, waist circumference, and BMI) and lowered total cholesterol, LDL cholesterol, triglycerides, fasting blood glucose, HbA1c , and blood pressure over the 5-year study. HDL cholesterol was increased. TU treatment resulted in a sustained improvement in erectile function and muscle and joint pain, which contributed to an improvement in long-term health-related quality of life. Furthermore, we found a relationship between health-related quality of life and waist circumference. Finally, we found no evidence that long-term treatment with TU increases the risk of prostate carcinoma., Conclusion: Long-term TU in men with LOH and ED reduces obesity parameters and improves metabolic syndrome and health-related quality of life., (© 2014 International Society for Sexual Medicine.)

Introduction: Late-onset hypogonadism may impair quality of life and contribute to metabolic and cardiovascular comorbidity in aging men. Testosterone replacement therapy is effective in treating hypogonadism. However, for the millions of men with a history of prostate cancer, exogenous testosterone has long been considered contraindicated, even though little data in such men are available. Clarification of this safety issue could allow treatment to be considered for a sizeable segment of the aging male population., Aim: The aim of this study is to examine population-based utilization and impact of testosterone replacement therapy in men with prostate cancer., Methods: Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 1181 (0.79%) men received exogenous testosterone following their cancer diagnosis. We used propensity scoring analysis to examine the effect of testosterone replacement on the use of salvage hormone therapy and overall and prostate cancer-specific mortality., Main Outcome Measures: We assessed overall mortality, cancer-specific mortality, and the use of salvage hormone therapy., Results: Following prostate cancer diagnosis, testosterone replacement was directly related to income and educational status and inversely related to age (all P < 0.001). Men undergoing radical prostatectomy and men with well-differentiated tumors were more likely to receive testosterone (all P < 0.001). On adjusted analysis, testosterone replacement therapy was not associated with overall or cancer-specific mortality or with the use of salvage hormone therapy., Conclusions: In this population-based observational study of testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality. These findings suggest testosterone replacement therapy may be considered in men with a history of prostate cancer, but confirmatory prospective studies are needed., (© 2014 International Society for Sexual Medicine.)

Introduction: There is a growing interest in the treatment of late-onset hypogonadism, another name for the study of testosterone deficiency in an older age group. Initial attempts at testosterone replacement have also brought attention to the possible adverse effects on the patients' cardiovascular risk factors and their prostate health. The "female" hormone estradiol is no longer considered as the feminizing hormone, as it has been identified to have an effect on the sexual and general well-being of adult males. Urologists and endocrinologists alike have started to pay attention to the serum T/E 2 (testosterone : estradiol) ratio that appears to be more important than the respective individual hormonal levels. Therein lies the possible role of aromatase inhibitors (AIs) in restoring the normal balance of serum testosterone and estradiol levels for the adequate treatment of late-onset hypogonadism, while limiting the potential adverse effects. Currently, other established clinical indications of AIs include the treatment of breast cancer in female patients and developmental growth problems in pediatric patients., Aim: This review evaluates the role of AIs as a treatment option for late-onset hypogonadism and the evidence for its other clinical uses in men, including its possible adverse effects., Methods: A literature review was performed with regards to the use of aromatase inhibitors in adult males, the role of estrogens in adult males, as well as adverse effect of AIs on bone health in adult males., Main Outcome Measures: To evaluate the evidence for the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, and male subfertility. To evaluate the evidence for the possible adverse effects on the bone health of adult males with the use of AIs., Results: Currently there is no literature to recommend the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, or male subfertility, although some positive effects have been reported. The adverse effects on bone health seen in females treated with AIs are not seen in males., Conclusions: With the better understanding of the T/E 2 ratio in adult males, the lack of scientific data to show that bone health is adversely affected by AI usage in adult males, the positive effects of AIs on the treatment of conditions like late-onset hypogonadism and male subfertility encourages conducting large-scale, multicenter, randomized controlled trials for the clinical use of AIs in adult males. Tan RBW, Guay AT, and Hellstrom WJG. Clinical use of aromatase inhibitors in adult males. Sex Med Rev 2014;2:79-90., (Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)