Distribution and Positive Predictive Value of Follicle Stimulating Hormone Among Nonazoospermic Men.

PURPOSE: Our goal was to characterize the distribution of follicle stimulating hormone (FSH) in fertile and subfertile nonazoospermic men, and to determine the ability of various FSH thresholds to predict fertility status. MATERIALS AND METHODS: We performed a retrospective cohort study of 1389 nonazoospermic men who presented for fertility evaluation. Men with at least 2 semen analyses and 1 FSH level were included. Men were dichotomized into fertile and subfertile groups based on total motile sperm count. FSH was evaluated within a multivariable model, and positive predictive values (PPVs) for subfertility were used to assess the clinical utility of various FSH thresholds. RESULTS: One thousand fifteen (80%) men were classified as fertile and 274 (20%) as subfertile. Age, presence of varicocele, and testosterone levels were not statistically different between the groups. Median FSH was 4.0 vs 6.0 (P < .001) among fertile vs subfertile men. Multiple FSH thresholds ranging from 2.9 to 9.3 performed similarly in predicting fertility status (PPV 0.49-0.59). Only FSH thresholds above the 95th percentile (12.1) had PPVs greater than 0.7. The highest PPV (0.84) was seen at an FSH of 20.8 (99th percentile). CONCLUSIONS: While there were significant differences in FSH levels among fertile and subfertile nonazoospermic men, multiple FSH cutoffs between 2.2 and 9.3 performed poorly for prediction of fertility status as determined by total motile sperm count. It was not until the 95th percentile FSH value that a clinically useful level of predictability for subfertility was reached, indicating that FSH should not be used as a standalone test of fertility status. Nonetheless, FSH testing remains clinically useful and may be most informative in the setting of extreme values or discordant FSH and semen analysis results.

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

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

Novel reference range values for serum testosterone: a cross-sectional study of 200,000 males.

PURPOSE: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency. METHODS: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels. RESULTS: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40's 12.29 in 50's 12.24 in 60's vs. 10.69 in 40's 10.56 in 50's 10.63 in 60's respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01). CONCLUSIONS: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals' hypogonadal symptoms.

Male pediatric, adolescent, and young adult reproductive survivorship.

As pediatric, adolescent, and young adult cancer survival rates increase, emphasis is placed on reducing late effects, including reproductive complications and potential impact to fertility. Male survivors are at risk of abnormalities in sperm, hormone deficiencies, and sexual dysfunction. This can impact one's progression into puberty and ability to have a biological child and impacts quality of life following treatment. Access to reproductive care is important and requires patient assessment and appropriate referral to reproductive specialists. This review addresses reproductive complications associated with therapy, standard-of-care testing, and therapeutic interventions. The psychologic impact on psychosexual functioning is also addressed.

Touch print smear of testicular tissue with thionine stain for intraoperative diagnosis in azoospermic men.

PURPOSE: To compare the diagnostic value of testicular tissue touch print smear (TPS) conducted on azoospermic patients with results obtained from histopathology and in vitro fertility (IVF) lab findings. METHODS: Microdissection testicular sperm extraction was performed on a group of 148 azoospermic patients and testicular samples obtained intraoperatively. Using TPS, the samples were smeared onto a sterile slide, followed with staining using thionine. The testis tissue bulk samples were also transferred to the IVF lab, and determinations of sperm presence or absence obtained from IVF lab tests were compared with the TPS sample results. Needle testis biopsy was separately performed on a group of 360 azoospermic patients, and results of pathohistology review on the biopsies were further compared with determinations of spermatogenesis stage obtained from TPS for those patients. RESULTS: When compared with IVF lab results, TPS was found to have 100% (126/126) positive predictive value and 95.5% (25/26) negative predictive value for predicting sperm presence or absence, respectively. Furthermore, TPS was further found to have a 93.6% correlation (337 of 360 biopsies) with results of histological diagnoses performed by needle biopsy. Results from histology and TPS for the detection of sperm presence were concordant in 96.1% (346/360) of biopsies. Diagnosis of SCO by TPS shows the highest correlation with histopathology (98.6%), followed by complete spermatogenesis (97.5%), early maturation arrest (78.9%), and late maturation arrest (27.3%). CONCLUSIONS: The results support the continued use of TPS in testicular tissue analysis for more rapid assessment of spermatogenesis and for detection of spermatozoa in azoospermic subjects.

Prediction of microdissection testicular sperm extraction outcomes of azoospermic patients post-chemotherapy using cyclophosphamide equivalent dose.

PURPOSE: We determined the sperm retrieval rate in men with persistent azoospermia post-chemotherapy in relation to cyclophosphamide equivalent dose (CED), a unit for quantifying alkylating agent exposure. METHODS: Medical records were retrospectively reviewed of 1098 patients diagnosed with non-obstructive azoospermia who had undergone microdissection testicular sperm extraction (mTESE) between January 2010 and 2021 at our institution. Twenty-three patients with a prior history of chemotherapy were included in the study. Oncological data, chemotherapy regime, and dosage were reviewed. The pretreatment hormone profile, CED, and mTESE outcomes were analyzed. RESULTS: Testicular spermatozoa were successfully retrieved from 11 patients (47%). The mean patient age was 37.3 years (range, 27-41 years), and mean time interval from chemotherapy to mTESE, 11.8 years (range, 1-45 years). Patients exposed to alkylating agents had significantly lower sperm retrieval rates than those not exposed to alkylating agents (1/9, 11% vs. 10/14, 71%, p = 0.009). No men with CED > 4000 mg/m2 (n = 6) had viable sperm in the testes during mTESE. Moreover, patients diagnosed with testicular non-seminomatous germ cell tumors had a favorable sperm retrieval rate (67%) compared to patients with lymphoma (20%) or leukemia (33%). CONCLUSION: Patients with permanent azoospermia post-chemotherapy have a lower testicular sperm retrieval rate when the chemotherapy regimen included alkylating agents. In cases where patients have undergone more intensive gonadotoxic treatments, such as higher CED, the likelihood of successful sperm retrieval is low. It is advisable to counsel such patients using the CED model prior to considering surgical sperm retrieval.

White paper: Oncofertility in pediatric patients with Wilms tumor.

The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.

Self-Reported Race/Ethnicity Is Not Associated with Abnormal Semen Parameters after Accounting for Body Mass Index and Socioeconomic Status.

PURPOSE: We evaluated whether consideration of body mass index (BMI) and socioeconomic status alters the reported association between race/ethnicity and abnormal semen parameters. MATERIALS AND METHODS: We conducted a retrospective review of all men who underwent semen analysis (SA) for fertility evaluation at an integrated academic health care system from 2002 to 2021. Men were excluded if they had a diagnosis of Klinefelter's syndrome, history of varicocele, prior testicular surgery, prior history of chemotherapy or radiation for cancer, or prior testosterone-modulating medication use. Chi-square and Kruskal-Wallis tests were used to analyze categorical and continuous variables across self-reported racial groups, respectively. Logistic regression was used to evaluate the association between race and abnormal semen parameters according to WHO 2010 criteria, controlling for potential confounders. RESULTS: Among 2,750 men meeting inclusion criteria, 2,037 (74.1%) identified as White Non-Hispanic, 207 (7.5%) as Black Non-Hispanic, 245 (8.9%) as Hispanic and 261 (9.5%) as Asian. Median age was 35 years (IQR 32-40). Black men had an older median age (37 years, IQR 33-42, p=0.002) than other groups at the time of index SA. While Black men had higher odds of abnormal sperm concentration (OR 1.46, 95% CI 1.06-2.02, p=0.02) and abnormal total motile sperm count (OR 1.65, 95% CI 1.21-2.25, p=0.001) compared to other men after adjusting for age alone, the association of race with abnormal semen parameters was rendered insignificant with the progressive inclusion of BMI, insurance status and neighborhood income as covariates. CONCLUSIONS: In men undergoing SA for fertility evaluation, we did not see evidence of an association between race/ethnicity and abnormal semen parameters after controlling for BMI, insurance status and neighborhood income.

The adverse association between stimulant use for attention deficit hyperactivity disorder (ADHD) and semen parameters.

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter's syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (ß: -18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (ß: -0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning.

The predictive factors of successful sperm retrieval for men with Y chromosome AZFc microdeletion.

PURPOSE: To identify key predictors for successful sperm retrieval in men with AZFc microdeletion. METHODS: Totally, 71 infertile men with confirmed AZFc microdeletion were studied. For each patient, the endocrine profile including serum follicle stimulating hormone (FSH), luteinizing hormone, total testosterone, prolactin, and estradiol was recorded, along with intratesticular testosterone levels (ITT), age, and testicular size. The factors were further analyzed to determine the key predictors for successful sperm retrieval. RESULTS: Of the 71 men with AZFc microdeletion, 52 (73.2%) were classified as having non-obstructive azoospermia (NOA), 7 (9.9%) as having cryptozoospermia, and 12 (15.8%) as having severe oligoasthenoteratozoospermia. Of the 52 men with azoospermia, 47 received microdissection testicular sperm retrieval, and sperm retrieval was successful in 35 of those cases (74.5%). A significantly lower serum FSH (p = 0.03) was found in those patients from whom sperm could be successfully retrieved. The area under the receiving operating characteristic curve for FSH was determined to be 0.721. Using an FSH cutoff point of 12.95 mIU/mL, the model for predicting successful sperm retrieval was found to have 51.4% sensitivity, 83.3% specificity, 90.0% positive predictive value, and 37.0% negative predictive value. ITT levels were obtained from 7 NOA patients, the mean ITT and the mean ITT/serum testosterone ratio was 1932.8 ng/ml and 567.2 in 6 men with successful sperm retrieval, whereas, in a patient with fail sperm retrieval, the levels were 2370 ng/ml and 393.0. CONCLUSION: Men exhibiting AZFc microdeletion with discernible spermatogenesis from whom sperm was successfully retrieved by mTESE generally presented with relatively lower FSH levels.

Practice patterns of vasal reconstruction in a large United States cohort.

We aimed to characterise diverse practice patterns for vasal reconstruction and to determine whether surgeon volume is associated with vasoepididymostomy performance at the time of reconstruction. We identified adult men who underwent vasal reconstruction from 2000 to 2020 in Premier Healthcare Database and determined patient, surgeon, cost and hospital characteristics for each procedure. We identified 3,494 men who underwent either vasovasostomy-alone (N = 2,595, 74.3%) or any-vasoepididymostomy (N = 899, 25.7%). The majority of providers (N = 487, 88.1%) performed only-vasovasostomy, 10 (1.8%) providers performed only-vasoepididymostomy and 56 (10.1%) providers performed both. Median total hospital charge of vasoepididymostomy was significantly higher than vasovasostomy ($39,163, interquartile range [IQR]$11,854-53,614 and $17,201, IQR$10,904-29,986, respectively). On multivariable regression, men who underwent procedures at nonacademic centres (OR 2.71, 95% CI 2.12-3.49) with higher volume surgeons (OR 11.60, 95% CI 8.65-16.00) were more likely to undergo vasoepididymostomy. Furthermore, men who underwent vasoepididymostomy were more likely to self-pay (OR 2.35, 95% CI 1.83-3.04, p < .001) and more likely had procedures in the Midwest or West region (OR 2.22, 95% CI 1.66-2.96 and OR 2.11, 95% CI 1.61-2.76, respectively; p < .001). High-volume providers have increased odds of performing vasoepididymostomy at the time of reconstruction but at a significantly higher cost. These data suggest possibly centralising reconstructive procedures among high-volume providers.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

The Association between Popular Diets and Serum Testosterone among Men in the United States.

PURPOSE: We examined the relationship of the serum testosterone level to low fat, Mediterranean and low carbohydrate diets in a large, nationally representative patient sample. MATERIALS AND METHODS: We queried the NHANES (National Health and Nutrition Examination Survey) from 1999 to 2000, 2003 to 2004 and 2011 to 2012. Men 18 to 80 years old who completed the 2-day dietary history and underwent serum testosterone testing were included in analysis. Diets were categorized as low fat, Mediterranean, low carbohydrate or nonrestrictive. Multivariable modeling was used to determine the relationship between diet and serum testosterone. RESULTS: Of the 3,128 men who met study inclusion criteria 457 (14.6%) and 764 (24.4%) met the criteria for a low fat and a Mediterranean diet, respectively. Only 2 men (less than 0.1%) met the criteria for a low carbohydrate diet, which was removed from further analysis. Mean ± SD serum testosterone was 435.5 ± 6.7 ng/dl. Mean testosterone was lower among men with a low fat diet (410.8 ± 8.1 vs 443.5 ± 7.3, p=0.005) and a Mediterranean diet (412.9 ± 9.1 vs 443.5 ± 7.3, p=0.002). Multivariable analysis controlling for age, body mass index, activity level, diabetes, comorbidities and prostate cancer showed that men with a nonrestrictive diet had higher serum testosterone than those adhering to a low fat diet (ß -57.2, 95% CI -105.6 to -8.8, p <0.05). CONCLUSIONS: Men adhering to low fat diets had lower serum testosterone levels even when controlling for comorbidities, age, body mass index and activity levels. As differences in serum testosterone between the diets were modest, the avoidance of fat restrictive diets should be weighed against the potential benefits on an individual basis.

Anti-TNF agents and potential effects on male fertility: are men being counseled?

BACKGROUND: Adult men with autoimmune conditions are commonly prescribed anti-tumor necrosis factor (anti-TNF) agents; however, there is a paucity of quality evidence as to their effect on male fertility (e.g. semen parameters and sperm quality). Our objective was to determine if men with autoimmune conditions are being counseled regarding the unknown reproductive effects of anti-TNF agents prior to initiation of therapy. METHODS: A retrospective analysis of 1010 male patients age 18-45 who were prescribed an anti-TNF agent were assessed for (1) receipt of counseling regarding potential reproductive effects; (2) screening for anatomic or laboratory abnormalities associated with infertility; (3) election for sperm cryopreservation. RESULTS: Only 10.3% of men received counseling, and this was not associated with age (p = 0.77). Those who received counseling were significantly more likely to have a genitourinary exam performed, be assessed for presence of a varicocele, be asked about or endorse low libido or erectile dysfunction, have a testosterone, LH, FSH, or prolactin level checked, and have a semen analysis performed (all, p < 0.0001). Rates of sperm cryopreservation were low, but statistically higher in men who received counseling (5.77% (+) counseling, 1.10% (-) counseling) (p = 0.002). CONCLUSIONS: The limited current literature lacks a consensus regarding the short- and long-term male reproductive effects of anti-TNF therapy. Despite this lack of clarity, rates of pre-initiation counseling were low. Rates of sperm cryopreservation, while improved in the counseled group remained low, suggesting prescribing physicians may be unaware of this option for patients.

Do partial AZFc deletions affect the sperm retrieval rate in non-mosaic Klinefelter patients undergoing microdissection testicular sperm extraction?

BACKGROUND: The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects on spermatogenesis in non-mosaic Klinefelter patients. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed. METHODS: We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery. RESULTS: Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3, one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p = 0.27). CONCLUSION: According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

Effects of nonsteroidal anti-inflammatory drug (NSAID) use upon male gonadal function: A national, population-based study.

Recent data have suggested that short-term NSAID use induces a state of compensated hypogonadism. Our aim was to investigate the association between chronic, regular NSAID use and compensated hypogonadism in a large, nationally representative cohort, the US National Health and Nutrition Examination Survey (NHANES) database. Men 20-80 years who answered the analgesic use questionnaire and underwent hormonal testing were included. Multivariable regression was utilised to determine the relationship between NSAID use and serum testosterone (T), anti-Mullerian hormone (AMH) and T:AMH ratio. Among 3,749 men, 505 (13.5%) reported regular NSAID use and 3,244 (86.5%) did not. Regular users had lower T (440.7 ± 27.0 vs. 557.0 ± 24.9 ng/dl, p = .005) and albumin (43.8 ± 0.2 vs. 45.1 ± 0.1, p < .001) compared to nonregular users. On multivariable analysis, only active smoking was significantly associated with T, AMH and T:AMH ratio (p < .001, p = .036 and p = .005 respectively). Regular NSAID use was not associated with T, AMH or T:AMH ratio (p = .523, p = .974, and p = .872 respectively). In this nationally representative sample of US men, regular and chronic NSAID use was not associated with alterations in T or compensated hypogonadism. These data should reassure patients and clinicians regarding the safety of NSAID use with respect to the risk of alteration in the hypothalamic-pituitary-gonadal axis.

What Is Priapism?

This JAMA Patient Page describes the diagnosis, prevention, and treatment of priapism.

Evaluation and Management of Testosterone Deficiency: AUA Guideline.

PURPOSE: There has been a marked increase in testosterone prescriptions in the past decade resulting in a growing need to give practicing clinicians proper guidance on the evaluation and management of the testosterone deficient patient. MATERIALS AND METHODS: A systematic review utilized research from the Mayo Clinic Evidence Based Practice Center and additional supplementation by the authors. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions (table 1 in supplementary unabridged guideline, http://jurology.com/). RESULTS: This guideline was developed by a multi-disciplinary panel to inform clinicians on the proper assessment of patients with testosterone deficiency and the safe and effective management of men on testosterone therapy. Additional statements were developed to guide the clinician on the appropriate care of patients who are at risk for or have cardiovascular disease or prostate cancer as well as patients who are interested in preserving fertility. CONCLUSIONS: The care of testosterone deficient patients should focus on accurate assessment of total testosterone levels, symptoms, and signs as well as proper on-treatment monitoring to ensure therapeutic testosterone levels are reached and symptoms are ameliorated. Future longitudinal observational studies and clinical trials of significant duration in this space will improve diagnostic techniques and treatment of men with testosterone deficiency as well as provide more data on the adverse events that may be associated with testosterone therapy.