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.

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.

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.

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.

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.

Blunt trauma pelvic fracture-associated genitourinary and concomitant lower gastrointestinal injury: incidence, morbidity, and mortality.

PURPOSE: Limited data exist on the characteristics, risk factors, and management of blunt trauma pelvic fractures causing genitourinary (GU) and lower gastrointestinal (GI) injury. We sought to determine these parameters and elucidate independent risk factors. METHODS: The National Trauma Data Bank for years 2010-2014 was queried for pelvic fractures by ICD-9-CM codes. Exclusion criteria included age ≤ 17 years, penetrating injury, or incomplete records. Patients were divided into three cohorts: pelvic fracture, pelvic fracture with GU injury, and pelvic fracture with GU and GI injury. Between-group comparisons were made using stratified analysis. Multivariable logistic regression was used to determine independent risk factors for concomitant GI injury. RESULTS: In total, 180,931 pelvic fractures were found, 3.3% had GU, and 0.15% had GU and GI injury. Most common mechanism was vehicular collision. Injury severity score, pelvic AIS, and mortality were higher with combined injury (p < 0.001), leading to longer hospital and ICU stays and ventilator days (p < 0.001) with more frequent discharges to acute rehabilitation (p < 0.01). Surgical management of concomitant injuries involved both urinary (62%) and rectal repairs (81%) or diversions (29% and 46%, respectively). Male gender (OR = 2.42), disruption of the pelvic circle (OR = 6.04), pubis fracture (OR = 2.07), innominate fracture (OR = 1.84), and SBP < 90 mmgh (OR = 1.59) were the strongest independent predictors of combined injury (p < 0.01). CONCLUSION: Pelvic fractures with lower GU and GI injury represent < 1% of pelvic fractures. They are associated with more severe injuries and increased hospital resource utilization. Strongest independent predictors are disruption of the pelvic circle, male gender, innominate fracture, and SBP < 90mm Hg.

The effect of tetrahydrocannabinol on testosterone among men in the United States: results from the National Health and Nutrition Examination Survey.

PURPOSE: To determine the association between tetrahydrocannabinol (THC) use and testosterone (T) levels among men in the United States. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data from the years 2011-2016, we identified all men 18 years and older who answered the substance use questionnaire and underwent laboratory testing for T. Regular THC users were defined as those who use THC at least one time per month, every month for at least 1 year. Multivariable linear regressions controlling for confounders were then used to determine the relationship between THC use and T levels. RESULTS: Among the 5146 men who met inclusion, 3027 endorsed using THC at least once in their life (ever-user). Nearly half of the THC ever-users (49.3%) were considered regular THC users. Multivariate analysis controlling for age, comorbidities, tobacco use, alcohol use, body mass index (BMI), exercise level, and race revealed a small but statistically significant increase in T among regular THC users at any measured level of use, compared to non-regular THC users (non-users). This increase was characterized by an inverse U-shaped trend with Regular THC users using two-three times per month demonstrating the greatest increase in T (+ 66.77 ng/dL) over non-users. CONCLUSION: THC use is associated with small increases in testosterone. This increase in T appears to decline as THC use increases, but nevertheless, T is still higher with any amount of regular use when compared to T in non-users. Prospective work is needed to validate the observed increase and to better elucidate the mechanism of impact THC use has on T levels.

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.

Germline Genetics of Prostate Cancer: Time to Incorporate Genetics into Early Detection Tools.

BACKGROUND: Prostate cancer (PCa) remains the most common solid malignancy in men, and its prevalence makes understanding its heritability of paramount importance. To date, the most common factors used to estimate a man's risk of developing PCa are age, race, and family history. Despite recent advances in its utility in multiple malignancies (e.g., breast and colon cancer), genetic testing is still relatively underutilized in PCa. CONTENT: Multiple highly penetrant genes (HPGs) and single-nucleotide polymorphisms (SNPs) have been show to increase a patient's risk of developing PCa. Mutations in the former, like DNA damage repair genes, can confer a 2- to 3-fold increased risk of developing PCa and can increase the risk of aggressive disease. Similarly, PCa-risk SNPs can be used to create risk scores (e.g., genetic or polygenic risk scores) that can be used to further stratify an individual's disease susceptibility. Specifically, these genetic risk scores can provide more specific estimates of a man's lifetime risk ranging up to >6-fold higher risk of PCa. SUMMARY: It is becoming increasingly evident that in addition to the standard family history and race information, it is necessary to obtain genetic testing (including an assessment of HPG mutation status and genetic risk score) to provide a full risk assessment. The additional information derived thereby will improve current practices in PCa screening by risk-stratifying patients before initial prostate-specific antigen testing, determining a patient's frequency of visits, and even help identify potentially at-risk family members.

Differences in inherited risk among relatives of hereditary prostate cancer patients using genetic risk score.

PURPOSE: Family history assigns equivalent risk to all relatives based upon the degree of relationship. Recent genetic studies have identified single nucleotide polymorphisms (SNPs) that can be used to calculate a genetic risk score (GRS) to determine prostate cancer (PCa) risk. We sought to determine whether GRS can stratify PCa risk among individuals in families considered to be at higher risk due their family history of PCa. MATERIALS AND METHODS: Family members with hereditary PCa were recruited and genotyped for 17 SNPs associated with PCa. A GRS was calculated for all subjects. Analyses compared the distribution of GRS values among affected and unaffected family members of varying relationship degrees. RESULTS: Data was available for 789 family members of probands including 552 affected and 237 unaffected relatives. Median GRSs were higher among first-degree relatives compared to second- and third-degree relatives. In addition, GRS values among affected first- and second-degree relatives were significantly higher than unaffected relatives (P = 0.042 and P = 0.016, respectively). Multivariate analysis including GRS and degree of relationship demonstrated that GRS was a significant and independent predictor of PCa (OR 1.52, 95%CI 1.15-2.01). CONCLUSION: GRS is an easy-to-interpret, objective measure that can be used to assess differences in PCa risk among family members of affected men. GRS allows for further differentiation among family members, providing better risk assessment. While prospective validation studies are required, this information can help guide relatives in regards to the time of initiation and frequency of PCa screening.

The Relationship between Sleep Disorders and Lower Urinary Tract Symptoms: Results from the NHANES.

PURPOSE: It is well established that sleep disorders are associated with the nocturia prevalence in men. While previous literature supports that patients with sleep disorders are at increased risk for nocturia, the risk of daytime lower urinary tract symptoms has not been well established. MATERIALS AND METHODS: We examined the NHANES (National Health and Nutrition Examination Survey) database between 2006 and 2008. Men older than 40 years who completed the sleep, prostate and kidney questionnaires were included in study. The presence of lower urinary tract symptoms was defined as 2 or more symptoms, including hesitancy, incomplete emptying and/or nocturia. Multivariable models using logistic regression were constructed to compare groups of men with and without a sleep disorder. RESULTS: Of the 3,071 men who completed all survey questions 270 (8.8%) reported a sleep disorder. Men with a sleep disorder had a significantly higher body mass index (30.8 vs 27.4 kg/m2), a greater likelihood of reporting diabetes (20.3% vs 10.2%) and more comorbidities (72.6% vs 45.2%, all p <0.01) than men without a sleep disorder. Multivariable logistic regressions demonstrated that men with a sleep disorder were more likely to report nocturia (OR 1.23), 2 or more lower urinary tract symptoms (OR 1.12) and daytime lower urinary tract symptoms (OR 1.27, all p <0.01). CONCLUSIONS: Sleep disorders are associated with an increased risk of nocturia and daytime lower urinary tract symptoms independent of body mass index, diabetes and an increased number of comorbidities. Based on the current data clinicians should consider assessing lower urinary tract symptoms in men with a sleep disorder since intervention could improve lower urinary tract symptoms and sleep disorders as well as daytime urinary symptoms.

Germline mutations in DNA repair genes are associated with bladder cancer risk and unfavourable prognosis.

OBJECTIVES: To perform a systematic evaluation of whether germline DNA repair gene mutations in bladder cancer (BCa) are associated with increased risk of BCa and aggressive disease. MATERIALS AND METHODS: Germline DNA from 98 patients with BCa was analysed for 54 DNA repair genes using a customized targeted sequencing panel. Population control data were obtained from the public databases the Exome Aggregation Consortium database and the Genome Aggregation Database. Mutation pathogenicity was annotated based on American College of Medical Genetics criteria, mutation frequencies in the general population and the ClinVar database. Mutation frequencies were compared based on case-control and case-case designs for disease risks, disease aggressiveness and outcomes. RESULTS: The frequency of pathogenic/likely pathogenic germline DNA repair gene mutations was 10.2% among patients with BCa. Within the subset of patients with carcinoma invading the bladder muscle, the frequency was 15.8%, ~2.4-fold higher than in patients with non-muscle invasive BCa (6.67%). The mutation frequency among patients with early-onset disease (at age <45 years) was ~3-fold higher than among those diagnosed after age 45 years (28.57% vs 8.79%). Mutation carriers had a significantly higher frequency of unfavourable clinical outcomes (disease recurrence or progression to metastatic BCa) than non-carriers (50.0% vs 13.64%; P = 0.013). CONCLUSION: Pathogenic and likely pathogenic mutations in DNA repair genes were associated with unfavourable prognosis of BCa.

Diagnosis and Management of Priapism.

This JAMA Clinical Guidelines Synopsis summarizes the 2022 American Urological Association/Sexual Medicine Society of North America guidelines on diagnosis and management of priapism.

The impact of seat belts and airbags on high grade renal injuries and nephrectomy rate in motor vehicle collisions.

PURPOSE: Motor vehicle collisions are the most common cause of blunt genitourinary trauma. We compared renal injuries with no protective device to those with seat belts and/or airbags using NTDB. Our primary end point was a decrease in high grade (grades III-V) renal injuries with a secondary end point of a nephrectomy rate reduction. MATERIALS AND METHODS: The NTDB research data sets for hospital admission years 2010, 2011 and 2012 were queried for motor vehicle collision occupants with renal injury. Subjects were stratified by protective device and airbag deployment. The AIS was converted to AAST renal injury grade and nephrectomy rates were evaluated. Intergroup comparisons were analyzed for renal injury grades, nephrectomy, length of stay and mortality using the chi-square test or 1-way ANOVA. The relative risk reduction of protective devices was determined. RESULTS: A review of 466,028 motor vehicle collisions revealed a total of 3,846 renal injuries. Injured occupants without a protective device had a higher rate of high grade renal injuries (45.1%) than those with seat belts (39.9%, p = 0.008), airbags (42.3%, p = 0.317) and seat belts plus airbags (34.7%, p <0.001). Seat belts (20.0%), airbags (10.5%) and seat belts plus airbags (13.3%, each p <0.001) decreased the nephrectomy rate compared to no protective device (56.2%). The combination of seatbelts and airbags also decreased total hospital length of stay (p <0.001) and intensive care unit days (p = 0.005). The relative risk reductions of high grade renal injuries (23.1%) and nephrectomy (39.9%) were highest for combined protective devices. CONCLUSIONS: Occupants of motor vehicle collisions with protective devices show decreased rates of high grade renal injury and nephrectomy. Reduction appears most pronounced with the combination of seat belts and airbags.

Testicular Cancer Survivorship and Fertility Preservation.

Testicular cancer disproportionally affects men of reproductive age making fertility an important aspect of testicular cancer survivorship. Men with testicular cancer have more semen parameter abnormalities and a higher incidence of infertility compared to the general population. All treatment options for testicular cancer negatively affect fertility with recovery rates varying by treatment. For these reasons, clinicians should offer sperm cryopreservation, ideally before orchiectomy to maximize the possibility of biologic paternity, if desired. Several innovations have positively impacted this space including direct-to-consumer cryopreservation and bench research demonstrating the feasibility of reintroducing testicular cells post-therapy.