Distribution and Positive Predictive Value of Follicle Stimulating Hormone Levels 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.

Reproductive Urology Consultation Is an Opportunity to Evaluate for Medical Comorbidity: The Prevalence of Elevated Blood Pressure and Obesity at Fertility Evaluation.

Purpose To evaluate the prevalence of elevated blood pressure (EBP), hypertension (HTN), and obesity among men presenting for fertility evaluation. Methods We retrospectively evaluated all men presenting for male infertility consultation at a single institution from 2000 to 2018. Blood pressure (BP) measurements were abstracted from the electronic health record, and EBP/HTN was defined according to American Heart Association/American College of Cardiology guidelines (systolic blood pressure (SBP) ≥ 120 mmHg or diastolic blood pressure (DBP) ≥ 80 mmHg). Descriptive statistics were used to compare demographic and clinical characteristics of men with and without EBP/HTN or obesity (BMI ≥ 30 kg/m2), and logistic regression was utilized to determine associations with EBP/HTN. Results Among 4,127 men, 1,370 (33.2%) had a recorded SBP and DBP within one year of their initial visit. EBP/HTN was noted in 857 (62.6%) men. A total of 249 (18.2%) men were obese, 863 (63.0%) were non-obese, and 258 (18.8%) did not have BMI recorded. HTN and obesity were jointly present in 195 (17.5%) men. There was no significant difference in age, ethnicity, or total motile sperm count between men with and without EBP/HTN. On multivariable analysis, BMI was significantly associated with EBP/HTN (OR: 1.13, 95% CI: 1.08-1.18, p < 0.001). Conclusion More than half of men presenting for initial fertility consultation have either EBP, obesity, or both. Reproductive urologists should consider routinely screening for these conditions and encourage men to seek further evaluation and treatment, when appropriate.

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.

Prevalence of infertility and barriers to family building among male physicians.

BACKGROUND: Fertility declines with increasing age and physicians often delay childbearing beyond prime reproductive years for the sake of medical training. However, the risks of infertility in male physicians compared to the general population remain poorly studied. OBJECTIVES: To characterize rates of infertility among male physicians and identify barriers in access to fertility care and family building. MATERIALS & METHODS: Between June 2022 and December 2022, male physicians were invited to complete a questionnaire regarding fertility and family building. Surveys were disseminated electronically via social media and professional medical societies using Qualtrics (Provo, UT). RESULTS: Two hundred thirty-five responses were included in the final analysis. The mean age of respondents was 36.3 ± 7.4 years. Of 151 respondents with children or currently attempting to have children, 66 (43.7%) delayed family building due to their medical training or career. The most influential factors affecting timing of children were lack of flexibility in schedule, lack of time, stress, and financial strain. Forty-three (18.3.%) respondents had seen a doctor for fertility evaluation; an additional 12 (5.1%) said they considered doing so but did not, mostly due to being too busy. Sixty (25.5%) had undergone semen testing in the past. Thirty-one (13.2%) reported a diagnosis of fertility issues in either themselves or their partner. Twenty-seven (11.5%) endorsed either them or their partner having undergone assistive reproductive technologies or other procedures for infertility. DISCUSSION: A significant proportion of male physicians delayed building their family or seeking fertility evaluation due to their medical career. Around 23.4% of male physicians have either seen or considered seeing a physician for fertility evaluation, suggesting a high prevalence of infertility in this cohort. CONCLUSION: Our results indicate a need for interventions to support family building and fertility evaluation and treatment among male physicians.

What Is Priapism?

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

Association of the minimal cyclophosphamide equivalent dose and outcome of microdissection testicular sperm extraction in patients with persistent azoospermia after chemotherapy.

Objective: To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors. Design: A retrospective cohort study conducted between 2002 and 2017. Setting: An academic medical center. Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Interventions: Chemotherapy exposure and mCED calculation. Main Outcome Measures: The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration. Results: Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m2 had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m2 (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates-100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively-although the numbers of patients in each group were small. Conclusion: Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m2.

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.

The association between frailty, hypogonadism, and postoperative outcomes among men undergoing radical cystectomy.

INTRODUCTION: Hypogonadism is associated with frailty, lower health-related quality of life, decreased muscle mass, and premature mortality, which may predispose patients to poor postoperative outcomes. We aimed to determine the prevalence of hypogonadism in men undergoing radical cystectomy (RC) and whether hypogonadism and frailty are associated with adverse postoperative outcomes. MATERIALS AND METHODS: The IBM MarketScan database was used to identify men who underwent RC between 2012 and 2021. Frailty was determined using published Hospital Frailty Risk Score ranges. Patients were considered to have hypogonadism if diagnosed within 5 years prior to RC. Length of stay (LOS), complications, emergency department (ED) visits and inpatient readmissions were compared. Sub-group analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 3,727 men who underwent RC, 226 (6.1%) had a diagnosis of hypogonadism. Overall, 565 (15.2%) men were low-risk frailty, 2,214 (59.4%) intermediate-risk frailty, and 948 (25.4%) were high-risk frailty, and men with hypogonadism were significantly more frail compared to men without hypogonadism (P = 0.027). There was no significant difference in LOS, complications, or rate of ED visits and inpatient readmissions between cohorts (P > 0.05). However, high-risk frailty was associated with an increased risk of 90-day ED visit (HR 1.19, 95%CI 1.00-1.41, P = 0.049) and 90-day readmission (HR 1.60, 95%CI 1.29-1.97, P < 0.001) after RC. Among men with hypogonadism, 58 (25.7%) were on TRT. There was no significant difference in frailty, LOS, complications, or 90-day ED visits or 90-day inpatient readmissions between patient with hypogonadism prescribed TRT and those without TRT. CONCLUSIONS: These findings suggest that hypogonadism and preoperative frailty may be important to evaluate prior to undergoing RC.

Prevalence of sexual dysfunction and pursuit of sexual medicine evaluation among male physicians-a survey.

We sought to characterize the prevalence of sexual dysfunction and barriers to treatment among male physicians. Between June and December 2022, male physicians were invited to complete a questionnaire regarding sexual function. Surveys were disseminated electronically via social media and professional medical societies using Qualtrics (Provo, UT). In totla, 235 responses were included in the final analysis. The mean age of respondents was 36.3 ± 7.4 years (range 23-72). 27 (11.5%) reported having seen a doctor for sexual health. Of these 27, 40.7% saw a physician for erectile dysfunction, 29.6% for low libido, 22.2% for premature ejaculation, 7.4% for delayed ejaculation, and 33.3% for other concerns. An additional 29 (12.3%) considered establishing care for sexual issues but didn't, mostly due to being too busy. 46 (19.6%) respondents reported having taken medication to improve erectile function. Therefore, in a cohort of young male physicians, 23.8% had seen or considered seeing a doctor for sexual health concerns, and nearly 1 in 5 had taken medication for erectile dysfunction. Male physicians appear to be at higher risk for sexual dysfunction than the general population and face significant and unique barriers in access to care for sexual dysfunction.

A Prior History of Cryptozoospermia Is Associated with a Significantly Higher Chance of a Successful Microdissection Testicular Sperm Extraction Compared to Non-Obstructive Azoospermia.

BACKGROUND: Our study sought to evaluate the rates of successful sperm retrieval following microdissection testicular sperm extraction (mTESE) in patients with a prior history of cryptozoospermia, compared to patients with non-obstructive azoospermia (NOA). METHODS: A retrospective chart analysis evaluating all mTESE procedures was performed from January 2004 to August 2018. Inclusion criteria involved all males >18 years of age with a diagnosis of cryptozoospermia and/or NOA that underwent a mTESE. The patient's genetic profile, hormonal profile, semen analysis, testicular volumes, pathology and comorbidities were analyzed. RESULTS: We identified 40 patients with cryptozoospermia and 221 patients with NOA. Successful mTESE occurred in 34/40 (85%) cryptozoospermic males compared to 104/221 (48%) NOA males (p < 0.001). In univariate and multivariate analyses, patients with cryptozoospermia were more likely to undergo a successful mTESE than patients with NOA (OR 5.56 [1.79-17.29], p = 0.003; OR 5.41 [1.94-15.08], p = 0.0013), respectively. Factors that were associated with a statistically significant lower chance of successful mTESE included Sertoli-cell only pathology, pre-operative testosterone < 300 ng/dL and FSH > 7.6 mIU/mL. CONCLUSION: Despite patients with a history of cryptozoospermia having a significantly higher chance of a successful sperm retrieval than patients with NOA, couples should be counselled on the possibility of an unsuccessful sperm extraction, in order to optimize the pre-operative IVF planning and to manage operative expectations.

Predictors of Semen Parameters Decline Following the Microsurgical Varicocelectomy.

Objective Varicocele is considered the most common reversible cause of male infertility. However, some men do not clinically improve after surgical repair. We aimed to identify preoperative factors associated with decreased semen parameters and clinical "downgrading" of total motile sperm count (TMSC) following varicocelectomy. Methods We examined men with preoperative laboratory testing and pre- and postoperative semen analyses (SA) who underwent varicocelectomy between 2010 and 2020. Ejaculate volume, sperm motility, sperm concentration, TMSC, and clinical grade of TMSC (in vitro fertilization: <5M sperm, intrauterine insemination: 5-9M sperm, natural pregnancy: >9M sperm) were used to determine postoperative outcomes. Demographic and clinical factors were compared between cohorts. Results Among 101 men who underwent varicocelectomy, 35 (34.7%) had decreased postoperative TMSC with a median follow-up of 6.6 months (interquartile range 3.9-13.6 months). Eleven (10.9%) men experienced TMSC clinical "downgrading" following surgery. Clinical grade III varicocele was significantly associated with decreased sperm motility on postoperative SA (OR 4.1, 95% CI 1.7-10.0, p=0.002), and larger left testicle volume (OR 1.4, 95% CI 1.1-1.8, p=0.02) was associated with clinical "downgrading" after varicocelectomy. Conclusion A small but significant proportion of men experienced a "downgrading" of semen parameters after varicocelectomy. Larger left testis size was associated with clinical downgrading, whereas clinical grade III varicoceles were associated with lower post-treatment sperm motility. These data are critical for preoperative patient counseling.

Factors associated with undergoing microdissection testicular sperm extraction among men with non-obstructive azoospermia following evaluation by a reproductive urologist.

Background: Microdissection testicular sperm extraction (mTESE) is the gold standard treatment for men with non-obstructive azoospermia (NOA). However, many men do not elect to pursue this surgical intervention. We aimed to identify factors associated with NOA patients undergoing mTESE after initial evaluation by a reproductive urologist (RU) through a retrospective cohort study. Methods: We retrospectively reviewed NOA patient who underwent evaluation by a RU between 2002-2018. Demographic and clinical data were collected. Our primary outcome was electing to undergo mTESE. Results: 44.4% (75/169) of NOA men underwent mTESE. These patients earned significantly higher median neighborhood income ($133,000 vs. $97,000, P<0.001), spent fewer years trying to conceive before seeking care {1.3 [interquartile range (IQR): 1-3] vs. 2.3 (IQR: 1-5), P=0.012}, and were more likely to be married (79.7% vs. 53.9%, P=0.001). On univariate analysis, married men [odds ratio (OR) 3.37, 95% confidence interval (CI): 1.67-6.79, P=0.001] and men with higher neighborhood income (OR 1.14, 95% CI: 1.06-1.21, P<0.001) were more likely to undergo mTESE, while couples attempting to conceive for a longer period of time prior to initial evaluation were less likely to undergo mTESE (OR 0.79, 95% CI: 0.68-0.92, P=0.003). On multivariable regression analysis, marital status and years attempting to conceive remained significantly associated with NOA patients undergoing mTESE (OR 4.61, 95% CI: 1.16-18.25, P=0.03; OR 0.67, 95% CI: 0.52-0.88, P=0.003, respectively). Conclusions: Higher neighborhood income and marital status were positively associated with patients undergoing mTESE, while couples who attempted to conceive for a longer period of time before seeking infertility care were less likely to undergo mTESE.

Assessing the Prevalence of Low Testosterone and Elevated Follicle Stimulating Hormone Among Men Presenting for Fertility Evaluation Without Oligospermia.

OBJECTIVE: To compare the prevalence of abnormal hormone parameters among men with and without oligospermia to determine the value of universal hormonal screening during initial fertility evaluation. MATERIALS AND METHODS: We retrospectively evaluated men who underwent semen analysis and hormonal evaluation (morning testosterone [T] and follicle-stimulating hormone [FSH]) between January 2002 and May 2021. Sperm concentration was dichotomized at 15 million/mL according to World Health Organization (WHO) criteria. We compared median and interquartile range (IQR) T and FSH levels according to sperm concentration using Kruskal-Wallis test. Differences in prevalence of low testosterone (<300 ng/dL) and abnormal FSH (>7.6mIU/mL) were determined using chi-square test. RESULTS: 1164 men had a morning serum T. There was no difference in median T among men with normal vs abnormal sperm concentration (316 ng/dL, IQR 250-399 vs 316 ng/dL, IQR 253-419; P = .52). FSH was measured in 1261 men. Median FSH was higher among men with sperm concentration <15 million/mL (6.0IU/mL, IQR 3.9-10.7 vs 3.8IU/mL, IQR 2.7-5.7; P < .001). Among men with ≥15 million/mL concentration, 44.1% were found to have low T (P = .874) and 10.8% had an FSH ≥7.6 mIU/mL (P < .001). Among men with ≥15 million/mL sperm concentration who underwent both T and FSH evaluation, 43.6% had at least 1 hormonal abnormality. CONCLUSION: Almost half of men with normal sperm concentration had low T. As low T may have long-term implications for both fertility and overall health, providers should consider universal T screening in men presenting for fertility evaluation.

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.

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.

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.

Compensated Hypospermatogenesis: Elevated Follicle-stimulating Hormone Predicts Decline in Semen Parameters Among Men With Normal Index Semen Analysis.

OBJECTIVE: To determine whether men with elevated follicle-stimulating hormone (FSH) and normal semen analysis (SA) are more likely to experience a decline in semen parameters over time compared to men with normal FSH. METHODS: Men presenting for fertility evaluation between 2002 and 2020 with normal initial SA were dichotomized according to baseline FSH as normal (<7.6 IU/mL) vs elevated (≥7.6 IU/mL). Primary outcomes included the development of abnormal sperm concentration (<15 million/mL) and total motile sperm count <9 million. Secondary outcomes included abnormal sperm motility (<40%), morphology (<4%), and total number of SA abnormalities. RESULTS: The final sample consisted of 858 men; 776 had normal FSH, and 82 had elevated FSH at presentation. Compared to men with normal FSH, men with elevated FSH had lower total motile sperm count (64.1 vs 107.3, P < .001) and higher testosterone levels (339 ng/dL vs 309 ng/dL, P = .03). At each follow-up timepoint, more men with elevated FSH had oligospermia compared to men with normal FSH. Men with elevated FSH were more likely to experience a decline in total motile sperm count below the intrauterine insemination threshold of 9 million and more likely to develop SA abnormalities over time. CONCLUSION: In men presenting for fertility evaluation with normal index SA, elevated FSH was associated with subsequent decline in semen parameters over time. Men with elevated FSH and normal SA, a condition we have termed compensated hypospermatogenesis, represent an at-risk population for whom close follow-up is warranted.