Low-dose prednisone is an effective rescue for deteriorating semen parameters following vasovasostomy.

OBJECTIVE: This retrospective study aimed to evaluate the effectiveness of low-dose prednisone as a rescue therapy for patients with deteriorating semen parameters following vasovasostomy. MATERIALS AND METHODS: Electronic medical records were queried at the University of Miami with documented CPT code 55400 (Bilateral Vasovasostomy) between January 2016 and April 2023. Records were then reviewed to identify patients who demonstrated ≥50% decrease in semen parameters, specifically sperm concentration, motility and total motile sperm count. Patients who were treated with 6 weeks of low-dose prednisone were identified, and baseline semen parameters and subsequent changes after prednisone therapy were assessed. A Mann-Whitney U Test was used to compare semen parameter changes before and after prednisone. Adverse effects associated with prednisone were monitored. RESULTS: A total of 8 patients were identified with deteriorating semen parameters who were treated with 6 weeks of low-dose prednisone. Following prednisone therapy, all patients demonstrated improvements in total motile sperm count (TMSC), with a median improvement of 6 million. The median relative improvement in TMSC was 433%. Sperm concentration and motility also improved compared to post-operative baseline. No adverse effects were reported during the treatment period. CONCLUSIONS: Low-dose prednisone therapy appears to be a safe and effective intervention for managing deteriorating semen parameters following VV. The observed improvements in TMSC suggest the potential of prednisone to rescue patients with delayed failure after VV. Further research with larger sample sizes is warranted to confirm the safety and efficacy of low-dose prednisone as a rescue therapy in this specific patient population. Optimizing VV outcomes is crucial in male infertility, and further exploration of steroid therapy and innovative biotechnologies is warranted.

Low-dose prednisone is an effective rescue for deteriorating semen parameters following vasovasostomy

ABSTRACT Objective: This retrospective study aimed to evaluate the effectiveness of low-dose prednisone as a rescue therapy for patients with deteriorating semen parameters following vasovasostomy. Materials and Methods: Electronic medical records were queried at the University of Miami with documented CPT code 55400 (Bilateral Vasovasostomy) between January 2016 and April 2023. Records were then reviewed to identify patients who demonstrated ≥50% decrease in semen parameters, specifically sperm concentration, motility and total motile sperm count. Patients who were treated with 6 weeks of low-dose prednisone were identified, and baseline semen parameters and subsequent changes after prednisone therapy were assessed. A Mann-Whitney U Test was used to compare semen parameter changes before and after prednisone. Adverse effects associated with prednisone were monitored. Results: A total of 8 patients were identified with deteriorating semen parameters who were treated with 6 weeks of low-dose prednisone. Following prednisone therapy, all patients demonstrated improvements in total motile sperm count (TMSC), with a median improvement of 6 million. The median relative improvement in TMSC was 433%. Sperm concentration and motility also improved compared to post-operative baseline. No adverse effects were reported during the treatment period. Conclusions: Low-dose prednisone therapy appears to be a safe and effective intervention for managing deteriorating semen parameters following VV. The observed improvements in TMSC suggest the potential of prednisone to rescue patients with delayed failure after VV. Further research with larger sample sizes is warranted to confirm the safety and efficacy of low-dose prednisone as a rescue therapy in this specific patient population. Optimizing VV outcomes is crucial in male infertility, and further exploration of steroid therapy and innovative biotechnologies is warranted.

Rises in Hematocrit Are Associated With an Increased Risk of Major Adverse Cardiovascular Events in Men Starting Testosterone Therapy: A Retrospective Cohort Claims Database Analysis.

PURPOSE: Elevated hematocrit (Hct) can result in increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). However, the impact of the magnitude of the change in Hct from baseline after starting TTh has never been assessed. MATERIALS AND METHODS: To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within 6 months before starting TTh, and who had follow-up Hct measurements within 3 and 24 months after beginning TTh from 2010 to 2021. Men with and without a subsequent increase in Hct after initiating TTh were propensity matched. MACE was defined as myocardial infarction, stroke, or death. RESULTS: After matching, 10,511 men who experienced an any increase in Hct after initiating TTh and an equal number of controls who did have an increase in Hct were included. Compared to controls who did not have an increase in Hct after starting TTh, the men who had an increase in subsequent Hct had a significantly increased risk of MACE compared to men with no change in Hct. CONCLUSIONS: We demonstrate that increases in Hct from baseline are associated with increased risk of MACE, compared to men whose Hct remains stable while receiving TTh.

Comparison of Hematocrit Change in Testosterone-deficient Men Treated With Intranasal Testosterone Gel vs Intramuscular Testosterone Cypionate: A Randomized Clinical Trial.

PURPOSE: Our primary aim was to compare changes in hematocrit in testosterone-deficient men treated with intranasal testosterone gel vs intramuscular testosterone cypionate. MATERIALS AND METHODS: This 2-arm, open-label, randomized trial recruited men with testosterone deficiency at the University of Miami between August 2020 and October 2022. Men with 2 total testosterone levels <350 ng/dL and hypogonadal symptoms, aged 18-75 years were randomly assigned to receive either intranasal testosterone gel 11 mg 3 times daily or intramuscular testosterone cypionate 200 mg every 2 weeks. The primary outcome was change in hematocrit after 4 months of treatment. Secondary outcomes were changes in serum testosterone, estradiol, prostate-specific antigen, 17-hydroxyprogesterone, and the 6-item International Index of Erectile Function. RESULTS: Of the 81 men randomized, 54 completed treatment (intranasal n=23; intramuscular n=31). The mean age was 47.5 vs 49.5 years, with mean baseline testosterone of 244.6 vs 240.7 ng/dL and mean hematocrit of 44.4% vs 42.7% in intranasal vs intramuscular groups, respectively. Men who received intramuscular injections had a significant increase after 4 months of treatment in mean hematocrit from 42.7% to 46.6% (P < .0001), but there was no significant change in men who received intranasal gel (P = .233). Men in both groups experienced significantly increased serum testosterone levels throughout the study period, though a larger increase was seen in men treated with intramuscular injections (mean change 511 vs 283, P = .025). Men who received injections also experienced an increase in estradiol (mean change 22.9, P < .001), decrease in 17-hydroxyprogesterone (mean change -39.8, P < .0001), and increase in the 6-item International Index of Erectile Function score (mean change 4.8, P = .015); men treated with intranasal gel experienced no such changes. Prostate-specific antigen levels were stable in both groups. CONCLUSIONS: Intranasal testosterone gel does not appear to significantly affect hematocrit levels. Men who wish to avoid polycythemia or changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as intranasal gel.

Prevalence of secondary erythrocytosis in men receiving testosterone therapy A matched-cohort analysis of intranasal gel, injections, and pellets.

INTRODUCTION: Increased hematocrit (HCT) is a common adverse effect in men on testosterone therapy (TTh). We aimed to uncover differences in HCT changes among men receiving different forms of TTh. METHODS: We conducted a single-center, retrospective, matched-cohort study of patients treated for testosterone deficiency (TD) to investigate the effect of three TTh regimens on HCT. We included men who received intranasal testosterone (NT), intramuscular testosterone (TC), or subcutaneous testosterone pellet (TP) regimens between January 2011 and December 2020. We matched treatment cohorts 1:1:1 for age, body mass index (BMI), and history of obstructive sleep apnea (OSA). Those taking TTh for <16 weeks were excluded. Comparison between groups was performed with Mann-Whitney U test, Student's t-test, ANOVA, or Kruskal-Wallis test as appropriate. RESULTS: Seventy-eight matched-cohort individuals with TD received either NT, TC, or TP. The most common TD symptoms prior to initiation of TTh were erectile dysfunction (38%), low libido (22%), and lack of energy (17%). Baseline serum testosterone and HCT were higher in NT recipients (p<0.05). As expected, all men receiving TTh were found to have increased serum testosterone levels at followup (p<0.001). Relative to their respective baselines, men receiving TC experienced the greatest increase in serum testosterone (240.8 ng/dL to 585.5 ng/dL), followed by NT (230.3 ng/dL to 493.5 ng/dL) and TP (210.8 ng/dL to 360.5 ng/dL) (all p<0.001). TC and TP were associated with significant increases in HCT (4.4% and 1.7%) while NT was associated with a decrease in HCT (-0.8%) at 16-week followup. CONCLUSIONS: When controlled for age, BMI, and OSA, men receiving NT experienced decreased HCT compared to TC or TP at 16-week followup. Intranasal testosterone, while able to increase serum testosterone levels to reference range, does not appear to have a significant impact on HCT compared to the longer-acting forms of TTh.

Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial.

Background: Testosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old, and testosterone therapy (TTh) can improve the quality of life in these patients. Aim: To evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively. Methods: This was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75 mg) and E100 (8 pellets of 100 mg). Outcomes: We evaluated adverse events after implantation and followed men at 2, 4, and 6 months for morning laboratory levels (prior to 10 am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen. Results: After randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6 months, with most men (82%) dropping to <300 ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone <300 ng/dL, with similar rates between the groups in the study. Clinical Implications: Men treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD. Strengths and Limitations: Strengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort. Conclusion: E100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD.

A Comparative Analysis of Ergonomic Risk Utilizing the 4K-3D Exoscope Versus Standard Operating Microscope for Male Fertility Microsurgery.

OBJECTIVE: To stratify ergonomic risk in a urologic microsurgeon using the 4K-3D exoscope versus the operating microscope (OM) with wearable technology. METHODS: The surgeon was calibrated with wearable sensor inertial measurement units (IMUs) on the head and upper arms. Each inertial measurement units contained an accelerometer, magnetometer, and gyroscope to measure surgeon joint angle change during microscopic procedures for male fertility. The validated modified rapid upper limb assessment was used to determine the proportion of time spent in ranges of risk. Categories 1-4 were assigned for the head and upper extremities (4= highest ergonomic risk). Chi-squared analysis was used to analyze differences in proportions. RESULTS: A total of 500 and 479 minutes from 4K-3D exoscope and OM guided surgeries were analyzed. The 4K-3D exoscope significantly favored upper arm category 1 positioning compared to the OM (56.2% vs 37.7%; P < .0001). The OM exposed the surgeon to higher category 3 positioning (14.6% vs 1.6%; P <.0001). More time was spent with the neck "extended" using the 4K-3D exoscope (51.8% vs 19.5%; P < .0001) with 67% of neck extension between 0-10° (category 1). Overall, more time was spent with the neck in risk group 1-2 with the OM (P < .0001). CONCLUSION: The 4K-3D exoscope offers favorable ergonomic positioning for the upper extremities which may reduce work stress-related injury. More operative time was spent with the neck in mild extension with 4K-3D exoscope utilization. However, the OM favored longer operative times in low-risk neck ergonomic positions.

Comparing Rates of Polycythemia in Hypogonadal Men Using Nasal Testosterone Gel Versus Intramuscular Testosterone: Update of a Randomized Clinical Trial.

Men with hypogonadism who use intranasal testosterone are less likely to develop polycythemia than men using intramuscular testosterone cypionate.

Fertility preservation in uro-oncology.

PURPOSE OF REVIEW: The purpose of this review is to highlight the demand for fertility preservation among cancer survivors and to draw attention to areas where healthcare workers need to improve. As technology advances, maximizing cryopreservation rates will be paramount to increase the ability individuals to conceive after cancer treatment. RECENT FINDINGS: Guidelines recommending discussion of fertility for those diagnosed with cancer have been shown to increase patient satisfaction and overall quality of life. Our review demonstrated that increasing counseling rates remains an ongoing challenge and should remain an area of improvement for all healthcare professionals working in the oncology field. Formal programs to improve patient and provider education and access to fertility preservation increase uptake of fertility preservation. For men, many options exist to cryopreserve sperm; a slight delay to achieve fertility preservation has not been shown to lead to worse outcomes. Cryopreservation strategies differ based on puberty status and remain an active area of clinical research. SUMMARY: Improving fertility outcomes for cancer survivors is possible with appropriate counseling techniques at the time of cancer diagnosis. Clinicians should challenge current barriers for patient access to fertility preservation surrounding cancer treatments.

Male Sexual Health Implications of the 2022 Global Monkeypox Outbreak.

The 2022 global monkeypox (MPX) outbreak is the largest in history to occur outside of endemic African regions. Disease spread during this outbreak has been primarily through human-to-human transmission, with sexual contact being of particular concern. Clinical presentations have commonly featured genital, perianal, and oral lesions associated with sexual activity among men who have sex with men (MSM), who compose the vast majority of MPX cases. This review discusses the epidemiology, clinical features, and evaluation of MPX with regards to men's sexual health. Comparisons were made between MPX and its relative from the Orthopoxvirus genus, smallpox, in order to make informed inferences on the potential effects of MPX on men's sexual health. This review also discusses the role of men's health specialists and urologists in addressing the current outbreak.

Incidence of fertility preservation procedures in prepubertal individuals with cancer.

BACKGROUND: Fertility Preservation (FP) for children and adolescents with cancer is underutilized. In prepubertal individuals, ovarian and testicular tissue can be frozen; however, this is still considered largely experimental. Our objective was to identify trends of FP in prepubertal individuals. METHODS: We performed a retrospective study of prepubertal children with cancer identified through the Pediatric Health Information System from 2011 to 2020. Children who underwent a testicular or ovarian biopsy were included. Any patients with testicular or ovarian malignancy, or other diagnoses which may have required a gonadal biopsy were excluded. RESULTS: A total of 418 boys under 13 and 333 girls under 12 who underwent a gonadal biopsy were identified. There was a total of 66,929 new cancer diagnoses in girls and 86,001 new cancer diagnoses in boys during this time. The most common cancer diagnosis was hematologic in both boys (50.96%) and girls (36.64%). A concurrent procedure at time of gonadal biopsy was performed in 84% of boys and 62% of girls, with line insertion being the most common. The only predictive variable of receiving a gonadal biopsy was increasing year. Overall, only 0.04% of children had a gonadal biopsy for FP during this time period. CONCLUSIONS: Gonadal biopsy rates have increased in prepubertal children with cancer, presumably for FP. While recent international guidelines support FP in this group, our findings highlight the need to establish protocols and tracking for FP procedures in the US.

Utility of evaluating semen samples from adolescents with Klinefelter Syndrome for cryopreservation: A multi-institution evaluation.

INTRODUCTION: Klinefelter Syndrome (KS) is the most common genetic condition cause of non-obstructive azoospermia (NOA). KS also often results in decreased testicular growth and testosterone production. Because of this, exogenous testosterone therapy is commonly prescribed for KS patients to treat hypogonadism, but this may have additional impacts to future fertility potential. KS adolescent patients may be asked to provide multiple semen samples to identify potential sperm for early cryopreservation. OBJECTIVE: To develop a multi-institutional database to evaluate the prevalence of sperm in the ejaculate of adolescent KS patients. METHODS: A retrospective study was performed of all adolescent KS patients seen at two high-volume tertiary male infertility clinics between 2015 and 2020. Adolescence was defined as individuals aged 12-19 years, as per the World Health Organization. Demographic information data including weight, height, medical comorbidities, and concurrent medications were collected. Serum hormone levels including FSH, LH, and testosterone were collected, as well as any available semen analysis data. RESULTS: A total of 116 patients were identified and included in the database. A total of 100 (86.2%) had hormone data available and 48 (41.3%) had semen analysis data. Of the 48 patients with semen analyses, only 4 (8.3%) patients had rare sperm in the ejaculate while the remaining had azoospermia (91.7%). None of the specimens were suitable for cryopreservation. The average serum total testosterone level of adolescent KS patients was 181 ± 216 ng/dL. FSH levels were 14.3 ± 18.8 IU/L (normal 0.3-10.0 IU/L) and LH levels were 7.8 ± 12.4 IU/L (normal 1.2-7.8 IU/L). A total of 17 patients repeated a semen analysis, and in no instance did this result in sperm where there was none previously. CONCLUSION: The findings from a large multicenter retrospective cohort of adolescent KS patients suggest that a single semen analysis is sufficient for attempted cryopreservation purposes, and that multiple semen analyses is not needed.

Testosterone Therapy is Associated With Depression, Suicidality, and Intentional Self-Harm: Analysis of a National Federated Database.

BACKGROUND: Long-term use of testosterone can be associated with mood destabilizing effects. Most studies investigating psychiatric complications of anabolic steroids have used small samples, but a comprehensive assessment of the risk of developing mental health disorders after testosterone use has not been performed at the population level. AIM: To determine whether testosterone therapy is associated with major depressive disorder or suicide attempts in men. METHODS: We conducted a retrospective cohort study of 70.3 million electronic health records collected from 46 healthcare organizations encompassing flagship hospitals, satellite hospitals, and outpatient clinics since 2008 to determine whether testosterone use is associated with major depressive disorder and suicide attempts in a large population. We included men 18 or older who either used testosterone or did not, defined by reported use, insurance claim, or prescription use of testosterone documented in the electronic health record. We propensity-score matched by age, race, ethnicity, obesity, and alcohol-related disorder. Additionally, a sub-group analysis was performed in testosterone deficient (<300 ng/dL) men comparing those with TD on testosterone therapy to a control group of men with TD who are not using testosterone. OUTCOMES: We determined measures of association with a new diagnosis of major depressive disorder and suicide attempt or intentional self-harm following testosterone use within 5 years. RESULTS: A total of 263,579 men who used testosterone and 17,838,316 men who did not were included in the analysis. Testosterone use was independently associated with both Major Depressive Disorder (OR 1.99, 95% CI 1.94-2.04, P < .0001) and Suicide Attempt/Intentional Self-Harm (OR 1.52, 95% CI 1.40-1.65, P < .0001). Results remained significant in testosterone deficient sub-group analysis. CLINICAL IMPLICATIONS: Men who use testosterone should be screened for and counseled about risks of depression and suicidality. STRENGTHS AND LIMITATIONS: Strengths of this study include a large sample size, the ability to account for chronology of diagnoses, the use of propensity score matching to control for potentially confounding variables, and the consistency of results with sub-group analyses. Limitations include the potential for incorrect coding within the electronic health record, a lack of granular information regarding testosterone therapy adherence, the possibility that unrecorded testosterone or anabolic steroid use were prevalent but not captured within the control group, and a lack of data regarding testosterone withdrawal. CONCLUSION: Testosterone use is independently associated with new-onset mental health disorders. Future studies are necessary to elucidate the role that androgen withdrawal plays and whether a causal relationship exists. Nackeeran S, Patel MS, Nallakumar DT, et al. Testosterone Therapy is Associated With Depression, Suicidality, and Intentional Self-Harm: Analysis of a National Federated Database. J Sex Med 2022;19:933-939.

Evaluation of Bacteria in a Novel In Vitro Biofilm Model of Penile Prosthesis.

BACKGROUND: Delayed infection, thought to be due to gradual biofilm formation, remains a feared complication after inflatable penile prosthesis (IPP) insertion. Understanding and preventing biofilm formation is necessary to prevent infections. AIM: To develop an in vitro model and compare growth of biofilm by different bacteria on IPPs and evaluate the anti-infective efficacy of the Coloplast Titan and AMS 700 InhibiZone. METHODS: Sterile IPPs (Coloplast) were cut into rings and incubated with S. epidermidis, S. aureus, P. aeruginosa, A. baumannii, or K. pneumoniae cultures in tryptic soy broth (TSB) (4 hour) to ensure adequate bacteria attachment, and then in only TSB (120 hours) to allow for biofilm formation. Rings were fixed with ethanol and biofilm measured by spectrophotometer (OD570) after crystal violet staining. This methodology was repeated for S. epidermidis and P. aeruginosa with Coloplast rings dipped in 10 ml of a 10 mg/ml Rifampin, 1 mg/ml Gentamicin, and deionized water solution and undipped AMS InhibiZone rings. Crystal violet assay (OD570) was repeated after incubation within bacteria (2 hour), and then only TSB (120 hours). OUTCOMES: The primary outcome of the study was OD570 readings, indirectly measuring biofilm mass on implant rings. RESULTS: S. epidermidis, S. aureus, A. baumannii, P. aeruginosa, and K. pneumoniae all formed significant biofilm. P. aeruginosa showed the strongest predilection to grow biofilm on IPPs. P. aeruginosa also formed significant biofilm on antibiotic-treated Coloplast and AMS rings, while S. epidermidis was inhibited. No significant difference was found in biofilm inhibition between the implants. CLINICAL TRANSLATION: Our findings suggest gram-negative bacteria may form biofilm more proficiently and quickly on IPPs than gram-positive organisms. Commonly used antibiotic treatments on IPPs may be effective against S. epidermidis but not against P. aeruginosa biofilm formation. STRENGTHS & LIMITATIONS: This is the first study comparing biofilm formation by different bacteria organisms on IPPs and the inhibitive ability of Coloplast and AMS implants against biofilm formation. Clinical data on organisms responsible for infected IPPs is needed to determine the clinical relevance of our findings. CONCLUSION: Our novel in vitro model of biofilm formation of IPPs evaluated the effect of a gentamicin/rifampin antibiotic dip on Coloplast Titan implants and the anti-infective capacity of the minocycline/rifampin precoated AMS 700 InhibiZone against S. epidermidis and P. aeruginosa. P. aeruginosa was able to grow on both antibiotic-treated implants, with no significant difference, and should continue to be a specific target of investigation to reduce delayed post-operative IPP infections. Narasimman M, Ory J, Bartra SS, et al. Evaluation of Bacteria in a Novel In Vitro Biofilm Model of Penile Prosthesis. J Sex Med 2022;19:1024-1031.

Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy.

PURPOSE: An unsafe hematocrit threshold for men receiving testosterone therapy (TT) has never been tested. This study seeks to determine whether secondary polycythemia among men receiving TT confers an increased risk of major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE). MATERIALS AND METHODS: Using a multi-institutional database of 74 million patients, we identified 2 cohorts of men with low testosterone (total testosterone <350 ng/dl) who received TT and subsequently either developed polycythemia (5,887) or did not (4,2784). Polycythemia was defined as hematocrit ≥52%. As a secondary objective, we identified 2 cohorts of hypogonadal men without polycythemia, who either did (26,880) or did not (27,430) receive TT. Our primary outcome was the incidence of MACE and VTE in the first year after starting TT. We conducted a Kaplan-Meier survival analysis to assess differences in MACE and VTE survival time, and measured associations following propensity score matching. RESULTS: A total of 5,842 men who received TT and developed polycythemia were matched and compared to 5,842 men who did not develop polycythemia. Men with polycythemia had a higher risk of MACE/VTE (number of outcomes: 301, 5.15%) than men who had normal hematocrit (226, 3.87%) while on TT (OR 1.35, 95% CI 1.13-1.61, p <0.001). In hypogonadal men who received testosterone, no increased risk of MACE and VTE was identified as compared to hypogonadal men naïve to TT. CONCLUSIONS: Developing polycythemia while on TT is an independent risk factor for MACE and VTE in the first year of therapy. Future research on the safety of TT should include hematocrit as an independent variable.

Testosterone therapy and secondary erythrocytosis.

Secondary erythrocytosis is one of the most common adverse events associated with testosterone therapy (TT). Upon encountering this, clinicians will often either adjust TT dosing, stop therapy, order a phlebotomy, or recommend a combination of these. Despite this, the evidence for secondary polycythemia causing harm during TT is scarce, and the hematocrit-based cutoffs present in multiple guidelines appear to be arbritrarily chosen. In this review, we present the pathophysiology behind TT and secondary erythrocytosis, the evidence connecting TT, secondary erythrocytosis and major adverse cardiovascular events (MACE), and the data supporting varying interventions upon diagnosis of secondary erythrocytosis.