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OBJECTIVE: To identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole. DESIGN: Multi-institutional retrospective cohort study. SETTING: Two Tertiary Academic Medical Centers. PATIENTS: A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses. INTERVENTION: Prescription of anastrozole (median 3 mg/wk). MAIN OUTCOME MEASURES: Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response. RESULTS: With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E2, 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E2 level or E2-T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00-1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1-78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77). CONCLUSION: Anastrozole therapy decreases serum E2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E2 level or E2-T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments.
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Infertilidad Masculina , Testosterona , Humanos , Masculino , Anastrozol/uso terapéutico , Hormona Folículo Estimulante , Infertilidad Masculina/diagnóstico , Infertilidad Masculina/tratamiento farmacológico , Hormona Luteinizante , Estudios Retrospectivos , SemenRESUMEN
BACKGROUND: In the original clinical trials evaluating intralesional collagenase Clostridium histolyticum for Peyronie disease (PD), treatment protocols were limited to 8 injections. AIM: We sought to describe our single-center experience with the use of multiple rounds (>8 injections) of intralesional collagenase in patients with PD. METHODS: We conducted a retrospective analysis of all patients with PD receiving intralesional collagenase injections at our institution from October 2015 through December 2020. Some patients who completed 1 round of treatment elected to undergo additional rounds (16 or 24 injections) based on persistent curvature and presence of penile plaque. Clinical improvement was defined as a 20% reduction in penile curvature from the start of a given round of treatment to the end of that round of treatment. We measured erect penile curvature before and after each round and collected demographics, medical and surgical history, curvature outcomes, and treatment-related adverse events. OUTCOME: The primary outcome was the reduction in penile curvature after multiple rounds of treatment with intralesional collagenase injections in patients with PD. RESULTS: A total of 330 patients underwent intralesional collagenase injections for PD, of whom 229 completed at least 8 injections and underwent pre- and posttreatment erect penile goniometry. An overall 42.8% (98/229), 38.6% (22/57), and 12.5% (1/8) of patients achieved clinical improvement after 1 round of therapy (8 injections), 2 rounds (16 injections), and 3 rounds (24 injections), respectively. Mean degree and mean percentage improvement of penile curvature for the start and end of each round of treatment were 8.3° and 16.4% (after 1 round), 7.2° and 16.8% (after 2 rounds), and 3.3° and 8.1% (after 3 rounds). Bruising was the most common complication, with an incidence of at least 50% in each round. CLINICAL IMPLICATIONS: Knowledge of patient responses to multiple rounds of intralesional collagenase injections may help guide physicians in management and counseling of patients regarding PD treatment options. STRENGTHS AND LIMITATIONS: This is the first study to evaluate multiple rounds (>8 injections) of intralesional collagenase for PD. Limitations include retrospective analysis and smaller sample size among patients undergoing 3 rounds (24 injections). CONCLUSION: For patients who did not achieve clinical improvement after 1 round of treatment, an additional round may be beneficial. However, no real improvement was observed for patients undergoing a third round.
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Induración Peniana , Masculino , Humanos , Induración Peniana/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Colagenasas/uso terapéutico , Colagenasa Microbiana , Pene/cirugía , Inyecciones IntralesionesRESUMEN
PURPOSE: Clomiphene citrate (CC) is prescribed off-label in men to improve testosterone and sperm parameters, but the duration of treatment needed to reach maximal benefit remains unclear. Our objective was to examine temporal effects of CC on total testosterone (TT) and semen analysis (SA) using longitudinal follow-up data in treated men. MATERIALS AND METHODS: We analyzed an IRB-approved database of men treated with CC (25 mg q.d. or 50 mg q.o.d.) from January 2016 through May 2021. We identified patients with 3, 6, 9, and 12 month follow-up data for TT and 3, 6, and 9 month follow-up SA. Mean absolute changes in TT and sperm concentration compared to baseline were calculated, along with 95% confidence intervals. Men with prior genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare TT and sperm concentration at each time point to baseline (alpha=0.05). RESULTS: One hundered thirty-four men received CC, mean age 37.7 years (SD 6.7, range 24-52). TT at all follow-ups (3, 6, 9, and 12 months) were available for 25 men, and SA at 3, 6, and 9 months for 26 men. Baseline TT was 358±145 ng/dL and sperm concentration was 13±17.2 M/mL. Significant improvement in TT was identified at 3 months (62.7 ng/dL, 95% CI: 0.49-125.0, p=0.048), additional benefit at 6 months (181.8 ng/dL, 95% CI: 114.1-249.5, p<0.01), and plateau at 9 and 12 months. Improvement in sperm concentration was first observed at 9 months (20.7 M/mL, 95% CI: 10.2-31.2, p<0.01). Semen volume and sperm motility did not change. CONCLUSIONS: Duration of treatment with clomiphene may impact testosterone and sperm concentration, and the historical 3 month milestone may be insufficient for clinical and research evaluation. Men taking CC may experience plateau in TT at 6 months and first benefit in sperm concentration at 9 months.
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Background: Peyronie's disease (PD) can be subdivided into acute and chronic phases. Intralesional collagenase Clostridium histolyticum has been shown to improve curvature in the chronic phase. Initial clinical trials excluded patients in the acute phase from treatment. Recent studies show comparable results among men in the acute phase. The definition of acute phase varies among existing studies, but it is generally understood to last 12-18 months and is accompanied by penile pain and progression of deformity. We sought to evaluate the safety and efficacy of intralesional collagenase injection therapy during the acute phase of PD using multiple definitions of the acute phase. Methods: All men receiving intralesional collagenase for PD from October 2015 through December 2020 at a single academic institution were retrospectively assessed for patient demographics and comorbidities, pre- and post-treatment curvature, and adverse events. Two definitions of acute phase were used: (I) acute phase duration ≤6 months, chronic phase duration >6 months; and (II) acute phase duration ≤12 months with penile pain, chronic phase duration >12 or no penile pain. Results: Of 330 patients identified, 229 underwent intralesional collagenase treatment with pre- and post-treatment erect penile goniometry. 65 (28%) met criteria for definition 1 of acute phase, 37 (16%) met criteria for definition 2, and 76 (33%) met criteria for either. Percent change in penile curvature was not significantly different between acute and chronic phases using definition 1 (16.0% vs. 16.6%, P=0.89), definition 2 (19.9% vs. 15.7%, P=0.43), or either (16.5% vs. 16.3%, P=0.96). The rates of development of bruising, swelling, hematoma, or corporal rupture were not significantly different between the acute and chronic phases under either definition (all P>0.05). Conclusions: This single-center, retrospective cohort analysis suggests that intralesional collagenase is both safe and effective for the treatment of men with acute phase PD. Limitations exist inherent to retrospective review, since many men did not return for post-treatment goniometry, possibly skewing our cohort toward incomplete responders. Prospective, randomized studies will be required to confirm these findings.
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PURPOSE: The safety label for collagenase Clostridium histolyticum was updated to include postinjection acute lower back pain as an adverse event observed with intralesional therapy for Peyronie's disease. Incidence and causality are unknown. We assessed frequencies and temporal associations for this adverse event in a large cohort. MATERIALS AND METHODS: Data on all men undergoing collagenase injections for Peyronie's disease at our institution from October 2015 through December 2020 were retrospectively assessed. The study included 330 patients, 300 completing at least 1 full course (8 injections). Measured outcomes included incidence and timing of back pain, and associations with demographics and comorbidities. RESULTS: Of 330 patients, 19 (5.8%) experienced at least 1 episode of postinjection acute lower back pain. Of 300 who completed at least 1 full course of 8 injections, 4 (1.3%) reported back pain within the 8-injection course. A subset underwent additional rounds (16 or 24 injections). Back pain increased to 8.7% (13/149) during a second round, 6.9% (3/43) during a third. No association was found with age, diabetes or back pain history. Most cases occurred shortly after injection; all were self-limited or resolved with a single dose of ketorolac. CONCLUSIONS: This single-center, retrospective analysis suggests that intralesional collagenase injections for Peyronie's disease may cause acute lower back pain in up to 6% of patients. Patients may benefit from counseling regarding this risk. Incidence rises with additional rounds of treatment. Prospective safety data regarding >8 injections do not exist. No patient had long-term sequelae of back pain.
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Dolor de la Región Lumbar , Colagenasa Microbiana , Induración Peniana , Humanos , Inyecciones Intralesiones , Dolor de la Región Lumbar/inducido químicamente , Masculino , Colagenasa Microbiana/administración & dosificación , Colagenasa Microbiana/efectos adversos , Induración Peniana/tratamiento farmacológico , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: Efficacy of clomiphene citrate (CC) in the treatment of male subfertility remains unclear, with inconsistent results in the literature and limited guidance from professional organizations. We sought to stratify the response to clomiphene in men based on their initial gonadotropins and semen parameters. Methods: We conducted a retrospective analysis of 234 patients from an academic center who took CC for subfertility. Patients with pre-treatment and 3 months follow-up total testosterone (TT) and semen analyses were included. Patients with previous hormone therapy, genitourinary surgery, prior success in conceiving pregnancy, or only one semen analysis were excluded. Primary outcomes were magnitudes of improvement in TT and semen parameters at 3 months. Student's t-test (alpha =0.05) was used for univariate analyses; multivariable linear regression was used for multivariate analysis. Results: One hundred and thirty-seven patients met inclusion criteria. Thirty-four percent of patients experienced improvement in sperm concentration after 3 months of CC treatment, 13% decreased, and 53% showed no change. Using a pre-treatment TT cutoff of 300 ng/dL and gonadotropin thresholds of 7 miU/mL, initial TT did not affect magnitude of improvement in semen parameters, while lower initial gonadotropins showed statistical improvement across all outcomes. Multivariate analysis showed pre-treatment follicle stimulating hormone (FSH) was inversely correlated with improvement in TT [odds ratio (OR): 2.64e-05, 95% confidence interval (CI): 1.32e-09 to 5.28e-01, P=0.04] and sperm concentration (OR: 0.22, 95% CI: 5.70e-02 to 8.48e-01, P=0.03). We also provide initial gonadotropin cutoffs that suggest statistical benefit from CC use. Conclusions: Men with lower gonadotropin levels may expect greater degree of improvement in both hormone and semen parameters with use of CC. Men with azoospermia do not benefit based on semen analyses alone. Degree of non-azoospermia does not affect magnitude of improvement. CC had decreasing efficacy at higher initial gonadotropin levels. These data may provide guidance in stratifying and counseling men for CC treatment.