Initial gonadotropin levels and sperm parameters differentiate the response to clomiphene citrate in subfertile men.

BackgroundEfficacy 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.MethodsWe 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.ResultsOne 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.ConclusionsMen 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

Temporal Changes of Clomiphene on Testosterone Levels and Semen Parameters in Subfertile Men

PurposeClomiphene 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 methodsWe 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).ResultsOne 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.ConclusionsDuration 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

Intralesional collagenase Clostridium histolyticum for acute phase Peyronie’s disease: a single-center, retrospective cohort study

BackgroundPeyronie'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.MethodsAll 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.ResultsOf 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).ConclusionsThis 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

Cross-Polarization Gain Calibration of Linearly Polarized VLBI Antennas by Observations of 4C 39.25

Radio telescopes with dual linearly polarized feeds regularly participate in Very Long Baseline Interferometry. One example is the VLBI Global Observing System (VGOS), which is employed for high-precision geodesy and astrometry. In order to achieve the maximum signal-to-noise ratio, the visibilities of all four polarization products are combined to Stokes I before fringe-fitting. Our aim is to improve cross-polarization bandpass calibration, which is an essential processing step in this context. Here we investigate the shapes of these station-specific quantities as a function of frequency and time. We observed the extra-galactic source 4C 39.25 for 6 hours with a VGOS network. We correlated the data with the DiFX software and analyzed the visibilities with PolConvert to determine the complex cross-bandpasses with high accuracy. Their frequency-dependent shape is to first order characterized by a group delay between the two orthogonal polarizations, in the order of several hundred picoseconds. We find that this group delay shows systematic variability in the range of a few picoseconds, but can remain stable within this range for several years, as evident from earlier sessions. On top of the linear phase-frequency relationship there are systematic deviations of several tens of degrees, which in addition are subject to smooth temporal evolution. The antenna cross-bandpasses are variable on time scales of ∼1 hr, which defines the frequency of necessary calibrator scans. The source 4C 39.25 is confirmed as an excellent cross-bandpass calibrator. Dedicated surveys are highly encouraged to search for more calibrators of similar quality.ISSN:0048-6604ISSN:1944-799

Racial and Ethnic Disparities in Colonoscopic Examination of Individuals With a Family History of Colorectal Cancer

BACKGROUND & AIMS: Guidelines recommend that persons with a high-risk family history of colorectal cancer (CRC) undergo colonoscopy examinations every 5 y, starting when they are 40 y old. We investigated factors associated with colonoscopy screening of individuals with a family history of CRC, focusing on race and ethnicity. METHODS: In a retrospective study, we analyzed data from the 2009 California Health Interview Survey on persons 40–80 y old with a first-degree relative (mother, father, sibling or child) with CRC who had visited a physician within the past 5 y. Our study included an unweighted and population-weighted sample of 2539 and 870,214 individuals with a family history of CRC, respectively. We performed a survey-weighted logistic regression analyses to adjust for relevant demographic and socioeconomic variables and used estimates to calculate relative risks (RR) and 95% confidence intervals (CI) for colonoscopy examination within the past 5 y. RESULTS: In the weighted sample, 60.0% of subjects received a colonoscopy within the past 5 y. A physician recommendation for CRC screening increased the odds that an individual would undergo colonoscopy examination (RR, 1.89; 95% CI, 1.61–2.24). Latinos were 31% less likely to receive colonoscopies than Whites (95% CI, 7%–55%). Among individuals 40–49 y old, African Americans were 71% less likely to have had a colonoscopy than Whites (95% CI, 13%–96%). CONCLUSION: Based on an analysis of data from the California Health Interview Survey, less than two-thirds of individuals with a family history of CRC reported receiving guideline-recommended colonoscopy examinations within the past 5 y. We observed racial and ethnic disparities in colonoscopy screening of this high-risk group; Latinos and African Americans were less likely to have had a colonoscopy than Whites