The 20-year public health impact and direct cost of testosterone deficiency in U.S. men.

INTRODUCTION: Testosterone deficiency (TD) imposes a substantial public health burden in the U.S. We modeled the costs associated with TD-related sequelae including cardiovascular disease (CVD), diabetes mellitus (DM), and osteoporosis-related fractures (ORFs). AIM: To quantify the incremental cost burden imposed by TD's cardiometabolic sequelae. METHOD: Incidence, prevalence, and mortality of these conditions were collected for men ages 45-74 from six national databases and large cross-sectional studies. Relative risk (RR) rates were determined for these sequelae in patients with T < 300 ng/dL. The prevalence of TD was determined for this cohort of men. MAIN OUTCOME MEASURES: Adjusted incidence and prevalence were determined. Annual costs for the three TD-related sequelae were inflated at a real rate of 3% for 20 years. RESULTS: Actual and adjusted (normalized for T deficiency) rates of CVD, DM, and ORFs in U.S. men aged 45-74 assuming a TD prevalence of 13.4% were calculated. We determined that, over a 20-year period, T deficiency is projected to be involved in the development of approximately 1.3 million new cases of CVD, 1.1 million new cases of DM, and over 600,000 ORFs. In year 1, the attributed cost burden of these diseases was approximately $8.4 billion. Over the entire 20-year period, T deficiency may be directly responsible for approximately $190-$525 billion in inflation-adjusted U.S. health care expenditures. CONCLUSION: TD may be a significant contributor to adverse public health. Further study is needed to definitively describe the whether TD is a modifiable risk factor for CVD, DM, and ORFs. This may represent an opportunity for nationwide public health initiatives aimed at preventive care.

Seasonal fluctuations in testosterone-estrogen ratio in men from the Southwest United States.

Although controversial, seasonal variations in testosterone have been observed in several populations of men throughout the world. This finding might have an impact on screening and treatment of hypogonadism. We examined the circannual patterns of sex hormones in the Southwest United States. A prospectively assembled database of almost 11 000 patients in a men's health practice was used to collect data on testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dehydroepiandrosterone-sulfate (DHEA-S). Patient age, address, and date of visit were recorded. Of note, testosterone-estrogen ratio (T/E ratio) and free testosterone were calculated values. The data were grouped by month and by season (3-month intervals beginning with June, July, and August as summer). Analysis of variance was used to compare hormone levels between seasonal and monthly data sets, with P < .05 regarded as statistical significance. Statistically significant differences in estradiol (P = .02), T/E ratio (P < .01), FSH (P = .02), and SHBG (P < .01) were observed between seasons. Peak-to-trough variations were as follows: 6% for estradiol, 16.5% for T/E ratio, 11.0% for FSH, and 11.6% for SHBG. The T/E ratio peaked in the spring and was at its nadir in the fall. No differences in testosterone (P = .21), LH (P = .25), free testosterone (P = .08), and DHEA-S (P = .11) were observed. Statistically significant evidence of variation in estradiol and T/E ratio were identified in the men included in this study. Although this is consistent with seasonal body habitus changes, physical activity levels, and hypothesized hormonal patterns, the variability reported in the literature makes further trials covering a broader geographic region important to confirm the findings.

A non-Karplus effect: evidence from phosphorus heterocycles and DFT calculations of the dependence of vicinal phosphorus-hydrogen NMR coupling constants on lone-pair conformation.

In contrast to literature reports of a Karplus-type curve that correlates (3)J(PH) with phosphorus-hydrogen dihedral angle, a recently reported glycine-derived 1,3,2-oxazaphospholidine (7c) has two hydrogen atoms on the ring with identical PNCH dihedral angles but measured coupling constants of ∼6 and 1.5 Hz. DFT calculations were in accord with these values and suggested that the smaller coupling constant is negative. Experimental evidence of the opposite signs of these coupling constants was obtained by analysis of the ABX NMR spectrum of the new glycine-derived N-p-toluenesulfonyl phosphorus heterocycle 6c. DFT calculations on 6c and on Me(2)NPCl(2) and t-BuPCl(2) were also in accord with NMR data and allowed confirmation of unusual features including a lone pair effect on (3)J(PH), the negative coupling constant, temperature-dependent chemical shifts due to rotation about the sulfonamide S-N bond, and vicinal phosphorus-hydrogen coupling constants over 40 Hz. Calculation of phosphorus-hydrogen coupling constants both as a function of PYCH dihedral angle θ (Y = O, N, C) and lone pair-PYC dihedral angle ω shows similar θ,ω surfaces for (3)J(PH) with a range of (3)J(PH) from -4.4 to +51 Hz and demonstrates the large non-Karplus effect of lone-pair conformation on vicinal phosphorus-hydrogen coupling constants.

Clomiphene citrate is safe and effective for long-term management of hypogonadism.

OBJECTIVE: To assess the efficacy and safety of long-term clomiphene citrate (CC) therapy in symptomatic patients with hypogonadism (HG). PATIENTS AND METHODS: Serum T, oestradiol and luteinizing hormone (LH) were measured in patients who were treated with CC for over 12 months. Additionally, bone densitometry (BD) results were collected for all patients. Demographic, comorbidity, treatment and Androgen Deficiency in Aging Men (ADAM) score data were also recorded. Comparison was made between baseline and post-treatment variables, and multivariable analysis was conducted to define predictors of successful response to CC. The main outcome measures were predictors of response and long-term results with long-term CC therapy in hypogonadal patients. RESULTS: The 46 patients (mean age 44 years) had baseline serum testosterone (T) levels of 228 ng/dL. Follow-up T levels were 612 ng/dL at 1 year, 562 ng/dL at 2 years, and 582 ng/dL at 3 years (P < 0.001). Mean femoral neck and lumbar spine BD scores improved significantly. ADAM scores (and responses) fell from a baseline of 7 to a nadir of 3 after 1 year. No adverse events were reported by any patients. CONCLUSIONS: Clomiphene citrate is an effective long-term therapy for HG in appropriate patients. The drug raises T levels substantially in addition to improving other manifestations of HG such as osteopenia/osteoporosis and ADAM symptoms.

Subcutaneous implantable testosterone pellets overcome noncompliance in adolescents with Klinefelter syndrome.

For adolescents with hypogonadism, failure to comply with a testosterone replacement therapy (TRT) regimen can be a barrier to obtaining adequate and consistent serum testosterone (T) levels. We evaluated 4 young men with hypogonadism secondary to Klinefelter syndrome to determine if implantable pellets represented a viable treatment option for such patients. Four patients (aged 14-20 years) had previously received TRT but were not compliant. Patients initially received 4 to 10 subcutaneous T pellets with subsequent doses implanted at 3- to 4-month intervals. In all 4 patients, total and free T levels were improved at follow-up, although fluctuations between levels were inconsistent. All patients reported improvement in their energy and concentration, and parents noted improved stability of mood. The mean baseline total T level of 108.3 ng/dL increased in all patients at the time of second pellet implantation. Average total T levels were 325 to 587 ng/dL over the course of therapy. There was significant variability of serum T levels while patients were on therapy. All patients eventually received an increased number of pellets at some point in their care. Subcutaneous implantation of T pellets is a viable option for TRT in young men with Klinefelter syndrome in whom compliance is an issue. However, the requirement for repeat implantation every 3 months, increased cost of therapy and monitoring, dramatic shifts in serum total and free T concentrations, and seemingly unpredictable response requires close monitoring and careful follow up and suggests this modality of therapy may not be appropriate for a substantial number of hypogonadal patients, but this strategy warrants consideration in noncompliant patients.

The use of GTX as second-line and later chemotherapy for metastatic pancreatic cancer: a retrospective analysis.

PURPOSE: There are limited data regarding the role of second-line treatment for metastatic pancreatic cancer (mPC) after the failure of initial chemotherapy. No data exist on the use of GTX after the failure of first-line therapy. PATIENTS AND METHODS: We identified patients who were given GTX chemotherapy for a diagnosis of mPC after the failure of initial therapy. Demographic features, progression-free (PFS) and overall survival (OS), response to treatment, and toxicities were recorded. RESULTS: The 59 evaluable patients received a median of 2 prior therapies. Three had no prior gemcitabine. Median PS was 1. Median survival was 22 weeks; progression-free survival was 9.9 weeks. Survival did not correlate with the number of prior regimens but trended with PS. There were no radiologic responses; those with stable disease (n = 21) had a better survival than those with progression (n = 29) or unevaluable patients (n = 9). Median survival was 38.3, 15.0, and 7.4 weeks, respectively. Grade 3 and 4 toxicities included leucopenia (n = 14), anemia (n = 7), and thrombocytopenia (n = 6). Hospitalizations were required in 21 patients, for febrile neutropenia (n = 7), non-neutropenic infection (n = 3), pulmonary embolus (n = 2), anemia or failure to thrive (n = 9). A 75% drop or more in CA 19-9 correlated with improved survival. CONCLUSIONS: GTX is an active regimen in patients previously treated with gemcitabine for mPC. Better performance status and >75% drop in pretreatment CA 19-9 were associated with longer survival. The number of prior regimens did not predict for survival duration.

Defining predictors of response to intralesional verapamil injection therapy for Peyronie's disease.

OBJECTIVE: • To assess factors that predict penile curvature responses to intralesional verapamil (ILV) injection therapy for men with Peyronie's disease (PD). PATIENTS AND METHODS: • Men with PD for <1 year were assessed at baseline and after 3 months of bi-monthly ILV-injection therapy. Curvature was assessed at the time of maximum penile rigidity. • Univariate relationships were tested with correlation or chi-square analyses. • Multivariate analyses included logistic and linear regression. • We analysed curvature improvement, defined as a decrease of ≥10 ° from baseline. Additionally, the relationship between curvature outcomes and patient age and degree of baseline penile curvature were assessed. RESULTS: • Data from 131 men were included and the rates of penile curvature change were:26% improved, 12% worsened, and 62% stable. • Age (r=-0.24, P < 0.01) and larger baseline penile curvature (r= 0.33, P < 0.01) were associated with improved curvature on univariate analysis. • On multivariate analysis (logistic regression), both age [odds ratio (OR) 0.93, P < 0.01, 95%CI 0.89-0.97] and larger baseline penile curvature (OR 1.07, P < 0.01, 95%CI 1.04-1.11) were associated with improvements in curvature after ILV-injection therapy. • Improvements in curvature were associated with age (≤40 years vs >40 years; OR 0.27, P < 0.05, 95%CI 0.10-0.75) and degree of penile curvature at baseline (≤30 ° vs >30 °; OR 9.12, P < 0.01, 95%CI 1.94-42.84) when dichotomized as indicated. CONCLUSION: • Younger age and larger baseline penile curvature were predictive of favourable curvature outcomes. • Analysis of dichotomized variables suggests that age and baseline curvature thresholds may be important to consider when deciding on ILV as a therapeutic strategy for PD.

Favorable female sexual function is associated with patient satisfaction after inflatable penile prosthesis implantation.

INTRODUCTION: The interrelationship between male and female sexual function suggests that partner outcomes after inflatable penile prosthesis (IPP) implantation must be assessed. AIM: We examined predictors of patient and partner satisfaction, and the relationship between patient satisfaction and female sexual function, after IPP implantation. METHODS: We designed a questionnaire (scored 1-5) assessing satisfaction with various domains related to the IPP (e.g., overall satisfaction and satisfaction related to: length, width, ease of use, and partner perception). Scores ≥3 were classified as satisfied. The Female Sexual Function Index (FSFI) was administered to the female partners of patients that underwent an IPP. MAIN OUTCOME MEASURES: Independent samples Students' t-test was used to compare various FSFI domain scores in relation to male and female satisfaction. Analysis of variance test was used to assess linear regression correlation between various continuous variables. RESULTS: 45 men and 32 partners with a mean follow-up of 2.2 years were contacted. Overall satisfaction for men and women was 3.60 and 3.62 (out of 5), respectively. Partner FSFI scores were higher, respectively, in men with higher implant satisfaction than those with lower implant satisfaction (25.09 ± 6.79 vs. 13.67 ± 12.70, P < 0.001). Regression analysis suggests a direct correlation between FSFI scores and the degree of patient (r = 0.50, r(2) = 0.23; P = 0.001) and partner (r = 0.70 r(2) = 0.50; P < 0.001) satisfaction with the IPP. CONCLUSION: Patient satisfaction after IPP implantation implies favorable partner sexual function compared to that of unsatisfied patients. The correlation observed suggests that patients not satisfied with their IPP are likely to have female partners at high risk for female sexual dysfunction. Further interventions may be needed to improve patient and partner sexual function, particularly unsatisfied men and their female partners.

Subjective characterization of nerve sparing predicts recovery of erectile function after radical prostatectomy: defining the utility of a nerve sparing grading system.

INTRODUCTION: Radical prostatectomy (RP) is a common technique for managing prostate cancer. Concern regarding functional outcomes in patients prompted the development of nerve sparing to improve recovery of erectile function. AIM: To assess if a cumulative nerve damage grading system is a more precise predictor of recovery of erectile function as compared to the current "all-or-none" grading system. METHODS: Baseline demographic, medical history, and International Index of Erectile Function (IIEF)-erectile function domain (EFD) scores were collected. At the time of RP, patients were assigned a nerve sparing score (NSS) by their surgeon for each neurovascular bundle (left and right) to assess the quality of intraoperative nerve sparing (1-complete preservation, 4-complete resection). Patients completed IIEF questionnaires at 24 months after RP. MAIN OUTCOME MEASURES: Group comparisons and multiple regression analyses were used to test the association between the NSS and IIEF-EFD scores for patients with preoperative EFD scores ≥ 24. RESULTS: A total of 173 patients were included in this analysis. Mean age for patients was 59, and 62% of patients had at least one comorbidity. Baseline EFD scores were comparable between all NSS assignments. At 24 months, EFD scores were reduced by 7.2, 11.6, 13.9, and 15.4 points for patients with NSS grades of 2, 3, 4, and 5-8, respectively (P < 0.01). Multivariate analysis demonstrated lower NSS predicted recovery of erectile function at 24 months (P = 0.001), as did age (P = 0.001) and baseline EFD score (P = 0.02). CONCLUSION: Our data support the adoption of a subjectively assigned NSS to more precisely predict erectile function outcomes and suggest that even minor nerve trauma significantly impairs the recovery of erectile function after procedures classically regarded as having achieved bilateral nerve sparing. Further studies are needed to identify the optimal NSS system.

Revision of penile prosthesis surgery after use of penile traction therapy to increase erect penile length: case report and review of the literature.

INTRODUCTION: Erectile dysfunction, a common consequence of radical prostatectomy (RP), can be managed with placement of a penile prosthesis. Patient satisfaction and functional outcomes have been related to penile length after prosthesis placement. AIM: We report a case demonstrating the impact of daily penile traction therapy in a patient with a previously placed penile prosthesis with the goal of enabling revision with a longer device. METHODS: A post-RP patient who underwent inflatable penile prosthesis placement 6 years ago complained of inability to maintain partner penetration with his device. The patient underwent vacuum erection device therapy twice daily for 10 minutes per session for approximately 1 year as well as 8 hours of penile traction therapy daily for 8 months. A revision implant surgery was subsequently attempted. MAIN OUTCOME MEASURE: Patient reported functional outcome. RESULTS: Stretched penile length increased 2.3 cm after 6 months of traction therapy. A revision surgery enabled the placement of a prosthesis that was 20% longer in length (15 cm to 18 cm), and erect penile length increased by 4.4 cm. The patient reported that the new prosthesis enabled satisfactory maintenance of partner penetration. CONCLUSIONS: This case suggests that the use of a penile traction device increases penile corporal length, and thus the length of a penile prosthesis that can be implanted in a patient with an unsatisfactory prosthesis already in place. Importantly, this patient experienced a substantial improvement in erect penile length after surgery. It is unknown whether these results are generalizable, either to all patients with a previously placed prosthesis or pre-prosthesis patients, representing an opportunity for further investigation.

The female factor: predicting compliance with a post-prostatectomy erectile preservation program.

INTRODUCTION: Early post-radical prostatectomy (RP) erectile preservation (EP) therapy may be critical to preserve erections after surgery. AIM: To assess if pre-RP female sexual function predicts of partner compliance with an EP protocol. MAIN OUTCOME MEASURES: Compliance, defined as use of localized penile EP therapy (intracavernosal injections [ICIs], vacuum erection device [VED], or alprostadil) at 3 and 6 months after RP. METHODS: Records of patients enrolled in our EP program from April 2007 to June 2008 were reviewed. Before surgery, patients completed the Sexual Health Inventory for Men (SHIM) and their female partners completed the Female Sexual Function Index (FSFI) questionnaire. Prior to surgery, patients were advised to take sildenafil 25 mg every nightly and use a 250-µg alprostadil suppository three times/week. At 1 month, additional daily use of a VED was encouraged. All patients unable to achieve erections sufficient for penetration were encouraged to initiate ICI of Trimix (phentolamine, papaverine, and PGE1) twice weekly after 3 months following surgery. Data were analyzed using binary logistic regression analysis holding all input variables constant. RESULTS: Twenty-nine patients had preoperative SHIM>7 and pre-RP partner FSFI data available. After a 4-week follow-up, compliance with alprostadil suppository declined and both ICI and VED usage increased. At 6 months, six (25.0%) patients had return of natural erectile function and 22 (91.7%) were achieving assisted erections. Higher preoperative partner FSFI scores were associated with greater compliance to the localized penile therapy component of our EP protocol (risk ratio 3.8, P=0.05). CONCLUSIONS: Preoperative female sexual function correlated with greater partner compliance with the localized component of our EP protocol. Consideration of a female partner's preoperative sexual function in predicting patient erectile function recovery after RP is warranted. Future studies are necessary to determine the clinical significance of this factor.

Drain data to predict clinically relevant pancreatic fistula.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a common and potentially devastating complication of pancreas resection. Management of this complication is important to the pancreas surgeon. OBJECTIVE: The aim of the present study was to evaluate whether drain data accurately predicts clinically significant POPF. METHODS: A prospectively maintained database with daily drain amylase concentrations and output volumes from 177 consecutive pancreatic resections was analysed. Drain data, demographic and operative data were correlated with POPF (ISGPF Grade: A--clinically silent, B--clinically evident, C--severe) to determine predictive factors. RESULTS: Twenty-six (46.4%) out of 56 patients who underwent distal pancreatectomy and 52 (43.0%) out of 121 patients who underwent a Whipple procedure developed a POPF (Grade A-C). POPFs were classified as A (24, 42.9%) and C (2, 3.6%) after distal pancreatectomy whereas they were graded as A (35, 28.9%), B (15, 12.4%) and C (2, 1.7%) after Whipple procedures. Drain data analysis was limited to Whipple procedures because only two patients developed a clinically significant leak after distal pancreatectomy. The daily total drain output did not differ between patients with a clinical leak (Grades B/C) and patients without a clinical leak (no leak and Grade A) on post-operative day (POD) 1 to 7. Although the median amylase concentration was significantly higher in patients with a clinical leak on POD 1-6, there was no day that amylase concentration predicted a clinical leak better than simply classifying all patients as 'no leak' (maximum accuracy = 86.1% on POD 1, expected accuracy by chance = 85.6%, kappa = 10.2%). CONCLUSION: Drain amylase data in the early post-operative period are not a sensitive or specific predictor of which patients will develop clinically significant POPF after pancreas resection.

Malignant head and neck paragangliomas: is there an optimal treatment strategy?

BACKGROUND: Little is known about management and prognosis for malignant head & neck paragangliomas. We reviewed records of these patients to determine optimal treatment strategies. METHODS: We reviewed 113 cases of head & neck paragangliomas treated at our institution from 1970 to 2005. Nineteen patients were included in the study. All had primary surgical treatment at another institution. Metastatic disease was treated with radiation, chemotherapy, or both. Survival and complications were evaluated. P values were determined by Fischer's exact test. RESULTS: All patients treated with chemotherapy and radiation age ≥ 40 years had disease progression. Of the patients < 40, two had stable disease; one had regression of disease with treatment. Patients without disease progression had better prognosis and were alive at last follow-up. CONCLUSIONS: Clinical benefit was derived from aggressive treatment. However, careful consideration of the risks of observation versus intensive therapy should be undertaken when managing these patients.

High body mass index does not affect outcomes following robotic assisted laparoscopic prostatectomy.

INTRODUCTION: Given the anatomic constraints of obese patients, concern exists as to whether robotic assisted laparoscopic prostatectomy (RALP) is appropriate in patients with higher body mass index (BMI). We reviewed a large RALP database to determine if clinical outcomes are related to BMI. METHODS: The records of patients who underwent a RALP from 2003-2009 were reviewed. BMI stratifications were concordant with the Centers for Disease Control (CDC) standards: > or = 30, > or = 25 and < 30, and < 25 were classified as obese, overweight, and normal weight, respectively. Baseline, perioperative, histopathologic, and functional outcome data were collected. RESULTS: A total of 1420 patients were identified and BMI information was available for 1112 patients. Median BMI in the three strata was 23.5 (n = 270), 27.3 (n = 600), and 32.1 (n = 242). There were no significant differences in preoperative prostate specific antigen (PSA), clinical staging, and preoperative Gleason scores. Operating time was 6 minutes longer in the obese (p < 0.001) and prostate weight was 8 g greater (p < 0.001). Other perioperative factors were similar, including: EBL, pathologic stage and Gleason score and rates of positive surgical margins. The overall incidence of postoperative complications was similar between the three groups. Biochemical recurrence rates were similar among all patients, although there was a trend toward increased recurrence in the obese (p = 0.09). Recovery of erectile function and continence was similar regardless of BMI. CONCLUSIONS: RALP is an effective approach to prostatectomy in obese patients as perioperative and functional outcomes are almost identical across BMI strata. This supports the continued utilization of RALP in obese and overweight men.