Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States.

PURPOSE: Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men. MATERIALS AND METHODS: This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy. RESULTS: Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001). CONCLUSIONS: In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae.

Vasectomy: AUA guideline.

PURPOSE: The purpose of this guideline is to provide guidance to clinicians who offer vasectomy services. MATERIALS AND METHODS: A systematic review of the literature using the search dates January 1949-August 2011 was conducted to identify peer-reviewed publications relevant to vasectomy. The search identified almost 2,000 titles and abstracts. Application of inclusion/exclusion criteria yielded an evidence base of 275 articles. Evidence-based practices for vasectomy were defined when evidence was available. When evidence was insufficient or absent, expert opinion-based practices were defined by Panel consensus. The Panel sought to define the minimum and necessary concepts for pre-vasectomy counseling; optimum methods for anesthesia, vas isolation, vas occlusion and post-vasectomy follow up; and rates of complications of vasectomy. This guideline was peer reviewed by 55 independent experts during the guideline development process. RESULTS: Vas isolation should be performed using a minimally-invasive vasectomy technique such as the no-scalpel vasectomy technique. Vas occlusion should be performed by any one of four techniques that are associated with occlusive failure rates consistently below 1%. These are mucosal cautery of both ends of the divided vas without ligation or clips (1) with or (2) without fascial interposition; (3) open testicular end of the divided vas with MC of abdominal end with FI and without ligation or clips; and (4) non-divisional extended electrocautery. Patients may stop using other methods of contraception when one uncentrifuged fresh semen specimen shows azoospermia or ≤ 100,000 non-motile sperm/mL. CONCLUSIONS: Vasectomy should be considered for permanent contraception much more frequently than is the current practice in the U.S. and many other nations. The full text of this guideline is available to the public at http://www.auanet.org/content/media/vasectomy.pdf.

Analysis of outcomes of cryopreserved surgically retrieved sperm for IVF/ICSI.

We evaluated our experience to date with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) after either cryopreserved sperm or sperm produced on the date of IVF/ICSI was used. We performed a retrospective statistical analysis of data derived from 188 women undergoing IVF/ICSI cycles using surgically retrieved sperm. A total of 318 IVF/ICSI treatment cycles with 3280 ova were performed using testicular sperm extraction (TESE, 304 cycles) or microsurgical epididymal sperm aspiration (MESA, 14 cycles). Sperm obtained at time of IVF/ICSI (fresh) or thawed cryopreserved sperm samples were used in 38 and 280 of the ICSI cycles, respectively. For IVF/ICSI cycles using both TESE and MESA sperm, the fertilization rate was 59.9% for cryopreserved sperm, and 53.6% when fresh sperm was used (chi2 P-alpha < .02, Cramer's 0.04). The fertilization rate for the TESE group alone was 60.0% for cryopreserved sperm and 55.1% for fresh sperm (chi2P-alpha = .075). Cohen effect size was computed at 0.03; yielding for P-beta = .8, 6597 ova would be required to demonstrate similarity between fresh and cryopreserved sperm in the TESE group. To demonstrate superiority of cryopreserved sperm in this group at a P-alpha significance level of .05, 7524 ova would be necessary. The pregnancy rate for the TESE group was 27.3% for cryopreserved sperm and 27% for fresh sperm. Further analysis of the pregnancy data in this group, using the methods described, yielded a chi2 P-alpha and power of 0.971 (effect size calculated at 0.002). While our fertilization rates for cryopreserved sperm are greater in analyses of surgically derived sperm, based on the 7 years required to obtain data on 3280 ova, full numerical resolution of the issue of whether cryopreserved sperm is superior or similar will not be available until approximately 2010. However, we believe these results, along with the similarity shown in pregnancy rates achieved with both types of sperm, clearly indicate that cryopreserved sperm is not inferior to fresh sperm.

Posthumous reproduction: current and future status.

Posthumous reproduction became possible with the technologies of sperm cryopreservation and ART. The legal and social status of children born as a result of these technologies continue to evolve. The proper disposition of unwanted stored gametes and embryos remains unknown. Physicians are increasingly asked to make quick judgments on posthumous gamete retrieval. The procedures for gamete harvest are technically simple; however, one must carefully select cases with definitive prior intent to have children. There is a need for standardized legal protocols to protect the physician and the patient. The physician must use sound judgment and comply with accepted standards, when present, before performing any service for posthumous sperm retrieval and reproduction.

Reproductive health care delivery.

Most patients in the United States with reproductive health disorders are not covered by their health insurance for these problems. Health insurance plans consider reproductive care as a lifestyle choice not as a disease. If coverage is provided it is, most often, directed to female factor infertility and advanced reproductive techniques, ignoring male factor reproductive disorders. This article reviews the history of reproductive health care delivery and its present state, and considers its possible future direction.

Computational models for detection of erectile dysfunction.

PURPOSE: Vascular comorbidities are well known to correlate with erectile dysfunction (ED) but a correlation with hypogonadism and depression is less clear. Using several linear and nonlinear mathematical models we investigated the correlation of age, hypogonadism and depression with ED using the Sexual Health Inventory for Men (SHIM) as a surrogate marker for ED. MATERIALS AND METHODS: A data set of 140 exemplars containing the input features age, total testosterone in ng/dl, Center for Epidemiologic Studies Depression scale score and output SHIM score (thresholded to 10 for moderate ED) was randomized into a modeling (training) set of 105 and a cross-validation (test) set of 35 with similar outcome frequencies preserved in each set. Using neUROn++, a set of C++ programs that we developed using the Cygwin (Red Hat, Raleigh, North Carolina) GNU C++ port for Windows (Microsoft, Redmond, Washington) distributed across Pentium (Intel, Santa Clara, California) platforms we modeled the data set using the linear methods, linear and quadratic discriminant function analysis, and logistic regression, and the nonlinear method of neural computation with several investigated architectures. RESULTS: A 4 hidden node network was found to have the highest accuracy compared to linear and quadratic discriminant function analyses, and logistic regression. ROC areas for the test set were 0.702, 0.645, 0.676 and 0.618, respectively. Analysis of the neural network demonstrated that moderate ED correlated with patient age and depression score. Forward and reverse regression of the neural network based on Wilk's generalized likelihood ratio test revealed that age was most significant (p <0.001), followed by Center for Epidemiologic Studies Depression Scale score (p <0.03), followed by testosterone (p >0.6). CONCLUSIONS: We investigated linear and nonlinear computational models of moderate ED. To our knowledge this is the first demonstration that SHIM correlates with age and a depression metric. Furthermore, moderate ED based on SHIM with a correlation with age may now provide a rationale and basis for future investigation into the understanding of age related erectile pathophysiology.

The influence of obstructive interval on patency rates following microsurgical epididymovasostomy.

To determine whether or not obstructive interval (OI) negatively affects patency rates in epididymovasostomy (EV) as a sole procedure alone, we reviewed medical records from obstructive azoospermia (OA) patients who underwent unilateral or bilateral epididymovasostomy. For the purpose of analysis, patients were placed into short OI (15 years or less) or long OI (more than 15 years) categories. Patency rate for the short OI group was 58%, compared to 15% for the long OI group (P<0.01). In conclusion, we observed that patency rates worsened with obstructive interval greater than 15 years. Epididymovasostomy is a challenging procedure that may not be successful, and, thus, patients should be counseled that obstructive interval might affect surgical outcomes. We routinely perform testicular sperm extraction (TESE) with sperm cryopreservation in this patient population due to the high likelihood that it will ultimately be required for assisted reproductive technology (ART).

The role of testicular biopsy in the modern management of male infertility.

PURPOSE: We evaluate the traditional role of isolated testicular biopsy as a diagnostic tool, as opposed to the value as a therapeutic procedure for azoospermic men. MATERIALS AND METHODS: The medical records of azoospermic patients who were evaluated, and treated between 1995 and 2000 were retrospectively analyzed for history, physical examination findings, endocrine profiles, testicular histology and sperm retrieval rates. Based on these parameters, cases were placed into diagnostic categories that included obstructive or nonobstructive azoospermia. Diagnostic parameters used to distinguish obstructive from nonobstructive azoospermia were subjected to statistical analysis with the t-test, analysis of variance and receiver operating characteristics curve. RESULTS: A total of 153 azoospermic men were included in our analysis. Of men with obstructive azoospermia 96% had follicle-stimulating hormone (FSH) 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. Conversely, 89% of men with nonobstructive azoospermia had FSH greater than 7.6 mIU/ml., or testicular long axis 4.6 cm. or less. Receiver operating characteristics analysis revealed that FSH, testicular long axis, and luteinizing hormone were the best individual diagnostic predictors, with areas 0.87, 0.83 and 0.79, respectively. CONCLUSIONS: In the vast majority of patients obstructive azoospermia may be distinguished clinically from nonobstructive azoospermia with a thorough analysis of diagnostic parameters. Based on this result, we believe that the isolated diagnostic testicular biopsy is rarely if ever indicated. Men with FSH 7.6 mIU/ml. or greater, or testicular long axis 4.6 cm. or less may be considered to have nonobstructive azoospermia and counseled accordingly. These men are best treated with therapeutic testicular biopsy and sperm extraction, with processing and cryopreservation for usage in in vitro fertilization and intracytoplasmic sperm injection if they accept advanced reproductive treatment. Diagnostic biopsy is of no other value in this group. Men with FSH 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. may elect to undergo reconstructive surgery with or without testicular biopsy and sperm extraction, or testicular biopsy and sperm extraction alone depending on their reproductive goals.

A neurocomputational model for prostate carcinoma detection.

BACKGROUND: Current guidelines for prostate carcinoma screening rely primarily on the digital rectal examination (DRE) and prostate specific antigen (PSA). Well described patient risk factors for prostate carcinoma also include age, ethnicity, family history, and complexed PSA. However, due to the nonlinear relation of each of these variables with prostate carcinoma, it is difficult to predict reliably each patient's risk based on linear univariate analysis. The authors investigated a neural network to model the risk of prostate carcinoma by seven readily available clinical features. METHODS: The database for the current study comprised 3268 men recently evaluated for the early detection of prostate carcinoma. The seven clinical features evaluated included age, race, family history, International Prostate Symptom Score (IPSS), DRE, and total and complexed PSA. Three hundred forty-eight subjects in the dataset included men with determined prostate biopsy outcomes and for whom at least 6 of 7 features were available. The dataset was divided randomly into a training set (60%) and a test set (40%), with n1/n2 cross-validation used to evaluate model accuracy, and was modeled with linear and quadratic discriminant function analysis and a neural computational system. After a model with acceptable goodness of fit was achieved, reverse regression analysis using Wilks's generalized likelihood ratio test was performed to evaluate the statistical significance of each input variable. RESULTS: The receiving operating characteristic (ROC) area for the neural computational system in the test set was 0.825, whereas total PSA and complexed PSA alone had ROC areas of 0.678 and 0.697, respectively. The ROC area of logistic regression in the test set was 0.510, linear discriminant function analysis was 0.674, and quadratic discriminant function analysis was 0.011. All were significantly less than the ROC area of the neural computational model (all Ps < 0.002). Reverse regression based on Wilks's generalized likelihood ratio test demonstrated each input feature to be highly significant to the model (all Ps << 0.000001). CONCLUSIONS: The authors modeled a combination of well described patient risk factors for prostate carcinoma using a neural computational system with acceptable goodness of fit. They demonstrated that each of the seven variates on which the model was based was critically significant to model performance. The authors presented this model for clinical use and suggested that clinicians use it in deciding to perform prostate biopsy.