Ryan P. Smith

Anabolic steroid induced hypogonadism in young men.

PURPOSEnThe use of anabolic androgenic steroids has not been traditionally discussed in mainstream medicine. With the increased diagnosis of hypogonadism a heterogeneous population of men is now being evaluated. In this larger patient population the existence of anabolic steroid induced hypogonadism, whether transient or permanent, should now be considered.nnnMATERIALS AND METHODSnWe performed an initial retrospective database analysis of all 6,033 patients who sought treatment for hypogonadism from 2005 to 2010. An anonymous survey was subsequently distributed in 2012 to established patients undergoing testosterone replacement therapy.nnnRESULTSnProfound hypogonadism, defined as testosterone 50 ng/dl or less, was identified in 97 men (1.6%) in the large retrospective cohort initially reviewed. The most common etiology was prior anabolic androgenic steroid exposure, which was identified in 42 men (43%). Because of this surprising data, we performed an anonymous followup survey of our current hypogonadal population of 382 men with a mean±SD age of 49.2±13.0 years. This identified 80 patients (20.9%) with a mean age of 40.4±8.4 years who had prior anabolic androgenic steroid exposure. Hypogonadal men younger than 50 years were greater than 10 times more likely to have prior anabolic androgenic steroid exposure than men older than 50 years (OR 10.16, 95% CI 4.90-21.08). Prior anabolic androgenic steroid use significantly correlated negatively with education level (ρ=-0.160, p=0.002) and number of children (ρ=-0.281, p<0.0001).nnnCONCLUSIONSnPrior anabolic androgenic steroid use is common in young men who seek treatment for symptomatic hypogonadism and anabolic steroid induced hypogonadism is the most common etiology of profound hypogonadism. These findings suggest that it is necessary to refocus the approach to evaluation and treatment paradigms in young hypogonadal men.

The effects of advanced paternal age on fertility

Modern societal pressures and expectations over the past several decades have resulted in the tendency for couples to delay conception. While women experience a notable decrease in oocyte production in their late thirties, the effect of age on spermatogenesis is less well described. While there are no known limits to the age at which men can father children, the effects of advanced paternal age are incompletely understood. This review summarizes the current state of knowledge regarding advanced paternal age and its implications on semen quality, reproductive success and offspring health. This review will serve as a guide to physicians in counseling men about the decision to delay paternity and the risks involved with conception later in life.

The evidence for seasonal variations of testosterone in men

Ample evidence exists to support the concept of diurnal variations in testosterone levels; however, substantiation for seasonal fluctuations is sparse and inconsistent. Since circadian disparities exist, laboratory screening for hypogonadism has traditionally been conducted using serum testosterone levels obtained in the early morning. Should circannual variability of testosterone be confirmed, it would make the monitoring of testosterone levels more difficult while forcing the development of seasonal reference standards to allow for comparison. Moreover, decisions to begin treatment and adjustment of practice patterns would likely follow. This review thoroughly explores all of the available evidence concerning seasonal variations in testosterone levels. The impacts of melatonin, vitamin D, sleep-wake cycles, light exposure, physical activity, BMI, and waist circumference are also discussed. Current research suggests that while some evidence exists to support the notion of seasonal testosterone variations, the discussed inconsistencies preclude the incorporation of this concept into current clinical standards.

Patient Satisfaction with Testosterone Replacement Therapies: The Reasons Behind the Choices

INTRODUCTIONnTestosterone replacement therapy (TRT) for male hypogonadism is rapidly gaining popularity and acceptance. Options include gels, injections, and implantable subcutaneous pellets.nnnAIMSnThe aim of this study was to determine rates of patient satisfaction and reasons for patient preferences in hypogonadal men on TRT.nnnMETHODSnAn anonymous, prospective survey was distributed to men presenting for TRT at an academic urology clinic. The survey was organized into multiple domains including patient satisfaction and treatment motivation.nnnMAIN OUTCOME MEASURESnPatient satisfaction responses obtained via anonymous survey.nnnRESULTSnAverage patient age was 49 ± 0.7 years (n = 382). Injectable testosterone was chosen by 53%, gel-based regimens by 31%, and pellets by 17%. Overall, 70% of patients were satisfied with their TRT and 14% reported dissatisfaction. Satisfaction rates were similar between gels (68%), injections (73%), and implantable pellets (70%). Doctor recommendation was the sole significant reason for patients preferring gel-based TRT (66% vs. 37% injection users vs. 31% pellet users). Injectable TRT was favored because of lower cost (35% vs. 21% gel users vs. 19% pellet users). Pellets were favored for ease of use (64% vs. 44% injection users vs. 43% gel users) and convenience (58% vs. 26% injection users vs. 19% gel users). Pellets had increased rates of satisfaction within the first 12 months. Improvements in concentration and mood occurred at higher percentages in satisfied patients.nnnCONCLUSIONSnPatients are satisfied with TRT. Lower costs are important to patients on injections. Convenience and ease of use are central in choosing pellet therapy. Men on TRT should be questioned about mood and concentration because these factors exhibited the greatest improvements in satisfied patients.

Factors Influencing Patient Decisions to Initiate and Discontinue Subcutaneous Testosterone Pellets (Testopel) for Treatment of Hypogonadism

INTRODUCTIONnA variety of modalities for testosterone replacement therapy (TRT) are available, including topical gels, injections, and Testopel subcutaneous testosterone pellets (STP). STP are becoming more commonly utilized in the United States; however, patient preferences, expectations, and usage patterns regarding this therapy remain poorly characterized.nnnAIMnTo identify factors influencing patients decisions to initiate or discontinue STP.nnnMETHODSnA total of 175 men from an academic urology clinic who were currently using or who had previously used STP for hypogonadism received a 32-item electronic survey.nnnMAIN OUTCOME MEASURESnAssessment of the impact of convenience, efficacy, side effects, cost, and symptom relief on initiation and discontinuation of STP.nnnRESULTSnOne hundred and thirteen men (64.6% response rate) of mean age 51.4 years who previously underwent a mean of 2.8 STP implant procedures completed the survey. Fifty-nine (52.2%) and 40 (35.4%) men had switched to STP from topical gel and injection therapy, respectively, whereas 14 (12.4%) men initially started TRT with STP. Convenience (68.8%) was the most important factor in patients decision to start STP, while cost of the previous form of TRT (14.7%) was least important. At the time of the survey, 32 men (28.3%) had discontinued STP therapy. Cost of therapy (50%) was the primary factor in discontinuing STP. There was no difference in serum testosterone levels between men who continued STP and those who discontinued therapy (642.8 vs. 629.0u2009ng/dL, Pu2009=u20090.83). Overall, 68.1% of patients continued STP therapy at the time of survey completion.nnnCONCLUSIONSnConvenience is the most important factor in a patients decision to initiate STP; however, physician recommendation also plays a substantial role. Cost was the primary reason for discontinuation. Upon survey completion, greater than two-thirds of respondents elected to continue STP therapy. STP are a viable treatment option for hypogonadal men seeking a convenient and efficacious alternative modality of TRT.

Impact of the 2012 American Urological Association Vasectomy Guidelines on Post-Vasectomy Outcomes

PURPOSEnThe 2012 American Urological Association (AUA) vasectomy guidelines recommend the finding of rare nonmotile sperm, representing 100,000 or fewer nonmotile sperm per ml, as a metric of post-vasectomy success. At our institution success was previously defined as 2 sequential azoospermic centrifuged semen pellets. The criteria change of including rare nonmotile sperm as a success end point may simplify post-vasectomy followup and decrease the number of post-vasectomy semen analyses required to assure occlusive success.nnnMATERIALS AND METHODSnIn the context of the new 2012 guidelines we retrospectively reviewed and analyzed the records of 972 of the 1,740 vasectomies (55.9%) performed between January 2000 and June 2012 after which at least 1 post-vasectomy semen analysis was done.nnnRESULTSnA total of 1,919 post-vasectomy semen analyses were obtained from 972 patients with a mean ± SE age of 39.7 ± 0.2 years. Occlusive success was evident in 337 azoospermic men (36.4%), while 514 (52.9%) underwent 2 or more post-vasectomy semen analyses and 458 (47.1%) returned for a single post-vasectomy semen analysis but were lost to followup. Of these noncompliant patients 76.0% were azoospermic, 19.7% had rare nonmotile sperm, 1.5% had greater than 100,000 nonmotile sperm per ml and 2.8% had motile sperm. Three patients underwent repeat vasectomy for persistent rare nonmotile sperm. If the criteria defined by the 2012 guidelines had been used to monitor these men, the occlusive success rate would have improved to 97.6% (949 patients) (p <0.05). Repeat vasectomies as well as 896 subsequent post-vasectomy semen analyses would have been avoided.nnnCONCLUSIONSnThe AUA vasectomy guidelines provide clear, evidence-based criteria for vasectomy success. The guidelines simplify followup protocols, improve patient compliance and help avoid unnecessary post-vasectomy semen analyses and repeat vasectomies.

Men with a complete absence of normal sperm morphology exhibit high rates of success without assisted reproduction.

In couples with infertility, abnormal strict morphology of 0% normal forms (NF) is a criterion to proceed rapidly to in vitro fertilization (IVF). Since no data currently exist, we investigated the outcomes for men with 0% NF to determine reproductive success without the use of assisted reproductive technologies (ART). A cohort of 24 men with 0% NF were identified (2010-2013) with 27 randomly selected men with ≥4% NF as controls. Patient charts were reviewed with men contacted and administered an Institutional Review Board (IRB)-approved telephone questionnaire to ascertain outcomes. After a median follow-up time of 2.5 years, 29.2% of men with 0% NF did not require ART for their first pregnancy (controls = 55.6%, P ≤ 0.05). When all pregnancies were analyzed together, men with 0% NF achieved twenty pregnancies of which 75% did not require IVF (controls = thirty pregnancies; 76.7% did not require IVF). The average age of men and female partners was similar between men with 0% NF and ≥4% NF. All men had normal follicle-stimulating hormone (FSH), testosterone, prolactin, sex hormone-binding globulin (SHBG), and estradiol. Although, global semen parameters were worse in men with 0% NF, when a first pregnancy was a natural conception (NC), 100% of men with 0% NF (n = 7/7) and 37.5% of controls (n = 3/8) went on to have a subsequent pregnancy via NC. Men with 0% NF conceived without IVF in 29.2% of cases compared to 55.6% of controls. Strict morphology should not be used to predict fertilization, pregnancy, or live birth potential. In men with 0% NF, alternative modalities should be considered before immediate IVF.

Measurement of endothelial dysfunction via peripheral arterial tonometry predicts vasculogenic erectile dysfunction

Endothelial cell dysfunction is associated with cardiovascular disease and vasculogenic erectile dysfunction (ED). Measured via peripheral artery tonometry (PAT), endothelial dysfunction in the penis is an independent predictor of future cardiovascular events. The aim of the study was to determine whether measurement of endothelial dysfunction differentiates men with vasculogenic ED identified by duplex ultrasound from those without. A total of 142 men were retrospectively assessed using patient history, penile duplex ultrasonography (US) and PAT (EndoPAT 2000). ED was self-reported and identified on history. Vasculogenic ED was identified in men who exhibited a peak systolic velocity (PSV) of ⩽25u2009cmu2009s−1 at 15u2009min following vasodilator injection. The reactive hyperemia index (RHI), a measurement of endothelial dysfunction in medium/small arteries, and the augmentation index (AI), a measurement of arterial stiffness, were recorded via PAT. Penile duplex US was used to categorize men into those with ED (n=111) and those without ED (n=31). The cohort with ED had a PSV of 21±1u2009cmu2009s−1 (left cavernous artery) and 22±1u2009cmu2009s−1 (right cavernous artery). The control group without ED had values of 39±2u2009cmu2009s−1 (left) and 39±2u2009cmu2009s−1 (right). Given the potential for altered endothelial function in diabetes mellitus, we confirmed that hemoglobin A1c, urinary microalbumin and vibration pulse threshold were not different in men with vasculogenic ED and those without. RHI in patients with ED (1.85±0.06) was significantly decreased compared to controls (2.15±0.2) (P<0.05). The AI was unchanged when examined in isolation, and when standardized to heart rate. Measurement of endothelial function with EndoPAT differentiates men with vasculogenic ED from those without. RHI could be used as a non-invasive surrogate in the assessment of vasculogenic ED and to identify those patients with higher cardiovascular risk.

Vasectomy reversal: a clinical update.

Vasectomy is a safe and effective method of contraception used by 42-60 million men worldwide. Approximately 3%-6% of men opt for a vasectomy reversal due to the death of a child or divorce and remarriage, change in financial situation, desire for more children within the same marriage, or to alleviate the dreaded postvasectomy pain syndrome. Unlike vasectomy, vasectomy reversal is a much more technically challenging procedure that is performed only by a minority of urologists and places a larger financial strain on the patient since it is usually not covered by insurance. Interest in this procedure has increased since the operating microscope became available in the 1970s, which consequently led to improved patency and pregnancy rates following the procedure. In this clinical update, we discuss patient evaluation, variables that may influence reversal success rates, factors to consider in choosing to perform vasovasostomy versus vasoepididymostomy, and the usefulness of vasectomy reversal to alleviate postvasectomy pain syndrome. We also review the use of robotics for vasectomy reversal and other novel techniques and instrumentation that have emerged in recent years to aid in the success of this surgery.

The Role of Regulatory Proteins and S‐nitrosylation of Endothelial Nitric Oxide Synthase in the Human Clitoris: Implications for Female Sexual Function

INTRODUCTIONnDuring female sexual arousal, clitoral blood flow is controlled by endothelial nitric oxide synthase (eNOS) and its product, nitric oxide (NO). The mechanisms regulating eNOS activity and NO bioavailability in the clitoris are largely unknown.nnnAIMnTo identify proteins involved in regulation of eNOS activity within the clitoris and to evaluate the effects of S-nitrosoglutathione reductase (GSNO-R) and eNOS nitrosylation/denitrosylation on clitoral blood flow.nnnMETHODSnImmunohistochemistry for eNOS, caveolin-1 (Cav1), heat shock protein-90 (Hsp90), phosphodiesterase type 5 (PDE5), GSNO-R, and soluble guanylate cyclase (sGC) was performed on human and murine clitoral tissue. Western blot analysis was performed for eNOS, phosphorylated eNOS (phospho-eNOS, Ser1177), Cav1, Hsp90, sGC, PDE5, phosphoinositide 3-kinase (PI3K), Akt (protein kinase B), and GSNO-R on protein from human clitoral tissue. A biotin switch assay was used to analyze the S-nitrosylation of eNOS, nNOS, and GSNO-R. Clitoral blood flow was measured in wild-type and GSNO-R(-/-) mice at baseline and during cavernous nerve electrical stimulation (CNES).nnnMAIN OUTCOME MEASURESnLocalization of eNOS regulatory proteins and clitoral blood flow.nnnRESULTSneNOS and GSNO-R co-localized to the vascular endothelium and sinusoids of human clitoral tissue. Immunohistochemistry also localized Cav1 and Hsp90 to the endothelium and PDE5 and sGC to the trabecular smooth muscle. Expression of S-nitrosylated (SNO)-eNOS and SNO-GSNO-R was detected by biotin switch assays. Wild-type control mice exhibited increased clitoral blood flow with CNES whereas GSNO-R(-/-) animals failed to show an increase in blood flow.nnnCONCLUSIONSnSeveral key eNOS regulatory proteins are present in the clitoral tissue in a cellular specific pattern. S-nitrosylation of eNOS may also represent a key regulatory mechanism governing eNOS activation/deactivation since mice deficient in GSNO-R failed to increase clitoral blood flow. Additional studies are necessary to define the role of S-nitrosylation in the genital vascular response and its subsequent impact on female sexual function.