Factors affecting post-vasectomy semen analysis compliance in home- and lab-based testing.

INTRODUCTION: We used a home-based (HB) post-vasectomy semen analysis (PVSA) between 2014 and 2017, but we have since reverted to local lab-based (LB) testing. In this study, we compared PVSA compliance rates in HB and LB test settings and describe factors that may influence completion rates. METHODS: We retrospectively identified patients who underwent vasectomy at our institution. Surgeons X and Y performed vasectomies from 2014-2017 using a HB immunochromatographic PVSA kit. From 2017-2020, surgeon X used a local LB PVSA. We collected data on PVSA completion status and patient demographics to perform two analyses. HB testing was examined by assessing all patients who had a vasectomy from 2014-2017. Another compared HB and LB testing by looking at surgeon X vasectomies from 2014-2017 and 2017-2020. RESULTS: We identified 285 patients who underwent vasectomy from 2014-2017 and were assessed with HB testing. Compliance with PVSA was 35% with HB PVSA. Age at vasectomy, number of children, and surgeon influenced PVSA completion in the 2014-2017 cohort. Surgeon X PVSA completion was 29% for the HB (n=136) testing cohort and 46% for the LB (n=201) cohort (odds ratio 0.47, 95% confidence interval 0.29-0.74). Again, more children decreased PVSA completion. CONCLUSIONS: Compliance with PVSA testing was inadequate in both test settings, although it was significantly higher in local LB setting. Based on these findings, the convenience of HB testing appears to decrease compliance with PVSA, although surgeon factors may be influential. These findings may help surgeons identify factors that improve PVSA compliance rates.

Testosterone Replacement Options.

The treatment of male hypogonadism is complicated by the multitude of treatments available, the lack of a clear understanding of the differences between treatment modalities, barriers to treatment, and patient misperceptions, unrealistic expectations, and anxieties. This article is intended to help the practitioner better understand the challenges of testosterone replacement options in order to better counsel and treat their patients with hypogonadism.

Post-vasectomy semen analysis compliance with use of a home-based test.

INTRODUCTION Although the importance of post-vasectomy semen analysis (PVSA) is well known, compliance with this test has historically been low. We sought to compare compliance with PVSA when using a home-based testing kit with traditional office based microscopy, and to estimate the impact of compliance differences on the risk of undetected vasectomy failure. MATERIALS AND METHODS: A retrospective review of vasectomies performed by three providers was performed. Patients were prescribed either traditional office-based PVSA testing (Group 1) or home-based PVSA testing (Group 2). Compliance with PVSA testing was defined as completion of at least one PVSA test. Decision analysis methodology was applied to estimate the risk of undetected vasectomy failure in each group. RESULTS: A total of 226 vasectomies were reviewed, 141 in Group 1 and 85 in Group 2. The compliance rate was 65.96% in Group 1 compared to 76.47% in Group 2 (p = .095). When utilizing a single home-based test, the estimated risk of undetected vasectomy failure was 3.65% in Group 1 compared to 4.09% in Group 2. When utilizing two serial home-based tests, the estimated risk in Group 2 decreased to 2.87%. CONCLUSION: As home-based PVSA tests become more widely available, it is important to understand their impact. The availability of such tests may lead to improved compliance with PVSA testing. In turn, increased compliance may offer increased detection of vasectomy failure. Further study is needed with regard to the impact of home-based tests.

The Use of Penile Computed Tomography Cavernosogram in the Evaluation of Peyronie's Disease: A Pilot Study.

BACKGROUND: Clinical assessment of Peyronie disease (PD) is unreliable and difficult to reproduce. AIM: To assess the utility of the computed tomography cavernosography (CTC) in evaluating the penile functional abnormalities of PD. METHODS: Men were placed in the Philips IQon Spectral CT scanner (Phillips, Cambridge, MA, USA) in the supine position. The penis was injected with trimix (papaverine 30 mg/cc, phentolamine 2 mg/cc, and prostaglandin 20 mcg/cc) in the left proximal base using a 27-gauge syringe. Clinical effect was assessed after 5 minutes. If penile erection was less rigid than adequate for penetration, the dose was repeated until a satisfactory result was achieved. A subcutaneous injection of 1% lidocaine for local analgesia was then injected into the left subcoronal corpora. After the maximum erection was obtained, a 20-gauge angiocatheter was inserted into the anesthetized area. The angiocatheter was connected via intravenous tubing to a 60-cc luer lock syringe of 50% mixture of iodinated contrast in normal saline. The penis was manually inflated until maximum erection was achieved as per the patient's report. The patient then underwent computed tomography scan. Upon completion, a reversal dose of phenylephrine was administered through the angiocatheter. The angiocatheter was then removed, and a penile compression dressing was applied. OUTCOMES: Images were assessed for degree of curvature, presence of corporal involvement, and location of corporal involvement. RESULTS: 63 men underwent CTC. The average age was 57 years (95% confidence interval [CI]: 54, 60). Duration of PD was 5.2 years (95% CI: 3, 7). Diabetes and hypogonadism were found in 15% and 50% of men, respectively. The primary angulation was 52° (95% CI: 40, 60). Multiple angulations were found in 80% of men with 3 or more degrees of angulation in 14%. Bilateral corporal involvement was found in 87%, and proximal involvement was found in 64%. Dorsal/dorsolateral, ventral/ventrolateral, lateral, and hourglass/corkscrew deformities were seen in 58%, 23%, 12%, and 7%, respectively. Average dose of trimix (mg-papaverine + mg-phentolamine + mcg-PGE-1), contrast dose, and radiation dose per scan were 26 (22, 31), 55 cc (47, 63), and 770 mGy∗cm (902, 638), respectively. CLINICAL IMPLICATIONS: CTC may reveal additional information regarding the anatomy of the penis in men with PD which is not readily available by existing methods of evaluation. STRENGTHS & LIMITATIONS: We evaluated a small cohort of men with CTC which allowed for detailed visualization and assessment of their PD. This study is limited by the small sample of patients, retrospective nature, and absence of clinical outcomes which will require further study in the future. CONCLUSION: The CTC may be useful in clearly defining the corporal abnormalities in men with PD. McCullough AR, Trussler J, Alnammi M, et al. The Use of Penile Computed Tomography Cavernosogram in the Evaluation of Peyronie's Disease: A Pilot Study. J Sex Med 2020;17:1041-1043.

Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials.

AIMS: Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit. METHODS: ION-02 (intravesical instillation) and ION-03 (direct injection) were double-blind, placebo-controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION-02 participants received either 5000 µg or 10 000 µg URO-902, or placebo. ION-03 participants received either 16 000 or 24 000 µg URO-902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO-902 administration; secondary efficacy variables also were evaluated. RESULTS: Among the safety outcomes, there were no dose-limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION-02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO-902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION-03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, -2.16, P = .044; 24 000 µg, -2.73, P = .047) were observed 1 week after injection. CONCLUSION: Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation.

Stress and the medial temporal lobe at rest: Functional connectivity is associated with both memory and cortisol.

When acute stress is experienced immediately after memory encoding (i.e., post-encoding stress) it can significantly impact subsequent memory for that event. For example, recent work has suggested that post-encoding stress occurring in a different context from encoding impairs memory. However, the neural processes underlying these effects are poorly understood. We aimed to expand this understanding by conducting an analysis of resting functional connectivity in the period following post-encoding stress that occurred in a different context than encoding, using seed regions in the medial temporal lobes known for their roles in memory. In the current study of 44 males randomized to stress (n = 23) or control (n = 21) groups, we found that stress increased cortisol, impaired recollection of neutral materials, and altered functional connectivity with medial temporal lobe regions. Although stress did not significantly alter hippocampus-amygdala functional connectivity, relative to participants in the control group, participants in the post-encoding stress group showed lower functional connectivity between the hippocampus and a region with a peak in the superior temporal gyrus. Across participants in both groups, functional connectivity between these regions was related to greater increases in cortisol, and it was also inversely related to recollection of neutral materials. In contrast, the stress group showed greater parahippocampal cortex functional connectivity with a region in the left middle temporal gyrus than the control group. Moreover, greater functional connectivity between the parahippocampal cortex and the observed cluster in the middle temporal gyrus was associated with greater cortisol changes from pre- to post-manipulation, but was not related to differences in memory. The results show that post-encoding stress can alter the resting-state functional connectivity between the medial temporal lobe and neocortex, which may help explain how stress impacts memory.

Using acute stress to improve episodic memory: The critical role of contextual binding.

Previous research has shown that encountering a brief stressor shortly after learning can be beneficial for memory. Recent studies, however, have shown that post-encoding stress does not benefit all recently encoded memories, and an adequate theoretical account of these effects remains elusive. The current study tested a contextual binding account of post encoding stress by examining the effect of varying the context in which the stressor was experienced. Participants encoded a mixture of negative and neutral images, immediately followed by a stressor (i.e., socially evaluated cold pressor) or a non-stress control task. Half of the participants received the stress/control manipulation in the same context as the study materials and half were moved to another context (i.e., a different room with a different experimenter). Two days later all participants returned to the original study room and received a recognition memory test. The results indicated that stress increased recognition memory only when the stressor occurred in the same context as the study materials, whereas stress did not benefit memory if the stressor occurred in a different context. Moreover, stress related increases in salivary cortisol were related to increases in memory when the stressor occurred in the same context as the study materials but not when the context changed. Similar effects were observed for negative and neutral materials and for males and females. These results are consistent with a contextual binding account and suggest that stress acts on memory by enhancing the encoding of the ongoing context of the stressor which benefits memory for the immediately preceding events that share the same context.

A 52-Week Study of Dose Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-Injector.

PURPOSE: In this open label, single arm, dose blinded, 52-week registration phase study we evaluated the efficacy and safety of a subcutaneous testosterone enanthate auto-injector administered weekly to men with hypogonadism. MATERIALS AND METHODS: A total of 150 patients were initiated on a 75 mg subcutaneous testosterone enanthate auto-injector self-administered weekly. Dose adjustments were made at week 7 to 50, 75 or 100 mg testosterone enanthate based on the week 6 total testosterone trough concentration. If required, dose adjustments continued through the extended treatment phase. Pharmacokinetic and clinical laboratory parameters, treatment emergent adverse events and injection site reactions were captured. RESULTS: The primary end point was met since 92.7% of patients achieved an average total testosterone concentration of 300 to 1,100 ng/dl (mean ± SD 553.3 ± 127.29) at week 12. A maximum concentration of less than 1,500 ng/dl was achieved by 91.3% of patients and no patient had a level greater than 1,800 ng/dl at week 12. The mean total testosterone trough concentration was 487.2 ± 153.33 ng/dl at week 52. Of the patients more than 95% reported no injection related pain. The most frequently reported treatment emergent adverse events were increased hematocrit, hypertension and increased prostate specific antigen, which led to discontinuation in 30 men. There were no study drug related serious adverse events. CONCLUSIONS: The dose adjusted subcutaneous testosterone enanthate auto-injector demonstrated a steady serum total testosterone pharmacokinetic profile with small peak and trough fluctuations. The device was safe, well tolerated and virtually painless, indicating that this subcutaneous testosterone enanthate auto-injector offers a testosterone delivery system that is a convenient weekly option to treat testosterone deficiency.

Hypoandrogenism is Prevalent in Males With Urethral Stricture Disease and is Associated with Longer Strictures.

OBJECTIVE: To assess the association of hypoandrogenism (HA) with urethral stricture disease in a series of patients undergoing urethroplasty at 2 institutions. HA has recently been associated with increased urethral atrophy in artificial sphincter failures and decreased androgen receptors and periurethral vascularity. HA might be an etiologic factor in urethral stricture disease. METHODS: We reviewed the charts in 202 men with anterior urethral strictures between 2011 and 2017. We excluded patients with radiation-induced stricture, previous prostatectomy, previous urethroplasty, pelvic fracture-related strictures, or those on testosterone replacement. We defined HA by a total testosterone of less than 300 ng/dL. We used as age-matched cohort from a national database (National Health and Nutrition Examination Survey), as a reference. Stricture characteristics, such as length, location, and etiology were compared in HA and eugonadal groups. RESULTS: Of 202 men with anterior urethral strictures, we excluded 45. Of the remaining 157 patients, 115 (73%) had preoperative testosterone measurements. Overall, hypoandrogenism (HA) was found in 65 of 115 (57%) men in the urethral stricture group compared with 28% of age-matched men in the national database. Mean stricture length in HA and eugonadal men was 7.2 cm and 4.8 cm, respectively (P = .02). CONCLUSION: HA may be more prevalent and associated with increased disease severity in men with anterior urethral strictures. The relationship between HA and stricture formation and its potential impact on therapeutic outcomes merit further prospective investigation.

Reward anticipation modulates the effect of stress-related increases in cortisol on episodic memory.

When acute stress is experienced shortly after an event is encoded into memory, this can slow the forgetting of the study event, which is thought to reflect the effect of cortisol on consolidation. In addition, when events are encoded under conditions of high reward they tend to be remembered better than those encoded under non-rewarding conditions, and these effects are thought to reflect the operation of the dopaminergic reward system. Although both modulatory systems are believed to impact the medial temporal lobe regions critical for episodic memory, the manner, and even the extent, to which these two systems interact is currently unknown. To address this question in the current study, participants encoded words under reward or non-reward conditions, then one half of the participants were stressed using the social evaluation cold pressor task and the other half completed a non-stress control task. After a two-hour delay, all participants received a free recall and recognition memory test. There were no significant effects of stress or reward on overall memory performance. However, for the non-reward items, increases in stress-related cortisol in stressed participants were related to increases in recall and increases in recollection-based recognition responses. In contrast, for the reward items, increases in stress-related cortisol were not related to increases in memory performance. The results indicate that the stress and the reward systems interact in the way they impact episodic memory. The results are consistent with tag and capture models in the sense that cortisol reactivity can only affect non-reward items because plasticity-related products are already provided by reward anticipation.

A retrospective review of single-institution outcomes with robotic-assisted microsurgical varicocelectomy.

We report the largest single-center experience with robotic-assisted microscopic varicocelectomy (RAMV) in male infertility. From August 2012 to February 2015, men with infertility of at least a year and varicoceles underwent RAMV by a single surgeon. Varicocele was diagnosed on physical examination and confirmed by ultrasound by a single ultrasonographer. Preoperative hormone panel, semen analyses, and testicular Doppler ultrasound were obtained from all men and repeated at 3 months. One hundred and forty consecutive men (258 varicocelectomies) were included. Mean age and duration of infertility was 36.4 and 2.8 years, respectively. Median total and free testosterone increased by 145 ng dl-1 and 4.3 pcg ml-1 (44.3%), respectively (P < 0.0001). Median sperm concentration increased by 37.3% (P < 0.03). Median sperm motility and morphology did not significantly change. Median left and right testicular volume increased by 22.3% (P < 0.0001) and 12.6% (P < 0.0006), respectively. Hydroceles occurred 0.8% of procedures. We had no testicular artery injuries. Persistence of varicocele by Doppler ultrasound was 9.6%. Only 37.3% of patients required pain medications postoperatively. We concluded that RAMV is a safe and effective alternative for varicocele repair with outcomes comparable to historical traditional microsurgical approach.

The effects of acute stress on episodic memory: A meta-analysis and integrative review.

A growing body of research has indicated that acute stress can critically impact memory. However, there are a number of inconsistencies in the literature, and important questions remain regarding the conditions under which stress effects emerge as well as basic questions about how stress impacts different phases of memory. In this meta-analysis, we examined 113 independent studies in humans with 6,216 participants that explored effects of stress on encoding, postencoding, retrieval, or postreactivation phases of episodic memory. The results indicated that when stress occurred prior to or during encoding it impaired memory, unless both the delay between the stressor and encoding was very short and the study materials were directly related to the stressor, in which case stress improved encoding. In contrast, postencoding stress improved memory unless the stressor occurred in a different physical context than the study materials. When stress occurred just prior to or during retrieval, memory was impaired, and these effects were larger for emotionally valenced materials than neutral materials. Although stress consistently increased cortisol, the magnitude of the cortisol response was not related to the effects of stress on memory. Nonetheless, the effects of stress on memory were generally reduced in magnitude for women taking hormonal contraceptives. These analyses indicate that stress disrupts some episodic memory processes while enhancing others, and that the effects of stress are modulated by a number of critical factors. These results provide important constraints on current theories of stress and memory, and point to new questions for future research. (PsycINFO Database Record

"Cherchez La Femme": Modulation of Estrogen Receptor Function With Selective Modulators: Clinical Implications in the Field of Urology.

INTRODUCTION: Selective estrogen receptor modulators (SERMs) have been used off-label in men for more than 50 years. SERMs exert their action on the estrogen receptor agonistically or antagonistically. A fundamental knowledge of the complex molecular action and physiology of SERMs is important in understanding their use and future directions of study in men. AIM: To review the basic science and mechanism of the action of estrogens, the estrogen receptor, and SERMs, and the existing clinical publications on the use of SERMs in men for infertility and hypogonadism with their strengths and weaknesses and to identify the need for future studies. METHODS: After a review of publications on the basic science of estrogen receptors, a chronologic review of published evidence-based studies on the use of SERMs in men for infertility and hypogonadism was undertaken. MAIN OUTCOME MEASURES: Clinical publications were assessed for type of study, inclusion criteria, outcome measurements, and results. Strengths and weaknesses of the publications were assessed and discussed. RESULTS: Few prospective rigorously controlled trials have been undertaken on the use of SERMs in men. Most existing trials are largely retrospective anecdotal studies with inconsistent inclusion and end-point measurements. The SERMs are complex and at times can produce paradoxical results. Their action likely depends on the genetics of the individual, his tissue-specific composition of estrogen receptors, the molecular structure and pharmacodynamics of the SERMs, and their metabolism. CONCLUSION: Rigorously controlled trials of the use of SERMs in men are needed to better identify their clinical benefit and long-term safety in infertile and hypogonadal men. Recent placebo-controlled pharmaceutical industry SERM trials have demonstrated short-term safety and efficacy in men with secondary hypogonadism and eventually might provide an alternative to exogenous testosterone replacement therapy in men with secondary hypogonadism. Helo S, Wynia B, McCullough A. "Cherchez La Femme": Modulation of Estrogen Receptor Function With Selective Modulators: Clinical Implications in the Field of Urology. Sex Med Rev 2017;5:365-386.

Sexual Rehabilitation After Treatment for Prostate Cancer-Part 1: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. AIM: To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning prevention and management strategies for post-RP erectile function impairment in terms of preoperative patient characteristics and intraoperative factors that could influence erectile function recovery. METHODS: A literature search was performed using Google and PubMed databases for English-language original and review articles published up to August 2016. MAIN OUTCOME MEASURES: Levels of evidence (LEs) and grades of recommendations (GRs) based on a thorough analysis of the literature and committee consensus. RESULTS: Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 1 states that clinicians should discuss the occurrence of postsurgical erectile dysfunction (temporary or permanent) with every candidate for RP (expert opinion, clinical principle). Recommendation 2 states that validated instruments for assessing erectile function recovery such as the International Index of Erectile Function and Expanded Prostate Cancer Index Composite questionnaires are available to monitor EF recovery after RP (LE = 1, GR = A). Recommendation 3 states there is insufficient evidence that a specific surgical technique (open vs laparoscopic vs robot-assisted radical prostatectomy) promotes better results in postoperative EF recovery (LE = 2, GR = C). Recommendation 4 states that recognized predictors of EF recovery include but are not limited to younger age, preoperative EF, and bilateral nerve-sparing surgery (LE = 2, GR = B). Recommendation 5 states that patients should be informed about key elements of the pathophysiology of postoperative erectile dysfunction, such as nerve injury and cavernous venous leak (expert opinion, clinical principle). CONCLUSIONS: This article discusses Recommendations 1 to 5 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment for Prostate Cancer-Part 1: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:285-296.

Sexual Rehabilitation After Treatment For Prostate Cancer-Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. AIM: To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning management strategies for post-RP erectile function impairment and to analyze post-RP sexual dysfunction other than erectile dysfunction. METHODS: A literature search was performed using Google and PubMed database for English-language original and review articles published up to August 2016. MAIN OUTCOME MEASURES: Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. RESULTS: Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 6 states that the recovery of postoperative erectile function can take several years (LE = 2, GR = C). Recommendation 7 states there are conflicting data as to whether penile rehabilitation with phosphodiesterase type 5 inhibitors improves recovery of spontaneous erections (LE = 1, GR = A). Recommendation 8 states that the data are inadequate to support any specific regimen as optimal for penile rehabilitation (LE = 3, GR = C). Recommendation 9 states that men undergoing RP (any technique) are at risk of sexual changes other than erectile dysfunction, including decreased libido, changes in orgasm, anejaculation, Peyronie-like disease, and changes in penile size (LE = 2, GR = B). CONCLUSION: This article discusses Recommendations 6 to 9 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment For Prostate Cancer-Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:297-315.

Stress as a mnemonic filter: Interactions between medial temporal lobe encoding processes and post-encoding stress.

Acute stress has been shown to modulate memory for recently learned information, an effect attributed to the influence of stress hormones on medial temporal lobe (MTL) consolidation processes. However, little is known about which memories will be affected when stress follows encoding. One possibility is that stress interacts with encoding processes to selectively protect memories that had elicited responses in the hippocampus and amygdala, two MTL structures important for memory formation. There is limited evidence for interactions between encoding processes and consolidation effects in humans, but recent studies of consolidation in rodents have emphasized the importance of encoding "tags" for determining the impact of consolidation manipulations on memory. Here, we used functional magnetic resonance imaging in humans to test the hypothesis that the effects of post-encoding stress depend on MTL processes observed during encoding. We found that changes in stress hormone levels were associated with an increase in the contingency of memory outcomes on hippocampal and amygdala encoding responses. That is, for participants showing high cortisol reactivity, memories became more dependent on MTL activity observed during encoding, thereby shifting the distribution of recollected events toward those that had elicited relatively high activation. Surprisingly, this effect was generally larger for neutral, compared to emotionally negative, memories. The results suggest that stress does not uniformly enhance memory, but instead selectively preserves memories tagged during encoding, effectively acting as mnemonic filter. © 2016 Wiley Periodicals, Inc.

Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment.

OBJECTIVES: To determine the relative concentrations of enclomiphene (ENC) and zuclomiphene (ZUC) isomers in men with hypogonadism on long-term clomiphene citrate (CC) therapy, and to determine whether patient age, body mass index (BMI) or duration of therapy were predictive of relative concentrations of ENC and ZUC. PATIENTS AND METHODS: Men already receiving CC 25 mg daily therapy for secondary hypogonadism for a minimum of 6 weeks were recruited to have their ENC and ZUC levels assessed. Total testosterone, free testosterone, oestradiol, follicle stimulating hormone (FSH), and luteinizing hormone (LH) before initiation of and while on CC therapy were recorded for all patients. Patient demographics including age, BMI and medical comorbidites were recorded. Serum samples were obtained at the time of enrolment to determine ENC and ZUC concentrations. RESULTS: A total of 15 men were enrolled in the period from June 2015 to August 2015. The median (range) patient age was 36 (22-70) years, BMI 32.0 (21.1-40.3) kg/m2 and duration of treatment 25.9 (1.7-86.6) months. Baseline median total testosterone, oestradiol and LH levels were 205.0 ng/dL, 17.0 pg/mL and 4.0 mlU/mL, respectively. The post-treatment median total testosterone, oestradiol and LH level increased to 488.0 ng/dL, 34.0 pg/mL and 6.1 mIU/mL, respectively (all P<0.001). The median ENC and ZUC concentrations were 2.2 and 44.0 ng/mL, respectively. After at least 6 weeks of CC therapy, the median ZUC: ENC serum concentration ratio was 20:1. On linear regression analysis. patient age, BMI, duration of treatment and serum testosterone levels were not predictive of ENC or ZUC concentrations. CONCLUSIONS: Long-term CC therapy resulted in a significant alteration of ENC and ZUC concentrations, with ZUC as the predominant isomer. Given the vastly different biochemical and toxicological properties of ENC and ZUC, this study supports the need for the development of a pure selective oestrogen receptor antagonist for the treatment of men with hypogonadism.

Diagnosis and Treatment of Testosterone Deficiency: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Testosterone deficiency (TD), also known as hypogonadism, is a condition affecting a substantial proportion of men as they age. The diagnosis and management of TD can be challenging and clinicians should be aware of the current literature on this condition. AIM: To review the available literature concerning the diagnosis and management of TD and to provide clinically relevant recommendations from the Fourth International Consultation for Sexual Medicine (ICSM) meeting. METHODS: A literature search was performed using the PubMed database for English-language original and review articles published or e-published up to January 2016. MAIN OUTCOME MEASURES: Levels of evidence (LoEs) and grades of recommendations are provided based on a thorough analysis of the literature and committee consensus. RESULTS: Recommendations were given for 12 categories of TD: definition, clinical diagnosis, routine measurement, screening questionnaires, laboratory diagnosis, threshold levels for the biochemical diagnosis of TD, prostate cancer, cardiovascular disease, fertility, testosterone (T) formulations, alternatives to T therapy, and adverse events and monitoring. A total of 42 recommendations were made: of these, 16 were unchanged from the Third ICSM and 26 new recommendations were made during this Fourth ICSM. Most of these recommendations were supported by LoEs 2 and 3. Several key new recommendations include the following: (i) the clinical manifestations of TD occur as a result of decreased serum androgen concentrations or activity, regardless of whether there is an identified underlying etiology [LoE = 1, Grade = A]; (ii) symptomatic men with total T levels lower than 12 nmol/L or 350 ng/dL should be treated with T therapy [LoE = 1, Grade = C]; (iii) a trial of T therapy in symptomatic men with total T levels higher than 12 nmol/L or 350 ng/dL can be considered based on clinical presentation [LoE = 3, Grade = C]; (iv) there is no compelling evidence that T treatment increases the risk of developing prostate cancer or that its use is associated with prostate cancer progression [LoE = 1, Grade = C]; and (v) the weight of evidence indicates that T therapy is not associated with increased cardiovascular risk [LoE = 2, Grade = B]. CONCLUSION: TD is an important condition that can profoundly affect the sexual health of men. We provide guidance regarding its diagnosis and management. Men with TD who receive treatment often experience resolution or improvement in their sexual symptoms and non-sexual health benefits.