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.

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.

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.

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.

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.

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.

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.

Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement.

OBJECTIVES: To determine the effects of daily oral doses of enclomiphene citrate compared with topical testosterone gel treatment on serum total testosterone (TT), luteinising hormone (LH), follicle-stimulating hormone (FSH), and sperm counts in men with secondary hypogonadism. PATIENTS AND METHODS: Two parallel randomised, double-blind, double-dummy, placebo-controlled, multicentre, phase III studies were undertaken to evaluate two doses of enclomiphene citrate vs testosterone gel (AndroGel(®) 1.62%) on TT, LH, FSH, and sperm counts in overweight men aged 18-60 years with secondary hypogonadism. Men were screened and enrolled in the trials (ZA-304 and ZA-305). All enrolled men had early morning serum TT levels in the low or low normal range (≤300 ng/dL; ≤10.4 nmol/L) and had low or normal LH (<9.4 IU/L) levels measured on two separate occasions 2-10 days apart. Serum samples were obtained over the course of the study to determine relevant hormone levels at baseline and after 16 weeks of treatment. Men provided semen samples twice to enroll at the beginning and twice at the end of the study. RESULTS: TT levels increased between baseline and after 16 weeks of treatment in all the treatment groups. FSH and LH levels increased in the enclomiphene citrate groups and decreased in the testosterone gel group at 16 weeks. Enclomiphene citrate maintained sperm concentration in the normal range over the treatment period, while there was a marked reduction in spermatogenesis in the testosterone gel group. CONCLUSIONS: Enclomiphene citrate consistently increased serum TT, LH and FSH, restoring normal levels of serum TT. Enclomiphene citrate treatment maintained sperm concentrations in the normal range. The effects on TT were also seen with testosterone replacement via testosterone gel but sperm counts were not maintained.

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015).

INTRODUCTION: Treatment of erectile dysfunction is based on pharmacotherapy for most patients. AIM: To review the current data on pharmacotherapy for erectile dysfunction based on efficacy, psychosocial outcomes, and safety outcomes. METHODS: A review of the literature was undertaken by the committee members. All related articles were critically analyzed and discussed. 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: Ten recommendations are provided. (i) Phosphodiesterase type 5 (PDE5) inhibitors are effective, safe, and well-tolerated therapies for the treatment of men with erectile dysfunction (LE = 1, GR = A). (ii) There are no significant differences in efficacy, safety, and tolerability among PDE5 inhibitors (LE = 1, GR = A). (iii) PDE5 inhibitors are first-line therapy for most men with erectile dysfunction who do not have a specific contraindication to their use (LE = 3, GR = C). (iv) Intracavernosal injection therapy with alprostadil is an effective and well-tolerated treatment for men with erectile dysfunction (LE = 1, GR = A). (v) Intracavernosal injection therapy with alprostadil should be offered to patients as second-line therapy for erectile dysfunction (LE = 3, GR = C). (vi) Intraurethral and topical alprostadil are effective and well-tolerated treatments for men with erectile dysfunction (LE = 1, GR = A). (vii) Intraurethral and topical alprostadil should be considered second-line therapy for erectile dysfunction if available (LE = 3, GR = C). (viii) Dose titration of PDE5 inhibitors to the maximum tolerated dose is strongly recommended because it increases efficacy and satisfaction from treatment (LE = 2, GR = A). (ix) Treatment selection and follow-up should address the psychosocial profile and the needs and expectations of a patient for his sexual life. Shared decision making with the patient (and his partner) is strongly recommended (LE = 2, GR = A). (x) Counterfeit medicines are potentially dangerous. It is strongly recommended that physicians educate their patients to avoid taking any medication from unauthorized sources (LE = 2, GR = A). The first seven recommendations are the same as those from the Third International Consultation for Sexual Medicine and the last three are new recommendations. CONCLUSION: PDE5 inhibitors remain a first-line treatment option because of their excellent efficacy and safety profile. This class of drugs is continually developed with new molecules and new formulations. Intracavernosal injections continue to be an established treatment modality, and intraurethral and topical alprostadil provide an alternative, less invasive treatment option.

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.

Differential effects of stress-induced cortisol responses on recollection and familiarity-based recognition memory.

Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol on the processes underlying recognition memory. Stress was induced with a cold-pressor test after incidental encoding of emotional and neutral pictures, and recollection and familiarity-based recognition memory were measured one day later. The relationship between stress-induced cortisol responses and recollection was non-monotonic, such that subjects with moderate stress-related increases in cortisol had the highest levels of recollection. In contrast, stress-related cortisol responses were linearly related to increases in familiarity. In addition, measures of cortisol taken at the onset of the experiment showed that individuals with higher levels of pre-learning cortisol had lower levels of both recollection and familiarity. The results are consistent with the proposition that hippocampal-dependent memory processes such as recollection function optimally under moderate levels of stress, whereas more cortically-based processes such as familiarity are enhanced even with higher levels of stress. These results indicate that whether post-encoding stress improves or disrupts recognition memory depends on the specific memory process examined as well as the magnitude of the stress-induced cortisol response.

A Randomized Prospective Double-Blind Comparison Trial of Clomiphene Citrate and Anastrozole in Raising Testosterone in Hypogonadal Infertile Men.

AIM: Clomiphene citrate (CC) and anastrozole (AZ) have been used off label to increase testosterone (T) in hypogonadal infertile men (HIM). Both medications have been shown to increase T with different effects on estradiol (E2) and T-to-E2 ratios. There are no reported randomized trials comparing CC and AZ to improve T levels in HIM. We aimed to establish equivalence of CC vs. AZ with respect to improvement in T levels in HIM. METHODS: We randomized 26 HIM (T less than 350 ng/dL and normal luteinizing hormone [LH]). Patients were randomized to CC (25 mg/day) or AZ (1 mg/day) for 12 weeks. Hormones assayed were total T, free T, E2, LH, follicle stimulating hormone (FSH), and sex hormone binding globulin (SHBG). Patient-reported outcomes were the International Index of Erectile Function, Erection Hardness Scale, and the Androgen Deficiency in the Aging Male questionnaires. Blood tests and questionnaires were recorded at baseline, 6 and 12 weeks. Semen analyses were performed at baseline and 12 weeks. RESULTS: T increased significantly from baseline in both groups at 6 and 12 weeks. There was a significantly larger increase in T and mean increase from baseline in CC vs. AZ (571 vs. 408 ng/dL, respectively). Whereas E-2 levels increased in the CC group, they decreased in the AZ group. Though both groups demonstrated an increase in T-to-E-2 ratio from baseline, statistic significance at 6 and 12 weeks was only achieved with AZ. Neither group demonstrated significant changes in seminal parameters or patient-reported outcomes. CONCLUSIONS: We failed to demonstrate equivalence of CC vs. AZ. CC resulted in significantly higher T levels than AZ. AZ resulted in a significantly larger increase in T/E-2 ratio than CC. No significant differences between CC and AZ on seminal parameters or patient-reported outcomes were demonstrated.

The International Society for Sexual Medicine's Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men.

INTRODUCTION: In 2014, the International Society for Sexual Medicine (ISSM) convened a panel of experts to develop an evidence-based process of care for the diagnosis and management of testosterone deficiency (TD) in adult men. The panel considered the definition, epidemiology, etiology, physiologic effects, diagnosis, assessment and treatment of TD. It also considered the treatment of TD in special populations and commented on contemporary controversies about testosterone replacement therapy, cardiovascular risk and prostate cancer. AIM: The aim was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of diagnosis and management of TD for clinicians without expertise in endocrinology, such as physicians in family medicine and general urology practice. METHOD: A comprehensive literature review was performed, followed by a structured, 3-day panel meeting and 6-month panel consultation process using electronic communication. The final guideline was compiled from reports by individual panel members on areas reflecting their special expertise, and then agreed by all through an iterative process. RESULTS: This article contains the report of the ISSM TD Process of Care Committee. It offers a definition of TD and recommendations for assessment and treatment in different populations. Finally, best practice treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with TD. CONCLUSION: Development of a process of care is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to new insights into the pathophysiology of TD, as well as new, efficacious and safe treatments. We recommend that this process of care be reevaluated and updated by the ISSM in 4 years.

Coadministration of anastrozole sustains therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion.

INTRODUCTION: Current U.S. Food and Drug Administration-approved therapies for hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP) require a minor office procedure every 3 to 4 months. The need for repeated insertions increases the likelihood of a complication. Anastrozole (AZ) is an aromatase inhibitor that has been used off-label for the treatment of male hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and increasing gonadotropin (GTP) levels. AIM: We hypothesized that the concomitant use of AZ with TP insertions would sustain therapeutic T levels and increase the interval between TP insertions. METHODS: Men treated with TP for hypogonadism at an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a way of potentially decreasing the frequency of TP insertions. Total T (TT), free T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle-stimulating hormone FSH levels were obtained prior to T replacement and at 6 and 15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics, TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a Tukey's test. MAIN OUTCOME MEASURE: TT level at 6, 15, or >15 weeks from TP insertion. RESULTS: Thirty-eight men with 65 insertions were analyzed. The TP AZ group had significantly higher TT and FT levels than the TP group at >120 days (P < 0.05). The TP group had significantly higher E2 levels at all time points (P < 0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion in TP AZ was 198 days vs. 128 days in the TP group. CONCLUSION: Men on TP AZ maintain therapeutic T levels longer than men on TP alone and have significantly less GTP suppression.

A pilot study to determine penile oxygen saturation before and after vacuum therapy in patients with erectile dysfunction after radical prostatectomy.

INTRODUCTION: Provoked and spontaneous nocturnal erections are thought to play a role in maintenance of male sexual health through oxygenation of the corpus cavernosa. Conversely, hypoxia is thought to be an etiological factor in the pathogenesis of cavernosal fibrosis and long-term erectile dysfunction. It has been hypothesized that the early penile hypoxia after radical prostatectomy (RP) may lead to fibrosis and consequently a decrease in stretched penile length and long-term erectile dysfunction. AIM: The aim of this study was to assess the changes in penile tissue oxygenation with vacuum erection device (VED) use. METHODS: Twenty men between 2 and 24 months following RP were enrolled prospectively. Each man cycled a VED to achieve full erection 10 consecutive times over a period of approximately 2 minutes without constriction ring. MAIN OUTCOME MEASURES: Tissue oximetry was measured at baseline and immediately after VED using a tissue oximeter at five sites: right thigh, right corpora, glans, left corpora, and left thigh. Additional measurements were captured over the course of an hour. RESULTS: Mean age and time from surgery was 58.2 years and 12.6 months, respectively, and the average Sexual Health Inventory for Men score was 7. Use of the VED significantly increased both glanular and corporal oximetry relative to the baseline values for the entire 60 minutes. An initial increase of 55% was seen in corporal oxygenation with VED use. CONCLUSIONS: This is the first study demonstrating that a single, brief application of the VED without a constriction ring results in significant improvement in penile oxygen saturation. The use of a VED has significant benefits for patients both with regard to cost and invasiveness when compared with other penile rehabilitation protocols.

Cold-pressor stress after learning enhances familiarity-based recognition memory in men.

Stress that is experienced after items have been encoded into memory can protect memories from the effects of forgetting. However, very little is known about how stress impacts recognition memory. The current study investigated how an aversive laboratory stressor (i.e., the cold-pressor test) that occurs after information has been encoded into memory affects subsequent recognition memory in an immediate and a delayed test (i.e., 2-h and 3-month retention interval). Recognition was assessed for negative and neutral photographs using a hybrid remember/know confidence procedure in order to characterize overall performance and to separate recollection- and familiarity-based responses. The results indicated that relative to a non-stress control condition, post-encoding stress significantly improved familiarity but not recollection-based recognition memory or free recall. The beneficial effects of stress were observed in males for negative and neutral materials at both immediate and long-term delays, but were not significant in females. The results indicate that aversive stress can have long-lasting beneficial effects on the memory strength of information encountered prior to the stressful event.

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.