Case Report: Longitudinal follow-up and testicular sperm extraction in a patient with a pathogenic NR5A1 (SF-1) frameshift variant: p.(Phe70Serfs*5).

Background: Steroidogenic factor 1 (SF-1), encoded by the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene, is a transcriptional factor crucial for adrenal and gonadal organogenesis. Pathogenic variants of NR5A1 are responsible for a wide spectrum of phenotypes with autosomal dominant inheritance including disorders of sex development and oligospermia-azoospermia in 46,XY adults. Preservation of fertility remains challenging in these patients. Objective: The aim was to offer fertility preservation at the end of puberty in an NR5A1 mutated patient. Case report: The patient was born of non-consanguineous parents, with a disorder of sex development, a small genital bud, perineal hypospadias, and gonads in the left labioscrotal fold and the right inguinal region. Neither uterus nor vagina was detected. The karyotype was 46,XY. Anti-Müllerian hormone (AMH) and testosterone levels were low, indicating testicular dysgenesis. The child was raised as a boy. At 9 years old, he presented with precocious puberty treated by triptorelin. At puberty, follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone levels increased, whereas AMH, inhibin B, and testicular volume were low, suggesting an impaired Sertoli cell function and a partially preserved Leydig cell function. A genetic study performed at almost 15 years old identified the new frameshift variant NM_004959.5: c.207del p.(Phe70Serfs*5) at a heterozygous state. He was thus addressed for fertility preservation. No sperm cells could be retrieved from three semen collections between the ages of 16 years 4 months and 16 years 10 months. A conventional bilateral testicular biopsy and testicular sperm extraction were performed at 17 years 10 months of age, but no sperm cells were found. Histological analysis revealed an aspect of mosaicism with seminiferous tubules that were either atrophic, with Sertoli cells only, or presenting an arrest of spermatogenesis at the spermatocyte stage. Conclusion: We report a case with a new NR5A1 variant. The fertility preservation protocol proposed at the end of puberty did not allow any sperm retrieval for future parenthood.

Delaying testicular sperm extraction in 47,XXY Klinefelter patients does not impair the sperm retrieval rate, and AMH levels are higher when TESE is positive.

STUDY QUESTION: Should testicular sperm extraction (TESE) in non-mosaic 47,XXY Klinefelter syndrome (KS) patients be performed soon after puberty or could it be delayed until adulthood? SUMMARY ANSWER: The difference in sperm retrieval rate (SRR) in TESE was not significant between the 'Young' (15-22 years old) cohort and the 'Adult' (23-43 years old) cohort of non-mosaic KS patients recruited prospectively in parallel. WHAT IS KNOWN ALREADY: Several studies have tried to define predictive factors for TESE outcome in non-mosaic KS patients, with very heterogeneous results. Some authors have found that age was a pejorative factor and recommended performing TESE soon after puberty. To date, no predictive factors have been unanimously recognized to guide clinicians in deciding to perform TESE in azoospermic KS patients. STUDY DESIGN, SIZE, DURATION: Two cohorts (Young: 15-22 years old; Adult: 23-43 years old) were included prospectively in parallel. A total of 157 non-mosaic 47,XXY KS patients were included between 2010 and 2020 in the reproductive medicine department of the University Hospital of Lyon, France. However 31 patients gave up before TESE, four had cryptozoospermia and three did not have a valid hormone assessment; these were excluded from this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data for 119 patients (61 Young and 58 Adult) were analyzed. All of these patients had clinical, hormonal and seminal evaluation before conventional TESE (c-TESE). MAIN RESULTS AND THE ROLE OF CHANCE: The global SRR was 45.4%. SRRs were not significantly different between the two age groups: Young SRR=49.2%, Adult SRR = 41.4%; P = 0.393. Anti-Müllerian hormone (AMH) and inhibin B were significantly higher in the Young group (AMH: P = 0.001, Inhibin B: P < 0.001), and also higher in patients with a positive TESE than in those with a negative TESE (AMH: P = 0.001, Inhibin B: P = 0.036). The other factors did not differ between age groups or according to TESE outcome. AMH had a better predictive value than inhibin B. SRRs were significantly higher in the upper quartile of AMH plasma levels than in the lower quartile (or in cases with AMH plasma level below the quantification limit): 67.7% versus 28.9% in the whole population (P = 0.001), 60% versus 20% in the Young group (P = 0.025) and 71.4% versus 33.3% in the Adult group (P = 0.018). LIMITATIONS, REASONS FOR CAUTION: c-TESE was performed in the whole study; we cannot rule out the possibility of different results if microsurgical TESE had been performed. Because of the limited sensitivity of inhibin B and AMH assays, a large number of patients had values lower than the quantification limits, preventing the definition a threshold below which negative TESE can be predicted. WIDER IMPLICATIONS OF THE FINDINGS: In contrast to some studies, age did not appear as a pejorative factor when comparing patients 15-22 and 23-44 years of age. Improved accuracy of inhibin B and AMH assays in the future might still allow discrimination of patients with persistent foci of spermatogenesis and guide clinician decision-making and patient information. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant from the French Ministry of Health D50621 (Programme Hospitalier de Recherche Clinical Régional 2008). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: NCT01918280.

Fertility in men with Klinefelter's syndrome.

Patients with a Klinefelter syndrome (KS), defined by a 47 XXY karyotype, were long considered infertile. Testicular sperm extraction (TESE) now allows them to access fatherhood. We will present the data of studies since first experiment of TESE. Several factors influencing TESE outcome were proposed in these different studies. Among them, clinical and hormonal parameters have reported by few studies, age has been one of the most discussed prognostic factor of positive sperm retrieval rate. Data seems to show that TESE carried out before an age greater than 30 has a poorer prognosis for positive sperm retrieval. In few studies performed in younger patient, before 20 years, SRR was closed to result for 20 to 30 year old patients. Offering a TESE before 16 years old does not improve positive sperm extraction rate. In fact, the few studies carried out before the age of 16 were of poorer prognosis, most often linked to insufficient maturation of the residual gametes. In addition, androgen therapy, frequently prescribed in case of Klinefelter syndrome, did not seem to show any effect on sperm retrieval but only few studies were interested in the possible impact of this treatment. In conclusion, further studies are necessary to determine the interest of new markers to predict the chance of sperm retrieval, taking into account age, hormonal therapy.

Effect of Recombinant Gonadotropin on Testicular Function and Testicular Sperm Extraction in Five Cases of NR0B1 (DAX1) Pathogenic Variants.

Background: NR0B1 pathogenic variants can cause congenital adrenal hypoplasia or primary adrenal insufficiency in early childhood usually associated with hypogonadotropic hypogonadism. NR0B1 is necessary for organogenesis of the adrenal cortex and to maintain normal spermatogenesis. In humans, restoration of fertility in patients carrying NR0B1 pathogenic variants is challenging. Objective: The aim of the study was to investigate the clinical, hormonal, histological, spermiological, and molecular genetic characteristics of a cohort of patients with NR0B1 pathogenic variants, monitored for fertility preservation. Patients: We included five patients, including four teenagers, with NR0B1 pathogenic or likely pathogenic variants. They all had primary adrenal insufficiency and were receiving replacement therapy with glucocorticoids and mineralocorticoids. Patients received recombinant follicle-stimulating hormone and recombinant human chorionic gonadotropin in order to induce spermatogenesis. Combined gonadotropin treatment was initiated between 13 years and 15 years and 6 months for the four teenagers and at 31 years and 2 months for the only adult. Physical and hormonal assessments were performed just before starting gonadotropin treatment. After 12 months of gonadotropin treatment, physical examination and hormonal assessments were repeated, and semen analyses were performed. If no sperm cells were observed in at least 2 semen collections at 3-month interval, testicular biopsy for testicular sperm extraction was proposed. Results: Bilateral testicular volume increased from 8 ml (interquartile range, 6-9) to 12 ml (10-16) after gonadotropin treatment. Inhibin B levels were relatively stable: 110 ng/L (46-139) before and 91 ng/L (20-120) at the end of gonadotropin treatment. Azoospermia was observed in all semen analyses for all cases during gonadotropin treatment. Three patients agreed to testicular biopsy; no mature sperm cells could be retrieved in any. Conclusion: We characterized a cohort of patients with NR0B1 pathogenic or likely pathogenic variants for fertility preservation by recombinant gonadotropin treatment, which began either at puberty or in adulthood. No sperm cells could be retrieved in semen samples or testicular biopsy even after gonadotropin treatment, indicating that gonadotropin treatment, even when started at puberty, is ineffective for restoring fertility.

Facing Counterfeit Medications in Sexual Medicine. A Systematic Scoping Review on Social Strategies and Technological Solutions.

INTRODUCTION: The counterfeit phenomenon is a largely under-reported issue, with potentially large burden for healthcare. The market for counterfeit drugs used in sexual medicine, most notably type 5 phosphodiesterase inhibitors (PDE5i), is rapidly growing. AIMS: To report the health risks associated with the use of counterfeit medications, the reasons driving their use, and the strategies enacted to contain this phenomenon. METHODS: A systematic scoping review of the literature regarding counterfeit PDE5i was carried between January and June 2021, then updated in August 2021. MAIN OUTCOME MEASURE: We primarily aimed to clarify the main drivers for counterfeit PDE5i use, the health risks associated, and the currently available strategies to fight counterfeiters. RESULTS: One hundred thirty-one records were considered for the present scoping review. Production of fake PDE5i is highly lucrative and the lacking awareness of the potential health risks makes it a largely exploitable market by counterfeiters. Adulteration with other drugs, microbial contamination and unreliable dosages make counterfeit medications a cause of worry also outside of the sexual medicine scope. Several laboratory techniques have been devised to identify and quantify the presence of other compounds in counterfeit medications. Strategies aimed at improving awareness, providing antitampering packaging and producing non-falsifiable products, such as the orodispersible formulations, are also described. CLINICAL IMPLICATIONS: Improving our understanding of the PDE5i counterfeit phenomenon can be helpful to promote awareness of this issue and to improve patient care. STRENGTHS & LIMITATIONS: Despite the systematic approach, few clinical studies were retrieved, and data concerning the prevalence of counterfeit PDE5i use is not available on a global scale. CONCLUSION: The counterfeit phenomenon is a steadily growing issue, with PDE5i being the most counterfeited medication with potentially large harmful effects on unaware consumers. Sansone A, Cuzin B, and Jannini EA. Facing Counterfeit Medications in Sexual Medicine. A Systematic Scoping Review on Social Strategies and Technological Solutions. Sex Med 2021;9:100437.

[Erectile dysfunction : up-date data and clinical guidelines]. / Nouvelles recommandations pour la prise en charge de la dysfonction érectile à l'usage du praticien.

In this paper, we are presenting a synthetic version of the third updated version of Guidelines for the first-line management by the non-sexologist practitioner of a man with erectile dysfunction (ED). This work applied the methodology recommended by the French High Authority of Health (in-depth documentary search of medical and scientific bibliographic data and review by a group of experts). Among the points to be highlighted since 2010, an important part has been devoted to updating epidemiological data that focus on the strong correlation between ED and vulnerable populations, on the question of the role of the partner's role in triggering or maintaining erectile dysfunction, previously poorly documented, and on the evolution of ED treatments and management algorithms.

Nous présentons dans cet article une synthèse de la troisième version actualisée des « Recommandations pour la prise en charge en première intention par le praticien non sexologue d'un homme souffrant de dysfonction érectile (DE) ¼. Ce travail a appliqué la méthodologie recommandée par la Haute autorité de santé française (analyse de la littérature par un groupe de travail et relecture par un groupe d'experts). Parmi les points à souligner depuis 2010, une part importante a été faite à l'actualisation des données épidémiologiques qui mettent l'accent sur la forte corrélation entre DE et populations vulnérables, sur la question du rôle du partenaire dans le déclenchement ou le maintien de la DE, auparavant peu documenté, ainsi que sur l'évolution des traitements de la DE et de ses algorithmes de prise en charge.

Alprostadil cream in the treatment of erectile dysfunction: clinical evidence and experience.

Erectile dysfunction (ED) is a very common disorder with a deep impact on quality of life on both patients and partners. Several options are available for treating ED: oral pharmacotherapy with phosphodiesterase 5 (PDE5) inhibitors currently represents the first-line option for many patients with ED. Alprostadil, a prostaglandin, has been marketed for many years as a urethral stick and an intracavernous injection for the treatment of ED. It is now available in the form of a cream (Vitaros/Virirec), a noninvasive treatment which combines an active drug (alprostadil, a synthetic prostaglandin E1) with a skin enhancer improving its local absorption directly at the site of action. Alprostadil has a favourable pharmacodynamic profile and is poorly absorbed in systemic circulation, which makes it suitable in a lot of circumstances and results in a reduced risk of adverse effects (AEs). Systemic AEs are reported in only 3% of the treated population. Clinical efficacy has been demonstrated in both phase II and III trials, showing a global efficacy up to 83% with the 300 µg dose in patients with severe ED, significantly better than placebo. Its fast onset of action and lack of interactions with other drugs makes alprostadil cream a possible first-line therapeutic option for some patients with ED: individuals who are reluctant to take systemic treatments or have AEs, patients who do not respond, cannot tolerate, or do not accept PDE5 inhibitor therapy, and patients treated with nitrates. Therefore, this new treatment for ED can be offered to patients and could help address the needs unmet by other treatments.

[Physiology and physiopathology of sexuality]. / Physiologie et physiopathologie de la sexualité.

From desire to orgasm, sexuality, in women and men, is underpinned by a complex organic, psychological and emotional function. Sexual dysfunction encompasses diverse aetiologies, including chronic diseases and iatrogenesis resulting from medication or surgery. The effects of a chronic disease can have an impact on all phases of the sexual response.

Effects of tadalafil treatment after bilateral nerve-sparing radical prostatectomy: quality of life, psychosocial outcomes, and treatment satisfaction results from a randomized, placebo-controlled phase IV study.

BACKGROUND: This multicenter, randomized, double-blind, double-dummy, placebo-controlled trial primarily evaluated the efficacy of tadalafil once-daily (OaD) or on-demand ("pro-re-nata"; PRN) treatment, started early post-nsRP. Secondary outcome-measures on quality-of-life (QoL) and treatment satisfaction are reported. METHODS: Patients, aged <68 yrs, with adenocarcinoma of the prostate (Gleason ≤ 7, normal preoperative erectile function [EF]) were randomized post-nsRP 1:1:1 to 9-month treatment with tadalafil 5 mg OaD, tadalafil 20 mg PRN, or placebo, followed by 6-week drug-free washout and 3-month open-label tadalafil OaD treatment (OLT). The main outcome measures were Changes in Expanded Prostate Cancer Index Composite (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and Self-Esteem and Relationship (SEAR) questionnaires (mixed-model-for-repeated-measures, including terms for treatment, visit, treatment-by-visit interaction, age-group, country, baseline-score). LS means with 95% confidence interval (CI) are reported. RESULTS: 423 patients were randomized to 3 treatment-groups: tadalafil OaD (N = 139), PRN (N = 143), or placebo (N = 141). In each group, 57 (41.0%), 58 (40.6%), and 50 (35.5%) patients were aged 61-68 yrs. At the end of double-blind treatment (DBT), patients' EPIC sexual domain-scores improved significantly with tadalafil OaD versus placebo (treatment effect [95% CI]: 9.6 [3.1,16.0]; p = 0.004); comparisons of PRN versus placebo at end of DBT, and comparisons of tadalafil OaD and PRN versus placebo after OLT were not significant. Only in older patients (61-68 yrs; age-by-treatment p ≤ 0.1), EPIC urinary incontinence domain-scores also improved significantly with tadalafil OaD versus placebo (overall treatment effect across all visits, 8.3 [0.4,16.1]; p = 0.040). Treatment satisfaction increased significantly in both tadalafil groups, EDITS total-scores increased significantly with OaD and PRN versus placebo during DBT (p = 0.005 and p = 0.041, respectively). At the end of OLT, improvement was significant for tadalafil OaD versus placebo only (p = 0.035). No significant differences were observed for SEAR. CONCLUSIONS: These results suggest that chronic dosing of tadalafil improves QoL of patients post-nsRP. The improvement of urinary incontinence in elderly patients randomized to tadalafil OaD may contribute to this effect. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT01026818.

Clinical efficacy and safety of Vitaros©/Virirec© (Alprostadil cream) for the treatment of erectile dysfunction.

Erectile dysfunction (ED) is a very common disorder with a deep impact on patients and their partners. Several options are now available for treating ED; oral pharmacotherapy with phosphodiesterase-5 (PDE5) inhibitors currently represents the first-line option for many ED patients. Vitaros©/Virirec© is new topical, non-invasive treatment for ED that offers the combination of an active drug (alprostadil, a synthetic PGE1) with a skin enhancer that improves its local absorption directly at the site of action. Vitaros©/Virirec© has a favorable pharmacodynamic profile and is poorly absorbed in systemic circulation. This makes it suitable in any circumstances and results in a reduced risk of adverse events (AEs), being systemic AEs reported in only 3% of the treated population. Its clinical efficacy has been demonstrated in both phase II and III trials, showing a global efficacy up to 83% with the 300 µg dose in patients with severe ED significantly better than placebo. Its fast onset of action together with its favorable toxicity profile and lack of interactions with other drugs makes Vitaros©/Virirec© a first-line therapeutic option for patients with ED, particularly for individuals who are reluctant to take systemic treatments or with AEs. It may also have an important role in patients not responding to PDE5 inhibitors, particularly those with ED after radical prostatectomy.

Preliminary results of a prospective study of testicular sperm extraction in young versus adult patients with nonmosaic 47,XXY Klinefelter syndrome.

CONTEXT: Testicular sperm extraction (TESE) in adult patients with nonmosaic 47,XXY provides a sperm retrieval rate (SRR) of approximately 50%. Age is the only significant prognostic factor. Whether TESE should be performed in adolescent patients for sperm cryopreservation remains to be determined. OBJECTIVE: The objective of the study was to compare SRR between young (15-23 y) and adult (> 23 y) patients with 47,XXY, and to determine whether previous androgenic treatment had a deleterious effect. DESIGN: We designed a prospective comparative study between two groups enrolled in parallel from September 2010 onward. SETTING: University hospital. PATIENTS: Forty one patients with nonmosaic 47,XXY karyotype and azoospermia were included. Twenty five patients from 15-22 years of age were assigned to the "Young" group, and 16 patients age 23 years or more, to the "Adult" group. INTERVENTION: A bilateral testicular open biopsy was performed by a single surgeon. The reproductive biologist who performed TESE was blind to the patient's age. Principal Outcome Measure: The main outcome measure was the SRR. The TESE procedure was considered positive if at least 20 sperm cells could be cryopreserved for intracytoplasmic sperm injection. RESULTS: SRR was 13/25 = 52% in the Young group and 10/16 = 62.5% in the Adult group, the difference being nonsignificant (P = .73). Ages were 24.3 ± 7.4 years in the 23 cases of positive TESE, and 23.7 ± 7.4 in the 18 cases of negative TESE, the difference being nonsignificant (P = .42). SRR was 9/17 = 52.9% for patients with and 14/24 = 59.1% for patients without previous testosterone (T) treatment, the difference being nonsignificant (P = .98). CONCLUSIONS: According to the present results, performing TESE at a younger age (15-23 y) in patients with azoospermic nonmosaic 47,XXY Klinefelter did not increase SRR relative to adult patients (25-39 y). Previous replacement treatment with moderate doses of T did not seem to be deleterious for the recovery of sperm cells by TESE.

Clinical safety and effectiveness of collagenase clostridium histolyticum injection in patients with Peyronie's disease: a phase 3 open-label study.

INTRODUCTION: Collagenase clostridium histolyticum (CCH; Xiaflex, Auxilium Pharmaceuticals, Inc., Chesterbrook, PA, USA) is a Food and Drug Administration-approved, intralesional treatment for Peyronie's disease (PD). AIM: The aim of this study was to assess the safety and effectiveness of CCH in the treatment of PD. METHODS: This phase 3, open-label study enrolled subjects who were CCH-naïve, were enrolled in a previous pharmacokinetic study, or had received placebo in an earlier phase 2 CCH study. Each treatment cycle included two intralesional injections of CCH 0.58 mg, approximately 24-72 hours apart, and plaque modeling 24-72 hours after the second injection of each cycle. The treatment cycle was repeated after 6 weeks for ≤4 treatment cycles. MAIN OUTCOME MEASURES: The co-primary end points were the mean percent change in penile curvature deformity and the mean improvement in PD bother score (range 0-16) from baseline to week 36. RESULTS: Of the 347 subjects treated with ≥1 injection, 238 had both a penile curvature measurement and a Peyronie's Disease Questionnaire response at baseline and ≥1 subsequent time point. Mean baseline penile curvature deformity was 53.0° and mean PD symptom bother was 7.3. Statistically significant mean improvements from baseline to week 36 were observed in both penile curvature deformity (34.4% [95% confidence interval {CI}, 31.2%, 37.6%]) and PD symptom bother score (3.3 [95% CI, 2.8, 3.7]). Most adverse events (AEs) were mild or moderate in severity and local to the penis. There were three serious treatment-related AEs, two penile hematomas and one corporal rupture; all resolved with treatment. CONCLUSIONS: Potentially clinically meaningful and statistically significant improvements in penile curvature deformity and PD symptom bother scores were observed with intralesional injection of CCH compared with baseline in men with PD. CCH was generally well tolerated, with AEs primarily transient and local to injection site. In conjunction with previous studies, the results of this open-label study support the use of CCH in the treatment of PD.

Klinefelter syndrome and TESE-ICSI.

Until few years ago, Klinefelter syndrome with a homogenous 47,XXY karyotype was considered a model of absolute male sterility. We will discuss first the potential fertility following Testicular Sperm Injection, then the physiopathology of spermatogenic failure and the origin of focal spermatogenesis and risk of aneuploidy in offspring, and third the advantage of searching spermatozoa earlier instead of adult age. The rate of positive sperm extraction seems to be better for younger patients. During childhood, there is a low rate of spermatogonia. The spermagonia, which completes the spermatogenesis, seems resulting from a rare clone of 46,XY gonia, having lost their extra X chromosome. Several arguments suggest that this focal spermatogenesis decreases with age. In addition, androgen treatment, frequently prescribed in case of Klinefelter syndrome, carries a risk of decreasing focal spermatogenesis by lowering gonadotropins. The question arises if it is necessary to expect the sperm cryopreservation before introducing androgen treatment. Further studies are necessary to determine the best age of sperm retrieval in case of Klinefelter syndrome.

Reconstructive surgery after female genital mutilation: a prospective cohort study.

BACKGROUND: Women who have undergone female genital mutilation rarely have access to the reconstructive surgery that is now available. Our objective was to assess the immediate and long-term outcomes of this surgery. METHODS: Between 1998 and 2009, we included consecutive patients with female genital mutilation aged 18 years or older who had consulted a urologist at Poissy-St Germain Hospital, France. We used the WHO classification to prospectively include patients with type II or type III mutilation. The skin covering the stump was resected to reveal the clitoris. The suspensory ligament was then sectioned to mobilise the stump, the scar tissue was removed from the exposed portion and the glans was brought into a normal position. All patients answered a questionnaire at entry about their characteristics, expectations, and preoperative clitoris pleasure and pain, measured on a 5-point scale. Those patients who returned at 1 year for follow-up were questioned about clitoris pain and functionality. We compared data from the 1-year group with the total group of patients who had surgery. FINDINGS: We operated on 2938 women with a mean age of 29·2 (SD 7·77 years; age at excision 6·1, SD 3·5 years). Mali, Senegal, and Ivory Coast were the main countries of origin, but 564 patients had undergone female genital mutilation in France. The 1-year follow-up visit was attended by 866 patients (29%). Expectations before surgery were identity recovery for 2933 patients (99%), improved sex life for 2378 patients (81%), and pain reduction for 847 patients (29%). At 1-year follow-up, 363 women (42%) had a hoodless glans, 239 (28%) had a normal clitoris, 210 (24%) had a visible projection, 51 (6%) had a palpable projection, and three (0·4%) had no change. Most patients reported an improvement, or at least no worsening, in pain (821 of 840 patients) and clitoral pleasure (815 of 834 patients). At 1 year, 430 (51%) of 841 women experienced orgasms. Immediate complications after surgery (haematoma, suture failure, moderate fever) were noted in 155 (5%) of the 2938 patients, and 108 (4%) were briefly re-admitted to hospital. INTERPRETATION: Reconstructive surgery after female genital mutilation seems to be associated with reduced pain and restored pleasure. It needs to be made more readily available in developed countries by training surgeons. FUNDING: French Urological Association.

Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study).

INTRODUCTION: Addition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels. AIMS: To confirm this add-on effect of T in men optimally treated with PDE5-Is and to specify the baseline T levels at which such an effect becomes significant. METHODS: A multicenter, multinational, double-blind, placebo-controlled study of 173 men, 45-80 years, nonresponders to treatment with different PDE5-Is, with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double-blind, placebo-controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory. Main Outcomes Measures. Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question). RESULTS: Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5-Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS: The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5-I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤ 3 ng/mL.

Application of cardiac autonomous indices in the study of neurogenic erectile dysfunction.

A research area of increasing interest consists of studying the benefits of using spectral analysis to screen neurogenic erectile dysfunctions. Our hypothesis is that spectral analysis consists of a non-invasive and simple procedure to investigate such patients. Subjects were allocated into two groups: control, no erectile dysfunction (n = 17), and patients with erectile dysfunction (n = 15). RR intervals (RRI), systolic blood pressure, diastolic blood pressure and baroreflex sensitivity recordings were performed continuously in the supine position, followed by the seated position, and finally standing position. In the supine position, the control group had a higher RRI and a lower diastolic blood pressure. For frequency domain analyses of RRI in the supine position, the erectile dysfunction group had a higher normalized low-frequency (LF) index and low-frequency/high-frequency (LF/HF) ratio while showing a lower normalized HF index. In the seated position, the erectile dysfunction group presented a higher LF/HF ratio. Regarding systolic blood pressure, the erectile dysfunction group showed lower normalized LF and higher normalized HF indices only in the supine position. The α index in HF was lower in the erectile dysfunction group in the three positions. Spectral analyses of cardiac sympathovagal drive constitute a fruitful non-invasive approach to evaluate alterations in cardiovascular autonomic modulation in neurogenic erectile dysfunction patients.

Improvement in quality of sexual life in female partners of men with erectile dysfunction treated with sildenafil citrate: findings of the Index of Sexual Life (ISL) in a couple study.

INTRODUCTION: Women's quality of sexual life is strongly impaired by erectile dysfunction (ED). Women's involvement in ED treatment is important for compliance and long-term efficacy but remains difficult. The Index of Sexual Life (ISL), specific of the quality of sexual life of women with ED partners, is used here to assess the impact of ED treatment on female partners. AIM: The study explored in a context close to routine clinical practice the effect of sildenafil citrate (Viagra(R); Pfizer, New York, NY, USA) treatment on women's quality of sexual life, in parallel with men's ED evaluations. METHODS: This prospective, open-labeled clinical trial was performed in France in 2006. Sexologists and andrologists recruited 67 volunteer couples for a 14-week sildenafil citrate treatment of male partners, without sex therapy in parallel. MAIN OUTCOME MEASURES: Women's quality of sexual life using ISL, and men's ED using International Index of Erectile Function (IIEF) and Self-Esteem And Relationship (SEAR) were assessed at baseline and at the end of the study. Satisfaction for treatment was measured using Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and EDITS Partner. RESULTS: The ISL sexual life satisfaction score was low at baseline (12.3), and increased by 8.3 during the study (P < 0.0001). Women were 79.0% to be responders according to ISL assessment. The other ISL dimensions also improved. The final ISL sexual life satisfaction score was dependant on women's age and final IIEF scores. The observed correlations between the ISL sexual life satisfaction dimension and the IIEF erectile function dimension, and the SEAR confidence dimension confirmed our assumptions. Both partners were highly satisfied with the treatment. CONCLUSION: Women satisfaction with their sex life was improved by ED treatment (sildenafil citrate). Couple global caring seemed to amplify the well-known effect of ED treatment for men. The ISL could be a useful tool to help women in their partner's treatment and to integrate ED treatment in a couple approach.

Vardenafil improves satisfaction rates, depressive symptomatology, and self-confidence in a broad population of men with erectile dysfunction.

INTRODUCTION: Vardenafil is a potent and selective phosphodiesterase 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction (ED). Fixed-dose and flexible-dose studies have previously established the efficacy and tolerability of vardenafil. AIM: To assess, besides the usual measures of efficacy, the quality of erection, satisfaction with the sexual experience, symptoms of depression, and overall confidence. METHODS: This 12-week double-blind, placebo-controlled flexible-dose study assessed patients from the general ED population. Patients underwent a 4-week treatment-free period before randomization to vardenafil or matching placebo. Initial dosage was vardenafil 10 mg for 4 weeks. At 4 weeks, patients could switch to 5 or 20 mg (or corresponding placebo), or remain on 10 mg for an additional 4 weeks; dose switching was also optional for the last 4 weeks. This paper describes per-patient success in satisfaction with hardness of erection, satisfaction with overall sexual experience, effect on overall self-confidence, and an assessment of symptoms of depression using the Center for Epidemiologic Studies Depression Scale. RESULTS: Mean per-patient satisfaction rates with erection hardness increased after vardenafil treatment to 43%, 59%, and 63% at weeks 4, 8, and 12, respectively, compared to placebo with 10%, 21%, and 23% (all P < 0.005 vs. placebo). Vardenafil also improved mean per-patient overall satisfaction 50-65% over the 4-12 week study period compared with 17-28% for placebo (P < 0.005). Symptoms of depression were statistically significantly reduced compared to placebo (P = 0.02); the effect was observed particularly in patients who were depressed at baseline (P = 0.01). Significantly more patients in the vardenafil treatment group reported improved self-confidence than those who received placebo (P < 0.005). CONCLUSIONS: A flexible-dose regimen of vardenafil improved satisfaction rates, symptoms of depression, and self-confidence, providing patients with an effective ED therapy that contributes to overall improvements in sexual function and confidence.