MAPK activation drives male and female mouse teratocarcinomas from late primordial germ cells.

Germ cell tumors (GCTs) are rare tumors that can develop in both sexes, peaking in adolescents. To understand the mechanisms that underlie germ cell transformation, we established a GCT mouse model carrying a germ-cell-specific BRafV600E mutation with or without heterozygous Pten deletion. Both male and female mice developed monolateral teratocarcinomas containing embryonal carcinoma (EC) cells that showed an aggressive phenotype and metastatic ability. Germ cell transformation started in fetal gonads and progressed after birth leading to gonadal invasion. Early postnatal testes showed foci of tumor transformation, whereas ovaries showed increased number of follicles, multi-ovular follicles (MOFs) and scattered metaphase I oocytes containing follicles. Our results indicate that MAPK (herein referring to Erk1/2) overactivation in fetal germ cells of both sexes can expand their proliferative window leading to neoplastic transformation and metastatic behavior.

Repeated sexual intercourse as a coping strategy for men with premature ejaculation.

BACKGROUND: Patients with premature ejaculation (PE) are often concerned and distressed about their sexual performance. Hence, they may be more willing to exploit their refractory period to employ sexual coping strategies in order to improve their unsatisfactory sexual intercourse compared with patients without PE. AIM: The study sought to verify the sexual coping strategies of patients with PE in the daily sexual activities. METHODS: We included both patients with PE and individuals without PE and analyzed their sexual behaviors and attitudes by means of detailed interviews and questionnaires. OUTCOMES: The main outcomes were perceived intravaginal ejaculatory latency time recording, Premature Ejaculation Diagnostic Tool score, and sexual frequency, attitudes, and behavior log. RESULTS: A total of 182 young patients with PE (age 31.2 ± 6.2 years) and 92 individuals without PE (age 30.7 ± 5.1 years) were included in the study. A total of 53.3% of patients with PE vs 17.4% of individuals without PE reported engaging in multiple sexual intercourse sessions within a single day in the past 4 weeks. PE patients who engaged in multiple intercourse sessions displayed better performance during the second attempt but performed poorly compared with individuals without PE. Scores for the first attempt in PE vs second attempt in individuals with PE vs without PE were the following: intravaginal ejaculatory latency time, 2.4 ± 1.6 vs 4.8 ± 5.7 vs 9.9 ± 9.4 (P < .001); Premature Ejaculation Diagnostic Tool, 14.9 ± 3.1 vs 12.7 ± 4.8 vs 5.2 ± 2.5 (P < .001); satisfaction, 2.9 ± 1.0 vs 3.1 ± 0.8 vs 3.7 ± 1.4 (P < .001). A total of 57.1% of patients held a negative attitude toward precoital masturbation, for reasons such as a reduced sexual desire (21.2%), the belief that masturbation is harmful (17.6%), concerns about erectile function (15.7%), fatigue (9.8%), and other mixed reasons (35.3%). CLINICAL IMPLICATIONS: Engaging in multiple intercourse sessions within a day is more common among the young PE population, and using precoital masturbation as a coping strategy is not universally applicable among patients with PE. STRENGTHS AND LIMITATIONS: This is the first study to explore symptom-coping strategies in patients with PE compared with individuals without PE. However, the conclusions cannot be generalized to the entire male population. CONCLUSION: Patients with PE, compared with individuals without PE, are more inclined to engage in multiple sexual intercourse sessions within a single sexual session, likely in an attempt to compensate for their first unsatisfactory sexual encounter. Moreover, the majority of patients with PE here studied hold a negative attitude toward using precoital masturbation as a coping strategy for symptoms.

Perception of normal and treatment level ejaculatory latency times in men with premature ejaculation.

BACKGROUND: Although the normal intravaginal ejaculation latency time (NIELT) as subjectively perceived by patients with premature ejaculation (PE) and expected IELT (EIELT), which represents the individual's expectations of what treatment for PE would achieve, are critically influential in the treatment of patients with PE, there is a significant dearth of exploratory research on NIELT and EIELT among patients with PE. AIM: To explore the NIELT and EIELT of patients with PE, understand why patients with PE perceive such a long IELT as normal, and identify factors associated with EIELT. METHODS: We recruited both patients with PE and control subjects, and analyzed the parameters related to IELT using detailed interviews and questionnaires. OUTCOMES: Parameters related to IELT. RESULTS: A total of 592 individuals (mean age 29.6 ± 6.2) were included in the study, comprising 466 patients with PE (mean age 28.3 ± 5.4) and 126 non-PE individuals (mean age 34.6 ± 6.5). The actual perceived intravaginal ejaculation latency time (PIELT), referring to the patient's self-assessed IELT at baseline, as well as NIELT, and EIELT of patients with PE, were 1.0 (1.0 - 2.0), 14.0 (10.0 - 15.0), and 15.0 (10.0 - 20.0), respectively. The control group's PIELT and EIELT were 15.0 (10.0 - 20.0) and 20.0 (15.0 - 24.3), respectively, showing statistical differences compared with the PIELT and EIELT in the PE group. In the PE group and the control group, 31.5% and 57.9% of individuals, respectively, have an EIELT greater than the average actual normal ejaculatory latency time of 15.0 minutes. Among patients with PE, 51.3% expressed a NIELT >10 minutes, identical to the EIELT in a higher percentage (59.4%). The control group's EIELT is 5 minutes longer than the PE group's EIELT. Multivariable linear regression analysis showed that age, marital status, education level, BMI, satisfaction evaluation of PIELT, PEDT score, and IIEF-6 score were not associated with EIELT; only NIELT (beta = 0.817, P < 0.001) and PIELT (beta = 0.056, P = 0.044) were related to EIELT. CLINICAL IMPLICATIONS: Sexual health care providers should be aware that patients with PE have excessively high expectations for IELT. STRENGTHS AND LIMITATION: The first study explores why patients with clinically diagnosed PE perceive long IELT as normal and examines factors associated with EIELT. Further validation is needed in different cultural contexts. CONCLUSION: Patients with PE often have excessively high expectations regarding IELT, primarily due to their insufficient understanding of IELT.

Psychosexological correlates of 372 women with vulvodynia, overactive pelvic floor, postcoital cystitis, and interstitial cystitis.

BACKGROUND: Among the plethora of urogynecological conditions possibly affecting women, some of them, less explored, have significant impacts on sexological and psychological health, with a mutual influence. AIM: The aim of this study was to investigate the sexological and psychological correlates of four urogynecological pathologies in a sample of women of childbearing age: overactive pelvic floor, vulvodynia, postcoital cystitis, and interstitial cystitis. Women cured of these conditions were also included, to assess the same aspects after the remission of physical symptoms. METHODS: We recruited 372 women with an average age of 33.5 years through an online platform shared by a popular forum for women with urogynecological pathologies between March and May 2021. The participants filled out a socio-anamnestic questionnaire and a set of psychometric tests. OUTCOMES: Participant data were collected by use of the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Toronto Alexithymia Scale-20, Female Sexual Function Index, and Orgasmometer-F, and the SPSS (Statistical Package for Social Sciences) v.26 was used for data analysis. RESULTS: Overactive pelvic floor was reported by 66.4% of the women, vulvodynia by 55%, postcoital cystitis by 58.8%, and interstitial cystitis by 8.3%, and these conditions were often comorbid with each other, with 9.4% and 7% of women reporting having suffered psychological and sexual abuse, respectively. The presence of past abuse was correlated with overactive pelvic floor (P < .05), vulvodynia (P < .01), and major depression (P < .01). Significantly more depression occurred in women with vulvodynia than in the other subgroups (P < .05), except for women with only an overactive pelvic floor. There was no difference between the subgroups in the occurrence of alexithymia, sexual function, and orgasm (P < .05). Interestingly, the prevalence of sexual dysfunction increased in cured women. CLINICAL IMPLICATIONS: The lack of significant differences, except for depression, between the pathological subgroups suggests a similar clinical and psychological relevance of the four pathologies studied. The persistence of sexual dysfunctions in cured women may be related to a residual dysfunctional relational modality with the partner. STRENGTHS AND LIMITATIONS: The evaluation of both psychological and sexological variables in a group of less-explored urogynecological conditions represents a strength of this study, while a lack of a face-to-face assessment could represent a limitation. CONCLUSION: The results of the present study should promote psychosexological interventions in women with these diseases, both during the pathological state and after remission.

Measurement of PDE5 concentration in human serum: proof-of-concept and validation of methodology in control and prostate cancer patients.

PURPOSE: We aimed to investigate if the type 5 phosphodiesterase (PDE5), an enzyme with cardinal biological functions in sexual and cardiovascular health, can be detected and quantited in human serum. METHODS: Blood samples were collected from control male and female subjects. PDE5 levels were measured by a specific ELISA kit. ROC curves weighted for age and serum levels of PSA (male subjects), or age (female subjects) were used to identify the predictive ability in the detection of PCa. Sensitivity, specificity, PPV and NPV values were determined for cut-off value determined during ROC curve analysis. RESULTS: 41 control male subjects, 18 control female subjects, and 55 consecutive subjects, of which 25 were affected by benign prostatic hypertrophy (BPH) and 30 with histologically confirmed prostate cancer (PCa), were studied. PDE5 serum levels were detectable in all subjects (range: 5 to 65 ng/ml). Analysis by MANCOVA identified a significant difference in serum PDE5 between control subjects or hyperplasia patients and PCa patients. Marginal means of serum PDE5 concentrations showed a significant difference (p < 0.001). The ROC curve demonstrated that PDE5 serum levels can predict men with or without PCa, with 0.806 AUC value (p < 0.0001). Using a 12.705 ng/ml PDE5 serum cut-off yielded sensitivity, specificity, PPV, and NPV of 83.3%, 77.27%, 62.5%, and 91.1% in detecting men with histologically proven PCa, respectively. CONCLUSIONS: We demonstrated, for the first time, that PDE5 levels can be detected in human sera and that PCa patients have significantly higher PDE5 concentration compared to BPH patients or male and female controls. While serum PDE5 level measurement may open new research avenues, the clinical relevance of PDE5 levels in PCa patients deserves further investigation.

Capacity to love and problematic sexuality: the role of defense mechanisms and psychopathological suffering.

BACKGROUND: Limitation to the capacity to love is often a feature of a suffering personality. AIM: We aimed to investigate the role of the capacity to love in hypersexual behavior, considering both distress and defense mechanisms as possible psychological mediators. METHODS: Through an online platform, we recruited a convenience sample of 521 subjects (390 [74.9%] females and 131 [25.1%] males; mean [SD] age, 26.46 [5.89] years). OUTCOMES: Recruited subjects completed a psychometric protocol that included completion of the following measurement tools: (1) the Capacity to Love Inventory (CTL-I), (2) the Hypersexual Behavior Inventory (HBI), (3) the 30-item self-report Defense Mechanisms Rating Scale, and (4) the Brief Symptom Inventory. We then performed correlation and regression analyses and used a mediation model for data analysis. RESULTS: A significant negative relationship between the capacity to love and hypersexual behavior was found. Furthermore, indirect effects were also statistically significant, supporting the hypothesis that limitation to the capacity to love is related to hypersexuality through the paths of psychological distress and immature defense mechanisms. Finally, compared to the other subjects, those with pathological scores for the HBI showed significantly lower scores on the CTL-I, which suggested limitations to the capacity to love. CLINICAL IMPLICATIONS: The relationship between limitation to the capacity to love and hypersexuality is fundamental to the diagnostic process in persons with problematic sexuality and psychopathological distress. STRENGTHS AND LIMITATIONS: This study is the first, to our knowledge, to highlight the role of the capacity to love in sexual behavior, although future studies in specific clinical sample groups would be suitable for further investigation of the relationships among the considered variables. CONCLUSION: The etiology of limitation in the capacity to love is related to dysfunctional aspects of psychological functioning, such as psychological distress and immature defense mechanisms, and these factors together generate problematic sexuality such as hypersexual behavior. Our results highlight the central role in mental and sexual health of the capacity to love. Based on these findings, clinicians should take these aspects into consideration for diagnosis and treatment of patients presenting with problematic sexuality.

Sexual Dysfunctions and Problematic Sexuality in Personality Disorders and Pathological Personality Traits: A Systematic Review.

PURPOSE OF REVIEW: This aim of the present systematic literature review is to critically analyze problematic sexuality and sexual dysfunctions in personality disorders (PDs) and pathological personality traits. RECENT FINDINGS: An initial pool of 123 studies was found, out of which 17 met the selection criteria and were therefore included. Traumatic experiences as childhood sexual abuse and adverse childhood experiences characterize the relationship between sexual behavior and PDs. From this point of view, sexual compulsivity and sexual risk behaviors, typical of BPD and ASPD, respectively, are among the pathognomonic aspects of PDs and of pathological personality traits. A maladaptive personality functioning may manifest through a problematic sexuality and a sexual impairment. In this regard, traumatic life experiences may structure personality together with sexual functioning. Therefore, it would be useful to consider the relationship between trauma, sexuality, and personality in research and in the clinical setting.

Nomogram for stratifying patients with lifelong premature ejaculation before using the PHQ-9: An observational study.

OBJECTIVE: A PHQ-9 score ≥ 15, represented as PHQ-9+ , indicates major depressive disorder (MDD). On using PHQ-9, the psychological burden of several patients with lifelong premature ejaculation (LPE) gets aggravated, which may lead to LPE development. We aim to construct a nomogram for predicting the individual risk of PHQ-9+ in patients with LPE and discerning those with low risks, who should avoid the PHQ-9. METHODS: The nomogram was constructed by analysing data of 802 patients from Xijing Hospital and Northwest Women's & Children's Hospital. The LASSO and multivariable logistic regressions were used to identify independent predictors of PHQ-9+ , used for developing the nomogram. The discrimination, calibration and clinical usefulness of the nomogram were assessed in the derivation cohort and an independent validation cohort, which was composed of 505 prospectively enrolled patients from Daxing Hospital and Xijing Hospital. RESULTS: The duration of PE, IELT, a history of PE exacerbation, IIEF-5 score, urinary frequency and physical pain score were identified as independent predictors. The nomogram showed excellent calibration, discrimination and clinical usefulness in the derivation and validation cohorts, with a predictive accuracy of 0.781 and 0.763, respectively. Based on this nomogram, patients were divided into not recommended, recommended and strongly recommended PHQ-9 filling groups, with PHQ-9+ rates of 3.5%, 9.3% and 30.7%, respectively. CONCLUSION: A nomogram to discern LPE patients with low risks of PHQ-9+ was established. This tool can increase the positivity of MDD screening and may improve the therapeutic outcomes of those in the low-risk group.

Genital Sensitivity and Perceived Orgasmic Intensity in Transgender Women With Gender Dysphoria After Gender-Affirming Surgery: A Pilot Study Comparing Pelvic Floor Evoked Somatosensory Potentials and Patient Subjective Experience.

BACKGROUND: The integrity of the neural pathways that link genital sensitive areas to the brain and the correlation with subjective sensations in transgender women with gender dysphoria after gender affirming surgery (GAS) have not been explored in detail and remain controversial, so far. AIM: To test with electrophysiology the integrity of the nervous paths after GAS, and to explore the relationship between genital sensitivity and self-perceived orgasmic intensity in transgender women after GAS. METHODS: Six patients who underwent GAS between 2016 and 2019 were enrolled in the study, and the evaluation of genital and pelvic neural pathways was performed. OUTCOMES: Genital sensory thresholds (at clitoral, vaginal, and anal sites) investigated by Somatosensory Evoked Potentials (SEP) and the intensity of orgasm (measured by a psychometric tool, the Orgasmometer) were combined to obtain an objective and subjective evaluation. RESULTS: SSEPs confirmed the integrity of the large diameter, dorsal column-lemniscus pathway subserving the genital area after GAS. Perceptual Threshold (PT) values were much lower at the neoclitoris compared to neovagina and anal sites. There was no correlation between Orgasmometer and SEP at anal and neovaginal level, while a trend was found at clitoral level. CLINICAL IMPLICATION: These findings could lead clinicians to a better understanding of postsurgical sexual life in transgender women in order to develop surgical techniques that could focus more on functional aspects of neovagina and neoclitoris. STRENGTHS & LIMITATIONS: Limitations: study very preliminary/exploratory; small number of patients; no long-term follow-up. Strengths: first assessment of sensory pelvic floor innervation in transgender women after GAS; use of objective methods; first attempt at correlating objectives findings to subjective experience of the sexual orgasm. CONCLUSIONS: Our evaluation showed that SSEPs is a good indicator of neural sensitivity, especially in neoclitoris, and that these measurements were consistent with the analysis of self-perceived orgasmic intensity. Canale D, Molinaro A, Marcocci C, et al. Genital Sensitivity and Perceived Orgasmic Intensity in Transgender Women With Gender Dysphoria After Gender-Affirming Surgery: A Pilot Study Comparing Pelvic Floor Evoked Somatosensory Potentials and Patient Subjective Experience. J Sex Med 2022;19:1479-1487.

Application of dual-energy CT angiography in diagnosis of arterial erectile dysfunction: new scanning technology, new scanning area.

OBJECTIVES: To explore the value of dual-energy computed tomography (DE-CT) angiography in diagnosis of arteriogenic erectile dysfunction (ED) patients and feasibility of new scanning area that excludes the testis. MATERIALS AND METHODS: Ninety-three patients suspected of suffering arterial ED and 40 health volunteers underwent penile duplex Doppler ultrasound and DE-CT angiography (DE-CTA). The scanning range of DE-CTA covered whole arterial system of pelvis and testis was excluded. Two blinded investigators independently evaluated the arterial system that supplies the penis. RESULTS: Finally, 1596 segments were evaluated and 470 segments were judged to be abnormal. The distribution was: 2 (0.4%) in common iliac artery, 7 (1.5%) in internal iliac artery, 82 (17.5%) in internal pudendal artery, 89 (18.9%) in penile artery, 120 (25.5%) in dorsal artery, and 170 (36.2%) in cavernosal artery. The specificity, sensitivity, positive predictive value, and negative predictive value of DE-CTA in diagnostic were 86.02%, 87.50%, 94.12%, and 72.92%. Besides, the new scan area allowed for effective evaluation of the arteries while excluding the testis. CONCLUSION: DE-CTA can provide unbiased, safe evaluation of the vascular status of the penile bed in patients with ED.

Investigating the microbial pathogens of sexually transmitted infections among heterosexual Vietnamese men with symptomatic urethritis.

OBJECTIVE: To explore the microbial etiology of urethritis in Vietnamese men and the association with patients' characteristics, especially their sexual behaviors. METHODS: This study was conducted on 349 men who presented with symptomatic urethritis and evidence of STIs (determined by multiplex PCR tests) at the Department of Andrology and Sexual Medicine-Hanoi Medical University Hospital. All information regarding medical history, sexual activities, and symptoms of urethritis was documented. RESULTS: C. trachomatis and N. gonorrhoea remained the two most common causative pathogens, followed by an unexpectedly high prevalence of Mycoplasma and Ureaplasma species. Coinfection was significant with a rate of 40.7%. Men who had sex with female sex workers (FSWs) were more likely to be positive with N. gonorrhoea but less likely to be positive with C. trachomatis and M. genitalium than those having sex with only one romantic partner. CONCLUSIONS: Our findings suggested the important role of other microorganisms, especially M. genitalium, in the etiology of urethritis in men besides the previously well-known causes of STIs. Since the coinfection rate is quite high, targeted treatment with clear microbial evidence should be considered rather than empiric antimicrobial therapy.

Ultrasonic testicular size of 24,440 adult Vietnamese men and the correlation with age and hormonal profiles.

Testicular size is an important parameter to investigate male reproductive and sexual functions. However, diagnosis and treatments are hindered by the lack of country-specific standard values for testicular volume. We conducted the present retrospective chart review study on 24,440 men who sought consultation at Andrology and Sexual Medicine-Hanoi Medical University Hospital to provide a reference range of testicular volume and to determine the correlations between testicular volume, age and hormonal profiles. These men were classified into groups being healthy fathers, hypogonadal men, unexplained infertile men, men with unknown fertility, testicular pathologies and other andrological condition groups. Hypogonadal men and unexplained infertile men had significantly smaller testicular sizes compared with healthy fathers. The mean value of testicular volume of healthy subjects was 13.64 ± 3.44 ml (left testis: 13.94 ± 3.72 ml; right testis: 13.34 ± 3.61 ml; p < 0.001). Testicular size of Vietnamese men was negatively correlated with LH and FSH (Rho = -0.16 and -0.33, p < 0.001) and positively correlated with testosterone after adjusting for confounding factors. Testicular volume was independent of the subject's age and smoking habits.

Benefits of Sexual Activity on Psychological, Relational, and Sexual Health During the COVID-19 Breakout.

BACKGROUND: The COVID-19-related lockdown has profoundly changed human behaviors and habits, impairing general and psychological well-being. Along with psychosocial consequences, it is possible that sexual behavior was also affected. AIMS: With the present study, we evaluated the impact of the community-wide containment and consequent social distancing on the intrapsychic, relational, and sexual health through standardized psychometric tools. METHODS: A case-control study was performed through a web-based survey and comparing subjects of both genders with (group A, N = 2,608) and without (group B, N = 4,213) sexual activity during lockdown. The Welch and chi-square tests were used to assess differences between groups. Univariate analysis of covariance, logistic regression models, and structural equation modeling were performed to measure influence and mediation effects of sexual activity on psychological, relational, and sexual outcomes. OUTCOMES: Main outcome measures were General Anxiety Disorder-7 for anxiety, Patient Health Questionnaire-9 for depression, Dyadic Adjustment Scale for quality of relationship and a set of well-validated sexological inventories (International Index of Erectile Function, Female Sexual Function Index, and male-female versions of the Orgasmometer). RESULTS: Anxiety and depression scores were significantly lower in subjects sexually active during lockdown. Analysis of covariance identified gender, sexual activity, and living without partner during lockdown as significantly affecting anxiety and depression scores (P < .0001). Logistic regression models showed that lack of sexual activity during lockdown was associated with a significantly higher risk of developing anxiety and depression (OR: 1.32 [95% CI: 1.12 - 1.57, P < .001] and 1.34 [95% CI: 1.15 - 1.57, P < .0001], respectively). Structural equation modeling evidenced the protective role of sexual activity toward psychological distress (ßmales = -0.18 and ßfemales = -0.14), relational health (ßmales = 0.26 and ßfemales = 0.29) and sexual health, both directly (ßmales = 0.43 and ßfemales = 0.31), and indirectly (ßmales = 0.13 and ßfemales = 0.13). CLINICAL TRANSLATION: The demonstrated mutual influence of sexual health on psychological and relational health could direct the clinical community toward a reinterpretation of the relationship among these factors. STRENGTHS AND LIMITATIONS: Based on a large number of subjects and well-validated psychometric tools, this study elucidated the protective role of sexual activity for psychological distress, as well for relational and sexual health. Main limitations were the web-based characteristics of the protocol and the retrospective nature of prelockdown data on psychorelational and sexual health of subjects recruited. CONCLUSIONS: COVID-19 lockdown dramatically impacted on psychological, relational, and sexual health of the population. In this scenario, sexual activity played a protective effect, in both genders, on the quarantine-related plague of anxiety and mood disorders. Mollaioli D, Sansone A, Ciocca G, et al. Benefits of Sexual Activity on Psychological, Relational, and Sexual Health During the COVID-19 Breakout. J Sex Med 2021;18:35-49.

Validity of Erectile Function Assessment Questionnaires in Premature Ejaculation Patients: A Comparative Study Between the Abridged Forms of the International Index of Erectile Function and Proposal for Optimal Cutoff Redefinition.

BACKGROUND: Patients with premature ejaculation (PE) are often diagnosed as having a comorbid erectile dysfunction (ED). When evaluating erectile function in PE patients with the popular International Index of Erectile Function-5 (IIEF-5, or Sexual Health Inventory for Men [SHIM]), question #5 (Q5) about sexual satisfaction in the intercourse often lowers the total score of the questionnaire, giving false-positive results for the presence of ED. AIM: We aimed to compare SHIM with the other abridged form of IIEF, which is IIEF-EF, and to discriminate which tool has the best diagnostic accuracy in the evaluation of erectile function in PE patients. METHODS: The study was conducted from March 2019 to January 2020. A total of 189 heterosexual males with lifelong PE (117, 61.9%) or acquired PE (72, 38.1%) were included. They all compiled Premature Ejaculation Diagnostic Tool, IIEF-15, SHIM, and IIEF-EF and underwent a full clinical examination to evaluate their erectile function. OUTCOMES: The scores of the 2 erectile function assessment questionnaires (SHIM and IIEF-EF) were compared in terms of their sensitivity and specificity in the diagnosis of ED in PE patients. RESULTS: In terms of diagnosing ED in PE patients, the sensitivity of SHIM is 100% while the specificity is only 36%; meanwhile, the sensitivity of IIEF-EF is 100% but specificity is 77.2%. Further analysis demonstrates that decreasing cutoff of SHIM to 17.5 would provide an increased specificity of 82.5%, while sensitivity would lower to 96.0%. However, the highest area under the curve (0.966 vs 0.941) is given by the IIEF-EF with 100% sensitivity and 80.7% specificity at the cutoff of 24.5, which is one point lower than the usual cutoff value of 25.5. CLINICAL IMPLICATIONS: Our study suggests that when evaluating erection function in PE patients, the cutoff of both SHIM and IIEF-EF should be amended. STRENGTHS & LIMITATIONS: We proposed the solution for the bias of erectile function assessment in PE patients. However, other trials are needed to further validate in larger cohorts of PE patients. CONCLUSION: We suggest that the cutoff of SHIM and IIEF-EF should be amended (SHIM at 17.5 and IIEF-EF at 24.5, respectively) when assessing erectile function among PE population. Xi Y, Colonnello E, Ma G, et al. Validity of Erectile Function Assessment Questionnaires in Premature Ejaculation Patients: A Comparative Study Between the Abridged Forms of the International Index of Erectile Function and Proposal for Optimal Cutoff Redefinition. J Sex Med 2021;18:440-447.

The Gynogram: A Multicentric Validation of a New Psychometric Tool to Assess Coital Pain Associated With VVA and Its Impact on Sexual Quality of Life in Menopausal Women.

BACKGROUND: Vulvo-Vaginal Atrophy (VVA) affects about fifty percent of postmenopausal women, contributing more vulnerable sexual and psycho-relational equilibrium. To date, no psychometric instruments have been designed to assess the impact of coital pain associated with VVA on sexual quality of life. AIM: To validate a new psychometric tool, the Gynogram, able to investigate coital pain and to quantify its impact on sexual well-being in menopause. METHODS: 214 sexually active postmenopausal women were enrolled in the study during clinical consultations in gynecological outpatient clinics in Italy. After gynecological examination and evaluation of the presence of VVA, the study sample was divided in a clinical group (103 women with certified diagnosis of VVA) and in a control group (111 women without certified diagnosis of VVA) according to the Vaginal Health Index (VHI) cut-off. Factor, Reliability and Receiving Operating Characteristics (ROC) analysis were performed in order to validate our newly created Gynogram. OUTCOMES: A structured questionnaire, named Gynogram, to assess coital pain and its impact, and the Female Sexual Function Index (FSFI). RESULTS: The factor analysis performed on the original form (80 items) reduced the Gynogram to 24 items. Reliability analysis conducted with Cronbach's Alpha coefficients showed high values in all the components (ranging from .813 to .972), both in the long and in the short form. The sensitivity analysis demonstrated that the Gynogram, with a cut-off ≤93, is able to recognize a clinically significant coital pain. With respect to the FSFI, statistically significant differences were found for all the domains. In addition, statistically significant differences were found for all the twelve factors of the Gynogram, showing that VVA profoundly affects the sexual quality of life of women in post-menopause. CLINICAL TRANSLATION: The utility of this tool consists in the possibility to improve prognosis, compliance/adherence and treatment outcomes. STRENGTHS AND LIMITATIONS: The Gynogram is able to evaluate and to quantify the impact of coital pain associated with VVA. Moreover, it can also recognize the areas of biopsychosocial functioning being more affected by this clinical condition. The main limit of the study is the impossibility to evaluate both mental health and partner's general and sexual health. CONCLUSIONS: The Gynogram is a new and validated psychometric tool able to detect the impact of symptomatic VVA on sexual quality of life among post-menopausal women, with a specific focus on the different areas of sexual functioning. Nappi RE, Graziottin A, Mollaioli A, et al. The Gynogram: A Multicentric Validation of a New Psychometric Tool to Assess Coital Pain Associated With VVA and Its Impact on Sexual Quality of Life in Menopausal Women. J Sex Med 2021;18:955-965.

Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study.

BACKGROUND: Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS). AIM: To define pooled prevalence estimates and correlates of erectile dysfunction (ED) and decreased libido (DL) in KS. METHODS: A thorough search of Medline, Embase and Web of Science was performed to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effect models and the between-studies heterogeneity was assessed by the Cochrane's Q and I2. The sources of heterogeneity were investigated by meta-regression and sub-group analyses. Funnel plot, Begg's rank correlation and trim-and-fill test were used to assess publication bias. MAIN OUTCOME MEASURE: The pooled prevalence of ED and DL in KS as well as 95% confidence intervals (CIs) were estimated from the proportion of cases of sexual dysfunction and the sample size. Variables that could affect the estimates were identified by linear meta-regression models. RESULTS: Sixteen studies included collectively gave information about ED and DL in 482 and 368 KS men, respectively, resulting in a pooled prevalence of 28% (95% CI: 19%-36%) for ED and 51% (95% CI: 36%-66%) for DL, with a large heterogeneity. The trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimates. At the meta-regression analyses, a higher prevalence of ED was significantly associated with an older age but not with lower testosterone levels. In series with a mean age >35 years, the ED prevalence estimate increased up to 38% (95% CI: 31%-44%) with no heterogeneity (I2=0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age. CLINICAL IMPLICATIONS: While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels. STRENGTH & LIMITATIONS: This is the first meta-analysis defining pooled prevalence estimates and correlates of ED and DL in KS. Nevertheless, caution is required when interpreting results, due to the high risk of bias in many studies, as well as the dearth of data about psychosocial and/or psychosexological variables and age at the diagnosis. CONCLUSIONS: ED and DL represent common clinical complaints in KS. While the prevalence of ED would increase with age, DL gets more common as serum testosterone decreases. Further studies are warranted to elucidate the pathogenetic mechanism(s) underlying the age-dependent increase in the prevalence of ED, apparently unrelated to the androgenic status. A Barbonetti, S D'Andrea, W Vena, et al. Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study. J Sex Med 2021;18:1054-1064.

Safety and efficacy of traditional Chinese medicine, Qiaoshao formula, combined with dapoxetine in the treatment of premature ejaculation: An open-label, real-life, retrospective multicentre study in Chinese men.

To evaluate the safety and efficacy of Chinese medicine, Qiaoshao formula combined with dapoxetine was used for the treatment of premature ejaculation in a real-life setting. Nine hundred and five males diagnosed with premature ejaculation were reviewed in this retrospective cohort study. We divided the patients into two groups: dapoxetine alone and Qiaoshao formula combined with dapoxetine according to actual interventions provided to patients in clinics. The perceived intravaginal ejaculation latency time and the premature ejaculation profile measures markedly improved in both groups. However, in men with severe premature ejaculation (baseline perceived intravaginal ejaculation latency time <1 min) and those with baseline age ≤30 years, the perceived intravaginal ejaculation latency time was slightly but significantly longer with combined therapy than with dapoxetine alone (p < .05). Therefore, combined therapy involving the Qiaoshao formula and dapoxetine proved to safe as well as effective for treating premature ejaculation while prolonging the perceived intravaginal ejaculation latency time, which significantly improved the overall satisfaction of the patient and likely that of the couple.

Regulation of Kit Expression in Early Mouse Embryos and ES Cells.

Kit is a growth factor receptor that regulates proliferation and/or survival of many embryonic and postnatal stem cell types. When mutated, it can induce malignant transformation of the host cells. To dissect the Kit role in the control of ESC pluripotency, we studied its expression during early mouse embryogenesis and during the process of ESC derivation from inner cell mass (ICM) cells. We followed the in vitro development of early mouse embryos obtained from transgenic mice carrying Kit promoter regions fused to EGFP (Kit-EGFP) and found that they initiate EGFP expression at morula stage. EGFP expression is then maintained in the blastocyst, within the ICM, and its levels increase when cultured in the presence of MAPK and GSK3ß inhibitors (2i) plus LIF compared with the LIF-only condition. Kit-EGFP ESCs showed nonhomogeneous EGFP expression pattern when cultured in LIF condition, but they upregulated EGFP expression, as well as that of Sox2, Nanog, Prdm14, when shifted to 2i-LIF culture. Similarly, primordial germ cells (PGCs) in the process of embryonic germ cell (EGC) conversion showed enhanced EGFP expression in 2i-LIF. Kit expression was affected by manipulating Sox2 levels in ESCs. Chromatin immunoprecipitation experiments confirmed that Sox2 binds Kit regulatory regions containing Sox2 consensus sequences. Finally, Kit constitutive activation induced by the D814Y mutation increased ESC proliferation and cloning efficiency in vitro and in teratoma assays in vivo. Our results identify Kit as a pluripotency-responsive gene and suggest a role for Kit in the regulation of ESC proliferation. Stem Cells 2019;37:332-344.

An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine.

BACKGROUND: Although the introduction of dapoxetine has ushered in a new era in the treatment of premature ejaculation, many patients with lifelong premature ejaculation (LPE) exhibit an unimproved clinical global impression even after treatment with dapoxetine. AIM: To investigate independent predictors of the improvement of Clinical Global Impression (iCGI) in patients with LPE treated with dapoxetine and develop a nomogram to predict a patient's likelihood of achieving iCGI. METHODS: Data of 243 patients with LPE diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) from January 2019 to May 2020 were analyzed. Independent predictors of iCGI were identified, and a nomogram was developed using R software based on a multivariate logistic regression model. The predictive accuracy of the nomogram was measured using the area under the receiver operating characteristic curve. The nomogram was calibrated by comparing predictions with observations. MAIN OUTCOME MEASURES: The primary outcome was the patient-rated Clinical Global Impression of Change scale score after a 4-week course of dapoxetine treatment, which was collected via an online questionnaire. A Clinical Global Impression of Change score of ≥1 was defined as iCGI in this study. RESULTS: Patients with LPE with at least a bachelor's degree, a self-reported intravaginal ejaculation latency time of >1 minute, and an International Index of Erectile Function question 5 score of ≥3 were independent factors associated with achieving iCGI, whereas a Premature Ejaculation Diagnostic Tool question 1 score of ≥2 was an independent factor negatively associated with achieving iCGI. The predictive accuracy of the nomogram, which was developed by integrating all variables with independent predictive significance, was 0.710 (95% confidence interval: 0.702-0.718). In addition, the calibration plot demonstrated excellent agreement between predictions and observations. CLINICAL IMPLICATIONS: If the predictive performance of our nomogram is further proven in multiple external validations, it can be used to select suitable patients for dapoxetine treatment, thereby reducing the number of patients discontinuing treatment. STRENGTHS & LIMITATIONS: This study developed the first nomogram for predicting the likelihood of achieving iCGI in patients with LPE treated with dapoxetine. However, our nomogram was not externally validated using independent cohorts from other institutions. CONCLUSION: This study identified several independent predictors of iCGI in patients with LPE treated with dapoxetine. An effective nomogram was developed to predict their likelihood of achieving iCGI. External validations using data of Western patients with LPE are required to test the broader applicability of this Chinese patient-based tool. Hou G, Gao M, Zhang L, et al. An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine. J Sex Med 2020;17:2341-2350.

The Masturbation Erection Index (MEI): validation of a new psychometric tool, derived from the six-item version of the International Index of Erectile Function (IIEF-6) and from the Erection Hardness Score (EHS), for measuring erectile function during masturbation.

OBJECTIVES: To validate a psychometric instrument, the Masturbation Erection Index (MEI) able to evaluate erectile function (EF) during masturbation. In fact, although the evaluation of EF during masturbation is pivotal in evaluating erectile dysfunction (ED), to date no specific psychometric tools have been developed to measure it both in the routine clinical practice and in the experimental setting. PATIENTS AND METHODS: Of 560 men attending our andrological outpatient clinic for the first time, 99 (17.7%) had ED. As a control group, we enrolled 102 sexually healthy men. All the men were requested to complete both the six-item version of the International Index of Erectile Function (IIEF-6) and the MEI. The MEI was used together with a standardised tool, the Erection Hardness Score (EHS). The MEI was validated in terms of content validity. Test-retest reliability was assessed using the intraclass correlation coefficient (ICC). Internal consistency was evaluated by Cronbach's α. The comparability between the MEI and IIEF-6 in measuring EF was tested by Bland-Altman analysis. The concordance correlation coefficient (CCC) between the two questionnaires was also determined. RESULTS: Internal consistency of the MEI was >0.93. Test-retest reliability was 0.982 (95% confidence interval [CI] 0.975-0.987). Bland-Altman analysis showed a good level of agreement between the IIEF-6 and MEI in the whole ED population, with stronger agreement in the organic-ED subpopulation. The estimated area under the curve of the MEI was 0.983 (P < 0.001; 95% CI 0.954-0.996), with a score of ≤27 as the optimal threshold to discriminate between the presence and absence of ED during self-induced masturbation. The CCC, Pearson ρ and bias correction factor (Cb) were 0.951 (95% CI 0.936-0.962), 0.968, and 0.982, respectively. CONCLUSION: The MEI showed good internal consistency and a good level of agreement with the IIEF-6. Hence, the MEI fulfills the major psychometric requirements for measuring EF during masturbation.