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Objectives: Low sexual desire is the most common sexual complaint in women. As a result, many women suffer from sexual dissatisfaction and related distress which often negatively interferes with their quality of life. Currently, limited drug treatments are available globally to treat women with Female Sexual Interest & Arousal Disorder (FSIAD). As a result, there is an unmet need, and relevance to develop a drug treatment for women with sexual dysfunction. LybridoTM (Freya Pharma Solutions, Amsterdam, the Netherlands) is a novel on-demand dual route/dual release fixed dose combination tablet of sublingual testosterone and oral sildenafil. It has shown a promising efficacy and safety profile in Phase 2 and is ready for Phase 3 testing. Methods: Design: A double-blind, randomized, placebo-controlled, 3-arm, 6-month study to evaluate the efficacy and safety of LybridoTM in premenopausal women with acquired FSIAD. Study Population: European premenopausal women, at least 18 years of age, with a clinical diagnosis of acquired FSIAD. Interventions: The study drug is a fixed-dose combination tablet consisting of an inner core containing sildenafil with an outer delayed immediate release coating and an additional outer film coating containing testosterone. Two dose strengths will be evaluated and compared with placebo. Results: Outcome Measures:Primary endpoint: change from baseline to Week 24 Female Sexual Function Index Desire Domain (FSFI-D) (Items 1 and 2). Secondary efficacy endpoints: Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) score; Elements of Desire Questionnaire (EDQ) 'event-based'; FSFI Arousal Domain (FSFI-A); FSFI total score; FSDS-DOA total score; Sexual Satisfaction of an Event Questionnaire (SSEQ), reported within 24 hours; Patient Global Impression of Improvement (PGI-I) Scale; Patient Global Impression of Severity (PGI-S) Scale; and total number of sexual events. Safety outcomes: frequency of (serious) adverse events. Conclusions: Study Planning: First Patient In: Q2 2023; Interim Analysis: Q4 2023; Last Patient Out: Q2 2024. Conflicts of Interest: Study supported by Freya Pharma Solution. [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to answer the question: is there an association between endogenous levels of androgens and sexual function in women? Methods: An extensive search was performed in MEDLINE, Embase and PsycInfo. Four separate meta-analyses were conducted for total T, free T, Free Androgen Index (FAI), and Dehydroepiandrosterone sulphate (DHEAS). Cohort, cross-sectional, and prospective studies were included. The effect measure was expressed as standardized mean difference (SMD). Results: The meta-analysis on total T included 34 studies involving 3,268 women, mean age 36.5 years. In 11 studies, a significant association was found between sexual desire, measured by validated psychometric instruments, and total T (SMD = 0.59 [0.29;0.88], P < 0.0001), with a moderate effect. The association with global sexual function (n = 12 studies) was also significant (SMD = 0.44 [0.21;0.67], P <0.0001). Overall, total T was associated with a better sexual function (SMD = 0.55 [0.28;0.82)], P < 0.0001), with similar results obtained when poor quality studies were removed. Age showed a negative relationship with the overall outcome. No differences were found when stratifying the studies according to menopausal status, type of menopause, age at menopause, use of hormonal replacement therapy, relationship status, method for T measurement, phase of the menstrual cycle or use of hormonal contraception. The meta-analysis of T derivatives (free T and FAI) also showed a significant, moderate association with sexual desire. In contrast, DHEAS seems not to exert any significant influence on desire, whilst showing a positive association with global sexual function. Conclusions: There appears to be a moderate association between total T and sexual desire/global sexual function, which is confirmed, although weak, in studies employing liquid chromatography-mass spectrometry (LC-MS). Similar results on desire were obtained for free T and FAI. DHEAS only showed a positive association with global sexual function. More research is needed. Conflicts of Interest: LV received scientific research grants, advisory board attendance and speaker honoraria from Therascience, Theramex, Bayer Schering Pharma, Intercept, Lipocine, Ibsa. EM and SC have nothing to declare. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the psychosexual correlates of obesity and the Metabolic Syndrome (MetS) in a large sample of women consulting for sexual symptoms; to investigate the change in measures of arousal after weight loss obtained with Very Low Calories Ketogenic Diet (VLCKD). Methods: In a retrospective study, n=322 women consulting for sexual symptoms were enrolled. The patients underwent a clinical, laboratory, sexual and psychometric examination and were studied by color-Doppler ultrasound with measurement of the Pulsatility Index (PI) of the clitoral artery. Twelve patients underwent a lifestyle intervention based on a VLCKD protocol and compared with patients treated with different strategies for sexual symptoms, in a 1: 1 case-control study. Results: Clitoral PI was significantly higher in obese women (p = 0.018) and in those diagnosed with MetS (p=0.043). A statistically significant inverse correlation emerged between WC ≥ 88 cm and FSFI Arousal score (R=-0.126, p=0.028). In patients undergoing a lifetsyle intervention (n = 12), after a mean follow-up of 20±2 weeks, BMI showed a reduction of 6.7±2.8 kg/m2 (p <0.001). At follow-up, the total FSFI and FSDS-R scores significantly improved (17.0±13.6 vs. 11.2±7.9, p=0.016, and 7.4±8.3 vs. 13.3±10.6, p=0.039, respectively). A significant increase was observed in FSFI Arousal (p=0.035), whereas clitoral PI displayed a non-significant reduction (p = 0.218). At multivariate analysis, the change in Total FSFI was correlated with the improvement in Body Image (BUT-B PSDI score: β=0.744, p=0.031; Eating Disorder Evaluation "Shape" domain: β=0.523, p=0.043), after adjusting for confounders. Finally, in the case-control study (subjects matched for age, BMI and menopausal state), the improvement in FSFI total score was more relevant in cases than in controls (p = 0.046). Conclusions: Our data suggest that weight loss obtained by VLCKD is associated with an improvement in sexual function, and in particular in Arousal, which could be mediated by improved body image. Conflicts of Interest: LV received scientific research grants, advisory board attendance and speaker honoraria from Therascience, Theramex, Bayer Schering Pharma, Intercept, Lipocine, Ibsa. EM and SC have nothing to declare. [ABSTRACT FROM AUTHOR]

Objectives: Metabolic syndrome (MetS) is often associated with male hypogonadism. Despite the well-known link, the role of testosterone [T] replacement therapy [TRT] on glycometabolic profile and body composition, in patients with metabolic syndrome [MetS], is still conflicting and argue of large scientific debate. The aim of the present study is to meta-analyze the role of TRT in MetS considering all placebo and non-placebo-controlled randomized clinical trials [RCTs]. Methods: An extensive Medline search was performed including the following words "testosterone", "metabolic syndrome" and "males". No search software was used, but we hand-searched bibliographies of retrieved papers for additional references. Results: Overall, 7 studies were available including 576 patients with a mean follow-up of 48.9 weeks. These trials differ in basal TT levels and type of T preparation used. In addition, only 6 were placebo controlled. TRT resulted to significantly improve waist circumferece, fasting glycemia, A1c serum levels, HOMA-Indes and serum tryglycerides (p < 0.001) when all studies were considered, however this difference was not significant when only placebo-controlled studies were considered, except for waist circumference (p= 0.05). When only placebo/controlled RCT were considered, TRT resulted to significantly improve body fat mass (p= 0.04). Conclusions: TRT was able to significantly decrease fasting glycaemia, glycosylated hemoglobin, HOMA-IR index, triglyceride levels, fat mass and waist circumference. In contrast, we did not observe any significant effect on total or HDL cholesterol, blood pressure and BMI. When considering only placebo-controlled studies, only differences of HbA1c, HOMA-IR index, triglyceride levels, fat mass and waist circumference retained statistical significance, but not fasting glycaemia, although a trend was apparent. Conflicts of Interest: No conflict of interest to declare. [ABSTRACT FROM AUTHOR]

Objectives: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarifed. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated. Methods: All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n=19), as well as those reporting data on semen analysis (n=5) and hormonal parameters (n=11) in infected/recovered patients without any arbitrary restriction were included. Results: Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1±12.6 years, and mean follow-up 24.3±18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological efects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality. Conclusions: The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specifc contribution of reduced T levels during the acute phase of the infection needs to be better clarifed. Conflicts of Interest: The authors declare that they have no confict of interest. [ABSTRACT FROM AUTHOR]

Objectives: Type 2 diabetes mellitus [T2DM] and hypogonadism are common conditions afflicting the aging male, often present together. The specific role of testosterone [T] replacement therapy [TRT] on glycometabolic profile and body composition, particularly in patients with T2DM, is still the object of an intense debate. The aim of the present study is to meta-analyze the role of TRT in T2DM considering all placebo and non-placebo-controlled randomized clinical trials [RCTs]. Methods: An extensive Medline, Embase and Cochrane search was performed. We did not employ search software but hand-searched bibliographies of retrieved papers for additional references. All RCTs studies investigating the impact of TRT on glycometabolic outcomes without any restriction were included. Results: Overall, 12 studies were available including 684 patients with a mean follow-up of 38.4 weeks. These trials differ in basal TT levels and type of T preparation used. In addition, only 10 were placebo controlled Conclusions: The overall data analysis indicates that TRT favorably affects glycemic control in diabetic subjects reducing fasting glycaemia, HbA1c and HOMA index and decreasing triglyceride levels and fat mass. All these differences were confirmed when only placebo-controlled studies were evaluated, with the exception for HbA1c decrease, where only a trend towards a decrease was apparent. Conversely no effects on TRT on erectile function was observed. Conflicts of Interest: No conflict of interest to delcare. [ABSTRACT FROM AUTHOR]

Objectives: Organic conditions underlying secondary hypogonadism (SH) may be ascertained by magnetic resonance imaging (MRI) of the hypothalamic-pituitary region that could not be systematically proposed to each patient. Based upon limited evidence, the Endocrine Society (ES) guidelines suggest total testosterone (T) < 5.2 nmol/L to identify patients eligible for MRI. The study aims to identify markers and their best threshold value predicting pathological MRI findings in men with SH. Methods: A consecutive series of 609 men seeking medical care for sexual dysfunction and with SH (total T < 10.5 nmol/L and LH ≤ 9.4 U/L) was retrospectively evaluated. An independent cohort of 50 men with SH was used as validation sample. 126 men in the exploratory sample and the whole validation sample underwent MRI. Results: In the exploratory sample, patients with pathological MRI findings (n = 46) had significantly lower total T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate specific antigen (PSA) than men with normal MRI (n = 80). Receiver Operating Characteristics analysis showed that total T, LH, FSH and PSA are accurate in identifying men with pathologic MRI (accuracy: 0.62-0.68, all p < 0.05). The Youden index was used to detect the value with the best performance, corresponding to total T 6.1 nmol/L, LH 1.9 U/L, FSH 4.2 U/L and PSA 0.58 ng/mL. In the validation cohort, only total T ≤ 6.1 nmol/L and LH ≤ 1.9 U/L were confirmed as significant predictors of pathologic MRI. Conclusions: In men with SH, total T ≤ 6.1 nmol/L or LH ≤ 1.9 U/L should arise the suspect of hypothalamus/pituitary structural abnormalities, deserving MRI evaluation. Conflicts of Interest: none [ABSTRACT FROM AUTHOR]

Objectives: The role of testosterone (T) replacement therapy (TRT) in subjects with late onset hypogonadism is still the object of an intense debate. Methods: All observational studies and placebo-controlled or -uncontrolled randomized trials (RCTs) comparing the effect of TRT on different bone parameters were considered. Results: Out of 349 articles, 36 were considered, including 3103 individuals with a mean trial duration of 66.6 weeks. TRT improves areal bone mineral density (aBMD) at the spine and femoral neck levels in observational studies, whereas placebo-controlled RTCs showed a positive efect of TRT only at lumber spine and when trials included only hypogonadal patients at baseline (total testosterone<12 nM). The effects on aBMD were more evident in subjects with lower T levels at baseline and increased as a function of trial duration and a higher prevalence of diabetic subjects. Either T or estradiol increase at endpoint contributed to aBMD improvement. TRT was associated with a signifcant reduction of bone resorption markers in observational but not in controlled studies. Conclusions: TRT is able to inhibit bone resorption and increase bone mass, particularly at the lumbar spine level and when the duration is long enough to allow the anabolic efect of T and estrogens on bone metabolism to take place. Conflicts of Interest: The authors declare no confict of interest. [ABSTRACT FROM AUTHOR]

Objectives: The level of education has been recognized as a cardiovascular (CV) risk factor; nevertheless, it is often neglected in CV risk prediction. To evaluate the psychobiological correlates of the level of education and if it could predict incident major adverse CV events (MACE) in men consulting for erectile dysfunction (ED). Methods: 3733 men (49.8±13.7 years old) attending an andrology outpatient clinic for ED were studied. Sexual and psychological symptoms, hormonal and metabolic as well as instrumental (penile color Doppler ultrasound; PCDU) parameters were evaluated according to the education level (university, upper secondary, lower secondary, and primary degree). For a subset of 956 patients data on incident MACE were retrospectively collected for 3.9±2.4 years. Results: As compared with men with university degree, those with a lower education had an increased frequency of moderate-severe ED (OR=1.21 [0.99;1.48], 1.41 [1.14;1.73], 1.70 [1.26;2.30] for upper secondary, lower secondary and primary school, respectively) and reduced flaccid peak systolic velocity at PCDU. Men with a lower level of education had a worse a greater probability of suffering from metabolic syndrome (OR=1.38 [1.06;1.79], 1.73 [1.34;2.24], 1.72 [1.24;2.37] for upper secondary, lower secondary and primary school, respectively) and were more likely to have history of previous CV events. In the longitudinal study, men with higher level of education had a significantly lower incidence of MACEs. The role of higher education as an independent predictor of MACE was established by multivariable Cox regressions (HR=2.14 [1.24-3.69]). Conclusions: In ED subjects, lower level of education is associated with a more severely impaired erectile function with atherogenic pathogenesis and with a worse cardio-metabolic profile. In addition, a lower level of education predicts forthcoming MACEs. Therefore, education level should be considered as a costless but valuable information in the assessment of CV risk in patients with ED. Conflicts of Interest: none [ABSTRACT FROM AUTHOR]