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Frontiers in Plant Science 2024(Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional...
(Sieb. et Zucc.) Maxim. (ESM) which accumulates several principal flavonoid compounds including epimedin A, B, C and icariin, is extensively utilized in traditional herbs for sexual dysfunction, osteoporosis etc. In China, ESM has a wealth of wild plant resources and characterized by significant variability in medicinal compounds accumulation. Understanding the diversity of ESMs can lead to better utilization of these plant resources. In this study, we integrated the metabolomic and transcriptomic analysis of three ESMs that originated in Anhui, Hubei and Jiangxi in China. Results showed that the flavonoid biosynthesis as well as the related gene expression in these ESMs revealed substantial differences. For example, the epimedin A, B, C and icariin as well as some related gene expression in ESMs from Anhui are significantly lower than those of in others. These results suggested that the ESMs from wild population without quality checkout may not be suitable for directly use as the materials for preparation of Chinese medicine and ESMs with different accumulation of metabolites could be used for distinct applications.
PubMed: 38919822
DOI: 10.3389/fpls.2024.1424956 -
Frontiers in Endocrinology 2024Gender incongruence (GI) is characterized by a marked incongruence between an individual's experienced/expressed gender and the assigned sex at birth. It includes strong...
INTRODUCTION
Gender incongruence (GI) is characterized by a marked incongruence between an individual's experienced/expressed gender and the assigned sex at birth. It includes strong displeasure about his or her sexual anatomy and secondary sex characteristics. In some people, this condition produces a strong distress with anxiety and depression named gender dysphoria (GD). This condition appears to be associated with genetic, epigenetics, hormonal as well as social factors. Given that L-glutamate is the major excitatory neurotransmitter in the central nervous system, also associated with male sexual behavior as well as depression, we aimed to determine whether metabotropic glutamate receptors are involved in GD.
METHODS
We analyzed 74 single nucleotide polymorphisms located at the metabotropic glutamate receptors (mGluR1, mGluR3, mGluR4, mGluR5, mGluR7 and mGluR8) in 94 transgender 94 cisgender people. The allele and genotype frequencies were analyzed by c2 test contrasting male and female cisgender and transgender populations. The strength of the associations was measured by binary logistic regression, estimating the odds ratio (OR) for each genotype. Measurement of linkage disequilibrium, and subsequent measurement of haplotype frequencies were also performed considering three levels of significance: P ≤ 0.05, P ≤ 0.005 and P ≤ 0.0005. Furthermore, false positives were controlled with the Bonferroni correction (P ≤ 0.05/74 = 0.00067).
RESULTS
After analysis of allele and genotypic frequencies, we found twenty-five polymorphisms with significant differences at level P ≤ 0.05, five at P ≤ 0.005 and two at P ≤ 0.0005. Furthermore, the only two polymorphisms (rs9838094 and rs1818033) that passed the Bonferroni correction were both related to the metabotropic glutamate receptor 7 (mGluR7) and showed significant differences for multiple patterns of inheritance. Moreover, the haplotype T/G [OR=0.34 (0.19-0.62); P<0.0004] had a lower representation in the transgender population than in the cisgender population, with no evidence of sex cross-interaction.
CONCLUSION
We provide genetic evidence that the mGluR7, and therefore glutamatergic neurotransmission, may be involved in GI and GD.
Topics: Humans; Male; Receptors, Metabotropic Glutamate; Female; Polymorphism, Single Nucleotide; Adult; Transgender Persons; Gender Dysphoria; Genotype; Young Adult; Middle Aged; Linkage Disequilibrium
PubMed: 38919484
DOI: 10.3389/fendo.2024.1382861 -
Reproductive Biology and Endocrinology... Jun 2024Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective.
BACKGROUND
Erectile dysfunction (ED) is a common male sexual dysfunction, with an increasing incidence, and the current treatment is often ineffective.
METHODS
Vascular endothelial growth factor (VEGFA) was used to treat bone marrow-derived mesenchymal stem cells (BM-MSCs), and their cell migration rates were determined by Transwell assays. The expression of the von Willebrand Factor (vWF)VE-cadherin, and endothelial nitric oxide synthase(eNOS) endothelial markers was determined by qRT‒PCR and Western blot analyses. The MALAT1-induced differentiation of BM-MCs to ECs via the CDC42/PAK1/paxillin pathway was explored by transfecting VEGFA-induced BM-MSC with si-MALAT1 and overexpressing CDC42 and PAK1. The binding capacity between CDC42, PAK1, and paxillin in VEGFA-treated and non-VEGFA-treated BM-MSCs was examined by protein immunoprecipitation. MiR-206 was overexpressed in VEGFA-induced BM-MSC, and the binding sites of MALAT1, miR-206, and CDC42 were identified using a luciferase assay. Sixty male Sprague‒Dawley rats were divided into six groups (n = 10/group). DMED modelling was demonstrated by APO experiments and was assessed by measuring blood glucose levels. Erectile function was assessed by measuring the intracavernosa pressure (ICP) and mean arterial pressure (MAP). Penile erectile tissue was analysed by qRT‒PCR, Western blot analysis, and immunohistochemical staining.
RESULTS
MALAT1 under VEGFA treatment conditions regulates the differentiation of BM-MSCs into ECs by modulating the CDC42/PAK1/paxillin axis. In vitro experiments demonstrated that interference with CDC42 and MALAT1 expression inhibited the differentiation of BM-MSCs to ECs. CDC42 binds to PAK1, and PAK1 binds to paxillin. In addition, CDC42 in the VEGFA group had a greater ability to bind to PAK1, whereas PAK1 in the VEGFA group had a greater ability to bind to paxillin. Overexpression of miR-206 in VEGFA-induced BM-MSCs demonstrated that MALAT1 competes with the CDC42 3'-UTR for binding to miR-206, which in turn is involved in the differentiation of BM-MSCs to ECs. Compared to the DMED model group, the ICP/MAP ratio was significantly greater in the three BM-MSCs treatment groups.
CONCLUSIONS
MALAT1 facilitates BM-MSC differentiation into ECs by regulating the miR-206/CDC42/PAK1/paxillin axis to improve ED. The present findings revealed the vital role of MALAT1 in the repair of BM-MSCs for erectile function and provided new mechanistic insights into the BM-MSC-mediated repair of DMED.
Topics: Male; Animals; RNA, Long Noncoding; MicroRNAs; Cell Differentiation; cdc42 GTP-Binding Protein; Rats, Sprague-Dawley; Signal Transduction; Rats; p21-Activated Kinases; Mesenchymal Stem Cells; Erectile Dysfunction; Paxillin; Endothelial Cells; Cells, Cultured; Vascular Endothelial Growth Factor A
PubMed: 38918809
DOI: 10.1186/s12958-024-01240-8 -
Gynecological Endocrinology : the... Dec 2024Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause. (Review)
Review
INTRODUCTION
Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause.
OBJECTIVE
The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women.
METHODS
A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration.
RESULTS
Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking.
CONCLUSIONS
Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.
Topics: Humans; Female; Testosterone; Sexual Dysfunctions, Psychological; Postmenopause; Libido
PubMed: 38913119
DOI: 10.1080/09513590.2024.2364220 -
Gynecological Endocrinology : the... Dec 2024To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age.
OBJECTIVE
To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age.
METHOD
This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls.
RESULTS
Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls.
CONCLUSION
PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.
Topics: Humans; Female; Polycystic Ovary Syndrome; Adult; Cross-Sectional Studies; Turkey; Young Adult; Insulin Resistance; Sexual Dysfunction, Physiological; Testosterone; Surveys and Questionnaires; Case-Control Studies; Hyperandrogenism; Sexual Behavior; Androstenedione; Dehydroepiandrosterone Sulfate; Obesity
PubMed: 38913084
DOI: 10.1080/09513590.2024.2362249 -
Journal of Clinical Trials 2024Erectile Dysfunction (ED) is a common challenge post Radical Prostatectomy (RALP), affecting men's sexual health after undergoing definitive cancer therapy. Despite...
Study Protocol for a Randomized Controlled Trial of Low Intensity Shockwave Therapy for the Treatment of Post-Radical Prostatectomy Erectile Dysfunction: "SHARP-ED TRIAL".
INTRODUCTION
Erectile Dysfunction (ED) is a common challenge post Radical Prostatectomy (RALP), affecting men's sexual health after undergoing definitive cancer therapy. Despite employing nerve-sparing techniques, ED remains a prevalent issue in this population. Studies indicate that approximately 70%-85% of men experience varying degrees of ED following RALP. The existing treatment landscape for post-RALP-ED presents limitations, and a discernible knowledge gap persists. To address this, our study aims to investigate the efficacy of Shockwave Therapy (SWT) as a potential intervention for managing ED after RALP.
METHODS
This prospective, randomized, sham-controlled clinical trial aims to recruit 189 eligible patients post-RP and assess the effects of SWT. Comprehensive screening, including medical history, physical examinations, and biochemical evaluations, will be conducted to confirm eligibility. The intervention involves utilizing a device to administer focal shockwaves targeted at cavernosal tissue. Safety measures include continuous monitoring for adverse events and rigorous reporting protocols. The primary endpoint assesses changes in participants' ability to engage in penetrative intercourse from baseline to study completion, while secondary endpoints encompass various measures of erectile function, including questionnaire-based assessments, ultrasound parameters, and clinical outcomes.
RESULTS
Statistical analysis, encompassing ANOVA for continuous variables and Fisher's exact test for categorical ones, will evaluate demographic characteristics, baseline data, and primary as well as secondary outcomes for statistical significance. Detailed analysis of trends, subgroup comparisons, and treatment effects will provide a comprehensive understanding of the impact of SWT on post-RP ED.
CONCLUSION
This study protocol represents a rigorous investigation into the potential therapeutic role of SWT in managing post-RP ED. The outcomes from this study aim to contribute valuable insights into the efficacy, safety, and potential improvements in erectile function following SWT, providing significant guidance for future interventions aimed at addressing this challenging condition affecting men's health and quality of life.
PubMed: 38911594
DOI: No ID Found -
BMC Women's Health Jun 2024Sexual dysfunction may lead to sexual distress in women with infertility, while polycystic ovarian syndrome (PCOS) may escalate this distress. This study aimed to...
BACKGROUND
Sexual dysfunction may lead to sexual distress in women with infertility, while polycystic ovarian syndrome (PCOS) may escalate this distress. This study aimed to investigate the role of PCOS in the relationship between sexual dysfunction and sexual distress in Iranian women with infertility.
METHODS
The Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and Depression and Anxiety modules of the DASS-21 were cross-sectionally investigated in 190 women with infertility (103 women with PCOS and 87 women without PCOS).
RESULTS
There were negative correlations between sexual function domains and sexual distress (P < .001) in the total sample. Moderation analysis revealed that higher levels of impaired desire, arousal, and pain elevated sexual distress in the PCOS group. After adjusting for depression and anxiety, only the association between sexual pain and sexual distress was moderated by PCOS condition (P = .008).
CONCLUSIONS
The findings suggest that impaired sexual function is associated with increased levels of sexual distress in infertile female patients. Importantly, comorbid PCOS renders patients susceptible to sexual distress where sexual pain is increased. Further research may shed light on the physiological, psychological, and relational aspects of sexual pain and associated distress in infertile female patients with comorbid PCOS.
Topics: Humans; Female; Iran; Adult; Polycystic Ovary Syndrome; Infertility, Female; Cross-Sectional Studies; Sexual Dysfunctions, Psychological; Depression; Anxiety; Sexual Dysfunction, Physiological; Young Adult
PubMed: 38909223
DOI: 10.1186/s12905-024-03181-1 -
The Primary Care Companion For CNS... Jun 2024
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Male; Female; Sexual Dysfunctions, Psychological; Adult; Middle Aged
PubMed: 38905514
DOI: 10.4088/PCC.23lr03697 -
Medicine Jun 2024Flibanserin, approved for the treatment of hypoactive sexual desire disorder (HSDD) in females, has demonstrated diverse therapeutic and adverse effect (AE) prospects in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Flibanserin, approved for the treatment of hypoactive sexual desire disorder (HSDD) in females, has demonstrated diverse therapeutic and adverse effect (AE) prospects in the extant randomized controlled trials (RCTs). This meta-analysis aimed to characterize the outcomes of flibanserin use in these patients comprehensively.
METHODS
RCTs involving women with HSDD receiving flibanserin in the intervention arm and placebo in the control arm were sought after throughout the electronic databases. The primary outcomes were the changes from baseline in satisfying sexual events (SSE) per month and sexual desire score per month measured using an electronic diary (eDiary).
RESULTS
From 478 initially screened articles, data from 8 RCTs involving 7906 women with HSDD were analyzed. In premenopausal women, flibanserin 100 mg was superior to placebo in improving the number of SSE per month (mean difference, MD 0.69, 95% CI [0.39, 0.99]), eDiary sexual desire score (MD 1.71, 95% CI [0.43, 2.98]), Female Sexual Function Index (FSFI) desire domain (FSFI-d) score (MD 0.30, 95% CI [0.29, 0.31]), FSFI total score (MD 2.51, 95% CI [1.47, 3.55]), Female Sexual Distress Scale-Revised (FSDS-R) Item 13 score (MD -0.30, 95% CI [-0.31, -0.29]), and FSDS-R total score (MD -3.30, 95% CI [-3.37, -3.23]). Compared to placebo, a higher number of premenopausal women using flibanserin 100 mg achieved improvements in the Patient's Global Impression of Improvement score (OR 1.93, 95% CI [1.58, 2.36], P < .00001) and responded positively at Patient Benefit Evaluation (PBE) (odds ratio, OR 1.76, 95% CI [1.34, 2.31], P < .0001). Postmenopausal women receiving flibanserin 100 mg also benefited in terms of the number of SSE per month, FSFI-d and total scores, FSDS-R Item 13 and total scores, and PBE response. Although flibanserin use was associated with higher risks of dizziness, fatigue, nausea, somnolence, and insomnia, these adverse events were mild in nature; the serious AEs and severe AEs were comparable between the flibanserin and placebo groups.
CONCLUSION
While flibanserin has demonstrated efficacy in the treatment of HSDD in both pre- and postmenopausal women, its therapeutic advantages may be overshadowed by the higher likelihood of AEs.
Topics: Female; Humans; Benzimidazoles; Libido; Premenopause; Randomized Controlled Trials as Topic; Sexual Dysfunctions, Psychological; Treatment Outcome
PubMed: 38905407
DOI: 10.1097/MD.0000000000038592 -
Cureus May 2024The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy.
OBJECTIVE
The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy.
METHODS
This study included 111 patients. The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS) were applied to the schizophrenia, and the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) to the bipolar patient group. The sociodemographic data form and the Arizona Sexual Experiences Scale (ASEX) were applied to both of the patient groups. Blood was drawn from all patients to evaluate the indicated gene polymorphisms and evaluate prolactin levels.
RESULTS
SD was detected in 45.9% (N = 34) of the schizophrenia group, and 59.5% (N = 22) in the bipolar disorder group. SD was significantly higher in elderly patients and patients with a high smoking amount and low education levels. The eNOS -786T>C T allele frequency was found to be significantly higher in patients with SD. The logistic regression analysis determined that eNOS -786T>C CT and TT genotypes increased the risk of SD.
CONCLUSION
In this study, the high rates of SD in patients with schizophrenia and bipolar disorder, and the presence of modifiable factors that influence the presence of SD, suggest that SD should be given more attention in these patient groups. On the other hand, the high rate of SD in patients with the eNOS -786T>C T allele indicates the importance of carrying out new studies investigating the factors affecting the enzyme activity in this genotype. There is a need for more studies on eNOS genotypes and enzyme activites in this area.
PubMed: 38899233
DOI: 10.7759/cureus.60654