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Open research questions in Sexual function and dysfunction studies

181 unresolved questions extracted from the limitations and future-work sections of 3,045 Sexual function and dysfunction studies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Persistent post-treatment dysfunction and pharma- cogenetic vulnerability also remain incompletely understood and require further longitudinal research (51–56).

    Sexual dysfunction associated with antidepressants and antipsychotics: a structured narrative review of mechanisms, assessment, and personalized management · 2026 · DOI

  • Conclusions Sexual dysfunction affects more than half of patients following CES and represents a persistent and under-recognised component of long-term morbidity.

    Sexual dysfunction after cauda equina syndrome: a systematic review of long-term outcomes · 2026 · DOI

  • Abstract Purpose Sexual dysfunction is a recognised but underreported outcome following cauda equina syndrome (CES), with existing evidence fragmented and methodologically heterogeneous.

    Sexual dysfunction after cauda equina syndrome: a systematic review of long-term outcomes · 2026 · DOI

  • Abstract Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by persistent pain, is significantly associated with sexual dysfunction, yet the underlying mechanisms remain poorly understood.

    Comprehensive multi-omics analyses elucidate the mechanism of male sexual dysfunction induced by chronic prostatitis/chronic pelvic pain syndrome in the experimental autoimmune prostatitis rat model · 2026 · DOI

  • A key limitation of this network meta-analysis is the star- shaped geometry of the evidence base. With no direct head- to-head randomized trials comparing PRECEDE versus PLISSIT, PRECEDE versus BETTER, or any other pair- wise comparison between active interventions, all relative treatment effects and rankings are derived entirely from indirect comparisons through a common control group. Indirect comparisons assume transitivity—that the distribu- tion of effect modifiers is balanced across different inter- vention studies—an assumption that cannot be empirically verified and is particularly tenuous given the high hetero- geneity observed (I2 = 97.7%). Therefore, the P-score rank- ings should be viewed as purely hypothesis-generating and not as a basis for clinical decision-making. Direct head-to- head trials are urgently needed to provide valid comparative effectiveness estimates.

    Comparative effects of psychological interventions (PRECEDE, PLISSIT, BETTER, and Counseling) on female sexual function index (FSFI) scores in women with diabetes: a systematic review and network meta-analysis · 2026 · DOI

  • 173 Jurnal Psikologi Ulayat: Indonesian Journal of Indigenous Psychology (2026), 13(1), 160–177 Future research should examine the moderating roles of family dynamics, peer influence, and digital media on the religiosity-virginity value relationship and exploring the findings across different developmental stages and diverse religious cultures to determine broader applicability.

    Virginity value in late adolescents: Can religiosity be a predictor? · 2026 · DOI

  • The cellular model validation relied exclusively on HUVECs to study endothelial dysfunction in erectile dysfunction, but ED pathogenesis involves synergistic interactions among corpus cavernosum smooth muscle cells, endothelial cells, and neuronal cells. Future studies must establish primary corpus cavernosum smooth muscle cell models, endothelial-smooth muscle co-culture systems, and animal models to evaluate target protein function and its impact on erectile function at the organismal level.

    Integrating multi-omics, EWAS, and reverse network toxicology to explore environmental pollutant risks in erectile dysfunction · 2026 · DOI

  • In vitro functional validation was conducted only for FIS1 in HUVECs, while mechanistic experiments for CNP and TNFSF12 targets were not equally detailed. Additionally, the epigenetic and transcriptional regulatory mechanisms by which the four identified pollutants influence FIS1 gene expression remain unexplored. Future research must conduct systematic functional experiments integrating ChIP–seq and methylation sequencing to construct regulatory networks linking pollutants, target genes, and downstream pathways.

    Integrating multi-omics, EWAS, and reverse network toxicology to explore environmental pollutant risks in erectile dysfunction · 2026 · DOI

  • The SMR causal inference approach with cis-QTLs and HEIDI testing cannot completely eliminate unmeasured confounding, horizontal pleiotropy, or weak instrument bias in linking environmental pollutants to erectile dysfunction. Future studies should validate the robustness of genetic associations between target genes and ED risk using colocalization analysis, multivariable MR, or prospective cohort studies.

    Integrating multi-omics, EWAS, and reverse network toxicology to explore environmental pollutant risks in erectile dysfunction · 2026 · DOI

  • Pollutant screening was based solely on in silico predictions from the CTD database and cannot account for the combined effects of exposure mixtures or inter-individual variability in real-world settings. Future research should adopt exposomic approaches by utilizing measured pollutant concentrations in human biosamples to validate associations between benzo[a]pyrene, bisphenol F, tetrabromobisphenol A, and chlorpyrifos exposure in more realistic environmental settings.

    Integrating multi-omics, EWAS, and reverse network toxicology to explore environmental pollutant risks in erectile dysfunction · 2026 · DOI

  • The ED-GWAS and eQTL, mQTL, and pQTL datasets used in this multi-omics analysis were predominantly derived from European populations, limiting cross-ancestry validation. Future studies must leverage multi-ancestry genetic resources to validate whether the identified core targets (FIS1, CNP, and TNFSF12) show consistent associations across non-European populations with sufficient sample sizes.

    Integrating multi-omics, EWAS, and reverse network toxicology to explore environmental pollutant risks in erectile dysfunction · 2026 · DOI

  • Psychological intervention is a critical yet often overlooked component of MDT management, led by psychiatrists or clinical psychologists. Arthritis-related chronic pain, disability, and functional to anxiety, depression, and sexual performance anxiety—factors that may amplify ED severity through a “pain-ED-anxiety” vicious cycle (Matsui et al., 2015) (Restoux et al., 2020). Routine screening with tools such as the HADS or BDI should be integrated into MDT assessments. CBT can help patients address negative frequently contribute sexual related to cause sexual dysfunction, thought patterns function, while to mindfulness-based stress reduction (MBSR) may alleviate anxiety associated with arthritis flares and ED (Bilal and Abbasi, 2020) (Sharpe et al., 2025). For patients with comorbid depression, selective serotonin reuptake inhibitors (SSRIs) should be prescribed cautiously, as these agents are known including ED and anorgasmia (Reisman, 2017); notably, some patients may experience persistent sexual symptoms after discontinuing SSRIs, termed SSRI-induced post-SSRI sexual dysfunction (PSSD), which presents as genital numbness, anorgasmia, or loss of libido (Healy and Mangin, 2024) (Bala et al., 2018). Thus, the psychiatric team should collaborate closely with urologists to balance mood management and sexual health. Endocrinology and clinical nutrition support address metabolic and hormonal drivers of ED. Endocrinologists should monitor (via testosterone homeostasis model assessment of insulin resistance, HOMA-IR), and glucose/lipid profiles, all of which are frequently dysregulated in arthritis patients and linked to ED (Perez-Garcia et al., 2020) (TT and FT), resistance insulin levels Frontiers in Cell and Developmental Biology 14 frontiersin.org Wang et al. 10.3389/fcell.2026.1729897 (Dilixiati et al., 2024) (Yao et al., 2013). Testosterone replacement therapy may be considered for patients with documented hypogonadism, though its use should be balanced against potential cardiovascular risks and coordinated with rheumatology teams to avoid worsening inflammation. Clinical nutritionists play a key role in lifestyle optimization: obese patients should receive personalized weight management plans to reduce joint burden and improve metabolic health (Wang H. et al., 2025); gout patients require strict limitation of high-purine foods (organ meats, seafood) and alcohol; and all patients should be advised to increase omega-3 fatty acid (deep-sea fish, flaxseeds) and dietary fiber intake, while reducing high-sugar and high-fat foods to mitigate inflammation and endothelial dysfunction (Hong et al., 2024) (Bauer et al., 2020).

    From arthritis to erectile dysfunction: potential pathophysiological mechanisms and multidisciplinary integrated management · 2026 · DOI

  • Results From the twelve empirical studies included, three themes were identified: (1) Theory–practice gap: HP’s recognition of the need to provide sexual support to patients with cancer and partners but current provision is lacking, (2) professional and organisational barriers to HPs providing sexual support for patients with cancer and (3) equipping HPs and enabling patients to discuss sexual challenges in cancer care could enhance delivery of sexual support.

    Factors Influencing the Provision of Healthcare Professional-Led Sexual Support to Patients with Cancer and Their Partners: An Integrative Review of Studies from 2017 to 2022 · 2024 · DOI

  • Objective There are inconsistent reports regarding the relationship between cannabis use and male sexual function with almost no data about synthetic cannabinoids (SC) and their effect on male sexual functions.

    Psychosexual dysfunction in male patients with cannabis dependence and synthetic cannabinoid dependence · 2024 · DOI

  • Background and aims: Despite the inclusion of Compulsive Sexual Behavior (CSB) as a diagnostic entity in the ICD-11 and the increasing number of studies addressing psychological factors leading to its onset and maintenance, little is known about the role of hormonal factors when accounting for this clinical condition (especially in women).

    Salivary testosterone levels are associated with Compulsive Sexual Behavior (CSB) in men but not in women in a community sample · 2023 · DOI

  • It is noted that though ovarian corticosteroids can produce some effect on sexual desire in women, their exact role in the appearance of HSD disorder in females remains unclear.

    Hypoactive Libido: Neurohumoral Characteristics, Regions of the Brain Regulating Sexual Desire, and Its Reactions to Erotic Stimuli · 2022 · DOI

  • The absence of group differences and mixed results related to cognitive and sensorimotor systems raise concerns to what extent CSBD resembles a wide spectrum of impairments observed in disorders, and demand further research.

    An empirical study of affective and cognitive functions in Compulsive Sexual Behavior Disorder · 2021 · DOI

  • The etiology of PGAD remains unclear and complex, hypothesized causes include vascular, neurological, hormonal, psychological, pharmacologic, dietary, mechanical factors or a combination of these factors.

    Persistent genital arousal disorder – the present knowledge · 2021 · DOI

  • Results: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD.

    International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women · 2021 · DOI

  • Premature ejaculation (PE) is a commonly reported sexual dysfunction in men and yet research remains scarce when looking at the psychopathological mechanisms involved in PE.

    An exploratory study examining the relationship between sexual self efficacy and premature ejaculation mediated by depression, anxiety and sexual fantasy among a British cohort · 2021 · DOI

  • However, the effect of CIT, attachment and alliance on progress in therapy has not yet been documented in patients consulting for sexual difficulties.

    Sexual satisfaction improvement in patients seeking sex therapy: evaluative study of the influence of traumas, attachment and therapeutic alliance · 2020 · DOI

  • The current estimates of doses needed to occupy brain re- ceptors identified by others for sexual benefits and for side effects agreed grossly with estimates previously made by 2 pharmacology experts, and the estimates of doses needed for hypnotic effects agreed grossly with clinical trials. However, brain concentrations of TRZ and its main active metabolite (mCPP) are not available for humans and were extrapolated from rat data for this article. This may limit the accuracy of these dose predictions. No clinical test results are available for the low doses of TRZ predicted here to be of sexual benefit. Thus, benefits for sexual dysfunction with such low doses are purely speculative. However, 1 psychiatrist published recommendations from his clinical practice and that of colleagues that 12.5 mg or less of IR TRZ has antiagitational/ sedative benefits.59 Such benefits might utilize the same receptors, and thus the same doses, as theorized for sexual ben- efits here. CONCLUSION The optimal dose of XR TRZ for improving sexual desire and arousal without causing CNS depression appears from the rele- vant receptor and pharmacokinetic data to be no more than 19.2 mg daily and as little as 3.5 mg. Quartering tablets of the lowest dose strength of XR TRZ commercially available to provide 37.5 mg per day, or quartering the lowest-strength IR tablet to provide 12.5 mg 2e3 times a day, might provide similar benefits while still minimizing CNS depressant effects. Animal pharmacology data support individualizing the dose in humans to achieve target levels in the brain. In other words, doses of about half and 1.5 times the optimized dose may be needed. Some men may require up to twice as large a dose of TRZ as women for optimal benefit. Corresponding Author: Robert E. Pyke, MD, PhD, Pykon- sult, LLC, 23 Eastview Drive, New Fairfield, CT 26812. Tel: 203-399-2390; E-mail: [email protected] Conflict of Interest: Dr Pyke is the president of Pykonsult, LLC, and a shareholder of S1 Biopharma, Inc, firms developing so- matic treatments for sexual dysfunction. Funding: None. Sex Med Rev 2018;-:1e11 STATEMENT OF AUTHORSHIP Category 1 (a) Conception and Design Robert E. Pyke (b) Acquisition of Data Robert E. Pyke (c) Analysis and Interpretation of Data Robert E. Pyke Category 2 (a) Drafting the Article Robert E. Pyke (b) Revising It for Intellectual Content Robert E. Pyke Category 3 (a) Final Approval of the Completed Article Robert E. Pyke REFERENCES 1. Ferguson JM, Shrivastava RK, Stahl SM, et al. Reemergence of sexual dysfunction in patients with major depressive dis- order: Double-blind comparison of nefazodone and sertraline. J Clin Psychiatry 2001;62:24-29. 2. Cyr M, Brown CS. Nefazodone: Its place among antidepres- sants. Ann Pharmacother 1996;30:1006-1012. 3. Borsini F, Evans K, Jason K, et al. Pharmacology of flibanserin. CNS Drug Rev 2002;8:117-142. 4. Serzone (nefazodone): Side effects, interactions, warning, dosage & uses. RxList. Available at: https://www.rxlist.com/ serzone-drug.htm. Accessed July 17, 2018. 5. Mashiko H, Niwa S, Kumashiro H, et al. Effect of trazodone in a single dose before bedtime for sleep disorders accompanied by a depressive state: Dose-finding study with no concomi- tant use of hypnotic agent. Psychiatry Clin Neurosci 1999; 53:193-194. 6. Shifren JL, Monz BU, Russo PA, et al. Sexual problems and distress in United States women: Prevalence and correlates. Obstet Gynecol 2008;112:970-978. 7. Johnson M. ADDYI: Cindy Whitehead on the ‘disappointment’ over libido drug launch. BizWomen. Available at: https://www. bizjournals.com/bizwomen/news/profiles-strategies/2016/04/ addyi-cindy-whitehead-on-the-disappointment-over.html? page¼all. Accessed July 16, 2018. 8. Wieczner J. Valeant is paying to get rid of its $1 billion ‘Female Viagra’ acquisition. Fortune. Available at: Fortune.com/2017/11/ 06/valeant-pharmaceuticals-sprout/. Accessed February 25, 2018. 9. Addyi prescribing information. Available at: http://www.addyi. com/hcp. Accessed February 11, 2017. 10. Zlott DA, Byrne M. Mechanisms by which pharmacologic agents may contribute to fatigue. PM R 2010;2:451-455.

    Trazodone in Sexual Medicine: Underused and Overdosed? · 2020 · DOI

  • Although there is no consensus about the treatment of Persistent Genital Arousal Disorder in the psychiatric literature, there are some case reports about the use of pregabaline, clomipramine, duloxetine, clonazepam, varenicline, olanzapine, risperidone in addition to the case reports on treatment with hypnotherapy, pelvic floor physiotherapy and electroconvulsive therapy (ECT).

    Persistent Genital Arousal Disorder Treated with Duloxetine: A Case Report · 2019 · DOI

  • Results of our analysis suggest insufficient evidence exists to consider any specific response-suppression technique an overarching treatment for decreasing ISB using the Horner et al.

    Behavioral Interventions for Inappropriate Sexual Behavior in Individuals With Developmental Disabilities and Acquired Brain Injury: A Review · 2018 · DOI

  • Inappropriate sexual behavior (ISB) is a common, but understudied, issue for individuals diagnosed with developmental disabilities (DD), intellectual disability (ID), and/or acquired brain injuries (ABI).

    Behavioral Interventions for Inappropriate Sexual Behavior in Individuals With Developmental Disabilities and Acquired Brain Injury: A Review · 2018 · DOI

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181 open questions have been extracted from the limitations and future-work passages of 3,045 Sexual function and dysfunction studies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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