Basic science and translational research: recommendations from the Fifth International Consultation for Sexual Medicine (ICSM 2024).

Erectile dysfunction associated with prostatectomy, diabetes, aging, and vascular disease develops through both common and distinct mechanisms involving multiple pathological processes.

• Mechanisms include neural injury, penile remodeling with smooth muscle apoptosis and increased collagen/fibrosis, dysregulated smooth muscle contractility, increased oxidative stress, immune response, and genomic instability.
• Cavernous nerve injury following prostatectomy and diabetes-related changes can lead to irreversible ED through penile tissue remodeling and fibrosis.
• The committee identified these pathways as priority targets for future research and therapeutic development.
• Literature was reviewed from 2015 through May 2024 by a multidisciplinary committee of sexual medicine experts.

Female sexual dysfunction involves multiple overlapping neurological and endocrine mechanisms affecting genital pain, arousal, sexual desire, and orgasm.

• Disorders of genital pain, arousal, sexual desire, and orgasm were identified as involving 'multiple, overlapping neurological and endocrine mechanisms.'
• Research on ED has been 'more extensive and the underlying molecular mechanisms have been better characterized than female sexual dysfunction.'
• Psychosocial factors have a 'greater influence' on female sexual function compared to male sexual function, demanding a multidisciplinary approach.
• Despite approved and off-label treatments for disorders of sexual desire and orgasm in women, significant gaps remain in understanding and treatment.

Nanotechnology-based vehicles and regenerative therapies represent an emerging frontier for targeted delivery of treatments for sexual dysfunction.

• The report examined 'novel nanotechnology-based vehicles and treatments to aid regeneration and clinical translation in men and women.'
• Progress in nanotechnology and regenerative therapies was described as 'an exciting frontier in the targeted delivery of ameliorative/restorative treatments.'
• These approaches were highlighted as potential solutions for the challenge of translating preclinical findings into clinical therapies.
• The committee treated this as a state-of-the-art summary integrating basic science and translational perspectives from the past decade.

Genome-wide association studies (GWAS) show potential for advancing the field of sexual medicine but require replication and functional validation.

• GWAS were identified as having 'great potential in advancing the field' of sexual medicine.
• Findings from bioinformatic analyses require 'replication and functional validation.'
• This represents a key methodological gap identified by the committee between genetic discovery and clinical application.
• The recommendation reflects broader concerns about translating genomic findings into actionable biological insights.

Key therapeutic targets for erectile dysfunction identified for future research include nerve regeneration, neuroprotection, smooth muscle contractility/relaxation, oxidative stress, immune response, and hormone function.

• Particular emphasis was placed on targets to improve or enhance 'nerve regeneration, neuroprotection, "on demand" sexual function, SM contractility/relaxation, oxidative stress, immune response, and hormone function.'
• Future research should focus on 'pathways that underlie penile tissue remodeling and fibrosis associated with cavernous nerve injury in prostatectomy and diabetes, since this leads to irreversible ED.'
• The identification of irreversibility of fibrosis-related ED was highlighted as a key reason for prioritizing these pathways.
• The committee used a consensus process, with findings presented at the ICSM meeting in Madrid in June 2024 and comments incorporated into the final report.

Research in sexual medicine has expanded through accelerated rates of discovery and increased breadth and diversity since the last ICSM report in 2015.

• The committee reviewed literature from approximately 2015 through May 2024, representing roughly a decade of progress.
• Despite expanded research, 'much work remains in translating preclinical findings into biomarkers and clinical therapies that can improve patient outcomes.'
• The review was performed by a multidisciplinary committee of sexual medicine experts between June 2023 and May 2024.
• The report was produced as a consensus document from the Fifth International Consultation for Sexual Medicine (ICSM 2024).

Predictive animal models are identified as a needed tool for advancing understanding of female sexual dysfunction, particularly for disorders of sexual desire and orgasm.

• The committee called for 'predictive animal models' as part of a multidisciplinary approach to female sexual dysfunction.
• This need was highlighted in the context of the strong psychosocial influences on female sexual function that complicate direct translation from animal studies.
• Approved and off-label treatments exist for disorders of sexual desire and orgasm in women, but mechanistic understanding remains limited.
• The gap between available treatments and mechanistic understanding underscores the need for better preclinical models.