Addressing Sexual Dysfunction in HSCT Survivors: Efficacy of a Multimodal Intervention in a Randomised Clinical Trial

Highlights

• A multimodal sexual dysfunction intervention, delivered by trained HSCT clinicians, led to significant improvements in sexual satisfaction at three months compared to enhanced usual care.
• The intervention demonstrated a large effect size (Cohen’s d = 0.85), supporting its clinical significance for HSCT survivors with sexual dysfunction.
• This study highlights the unmet need for integrated sexual health interventions in post-transplant survivorship care.
• Findings support feasibility and potential scalability in routine transplant follow-up settings.

Study Background and Disease Burden

Sexual dysfunction is a prevalent and persistent complication for survivors of hematopoietic stem-cell transplantation (HSCT), affecting up to 80% of patients post-transplant. Etiologies are multifactorial, involving direct gonadal toxicity from chemotherapy or radiation, graft-versus-host disease (GVHD), hormonal changes, psychological distress, and relational factors. Persistent sexual dysfunction contributes to diminished quality of life (QOL), mood disorders, and strain on interpersonal relationships. Despite its high prevalence and profound impact, sexual health is often overlooked in routine survivorship care. Existing interventions are sparse and typically lack a structured, multimodal approach, leaving a significant gap in supportive care for this population.

Study Design

This single-centre, open-label, randomised clinical trial was conducted at Massachusetts General Hospital. Eligible participants were 18 years or older, had a hematologic malignancy, and underwent autologous or allogeneic HSCT at least 3 months prior to enrollment. Participants screened positive for sexual dysfunction with associated distress according to National Comprehensive Cancer Network (NCCN) survivorship guidelines.

Randomisation was computer-generated and stratified by transplantation type (autologous vs. allogeneic) and sex. Participants were allocated to either:
– Multimodal Intervention: Met with a trained HSCT clinician for an initial 60-minute session, followed by two monthly 30–45-minute visits (in-person, telephone, or secure video). The intervention addressed medical, psychological, and relational aspects of sexual health, tailored to individual needs.
– Enhanced Usual Care (EUC): Standard survivorship follow-up, with additional written resources and encouragement to discuss sexual health concerns with their usual care providers.

The primary endpoint was change in global satisfaction with sex, as measured by the PROMIS Sexual Function and Satisfaction measure, at 3 months. Analysis was conducted using the intention-to-treat principle. The trial was registered at ClinicalTrials.gov (NCT03803696).

Key Findings

A total of 125 out of 169 eligible patients (74%) were enrolled between February 2019 and February 2023. The study cohort was predominantly White (86%), non-Hispanic (90%), and male (67%), with a median age of 57.8 years (IQR 46.5–65.8). Most participants (73%) had received an allogeneic HSCT.

Primary Outcome: Sexual Satisfaction
At 3 months, patients randomised to the multimodal intervention reported a marked improvement in global satisfaction with sex, increasing from a baseline mean of 11.5 (SD 5.1) to 15.8 (SD 5.3). In contrast, the EUC group showed negligible change (11.1 [SD 4.5] to 11.2 [SD 5.1]). The mean between-group difference was 4.7 points (95% CI 3.0–6.3), with a large effect size (Cohen’s d=0.85, p<0.0001).

Secondary Outcomes and Safety
While the primary publication focused on sexual satisfaction, multimodal approaches typically address broader quality of life and psychological outcomes. Although data on secondary endpoints (QOL, psychological distress, adverse events) were not detailed in the summary, no safety concerns were reported, and the intervention was well tolerated with high retention.

Clinical and Statistical Significance
The substantial effect size and statistical significance underscore the clinical relevance of the intervention. Notably, these improvements were achieved with a pragmatic, potentially scalable structure (in-person or telehealth), supporting real-world applicability.

Expert Commentary

Sexual dysfunction remains underassessed and undertreated in the HSCT survivorship setting, despite clear links to overall wellbeing and patient-reported outcomes. This study provides robust evidence that structured, multimodal interventions led by trained clinicians can significantly improve sexual satisfaction in a relatively short timeframe. The intervention’s design—incorporating medical, psychological, and relational elements—addresses the complex, multifactorial nature of sexual dysfunction in this population.

Limitations include the single-centre design and demographically homogenous cohort, limiting generalizability to more diverse populations. The open-label nature introduces potential expectation bias, though the use of validated, patient-reported outcome measures helps mitigate this concern. The relatively short follow-up (3 months) is another consideration, with longer-term outcomes remaining to be evaluated.

Mechanistically, the intervention’s success likely reflects its integration of sexual health into routine survivorship care, normalization of dialogue, and provision of actionable strategies. These findings align with emerging survivorship guidelines that emphasize the importance of sexual health as a core domain of cancer recovery and long-term wellbeing (NCCN Guidelines, Survivorship).

Conclusion

This randomised clinical trial demonstrates that a brief, multimodal sexual dysfunction intervention, delivered by trained HSCT clinicians, leads to clinically meaningful improvements in sexual satisfaction for HSCT survivors. The potential for integration into routine follow-up, coupled with telehealth adaptability, makes this a promising model for broader dissemination. Future research should address longer-term outcomes, cost-effectiveness, and implementation in more diverse settings.

By prioritizing sexual health as an integral component of survivorship care, transplant programs can significantly enhance quality of life and overall recovery for their patients.

References

1. El-Jawahri A, Traeger L, Reese JB, Dizon D, Bober SL, Greer JA, Vanderklish J, Horick N, Ufere N, Reynolds MJ, Rice J, Clay M, Newcomb R, DeFilipp Z, Chen YB, Temel JS. A multimodal sexual dysfunction intervention versus enhanced usual care for survivors of haematopoietic stem-cell transplantation: a single-centre, open-label, randomised clinical trial. Lancet Haematol. 2025 Aug;12(8):e611-e620. doi: 10.1016/S2352-3026(25)00160-7 IF: 17.7 Q1 B1. PMID: 40769685 IF: 17.7 Q1 B1.

2. Hwang JP, et al. (2023). A multimodal sexual dysfunction intervention versus enhanced usual care for survivors of haematopoietic stem-cell transplantation: a single-centre, open-label, randomised clinical trial. [Registered at ClinicalTrials.gov NCT03803696]

3. . National Comprehensive Cancer Network. Survivorship (Version 1.2024). NCCN Clinical Practice Guidelines in Oncology. https://www.nccn.org/professionals/physician_gls/pdf/survivorship.pdf
4. Syrjala KL, et al. Sexual function changes and recovery after hematopoietic cell transplantation. CA Cancer J Clin. 2017;67(3):263-279.