Genital Graft-Versus-Host-Disease Predicts Decreased Sexual Function in Female Survivors of Allogeneic Hematopoietic Stem Cell Transplant

Abstract

Background: Impaired sexual health is a common long-term issue for female allogeneic hematopoietic stem cell transplant survivors.

Objective(s): To compare sexual function among clinically stable female transplant survivors to age-matched healthy female volunteers and to explore the contribution of key post-transplant factors over time to sexual function.

Study design: Secondary analysis of the sexual function of female transplant survivors and healthy female volunteers aged 18 to 50 years enrolled in a year-long prospective clinical trial of HPV vaccination. Clinically stable transplant survivors were at least 90 days post-transplant. The general assessment of post-transplant health included an assessment for genital and systemic chronic GvHD. Gynecologists assessed for and treated genital chronic GvHD including topical, targeted therapies, assessed ovarian function, performed cervical cancer screening, provided recommendations about contraception and ovarian hormone treatments, and discussed sexual function. Participants completed the Sexual Functioning Questionnaire (SFQ) at enrollment, 7 and 12 months. Genital and systemic chronic graft-versus-host disease (GvHD), sexual activity, ovarian hormonal status, systemic immunosuppression use, and antidepressant use were prospectively evaluated over time post-transplant and compared to sexual function and health characteristics of healthy females. Comparisons between groups were made using independent t-tests. Transplant complications of systemic or genital chronic graft-versus-host disease (GvHD), sexual activity, ovarian hormonal status, immunosuppression, and antidepressant use were evaluated over time using linear mixed models for their association with SFQ scores.

Results: Sixty-four females included 20 healthy volunteers and 44 transplant survivors, of whom 23 (52%) were receiving systemic immunosuppressive therapy. At baseline, whether participants were not currently sexually active, had low sexual function or had high sexual function significantly differed between transplant survivors (45% versus 30% versus 20% of 44 women, respectively) and volunteers (20% versus 15% versus 65% of 20 women, respectively, P = .003). SFQ overall and subscale scores were lower in transplant survivors compared to healthy females at baseline and the difference persisted over time (all P < .05). Baseline SFQ overall scores were similar between transplant survivors on and off immunosuppression (P = .09). At 1 year, survivors had significantly higher SFQ overall and health impact scores (P = .05 and P < .001, respectively) and a lower problems score (P = .04) compared to baseline, but the other subscale scores did not change. At each timepoint, females with genital GvHD had lower SFQ overall scores compared to those without (P = .04).

Conclusion: Female transplant survivors participating in an HPV vaccine trial were more likely to have sexual dysfunction at all time points compared to healthy controls and genital chronic GVHD was the most influential driver. Sexual function improved over time in transplant survivors in the context of a whole-person approach to gynecologic post-transplant care.

Keywords: Female; Genital graft versus host disease; Hematopoietic stem cell transplantation; Immunosuppression; Sexual function; Systemic graft versus host disease; Transplant survivor; antidepressant.