Genital Chronic GVHD in Men after Hematopoietic Stem Cell Transplantation: A Single-Center Cross-Sectional Analysis of 155 Patients

Abstract

We assessed the prevalence and clinical features of genital skin changes in men after allogeneic hematopoietic stem cell transplantation (HSCT) and evaluated the correlation between genital chronic graft-versus-host disease (cGVHD) and other manifestations of cGVHD as well as sexual issues. In a cross-sectional cohort study, 155 male recipients alive 1 year or more after HSCT were assessed during their annual follow-up evaluation. Correlation between genital skin changes and other cGVHD manifestations was evaluated, and post-transplantation sexual contentment and sexual functioning were assessed by 2 self-assessment questionnaires, including the 5-item version of the International Index of Erectile Function (IIEF-5) and the modified Brief Sexual Symptom Checklist (mBSSC). Median time between HSCT and genital examination was 5.9 years (range, 1 to 30.3 years). Thirty-one of 155 patients (20%) presented with genital skin changes. Twenty-one of those (13%) presented clinically inflammatory genital skin changes considered as genital cGVHD: 12 had inflammatory (noninfectious) balanoposthitis, 6 had lichen sclerosis-like lesions, 5 had phimosis, and 2 patients had more than 1 feature. Patients with inflammatory genital skin changes had a significantly higher coincidence of oral (P < .0001), ocular (P < .002), and/or cutaneous cGVHD (P < .026) when compared with patients without genital lesions. The rate of IIEF-5 questionnaire response was 59% (91 of 155). Among them, 67% reported erectile dysfunction. Erectile dysfunction was significantly more frequent in patients with genital cGVHD (P = .0075). Seventy-five of 155 patients (48%) answered the mBSSC questionnaire. Only 40% of them reported sexual contentment. Genital skin changes in male recipients after allogeneic HSCT are frequent and seem to be an under-reported relevant late effect. Inflammatory genital skin changes can be considered as a form of genital cGVHD often associated with manifestations of extragenital mucocutaneous cGVHD.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report

“…Patients may report painful sexual intercourse and a burning sensation. Genital signs of GVHD include non-infectious balanoposthitis, lichen sclerosus-like or lichen planus-like features, phimosis, or urethra or meatus scarring or stenosis 35,36 .…”

“…Genitalia: Scoring is now based on severity of the signs instead of symptoms, based on limited available data 29,31,35,36 and the opinions of experts (Supplemental Figure 1 represents an exploratory measure to be completed by specialists or trained practitioners). Female or male genital GVHD is not scored if a practitioner is unable to examine the patient.…”

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. The 2014 Ancillary Therapy and Supportive Care Working Group Report

“…Over 40% of females remain sexually inactive even 5 years after treatment [167], and chronic GVHD increases this risk for both men and women [168]. Contributing factors include GVHD of the skin and genitalia, hormonal changes, and glucocorticoid therapy [147,169]. Phosphodiesterase type 5 inhibitors for men and brief therapeutic options for sexual dysfunction in this population are understudied but are beginning to demonstrate efficacy in other cancer populations [170–172].…”

Sexual health in hematopoietic stem cell transplant recipients

“…26 TBI has been reported to play a central role in male and female infertility in several studies, with a more profound effect noted in men. 12,27,28 Long-term effects on the hypothalamic-pituitary-gonadal axis from conditioning regimens can cause vaginal dryness, dyspareunia, and premature ovarian insufficiency in women. The incidence of premature ovarian failure after HSCT ranges from 40% to 100%.…”

“…Studies have shown that graft-versus-host disease (GVHD) and conditioning regimens, including chemotherapies and total body irradiation (TBI), may play a direct or indirect role in sexual health after transplantation. 7,11,12 Documented complications affecting sexuality include decreased libido, genital GVHD, hormonal dysfunction, erectile dysfunction (ED), dyspareunia, and infertility. 11–13 In addition to physical health conditions, psychosocial problems also may contribute to sexual dysfunction in survivors of HSCT.…”