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Table.  Multivariable Analysis of Factors and Markers Associated With ED Among Study Participants
Multivariable Analysis of Factors and Markers Associated With ED Among Study Participants
1.
Hudson  MM, Ness  KK, Nolan  VG,  et al.  Prospective medical assessment of adults surviving childhood cancer: study design, cohort characteristics, and feasibility of the St. Jude Lifetime Cohort study.  Pediatr Blood Cancer. 2011;56(5):825-836. doi:10.1002/pbc.22875PubMedGoogle ScholarCrossref
2.
Cappelleri  JC, Rosen  RC, Smith  MD, Mishra  A, Osterloh  IH.  Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function.  Urology. 1999;54(2):346-351. doi:10.1016/S0090-4295(99)00099-0PubMedGoogle ScholarCrossref
3.
Fried  LP, Tangen  CM, Walston  J,  et al; Cardiovascular Health Study Collaborative Research Group.  Frailty in older adults: evidence for a phenotype.  J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M156. doi:10.1093/gerona/56.3.M146PubMedGoogle ScholarCrossref
4.
Ritenour  CW, Seidel  KD, Leisenring  W,  et al.  Erectile dysfunction in male survivors of childhood cancer—a report from the Childhood Cancer Survivor Study.  J Sex Med. 2016;13(6):945-954. doi:10.1016/j.jsxm.2016.03.367PubMedGoogle ScholarCrossref
5.
Selvin  E, Burnett  AL, Platz  EA.  Prevalence and risk factors for erectile dysfunction in the US.  Am J Med. 2007;120(2):151-157. doi:10.1016/j.amjmed.2006.06.010PubMedGoogle ScholarCrossref
6.
Chemaitilly  W, Li  Z, Huang  S,  et al.  Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study.  J Clin Oncol. 2015;33(5):492-500. doi:10.1200/JCO.2014.56.7933PubMedGoogle ScholarCrossref
Research Letter
November 2018

Erectile Dysfunction in Male Survivors of Childhood Cancer

Author Affiliations
  • 1Department of Endocrinology, St Jude Children’s Research Hospital, Memphis, Tennessee
  • 2Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, Tennessee
  • 3Department of Behavioral Science, MD Anderson Cancer Center, Houston, Texas (retired)
  • 4Department of Oncology, St Jude Children’s Research Hospital, Memphis, Tennessee
  • 5Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
JAMA Oncol. 2018;4(11):1613-1616. doi:10.1001/jamaoncol.2018.4420

Male sexual dysfunction and its association with psychological and physical well-being have been underreported in childhood cancer survivors (CCSs). To our knowledge, this study provides the first data on a large population of systematically and clinically assessed CCSs, enumerating the prevalence and consequences of erectile dysfunction (ED) and identifying potential targets for intervention.

Methods

This cross-sectional, single-institution study included male CCSs, 18 years or older, 10 years or more from diagnosis of childhood cancer who completed questionnaires on sexual health.1 In sexually active participants, mild to severe ED was defined by scores of 25 or less, using the validated, 6-item version of the International Index of Erectile Function.2 In non–sexually active participants, responses to items that queried problems achieving or sustaining an erection were used to characterize ED. Low total testosterone level was defined as morning serum concentrations less than 250 ng/dL (to convert to nanomoles per liter, multiply by 0.0347). Psychological distress, body image dissatisfaction, and health-related quality of life were measured using the Brief Symptom Inventory, the Body Image Scale, and the 36-Item Short-Form Health Survey, respectively. Physical health outcomes included lean muscle mass, vitality, physical activity, slowness, weakness, and exercise tolerance.3 This study was approved by the institutional review board at St Jude Children's Research Hospital; written informed consent was obtained from all participants.

To limit false-positive results, elastic net regression was used to select variables for multivariable analyses. Associations between demographic and treatment-related risk factors, psychological distress, physical health, and ED were evaluated (relative risk [RR], 95% CI). Statistical significance was set at α = .05 (2-sided).

Results

The survey participant rate was 62.6% (1021 of 1631 eligible patients). A total of 1021 participants (median age, 31.3 years; range, 18.8-61.5 years) were included. ED scores were available for 956. Erectile dysfunction was reported by 277 (29.0%; 95% CI, 26.1%-32.0%) of the participants. In sexually active participants (n = 873 [85.5%]), independent risk factors for ED included Hispanic or other race/ethnicity (RR, 1.94; 95% CI, 1.05-3.61), age at the time of the study (RR, 0.98; 95% CI, 0.96-1.00), and low testosterone levels (RR, 1.70; 95% CI, 1.20-2.41) (Table). When data of both sexually and non–sexually active participants were combined, black race (RR, 1.51; 95% CI, 1.14-2.02) was also a risk factor for ED. Individuals with greater body image dissatisfaction and low lean muscle mass were more likely to report ED in both the sexually active and combined groups (Table).

Discussion

The prevalence of ED in our study was considerably higher compared with other CCS cohorts or the general population.4,5 Hypogonadism, a condition often undiagnosed in CCSs, could explain the associations between low testosterone levels, low lean muscle mass, and ED.6 We also found an association between nonwhite race/ethnicity and ED. The reasons for this association are not clear and need further exploration in populations enriched for racial/ethnic minorities. The finding that younger age at assessment was associated with a higher risk for ED is likely a reflection of the differential age distributions between tumor types in our population: protocols to treat patients with brain tumors were introduced at our institution in the mid-1980s. Therefore, this association is likely driven by including younger survivors treated for brain tumors, which is a population at risk for hypogonadism.6

The association between ED and greater body image dissatisfaction may be bidirectional and emphasizes that ED requires multidisciplinary treatment that combines psychological counseling and medical treatment. The lack of validated questionnaires has limited the reliable assessment of ED in non–sexually active CCSs; further diagnostic research is warranted. Furthermore, potential selection bias and misclassification may have overestimated the prevalence of ED in our cohort. Although the results from these analyses are hypothesis generating and need validation in an independent cohort, our data support the hypothesis that ED may be a modifiable condition in CCSs. Clinicians should be aware that appropriate management of hypogonadism may improve impaired sexual functioning in CCSs.

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Article Information

Accepted for Publication: July 30, 2018.

Corresponding Author: Laura van Iersel, MD, Department of Endocrinology, St Jude Children’s Research Hospital, MS 737, 262 Danny Thomas Pl, Memphis, TN 38105 (laura.vaniersel@stjude.org).

Published Online: October 4, 2018. doi:10.1001/jamaoncol.2018.4420

Author Contributions: Dr Klosky had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis

Concept and design: Chemaitilly, Schover, Hudson, Klosky.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: van Iersel, Chemaitilly, Klosky.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: van Iersel, Li, Klosky.

Obtained funding: Hudson.

Administrative, technical, or material support: Hudson, Klosky.

Supervision: Chemaitilly, Ness, Klosky.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by American Lebanese Syrian Associated Charities, National Cancer Institute grant U01 CA195547, and National Cancer Institute Cancer Center Support grant P30 CA021765 for St Jude Children’s Research Hospital.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Deo Kumar Srivastava, PhD (Department of Biostatistics, St Jude Children's Research Hospital), assisted with statistical analysis, and Joseph Gleason, MD (Department of Urology, University of Tennessee Health Science Center), Victoria W. Willard, PhD, and Lisa M. Jacola, PhD (Department of Psychology, St Jude Children’s Research Hospital), Daniel M. Green, MD, Leslie L. Robison, PhD, and Tara M. Brinkman, PhD (Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital), Charles A. Sklar, MD (Department of Pediatrics, Memorial Sloan-Kettering Cancer Center), and Hanneke M. van Santen, MD, PhD (Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital) assisted with reviewing the manuscript. There was no financial compensation.

References
1.
Hudson  MM, Ness  KK, Nolan  VG,  et al.  Prospective medical assessment of adults surviving childhood cancer: study design, cohort characteristics, and feasibility of the St. Jude Lifetime Cohort study.  Pediatr Blood Cancer. 2011;56(5):825-836. doi:10.1002/pbc.22875PubMedGoogle ScholarCrossref
2.
Cappelleri  JC, Rosen  RC, Smith  MD, Mishra  A, Osterloh  IH.  Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function.  Urology. 1999;54(2):346-351. doi:10.1016/S0090-4295(99)00099-0PubMedGoogle ScholarCrossref
3.
Fried  LP, Tangen  CM, Walston  J,  et al; Cardiovascular Health Study Collaborative Research Group.  Frailty in older adults: evidence for a phenotype.  J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M156. doi:10.1093/gerona/56.3.M146PubMedGoogle ScholarCrossref
4.
Ritenour  CW, Seidel  KD, Leisenring  W,  et al.  Erectile dysfunction in male survivors of childhood cancer—a report from the Childhood Cancer Survivor Study.  J Sex Med. 2016;13(6):945-954. doi:10.1016/j.jsxm.2016.03.367PubMedGoogle ScholarCrossref
5.
Selvin  E, Burnett  AL, Platz  EA.  Prevalence and risk factors for erectile dysfunction in the US.  Am J Med. 2007;120(2):151-157. doi:10.1016/j.amjmed.2006.06.010PubMedGoogle ScholarCrossref
6.
Chemaitilly  W, Li  Z, Huang  S,  et al.  Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study.  J Clin Oncol. 2015;33(5):492-500. doi:10.1200/JCO.2014.56.7933PubMedGoogle ScholarCrossref
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