Consortium Research Reveals Sex-Based Differences in Sickle Cell Disease

By Keightley Amen - Last Updated: December 2, 2021

Sickle cell disease (SCD) affects the sexes differently, with men experiencing more life-threatening complications and women experiencing higher rates of depression and anxiety, more vaso-occlusive episodes (VOEs), and worse pain severity, according to new research from the Sickle Cell Disease Implementation Consortium (SCDIC), published in PLoS One.

The consortium undertook the research because “Sex-based clinical outcome differences in SCD remain largely unknown despite evidence that female sex is associated with an increased lifespan,” wrote the authors, led by Rita V. Masese, MSc, MD, of the School of Nursing at Duke University in Durham, North Carolina.

The researchers gathered data on pain, treatment characteristics, laboratory measures, and complications among men and women with SCD who are enrolled in the SCDIC registry, which includes eight comprehensive SCD centers and one data coordinating center and is funded by the National Heart Lung and Blood Institute (NHLBI).

Eligible patients were 15 to 45 years old with a laboratory-confirmed diagnosis of SCD. The study analyzed data from 2,124 participants with a mean age of 27.8 years. Most participants were female (56%), Black or African American (95.6%), and had the hemoglobin SS SCD genotype.

The researchers pulled data from patients’ self-report surveys and medical records. Analyses revealed that female participants had higher:

  • anxiety and depression
  • autoimmune diseases
  • hospital admissions
  • pain severity
  • VOEs

Male participants had more:

  • acute chest syndrome
  • cardiovascular complications
  • genitourinary complications
  • hydroxyurea use
  • musculoskeletal complications
  • respiratory complications
  • skin ulcers

Men also had significantly higher values of:

  • blood urea nitrogen (BUN)
  • liver enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin)
  • serum creatinine

“Our findings suggest key sex differences in the presentation of SCD, with males having more life-threatening, chronic, end-organ complications and females having higher rates of depression and anxiety,” the authors emphasized.

The article called for future research to determine the exact mechanisms causing sex-related differences in clinical outcomes. For example, they highlighted the potential role of hormones and physiologic changes during menstruation as a possible explanation for higher rates of VOEs in women.