O-35 Exploring Associations between Sex Hormones and Pain Detection Thresholds Among Premenopausal Women with Sickle Cell Disease
Author(s):
Z Ramsay, D Sharma, M Wisdom-Phipps, N Chin, L Campbell, J Knight-Madden , M Asnani
Year of Presentation:
2025
Objective: Women with sickle cell disease (SCD) often
report worse pain compared to men. Vaso-occlusive crisis
(VOC) pain episodes are frequently associated with menses,
and their frequency is often reduced with concurrent use
of hormonal contraceptives. Based on these findings, this
study tested the hypothesis that sex hormones are associated
with pain detection thresholds among women with SCD.
Methods: Premenopausal SCD women aged minimum 18 years with regular menses, and without acute illnesses, pregnancy, oophorectomy or hormonal contraceptives within three months prior, were included. Measurements of pain detection thresholds for heat (HPT) and pressure (PPT), and serum hemoglobin, estradiol, progesterone and testosterone were taken at follicular and luteal visits. Validated questionnaires included the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) which measured quality-of-life and VOC frequency and severity. A study instrument assessed menstrual characteristics and medical history. Multivariate generalized linear mixed models were performed, including days since the last menstrual period standardized by cycle length.
Results: The study recruited 125 participants (mean age 29.0±7.5 years and 79.2% with severe genotype of either homozygous SS or Sβ-Thalassemia0). In multivariate analyses, worse VOC scores (β=1.7) and severe genotype (β=- 46.0) were associated with higher and lower trapezius PPT, respectively. Older age was associated with lower forearm HPT (β=-0.1). Among leg measurements, the presence of ovulatory cycles (β=-1.1) and hydroxyurea use (β=-1.2) were associated with lower HPT, while worse VOC scores (β=0.1) were associated with higher HPT. Higher estradiol was associated with lower HPT at the leg (β=-0.02), with an interaction with the cycle day (β=0.001) predicting lower thresholds earlier in the cycle for the same estradiol level.
Conclusion: Estradiol is associated with a time-varying, length-dependent peripheral neuropathy among SCD women; and may be a potential therapeutic target and biomarker for cyclical pain and neuropathic pain.