The association between supra-physiological levels of estradiol and response patterns to experimental pain

The precise mechanism by which gonadal hormones influence pain perception is still obscure. However, no studies have examined experimental pain responses at supra-physiological hormone levels. This study explored the influence of pharmacological estradiol (E2) levels on the stability of pain perception obtained via quantitative sensory testing. A repeated measures design was used with 31 women, treated by a same In Vitro Fertilization (IVF) protocol. Patterns of experimental pain response were assessed in three different sessions (baseline, down regulation, maximal ovarian stimulation). Correlations between hormonal levels (E2, progesterone, luteinizing hormone (LH)) and pain perceptions were assessed at each session. While in the entire sample the pattern of response to pain stimulations remained unchanged regardless of hormonal manipulations, a greater pain sensitivity was associated with supra-physiological levels of E2 during the maximal ovarian stimulation session (for 47 °C stimulation: r = .383, p = 0.044). Mixed model repeated measures ANOVA indicated that participants who over-responded to the ovarian stimulation session (E2 > 10,500 pmol/l) showed significant enhanced pain responses under this condition (p = 0.004). No correlations between progesterone, LH and experimental pain perception were found in any of the study sessions. Although pain perceptions at different E2 levels remained constant, the enhancement of pain scoring at supra-physiological E2 levels, underscore the possible role of sex hormones in pain modulation and experience.