Association between supraphysiological estradiol levels and propofol injection pain: a prospective observational study

Mahmut Sami Tutar; Ahmet Erarkadas; Serife Nur Yildirim; Dilay Gok Korucu; Oguzhan Gunenc; Munise Yildiz; Dilek Tutar; Betul Kozanhan

doi:10.1186/s12871-026-03823-x

Association between supraphysiological estradiol levels and propofol injection pain: a prospective observational study

BMC Anesthesiol. 2026 Apr 11;26(1):322. doi: 10.1186/s12871-026-03823-x.

Authors

Mahmut Sami Tutar¹, Ahmet Erarkadas², Serife Nur Yildirim², Dilay Gok Korucu³, Oguzhan Gunenc³, Munise Yildiz², Dilek Tutar³, Betul Kozanhan²

Affiliations

¹ Department of Anesthesiology and Reanimation, University of Health Sciences Konya City Hospital, Akabe, Adana Cevre Yolu St. No: 135/1, Karatay, Konya, 42020, Türkiye. masatu42@gmail.com.
² Department of Anesthesiology and Reanimation, University of Health Sciences Konya City Hospital, Akabe, Adana Cevre Yolu St. No: 135/1, Karatay, Konya, 42020, Türkiye.
³ Department of Gynecology and Obstetrics, University of Health Sciences Konya City Hospital, Konya, Türkiye.

Abstract

Background: Pain on propofol injection (POPI) remains a distressing problem despite preventive strategies. Estradiol, a major estrogen, has been implicated in nociceptive and inflammatory pathways. This study aimed to determine whether supraphysiological estradiol levelsare associated with the incidence of POPI and with pain severity among patients experiencing pain.

Methods: Ninety female patients (ASA I–II, 18–45 years) undergoing elective surgery under general anesthesia were enrolled in this prospective observational study. Patients were divided into two groups based on preoperative estradiol concentration: supraphysiological (IVF, > 350 pg/mL) and normal (non-IVF, 15–350 pg/mL). Propofol (2–2.5 mg/kg) was injected without lidocaine pretreatment. POPI severity was assessed using a four-point behavioral scale (0–3). Correlation analyses and receiver operating characteristic (ROC) analyses were performed to evaluate the association and discriminative performance of estradiol concentration with propofol injection pain.

Results: POPI occurred more frequently in the IVF group (95.6%) than in the non-IVF group (68.9%, p = 0.001). Median estradiol levels were significantly higher in patients with pain (1096.5 vs. 88 pg/mL, p < 0.001). Among patients experiencing pain, estradiol levels showed a modest positive correlation with pain severity (r = 0.34, p = 0.003). ROC analysis yielded an area under the curve (AUC) of 0.847 (95% CI: 0.755–0.939) with an optimal cut-off of 122 pg/mL (sensitivity 87.8%, specificity 75%). This cut-off should be considered exploratory within this single-center cohort.

Conclusions: Supraphysiological estradiol levels were associated with a higher incidence of POPI. In addition, estradiol concentration showed a modest correlation with pain severity among patients who experienced pain. These findings demonstrate an association between estradiol concentration and propofol injection pain within the studied population.

Trial registration: NCT06929416, date: April 8, 2025, first patient registration date: May 2, 2025.

Keywords: Estradiol; In vitro fertilization; Injection pain; Propofol.