A-163 Elevated Serum Estradiol in Levonorgestrel-Releasing Intrauterine System Users: A Case Series Highlighting Post-Analytical Challenges

Abstract

The levonorgestrel-releasing intrauterine system (LNG-IUS) acts predominantly at the endometrial level without consistently suppressing the hypothalamic–pituitary–gonadal axis. Residual ovarian activity may persist, occasionally resulting in functional follicular cysts capable of producing estradiol. Serum estradiol concentrations >350 pg/mL in LNG-IUS users generate diagnostic uncertainty, requiring systematic differentiation between physiologic ovarian function, exogenous hormone exposure, and analytical interference. This retrospective case series (n = 7) was derived from routine clinical data at a reference laboratory in Fortaleza, Brazil (2023–2025). Eligible patients were LNG-IUS users aged 34–51 years presenting with serum estradiol >350 pg/mL on routine testing. Estradiol was measured by chemiluminescent immunoassay (CLIA). Post-analytical review was conducted using the laboratory information system (LIS), focusing on clinically discordant results. Concurrent FSH and LH levels were used as indirect markers of ovarian activity, and medication histories were reviewed for exogenous hormone exposure. All seven cases involved LNG-IUS users with estradiol levels ranging from 358.6 to 1,526.6 pg/mL (median: 779.7 pg/mL; mean age: 46.0 years). Concurrent FSH levels were low-to-normal where available, suggesting preserved ovarian feedback. The three highest values (1,526.6; 1,487.2; and 1,225.8 pg/mL) occurred in documented LNG-IUS users. Notably, the peak estradiol was identified in a patient with concomitant topical estradiol use (Estrogel), detected only through post-analytical LIS review — underscoring the critical role of medication reconciliation. In the remaining cases, no exogenous estrogen was documented, supporting ongoing follicular activity. One patient underwent same-day pelvic ultrasound following biochemical detection, illustrating how unexpected hormonal findings may prompt immediate clinical action. In LNG-IUS users, estradiol levels >350 pg/mL may reflect residual follicular activity or unrecognized exogenous estrogen exposure. These findings support the integration of structured pre-analytical questions — including IUD type and hormone use — into laboratory requisitions and LIS workflows. A standardized reflex protocol comprising medication review, FSH/LH co-assessment, and confirmatory testing where indicated may reduce diagnostic uncertainty and prevent unnecessary investigations. Prospective studies are needed to define clinical thresholds and validate laboratory management algorithms in this population.