SAT-144 - Treatment of Refractory Endometriosis with Nestorone: Clinical and Radiological Control Without Mood Episode Recurrence in a Patient with Bipolar Disorder - A Case Report

Endometriosis (EMS) affects approximately 10% of women of reproductive age and is associated with dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. Therapeutic options include combined oral contraceptives (COCs), progestin-only pills (POPs), GnRH analogs, and other hormonal modulators; however, approximately 30–40% of patients exhibit inadequate response or symptom recurrence. Nestorone (segesterone acetate) is a potent progestin characterized by high progestogenic activity, low androgenic activity, and an antiandrogenic profile, with a potentially lower metabolic impact compared to progestins such as medroxyprogesterone or etonogestrel-containing implants.
A 25-year-old female patient with a prior diagnosis of bipolar affective disorder (BAD) and Hashimoto’s thyroiditis presented with severe dysmenorrhea, menorrhagia, dyspareunia, and marked premenstrual symptoms associated with debilitating mood fluctuations. During psychiatric follow-up, she experienced recurrent episodes of hypomania and emotional instability, with previous therapeutic failure to four mood stabilizers, ultimately achieving stabilization on aripiprazole monotherapy. From a gynecological perspective, multiple hormonal treatments, including COCs and POPs, failed to improve pelvic pain or menstrual symptoms. An investigation for EMS was initiated. Initial transvaginal ultrasound showed no abnormalities; due to persistent symptoms, pelvic MRI with bowel preparation was performed. During the diagnostic workup, the patient developed acute appendicitis. Following appendectomy, histopathological analysis revealed endometriotic foci, confirming the diagnosis. Hormonal therapies were instituted according to current EMS treatment guidelines; however, the patient remained symptomatic, characterizing refractory disease.A Nestorone implant was then initiated. Following treatment onset, the patient developed amenorrhea, with significant improvement in pelvic pain and overall gynecological symptoms. Additionally, mood stabilization was observed, with no further manic or hypomanic episodes, maintaining psychiatric stability on aripiprazole monotherapy. Clinical and radiological follow-up demonstrated disease control, with imaging showing reduction of lesions consistent with EMS.
The observed clinical and radiological improvement may be related to the high progestogenic potency, antiandrogenic profile, and low metabolic impact of Nestorone. Furthermore, its mild antiestrogenic activity and potential modulation of neurosteroidal pathways, including GABAergic mechanisms, may have contributed to mood stabilization and maintenance of bipolar disorder control. However, further studies are needed to clarify the role of this progestin in the management of refractory EMS and its potential interactions in mood regulation.

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