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Ultrasound Transformation of Myomas During Relugolix-Estradiol-Norethisterone Treatment: The MySaturn Study

Not yet recruiting
Conditions
Uterine Bleeding
Uterine Leiomyomas
Uterine Hemorrhage
Uterine Neoplasms
Interventions
Drug: Relugolix/estradiol/norethisterone acetate
Registration Number
NCT06953076
Lead Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Brief Summary

Uterine fibroids are benign tumors originating from the uterine muscle, affecting up to 70% of women by their 50s. Risk factors include African descent, nulliparity, obesity, and diabetes. While many fibroids are asymptomatic, 25-50% of affected women experience symptoms like heavy menstrual bleeding, pelvic pain, and pressure-related issues. Accurate diagnosis and differentiation from rare malignant tumors (e.g., uterine sarcomas) remain challenging, particularly before surgery.

Ultrasound is the first-line tool for evaluating fibroids, with specific features (e.g., shape, vascularity) helping distinguish benign from suspicious lesions. The MUSA guidelines standardize ultrasound terminology for myometrial assessments. Current treatment options vary based on symptoms and malignancy risk. Among pharmacologic options, the combination of relugolix, estradiol, and norethisterone has shown efficacy in reducing bleeding and pain in symptomatic fibroids, with a favorable safety profile. However, its impact on fibroid morphology and ultrasound appearance is not yet well understood.

Detailed Description

Uterine fibroids are the most common benign tumors in women of reproductive age, affecting up to 70% of women in their 40s and 50s. While often asymptomatic, around 25-50% experience symptoms such as heavy menstrual bleeding, pelvic pain, and pressure-related issues. The severity depends on the number, size, and location of the fibroids.

Though most fibroids are benign, a small risk exists for malignant uterine tumors (e.g., leiomyosarcomas, STUMPs). Diagnosing these malignancies preoperatively remains a challenge due to the lack of reliable imaging markers. Ultrasound is the first-line diagnostic tool, guided by MUSA criteria, but further prospective data are needed to improve risk stratification.

The combination of Relugolix, Estradiol, and Norethisterone (Ryeqo®) is an effective medical treatment for symptomatic fibroids, especially in premenopausal women. It reduces bleeding while minimizing side effects of estrogen deprivation. Over 70% of women in clinical trials have shown significant improvement within 24 weeks. However, its effect on fibroid morphology and ultrasound features remains unclear.

The MySaturn Study aims to assess whether this therapy modifies the ultrasound appearance of myometrial lesions over 12 months. The study also tracks symptom changes and adverse events. It involves 111 premenopausal women in a monocentric ambispective observational design, combining retrospective and prospective data from July 1, 2023. The study spans 3 years (2 years of enrollment + 1 year follow-up) and uses routine clinical, laboratory, and imaging data for analysis.

Adverse events will be monitored and reported in accordance with national pharmacovigilance regulations.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
111
Inclusion Criteria
  1. Age ≥ 18 years.
  2. Pre-menopausal status.
  3. Ultrasound diagnosis of benign myometrial lesion.
  4. Symptomatic patients presenting with abnormal uterine bleeding (menorrhagia/metrorrhagia).
  5. Availability of ultrasound images in digital format.
Exclusion Criteria
  1. Patient refusal.
  2. Age < 18 years.
  3. Postmenopausal women.
  4. Myometrial lesion ≤ 10 mm.
  5. Myometrial formation suspected of malignancy on ultrasound (e.g., STUMP - Uterine Leiomyosarcoma).
  6. Asymptomatic patients with uterine fibromatosis.
  7. Personal history of malignant or premalignant uterine neoplasia (e.g., STUMPs, leiomyosarcoma, atypical endometrial hyperplasia, endometrial carcinoma, cervical carcinoma).
  8. Patients with ovarian pathology.
  9. Patients currently undergoing treatment for another malignancy.
  10. Patients lacking available digital ultrasound images or whose image quality is insufficient to adequately characterize the target lesion's ultrasound features

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Uterine fibroids symptomatic for abnormal uterine bleedingRelugolix/estradiol/norethisterone acetatePatients with ultrasound diagnosis of uterine fibroids, symptomatic for abnormal uterine bleeding, eligible for oral medical therapy with relugolix/estradiol/norethisterone
Primary Outcome Measures
NameTimeMethod
To observe modifications in the volume of the myometrial lesion during treatment with relugolix/estradiol/norethisteroneat baseline, and after 3 months, 6 months, and 12 months from treatment initiation

Modifications in the volume of the myometrial lesion

To observe the ultrasound features of myometrial lesions during treatment with relugolix/estradiol/norethisteroneat baseline, and after 3 months, 6 months, and 12 months from treatment initiation

* Uterine volume

* Outer contour: regular or irregular;

* Echogenicity of the myometrial formation: mixed or homogeneous;

* Presence of cystic areas;

* Presence of acoustic shadows;

* Vascularization of the lesions, expressed on a 1 to 4 ordinal scale;

* "Cooked aspect" , if present

Secondary Outcome Measures
NameTimeMethod
Description of the clinical characteristics of the study population during treatment with relugolix/estradiol/norethisterone.at baseline, and after 3 months, 6 months, and 12 months from treatment initiation

* Effect on abnormal uterine bleeding, measured as the number of sanitary pads used during the cycle in patients who do not develop amenorrhea;

* Hemoglobin, serum iron, and ferritin levels

* Dyspareunia, assessed using NRS or VAS scales;

* Chronic pelvic pain, assessed using NRS or VAS scales;

* Compression-related symptoms;

* Pollakiuria and dyschezia;

* Dyspareunia

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