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

August 15, 2025 updated by: ROMUALDI DANIELA, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

MyomaS Aspect Transformation at Ultrasound During Relugolix Estradiol Noretisterone Treatment: MySaturn Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

111

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Roma, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Ginecologia Oncologica
        • Contact:
        • Principal Investigator:
          • Daniela Romualdi

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients with ultrasound diagnosis of uterine fibroids, symptomatic for abnormal uterine bleeding, eligible for oral medical therapy with relugolix/estradiol/norethisterone

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Uterine fibroids symptomatic for abnormal uterine bleeding
Patients with ultrasound diagnosis of uterine fibroids, symptomatic for abnormal uterine bleeding, eligible for oral medical therapy with relugolix/estradiol/norethisterone
Drug: Relugolix/estradiol/norethisterone acetate
Oral therapy administered to patients with symptomatic uterine fibroids presenting with abnormal uterine bleeding
Other Names:
  • Ryeqo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To observe modifications in the volume of the myometrial lesion during treatment with relugolix/estradiol/norethisterone
Time Frame: at baseline, and after 3 months, 6 months, and 12 months from treatment initiation
Modifications in the volume of the myometrial lesion
at baseline, and after 3 months, 6 months, and 12 months from treatment initiation
To observe the ultrasound features of myometrial lesions during treatment with relugolix/estradiol/norethisterone
Time Frame: at 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
at baseline, and after 3 months, 6 months, and 12 months from treatment initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Description of the clinical characteristics of the study population during treatment with relugolix/estradiol/norethisterone.
Time Frame: 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
at baseline, and after 3 months, 6 months, and 12 months from treatment initiation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

  • Principal Investigator: Daniela Romualdi, MD, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2025

Primary Completion (Estimated)

May 2, 2026

Study Completion (Estimated)

May 2, 2027

Study Registration Dates

First Submitted

April 21, 2025

First Submitted That Met QC Criteria

April 29, 2025

First Posted (Actual)

May 1, 2025

Study Record Updates

Last Update Posted (Actual)

August 17, 2025

Last Update Submitted That Met QC Criteria

August 15, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7427 (CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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