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

NCT06953076 | Recruiting DMC FDA Drug

• 1 other identifier: 7427
• Study Type: observational
• Target: 111
• Locations: 1 country
• Sites: 1

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.

Conditions

Uterine Bleeding; Uterine Leiomyomas; Uterine Hemorrhage; Uterine Neoplasms

Keywords

myomas; uterine bleeding; fibroids; relugolix; ormonal therapy; smooth muscle cells tumor

Outcome Measures

Primary Outcomes (2)

• To observe modifications in the volume of the myometrial lesion during treatment with relugolix/estradiol/norethisterone

  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

  * 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 Outcomes (1)

• 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

Study Arms (1)

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

Interventions

Relugolix/estradiol/norethisterone acetate DRUG

Oral therapy administered to patients with symptomatic uterine fibroids presenting with abnormal uterine bleeding

Also known as: Ryeqo

Uterine fibroids symptomatic for abnormal uterine bleeding

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• Age ≥ 18 years.
• Pre-menopausal status.
• Ultrasound diagnosis of benign myometrial lesion.
• Symptomatic patients presenting with abnormal uterine bleeding (menorrhagia/metrorrhagia).
• Availability of ultrasound images in digital format.

You may not qualify if:

• Patient refusal.
• Age \< 18 years.
• Postmenopausal women.
• Myometrial lesion ≤ 10 mm.
• Myometrial formation suspected of malignancy on ultrasound (e.g., STUMP - Uterine Leiomyosarcoma).
• Asymptomatic patients with uterine fibromatosis.
• Personal history of malignant or premalignant uterine neoplasia (e.g., STUMPs, leiomyosarcoma, atypical endometrial hyperplasia, endometrial carcinoma, cervical carcinoma).
• Patients with ovarian pathology.
• Patients currently undergoing treatment for another malignancy.
• Patients lacking available digital ultrasound images or whose image quality is insufficient to adequately characterize the target lesion's ultrasound features

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC GINECOLOGIA ONCOLOGICA

Roma, 00168, Italy

RECRUITING

Related Publications (8)

• Education and Practical Standards Committee, European Federation of Societies for Ultrasound in Medicine and Biology. Minimum training recommendations for the practice of medical ultrasound. Ultraschall Med. 2006 Feb;27(1):79-105. doi: 10.1055/s-2006-933605. No abstract available.

  PMID: 16508866 RESULT

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, Critchley HOD, Li Y, McKain L, Arjona Ferreira JC, Langenberg AGM, Wagman RB, Stewart EA. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy. N Engl J Med. 2021 Feb 18;384(7):630-642. doi: 10.1056/NEJMoa2008283.

  PMID: 33596357 RESULT

• Al-Hendy A, Venturella R, Arjona Ferreira JC, Li Y, Soulban G, Wagman RB, Lukes AS. LIBERTY randomized withdrawal study: relugolix combination therapy for heavy menstrual bleeding associated with uterine fibroids. Am J Obstet Gynecol. 2023 Dec;229(6):662.e1-662.e25. doi: 10.1016/j.ajog.2023.08.030. Epub 2023 Sep 2.

  PMID: 37666383 RESULT

• Al-Hendy A, Lukes AS, Poindexter AN 3rd, Venturella R, Villarroel C, McKain L, Li Y, Wagman RB, Stewart EA. Long-term Relugolix Combination Therapy for Symptomatic Uterine Leiomyomas. Obstet Gynecol. 2022 Dec 1;140(6):920-930. doi: 10.1097/AOG.0000000000004988. Epub 2022 Nov 2.

  PMID: 36357960 RESULT

• De La Cruz MS, Buchanan EM. Uterine Fibroids: Diagnosis and Treatment. Am Fam Physician. 2017 Jan 15;95(2):100-107.

  PMID: 28084714 RESULT

• Van den Bosch T, Dueholm M, Leone FP, Valentin L, Rasmussen CK, Votino A, Van Schoubroeck D, Landolfo C, Installe AJ, Guerriero S, Exacoustos C, Gordts S, Benacerraf B, D'Hooghe T, De Moor B, Brolmann H, Goldstein S, Epstein E, Bourne T, Timmerman D. Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound Obstet Gynecol. 2015 Sep;46(3):284-98. doi: 10.1002/uog.14806. Epub 2015 Aug 10.

  PMID: 25652685 RESULT

• Ciccarone F, Biscione A, Robba E, Pasciuto T, Giannarelli D, Gui B, Manfredi R, Ferrandina G, Romualdi D, Moro F, Zannoni GF, Lorusso D, Scambia G, Testa AC. A clinical ultrasound algorithm to identify uterine sarcoma and smooth muscle tumors of uncertain malignant potential in patients with myometrial lesions: the MYometrial Lesion UltrasouNd And mRi study. Am J Obstet Gynecol. 2025 Jan;232(1):108.e1-108.e22. doi: 10.1016/j.ajog.2024.07.027. Epub 2024 Jul 30.

  PMID: 39084498 RESULT

• Stewart EA, et al. Uterine fibroids. Lancet. 2022; 400(10352):1341-1351

  RESULT

MeSH Terms

Conditions

Uterine Hemorrhage; Myofibroma; Uterine Neoplasms; Myoma; Leiomyoma

Interventions

relugolix

Condition Hierarchy (Ancestors)

Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Muscle Tissue

Study Officials

• Daniela Romualdi, MD

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

DANIELA ROMUALDI, MD

CONTACT

+393392996830; daniela.romualdi@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: April 21, 2025
• First Posted: May 1, 2025
• Study Start: May 2, 2025
• Primary Completion: May 2, 2026
• Study Completion (Estimated): May 2, 2027
• Last Updated: August 17, 2025

Record last verified: 2025-08

Locations

IT (1)