Clinical trial NCT06953076: Ultrasound Transformation of Myomas During Relugolix-Estradiol-Norethisterone Treatment: The MySaturn Study
Official title: MyomaS Aspect Transformation at Ultrasound During Relugolix Estradiol Noretisterone Treatment: MySaturn Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Uterine Bleeding
Uterine Leiomyomas
Uterine Hemorrhage
Uterine Neoplasms
Keywords: myomas
uterine bleeding
fibroids
relugolix
ormonal therapy
smooth muscle cells tumor
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2025-05-01
Enrollment: 111
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: OTHER
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: To observe modifications in the volume of the myometrial lesion during treatment with relugolix/estradiol/norethisterone
timeFrame: at baseline, and after 3 months, 6 months, and 12 months from treatment initiation
measure: To observe the ultrasound features of myometrial lesions during treatment with relugolix/estradiol/norethisterone
timeFrame: at baseline, and after 3 months, 6 months, and 12 months from treatment initiation
Secondary outcomes:
measure: Description of the clinical characteristics of the study population during treatment with relugolix/estradiol/norethisterone.
timeFrame: at baseline, and after 3 months, 6 months, and 12 months from treatment initiation
Other outcomes:
Locations:
Study officials:
affiliation: Fondazione Policlinico Universitario A. Gemelli, IRCCS
name: Daniela Romualdi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: Stewart EA, et al. Uterine fibroids. Lancet. 2022; 400(10352):1341-1351