Heavy Menstrual Bleeding Progestin Treatment in Bleeding Disorders Study (HMB-BD)

The goal of this multicenter prospective observational study and registry of U.S. adolescents and young adults with heritable bleeding disorders is to determine the bleeding outcomes, satisfaction, hemostatic parameter changes, and patient reported quality of life after 6 months of use of either of two commonly used hormonal treatments for menstrual suppression - levonorgestrel intrauterine device (LNG-IUD) and norethindrone acetate (NETA). Under this application the study will compare the two treatments and compare outcomes after LNG-IUD treatment results to a control group without a bleeding disorder, with the goal of determining the benefits and expected outcomes of these treatment options for this population.

Study Overview

• Status: Recruiting
• Conditions: Bleeding Disorder; Von Willebrand Diseases; Heavy Menstrual Bleeding
• Intervention / Treatment: Drug: Levonorgestrel Intrauterine System; Drug: Norethindrone Acetate

Detailed Description

Heavy menstrual bleeding (HMB) is common among adolescents and young adults with an inherited bleeding disorder (BD) and negatively impacts health-related quality of life and physical and mental health status. Effective treatment options are available that decrease bleeding and improve quality of life, but were not studied in those with BD, so investigators do not know if there is similar effectiveness in this condition. The impact of treatment on diagnostic testing for BD or on improvement of iron deficiency is also not known. Given these gaps in knowledge, the primary objective of the Heavy Menstrual Bleeding Progestin Treatment in Bleeding Disorders Study is to conduct a multicenter prospective observational cohort study and registry, enrolling adolescents and young adults with heavy menstrual bleeding cared for at collaborating interdisciplinary menstrual clinic sites nationally who are choosing to start use of either of two commonly used progestin menstrual treatment options: levonorgestrel-releasing intrauterine system (LNG-IUD) or oral norethindrone acetate 5 mg daily (NETA) (N=300). In Aim 1, the study will compare outcomes related to (a) bleeding management, (b) quality of life, and (c) repletion of iron storage levels after six months of treatment with either option in those with a diagnosed inherited bleeding disorder. The primary outcome will be treatment success with a Pictorial Blood Loss Assessment Chart (PBAC) score <50 points by six months. Secondary objectives to assess bleeding management will include need for adjuvant management, change in PBAC from baseline to 6 months, and self-reported treatment success. Quality of life outcomes will include change in validated scales to assess health-related quality of life which are specific to adolescents and young adults in the setting of heavy menstrual bleeding. The study will compare ferritin levels at six months compared to baseline to determine the relative amount of benefit obtained from either treatment option. In Aim 2, the study will compare outcomes after LNG-IUD in those with and without a bleeding disorder, assessing rates of expulsion and method continuation between the two groups in addition to the outcomes assessed for Aim 1. Aim 3 will improve our understanding of the impact of physiological stress on BD diagnostic studies by comparing change in hemostatic parameters before and after successful treatment in those with HMB without a previously diagnosed bleeding disorder. This study will demonstrate the relative benefits of menstrual suppression treatment options for adolescents and young adults with heavy menstrual bleeding and inherited bleeding disorders, will provide population-specific estimates for expected benefit that can be used in treatment counseling, and will highlight the impact of treatment status on diagnostic test results.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: OHSU Women's Health Research Unit; Phone Number: 5034943666; Email: whru@ohsu.edu
• Study Contact Backup: Name: Maureen Baldwin, MD MPH; Phone Number: 5034949762; Email: schaum@ohsu.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Not yet recruiting
      • Stanford
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • Colorado Anschutz Medical Campus
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Not yet recruiting
      • University of Michigan Medicine
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Not yet recruiting
      • Children's Mercy
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Women's Health Research Unit; Phone Number: 503-494-3666; Email: whru@ohsu.edu
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17003
      • Not yet recruiting
      • Penn State Health
  • Washington
    • Seattle, Washington, United States, 98105
      • Not yet recruiting
      • Seattle Children's Hospital
    • Seattle, Washington, United States, 98101
      • Not yet recruiting
      • University of Washington
      • Contact: Washington Center for Bleeding Disorders; Phone Number: 206-614-1200; Email: WICResearch@WACBD.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adolescents and young adults ages 10-24 with and without a heritable bleeding disorder who receive medical care for heavy menstrual bleeding at a participating U.S. clinical site. All clinical sites participate in a national consortium of interdisciplinary hematology-gynecology clinics.

Description

Inclusion Criteria:

• Post-menarcheal
• Ages 10-24
• Decision to initiate a trial of progestin therapy with either LNG-IUD or NETA
• Able to provide assent and written informed consent by one parent (ages <18) or written informed consent (age 18+)
• Must meet trial criteria for heavy menstrual bleeding
• Must meet trial criteria for a bleeding disorder or have minimum workup to rule out bleeding disorder

Exclusion Criteria:

• Pregnant or seeking pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bleeding disorder using LNG-IUD; Adolescents and young adults ages 10-24 with diagnosed bleeding disorder planning use of LNG-IUD.	Drug: Levonorgestrel Intrauterine System; 52 mg levonorgestrel intrauterine system; Other Names: Mirena; Liletta
Non-bleeding disorder using LNG-IUD; Adolescents and young adults ages 10-24 without diagnosed bleeding disorder planning use of LNG-IUD.	Drug: Levonorgestrel Intrauterine System; 52 mg levonorgestrel intrauterine system; Other Names: Mirena; Liletta
Bleeding disorder using NETA; Adolescents and young adults ages 10-24 with diagnosed bleeding disorder planning use of NETA.	Drug: Norethindrone Acetate; norethindrone acetate 5 mg daily; Other Names: Aygestin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment success rate	Proportion with pictorial blood loss assessment score <50 points	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in von Willebrand Factor (VWF) levels	Group median of individual change in von Willebrand Factor levels	Baseline to 6 months
Median Pictorial Blood Assessment Chart (PBAC) score	Group median of pictorial blood loss assessment score. PBAC scores start at 0 to represent no bleeding with higher PBAC scores representing heavy menstrual bleeding. There is no maximum PBAC score.	6 months
Patient-reported treatment success rate	Proportion with patient-reported treatment success. Treatment success will be measured with Yes or No bivariate response.	6 months
Change in Adolescent Menstrual Bleeding Questionnaire (aMBQ) score	Group median of individual change in adolescent menstrual bleeding questionnaire score. aMBQ scores can range from 0 to 77 with higher scores representing worse health-related quality of life.	Baseline to 6 months
Change in Patient-Reported Outcomes Measurement Information System (PROMIS-25 or PROMIS-29) scores	Group median of individual change in patient-reported outcomes measurement information system score after treatment. PROMIS-25 and PROMIS-29 scores are measured on a standardized scale of T-scores with a score of 50 representing the population average and higher scores representing worse outcomes. Participants who will be age 18 or older at six months after treatment initiation will be administered the PROMIS-25 adult version and age <18 will be administered the PROMIS-29 pediatric version.	Baseline to 6 months
Change in serum ferritin after treatment	Group median of individual change in ferritin	Baseline to 6 months

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: University of Washington; NIH National Heart, Lung, and Blood Institute
• Investigators: Principal Investigator: Maureen Baldwin, MD MPH, Oregon Health and Science University; Principal Investigator: Allison Wheeler, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: June 14, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Actual): June 23, 2023

Study Record Updates

• Last Update Posted (Estimated): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Uterine Diseases; Genital Diseases, Female; Hemorrhage; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Uterine Hemorrhage; Menstruation Disturbances; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Menorrhagia; Hemostatic Disorders; von Willebrand Diseases; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Norethindrone; Norpregnenes; Norpregnanes; Norsteroids; Norgestrel; Norethindrone Acetate; Levonorgestrel
• Other Study ID Numbers: LNG-IUD BD Study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will collect clinical, laboratory, and survey data from participants ages 10-24 at multiple academic clinical sites. Participant-level clinical data will be preserved through deposition of the data in a controlled access public repository. We will make our scientific data as widely and freely available as possible while safeguarding the privacy of participants (de-identified prior to repository submission) and protecting confidential and proprietary data.
• IPD Sharing Time Frame: Scientific data will be shared as soon as possible following study participant completion. Scientific data included in published manuscripts will be available at the time of publication; all other generated scientific data will be shared no later than the end of the award. The study data will be stored in the repository indefinitely, for at least 5 years.
• IPD Sharing Access Criteria: The study datasets will be collected with the following informed consent: The dataset can only be used for studying health, medical, or biomedical conditions and does not include the study of population origins or ancestry. We will also require all individuals requesting data to enter into a data sharing agreement that: 1) acknowledges the data will be stripped of identifying markers and identification; 2) acknowledges that these data will only be used for research purposes; and 3) requests investigators to reference the seminal publication describing data collection. The dataset can only be used for studying health, medical or biomedical conditions and does not include the study of population origins or ancestry. The requesting institution's IRB or equivalent body must approve the requested use.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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