An Observational Study to Learn How Mirena and Other Progestogen Treatments Are Used for Endometrial Protection in Women 40+ With a Uterus in the United States Receiving Estrogen Therapy, and Their Respective Health Outcomes (SHIELD-ET)

August 26, 2026 updated by: Bayer

Study of Real-world Use of Hormonal Levonorgestrel Intra-uterine System for Endometrial Defense With Estrogen Therapy

This is an observational study in which researchers will use claims data already collected from women in the United States who received their usual care. The study will look at women aged 40 years and older who have a uterus and started estrogen therapy.

Estrogen therapy is often used to treat menopause symptoms, such as hot flashes and night sweats, or to help prevent bone loss. Women who take estrogen and still have a uterus usually also need a progestogen to help protect the lining of the uterus. Without this protection, the lining may become too thick. This can lead to endometrial hyperplasia and may increase the risk of endometrial cancer.

This study will look at how Mirena and other progestogen treatments are used in routine medical care to protect the lining of the uterus during estrogen therapy. Mirena is a small device placed in the uterus that releases the hormone levonorgestrel (a synthetic progestogen, similar to progesterone). In the United States, Mirena is approved for birth control and for treatment of heavy menstrual bleeding. Clinicians may also use it for endometrial protection during estrogen therapy. Bayer's Mirena levonorgestrel-containing intrauterine system (LNG-IUS) 52 mg is approved for endometrial protection during hormone therapy in over 100 countries outside of the US.

The main purpose of this study is gain insight into how different progestogen treatments are used in the context of estrogen therapy in women with a uterus, and the health outcomes linked with them. Researchers will describe how often women use estrogen alone, estrogen with Mirena, or estrogen with other progestogen treatments in the past 10 years. Researchers will also look at how often endometrial hyperplasia, endometrial cancer, abnormal or heavy bleeding, and hysterectomy occur in these groups over time.

The data will come from two U.S. health insurance claims databases: Optum Clinformatics Data Mart and MarketScan Commercial Claims and Encounters Database. The study period covers 2014 through 2025, depending on the database. Optum: January 2015-December 2025 and MarketScan: October 2014-September 2025, with patient identification periods of Optum: January 2016-December 2024 and MarketScan: October 2015-September 2024. Researchers will follow each participant's available data for at least 12 months before and at least 12 months after starting estrogen therapy, with follow-up of up to 10 years.

No study treatment will be given as part of this study. Researchers will only review anonymous health insurance claims data that were already collected during routine care.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
456000

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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48108
        • Mirative MarketScan Commercial Claims and Encounters Database
    • Minnesota
      • Eden Prairie, Minnesota, United States, 55344
        • Optum Clinformatics™ Data Mart (CDM)

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study population for the SHIELD-ET study are patients 40+ years of age with a uterus receiving estrogen therapy. Special populations or subpopulations among menopausal women (e.g. chemotherapy- or drug-induced menopause), as well as women without a uterus will be excluded.

Description

Inclusion Criteria:

  • At least one claim of estrogen therapy (ET) during the patient identification period (Index date: the first claim for ET)
  • Age ≥ 40 years at the index date
  • Patients with minimum continuous enrollment 12 months prior and 12 months at minimum after index date

Exclusion Criteria:

  • Women without a uterus (claims of hysterectomy) in the 12-month baseline period
  • Use of any hormonal contraception in the 12-month baseline period
  • Claims indicative of atypical endometrial hyperplasia or endometrial cancer or heavy menstrual bleeding (HMB)/abnormal uterine bleeding (AUB)/postmenopausal bleeding (PMB), or any treatment for late state or metastatic endometrial cancer, in the baseline period.
  • Claims in the baseline period for any of the treatments of interest
  • Claims of chemotherapy/endocrine therapy in the baseline period

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

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Estrogen therapy (ET) unopposed
Women receiving estrogen therapy (ET) alone without evidence of concomitant progestogen use during the exposure assessment period.
Drug: Estrogen therapy
Estrogen therapy prescribed during routine clinical practice and identified through prescription claims data. Exposure to estrogen therapy is determined using study-specific claims-based definitions.
ET + Mirena LNG-IUS
Women receiving estrogen therapy (ET) with recurring prescription fills and evidence of Mirena levonorgestrel-releasing intrauterine system (LNG-IUS) use, identified through a Mirena insertion procedure code and/or device code during the exposure assessment period.
Device: Mirena levonorgestrel-releasing intrauterine system
A levonorgestrel-releasing intrauterine system used for endometrial protection in women receiving estrogen therapy. Exposure is identified through Mirena insertion procedure codes and/or device codes in claims data. Contraception use of this product is not exposure of interest and baseline hormonal contraception is an exclusion criterion.
Other Names:
  • Mirena LNG-IUS
ET + other progestogen
Women receiving estrogen therapy (ET) with recurring prescription fills and evidence of concomitant progestogen use other than Mirena LNG-IUS during the exposure assessment period. Other progestogen therapies include progesterone, synthetic progestins, Liletta LNG-IUS 52 mg, and combination estrogen-progestogen products.
Drug: Other progestogen therapy
rogestogen therapy used for endometrial protection in women receiving estrogen therapy, including progesterone, synthetic progestins, Liletta LNG-IUS 52 mg, and combination estrogen-progestogen products. Exposure is identified through claims data. Contraceptive use of these products is not exposure of interest, and baseline hormonal contraception is an exclusion criterion.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of patients receiving estrogen therapy
Time Frame: Retrospective analysis from January 2025 to December 2025
Proportion of eligible female patients aged 40 years and older with a uterus who received at least one claim for estrogen therapy during the study period. The numerator is the number of patients with at least one estrogen therapy claim during the study period, and the denominator is the number of eligible female patients contributing at least one observable person-day during the study period.
Retrospective analysis from January 2025 to December 2025
Number of patients by treatment subgroup within 30 and 90 days of estrogen therapy initiation
Time Frame: Within 30 days and 90 days after estrogen therapy initiation during the study period (January 2025 to December 2025)
Number of patients in each treatment subgroup (ET unopposed, ET + Mirena LNG-IUS, and ET + other progestogen) within 30 and 90 days after initiation of estrogen therapy.
Within 30 days and 90 days after estrogen therapy initiation during the study period (January 2025 to December 2025)
Proportion of patients by treatment subgroup within 30 and 90 days of estrogen therapy initiation
Time Frame: Within 30 days and 90 days after estrogen therapy initiation during the study period (January 2025 to December 2025)
Proportion of patients in each treatment subgroup (ET unopposed, ET + Mirena LNG-IUS, and ET + other progestogen) within 30 and 90 days after initiation of estrogen therapy.
Within 30 days and 90 days after estrogen therapy initiation during the study period (January 2025 to December 2025)
Average length of estrogen therapy use
Time Frame: Retrospective analysis from January 2025 to December 2025
The average length of estrogen therapy (ET) use will be expressed as the mean duration (in days) among all eligible patients. The length of ET use will be measured as the time from the first ET prescription date to the last ET prescription date, with a maximum allowable gap of 30 days between consecutive prescriptions to be considered continuous therapy.
Retrospective analysis from January 2025 to December 2025

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall (10-year) incidence of atypical, non-atypical and unspecified endometrial hyperplasia, endometrial cancer, abnormal/unscheduled/heavy menstrual bleeding and hysterectomy
Time Frame: Retrospective analysis from January 2016 to December 2025
Overall incidence of atypical, non-atypical, and unspecified endometrial hyperplasia, endometrial cancer, abnormal/unscheduled/heavy menstrual bleeding, and hysterectomy among patients in each treatment subgroup (ET unopposed, ET + Mirena LNG-IUS, and ET + other progestogen). Overall incidence will be evaluated over the 10-year study period. For each outcome, incident cases are defined as patients with at least one new claim for the condition of interest during follow-up. Only the first occurrence of each outcome after the index date will be counted as an incident event. Outcomes are assessed after completion of the 30- and 90-day exposure assessment periods, and only first incident events during follow-up are counted.
Retrospective analysis from January 2016 to December 2025
Annual incidence of atypical, non-atypical and unspecified endometrial hyperplasia, endometrial cancer, abnormal/unscheduled/heavy menstrual bleeding and hysterectomy
Time Frame: Annually from January 2016 through December 2025
Annual incidence of atypical, non-atypical, and unspecified endometrial hyperplasia, endometrial cancer, abnormal/unscheduled/heavy menstrual bleeding, and hysterectomy among patients in each treatment subgroup (ET unopposed, ET + Mirena LNG-IUS, and ET + other progestogen). For each outcome, incident cases are defined as patients with at least one new claim for the condition of interest during follow-up. Patients will be counted only in the calendar year of their first occurrence for each outcome.
Annually from January 2016 through December 2025
Participant demographic characteristics: age
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Participant demographic characteristics: race
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Participant demographic characteristics: ethnicity
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Participant demographic characteristics: region
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Participant demographic characteristics: health plan type
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Gynecologic history: endometrial polyps, fibroids, adenomyosis, endometriosis
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Clinical characteristics: relevant comorbidities
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Clinical characteristics: Charlson Comorbidity Index (CCI)
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
The CCI is a method of estimating the one-year mortality for a patient with certain comorbid conditions. Each comorbid condition is given a score of 1, 2, 3 or 6 based on the degree of mortality attributed to the condition. The scores are summed to yield a total index score which can be used to predict long-term survival. Higher scores indicate a greater comorbidity burden and a higher predicted risk of mortality.
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
Proportion of patients with a diagnosis of menopause
Time Frame: At baseline (within 12 months before the first estrogen therapy prescription claim [index date])
At baseline (within 12 months before the first estrogen therapy prescription claim [index date])

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 31, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 26, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 31, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 31, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 23357

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings