Not Yet Recruiting

estrogen therapy

Bayer Identifier:

23357

ClinicalTrials.gov Identifier:

NCT07795606

EudraCT Number:

Not Available

EU CT Number:

Not Available

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

Trial purpose

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.

Key Participants Requirements

Sex

Female

Age

40 - N/A (No Limit)

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

Trial summary

Enrollment Goal

456000

Trial Dates

August 2026 - December 2026

Phase

N/A (Not Applicable)

Could I Receive a placebo

Products

Levonorgestrel, BAY 865028

Accepts Healthy Volunteer

Primary Outcome

Proportion of patients receiving estrogen therapy
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.
Time Frame:
Retrospective analysis from January 2025 to December 2025
Number of patients by treatment subgroup within 30 and 90 days of estrogen therapy initiation
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.
Time Frame:
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
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.
Time Frame:
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
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.
Time Frame:
Retrospective analysis from January 2025 to December 2025

Secondary Outcome

Overall (10-year) incidence of atypical, non-atypical and unspecified endometrial hyperplasia, endometrial cancer, abnormal/unscheduled/heavy menstrual bleeding and hysterectomy
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.
Time Frame:
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
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.
Time Frame:
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])
Participant demographic characteristics: race
Time Frame:
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])
Participant demographic characteristics: region
Time Frame:
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])
Gynecologic history: endometrial polyps, fibroids, adenomyosis, endometriosis
Time Frame:
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])
Clinical characteristics: Charlson Comorbidity Index (CCI)
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.
Time Frame:
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])

Trial design

Acronym/OS (concept) Title SHIELD-ET. Study of real-world use of Hormonal Levonorgestrel intra-uterine system for Endometrial Defense with Estrogen therapy

Trial Type

Observational

Intervention Type

Drug

Trial Purpose

N/A

Allocation

N/A

Blinding

Open Label

Assignment

N/A

Trial Arms

N/A

Additional Information

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