Endometriosis and Microvascular Dysfunction; Simvastatin and Duavee (Endo2/SA3)

July 24, 2026 updated by: Lacy Alexander, Penn State University

Mechanisms and Interventions Addressing Accelerated Cardiovascular Disease Risk in Women With Endometriosis

Purpose: To determine the effects of SERM and simvastatin interventions on endothelial dysfunction in women with endometriosis.

Hypothesis: Treatment with the SERM (bazedoxifene + conjugated estrogen) or with simvastatin will decrease systemic inflammation and improve specific measures of cardiovascular function including endothelium-dependent vasodilation.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Endometriosis is an estrogen dependent gynecological disorder associated with considerable chronic pelvic pain, pain during intercourse and is a major cause of infertility. While endometriosis is a local inflammatory syndrome, the inflammatory process is systemic and underlies many of the co-morbidities associated with this devastating disease. Endometriosis and atherosclerotic cardiovascular disease (CVD) are both inflammation-induced diseases. Robust epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and CVD risk, the leading cause of death in women worldwide. Estrogen exposure is beneficial for women from a CVD standpoint, but the standard of treatment for endometriosis includes estrogen suppression. This creates a conundrum for the long-term management of CVD risk in women with endometriosis. Moreover, there is a significant gap in prior research into the role of inflammatory signaling, CVD risk and effective interventions to mitigate cardiovascular comorbidities.

Endometriosis and Endothelial Dysfunction: Circulating LDL and oxidized (ox)LDL are two of many biomarkers of cardiovascular and inflammatory disease elevated in women with endometriosis. These circulating factors and inflammatory cytokines stimulate the ubiquitously expressed scavenger lectin-like oxidized LDL receptor (LOX-1) on the vasculature resulting in increased oxidant production and reduced nitric oxide (NO) metabolism, resulting in pronounced endothelial dysfunction, one of the earliest detectable indicators of increased CVD risk. Interestingly, estrogen directly inhibits LOX-1-dependent endothelial dysfunction. Our working model is that endometriosis-associated systemic inflammatory mediators increase LOX-1 receptor activity and result in endothelial dysfunction.

Therapies approved in 2018 for the treatment of endometriosis reduce endogenous estrogen production (elagolix) or selectively modulate estrogen receptors (SERM, bazedoxifene). Additionally, in preclinical models, therapies that modulate vascular function (statins) are also efficacious for reducing endometriosis proliferation. However, to date no studies have evaluated outcomes specific to systemic inflammation and cardiovascular function with these emerging endometriosis therapies.

This is a single arm pre/post study design. Only women with endometriosis will complete this study. Women will be between the ages of 18 and 45 years and previously diagnosed (within the past 5 years) with endometriosis. Once consented and screened, each subject is block randomized to either 30 days of a treatment (Simvastatin or 30 days of SERM (bazedoxifene + conjugated estrogen; BZE+CE)) and , or statin. This will be done in a counterbalanced fashion. Subjects will only complete one of the treatments and the placebo with a 60 day washout to minimize potential carryover effects. On day 30 of pretreatment , each subject participates in a cutaneous microdialysis (MD) and flow mediated dilation (FMD) experiment. After a 60-day washout, the participant will start either the treatment or placebo and returns to repeat the study with the other pre-treatments (SERM/Statin/Placebo)undergo the MD and FMD experiments. These treatments/placebo are blinded to the investigators collecting and analyzing the data.

Study Type

Interventional

Enrollment (Estimated)

28

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • The John B. Pierce Laboratory

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

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women between the ages of 18 and 45 years with endometriosis (diagnosis by prior laparoscopy by subject's own physician <10 years prior, and reported by the subject to the researchers)
  • Tylenol if the subject has acute pain is allowed
  • IUD contraceptive use (copper or levonogestrel) is allowed

Exclusion Criteria:

  • Use of nicotine-containing products (e.g. smoking, chewing tobacco, etc.)
  • Diabetes (HbA1C .6.5%)
  • BP>140/90
  • Taking pharmacotherapy that could alter peripheral vascular control (e.g. insulin sensitizing, cardiovascular medications)
  • Pregnancy
  • Breastfeeding
  • Taking illicit and/or recreational drugs
  • Abnormal liver function
  • Rash, skin disease, disorders of pigmentation, known skin allergies
  • Diagnosed or suspected metabolic or cardiovascular disease
  • Persistent unexplained elevations of serum transaminases
  • Known allergy to latex or investigative substances

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

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Simvastatin
30 days of Simvastatin (10mg/day)
Drug: simvastatin 10mg
Simvastation acts as a systemic LOX inhibitor.
Other: bazedoxifene + conjugated estrogen
30 days of bazedoxifene + conjugated estrogen (0.45mg/20mg/day)
Drug: Bazedoxifene 20/Estrogens,Con 0.45Mg Tb
Duavee is a selective estrogen receptor modulator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in skin blood flow
Time Frame: before intervention and 30 days post-intervention
cutaneous vascular conductance (units = red cell flux/mean arterial pressure)
before intervention and 30 days post-intervention
Change in peripheral blood flow
Time Frame: before intervention and 30 days post-intervention
brachial artery flow mediated dilation
before intervention and 30 days post-intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in LOX-1 activity
Time Frame: before intervention and 30 days post-intervention
LOX-1 receptor expression
before intervention and 30 days post-intervention
Change in reproductive hormones
Time Frame: before intervention and 30 days post-intervention
blood hormone concentrations
before intervention and 30 days post-intervention
Change in inflammation
Time Frame: before intervention and 30 days post-intervention
inflammatory cytokine concentration
before intervention and 30 days post-intervention
Change in microRNA activity
Time Frame: before intervention and 30 days post-intervention
microRNA expression
before intervention and 30 days post-intervention

Collaborators and Investigators

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

Sponsor

Penn State University

Collaborators

The John B. Pierce Laboratory

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 (Actual)

December 1, 2023

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

September 10, 2021

First Submitted That Met QC Criteria

September 20, 2021

First Posted (Actual)

September 28, 2021

Study Record Updates

Last Update Posted (Actual)

July 27, 2026

Last Update Submitted That Met QC Criteria

July 24, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18347

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

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.

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