Endometriosis
Conditions
Keywords
Skin blood flow, Cholesterol, Statin, Intradermal Microdialysis
Brief summary
Endometriosis is a disorder that occurs in women. With endometriosis, tissue that should be found in the womb is found in sites outside of the womb. This disorder impairs the function of the cells that line the body's blood vessels (endothelium). The endothelium helps to control blood flow in healthy vessels. Women with this disorder have an increased risk for high blood pressure and high cholesterol. They have a higher risk for cardiovascular disease, too. With this study, we will learn how endometriosis impairs the lining of blood vessels and increases the risk for disease.
Detailed description
Epidemiologic data demonstrate a clear association between endometriosis, reproductive risk factors, inflammation and cardiovascular (CV) risk. Circulating factors, Low-density lipoprotein (LDL) and oxidized LDL (oxLDL), are two of many biomarkers of cardiovascular and inflammatory disease of endometriosis. An important signaling mechanism through which circulating LDL and oxLDL act is the lectin-like oxidized LDL receptor (LOX-1). LOX-1 signal transduction functionally results in pronounced endothelial dysfunction, a hallmark of CV. We hypothesis that one factor mediating the elevated risk of cardiovascular disease in endometriosis is microRNA (miRNA) activation of LOX-1 receptor mechanisms. Specific Aim 1. To test the hypothesis that LOX-1 receptor activation is increased leading to endothelial dysfunction in endometriosis. Specific Aim 2. To test the hypothesis that decreased microRNAs (i.e. let7-a, let7-b, let7-g, MiR98, Mi590-p) are driving increased LOX-1 receptor expression and function in endometriosis.
Interventions
DRUGAtorvastatin
Simvastation acts as a systemic LOX inhibitor.
Sponsors
Penn State University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Only women with endometriosis will complete this study. Once consented and screened, each subject is asked to take Atorvastatin (Lipitor, 10mg/day) for seven days. Participants will undergo experimental testing before and after the seven day intervention.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Women between the ages of 18 and 45 years with endometriosis (diagnosis by prior laparoscopy by subject's own physician \<5 years prior, and reported by the subject to the researchers)
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nitric Oxide Dependent Vasodilation in the Skin | before and after intervention (7 days) | area under the curve of laser Doppler flux/mean arterial pressure \* log acetylcholine (mol/L) |
Countries
United States
Participant flow
Recruitment details
All endometriosis patients had a confirmed diagnosis prior to enrollment via laparoscopy.
Pre-assignment details
6 enrolled
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin Oral atorvastatin (Lipitor) therapy (10mg/day) for seven days.
Atorvastatin acts as a systemic LOX inhibitor.
Atorvastatin: Simvastation acts as a systemic LOX inhibitor. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Atorvastatin |
|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Change in Nitric Oxide Dependent Vasodilation in the Skin
area under the curve of laser Doppler flux/mean arterial pressure \* log acetylcholine (mol/L)
Time frame: before and after intervention (7 days)
Population: A subset (n = 6) of endometriosis patients participated in a seven-day oral atorvastatin (Lipitor®) therapy (10 mg/day). These subjects returned to the laboratory on day 7, having taken the final dose that morning.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Change in Nitric Oxide Dependent Vasodilation in the Skin | 200 flux/MAP*logAch(mol/L) | Standard Error 80 |