Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

Sponsor

Cedars-Sinai Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03018366

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether low estrogen levels in young women with hypothalamic amenorrhea (premenopausal HypoE) is associated with risk factors for cardiovascular disease.

For this study, the investigators will measuring vascular function and immune markers on:

young women with hypothalamic amenorrhea (>3 months of no menstrual cycle due to low estrogen)
young women with regular menstrual cycles not on hormone therapy.
recently menopausal women (<3 years from final menstrual period) not on hormone therapy.

Premenopausal HypoE participants will then be randomized to use either an estrogen patch or a placebo patch (no active medicine) for 3 months, followed by estrogen or placebo patch plus progesterone or placebo pills for 2 additional weeks. The investigators are looking to see if estrogen improves vascular and immune function.

Condition or Disease	Intervention/Treatment	Phase
Estrogen Deficiency Cardiovascular Disease (CVD) Hypothalamic Amenorrhea	Drug: 17beta Estradiol Drug: Transdermal placebo patch Drug: Progesterone Drug: Placebo Pill	Phase 2

Detailed Description

Study Aims:

To test the hypothesis premenopausal HypoE is associated with pre-clinical CVD as determined by reductions in vascular endothelial function and increased central arterial stiffness.
To test the hypothesis premenopausal HypoE is associated with increased immune-mediated inflammation.
To test the hypothesis estrogens can reduce inflammation, improve vascular endothelial function and central arterial stiffness in premenopausal HypoE women.

In a randomized, double-blind placebo-controlled trial in premenopausal HypoE women the investigators will test 12 weeks of transdermal estradiol 0.1 mg/day patch or placebo followed by 2 weeks of estradiol plus progesterone 200mg on vascular endothelial function, arterial stiffness and immune-mediated inflammation versus placebo. Patches will be applied by the participant to the lower abdomen twice weekly, alternating sides.

The investigators will be using non-invasive tests to measure vascular function including:

Peripheral arterial tonometry (PAT)
SphygmoCor measurements of central blood pressure
Carotid intima-media thickness (CIMT)

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

Actual Study Start Date :

Jan 1, 2017

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 17Beta Estradiol, Progesterone 17Beta Estradiol (0.1mg/day) , Progesterone (200mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 200mg is a peanut based product	Drug: 17beta Estradiol Participants will use a dose of transdermal estradiol 0.1 mg/day patch for 12 weeks +/- 1week. PAT index and sphygmoCor vascular measures and serum immune markers will be measured after 6 and 12 weeks +/- 1week on estrogen patches. Patches will be applied by the participant to the lower abdomen twice weekly, alternating sides. Other Names: Estradiol Transdermal Patch Vivelle-Dot Drug: Progesterone After 12 weeks +/- 1week of transdermal estradiol patch, participants will use estrogen patch plus progesterone for 2 additional weeks +/- 3 days. Progesterone 200mg is a peanut based product and for patients with a peanut allergy we will replace this with a synthetic progestin at an equivalent dose, medroxyprogesterone 10mg. Other Names: Prometrium
Placebo Comparator: Transdermal Placebo Patch, Placebo Pill Placebo Transdermal Patch, Placebo Pill	Drug: Transdermal placebo patch Participants will use a dose of placebo patches for 12 weeks +/- 1 week. Placebos will be applied by the participant to the lower abdomen twice weekly, alternating sides. Drug: Placebo Pill After 12 weeks +/- 1week of transdermal placebo patch, participants will use placebo patch plus placebo pill for 2 additional weeks +/- 3 days. Other Names: Placebo Oral Pill

Arm

Intervention/Treatment

Active Comparator: 17Beta Estradiol, Progesterone

17Beta Estradiol (0.1mg/day) , Progesterone (200mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 200mg is a peanut based product

Drug: 17beta Estradiol

Participants will use a dose of transdermal estradiol 0.1 mg/day patch for 12 weeks +/- 1week. PAT index and sphygmoCor vascular measures and serum immune markers will be measured after 6 and 12 weeks +/- 1week on estrogen patches. Patches will be applied by the participant to the lower abdomen twice weekly, alternating sides.

Other Names:

Estradiol Transdermal Patch

Vivelle-Dot

Drug: Progesterone

After 12 weeks +/- 1week of transdermal estradiol patch, participants will use estrogen patch plus progesterone for 2 additional weeks +/- 3 days. Progesterone 200mg is a peanut based product and for patients with a peanut allergy we will replace this with a synthetic progestin at an equivalent dose, medroxyprogesterone 10mg.

Other Names:

Prometrium

Placebo Comparator: Transdermal Placebo Patch, Placebo Pill

Placebo Transdermal Patch, Placebo Pill

Drug: Transdermal placebo patch

Participants will use a dose of placebo patches for 12 weeks +/- 1 week. Placebos will be applied by the participant to the lower abdomen twice weekly, alternating sides.

Drug: Placebo Pill

After 12 weeks +/- 1week of transdermal placebo patch, participants will use placebo patch plus placebo pill for 2 additional weeks +/- 3 days.

Other Names:

Placebo Oral Pill

Outcome Measures

Primary Outcome Measures

Rate of change of peripheral arterial tonometry (PAT) [Baseline, week 6, 12, and 14 on trial]
PAT measured as reactive hyperemia index (RHI%)

Secondary Outcome Measures

Rate of change of pulse wave analysis [Baseline, week 6, 12, and 14 on trial]
SphymoCor measured as augmentation index
Rate of change of pulse wave velocity [Baseline, week 6, 12, and 14 on trial]
SphymoCor measured as meters/second
Rate of change of distal common carotid artery, Carotid Intima-Media Thickness (cIMT) [Baseline, week 6, 12, and 14 on trial]
Measurement of distal common carotid artery in millimeters
Serum Inflammatory Markers [Baseline, week 6, 12, and 14 on trial]
Hormone levels [Baseline, week 6, 12, and 14 on trial]
Quality of life (questionnaire) [Baseline, week 6, 12, and 14 on trial]
Short-Form Health Survey 12
Depression [Baseline, week 6, 12, and 14 on trial]
Patient Health Questionnaire (PHQ-9)
Sleep changes [Baseline, week 6, 12, and 14 on trial]
Insomnia Severity Index
Anxiety [Baseline, week 6, 12, and 14 on trial]
Overall Anxiety Severity and Impairment Scale (OASIS)
Stress [Baseline, week 6, 12, and 14 on trial]
Cohen Perceived Stress Scale
DEXA Scan [Baseline]
dual-energy x-ray absorptiometry (DEXA) bone mass

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

For premenopausal Hypo E and normal control women inclusions include:

Premenopausal currently not on hormone therapy,
English speaking (for the purposes of complete psychosocial assessment)
able to give informed consent
a gynecological age (age since menarche) > 10 and < 25 years, and chronological age > 18 years
Within 90-110% of ideal body weight as determined by the 1983 Metropolitan height and weight table for women
All participants with hypothalamic amenorrhea will be diagnosed based on exclusion of other etiologies for their amenorrhea, including pregnancy, thyroid dysfunction, hyperprolactinemia, premature ovarian insufficiency, and polycystic ovary disease

For recently menopausal women inclusions include:

Follicle stimulating hormones (FSH) >30 and 12 months of amenorrhea,92 within 3 years of final menstrual period with natural menopausal not on hormone therapy
English speaking
Able to give informed consent
Within 90-110% of ideal body weight