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Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

Primary Purpose

Estrogen Deficiency, Cardiovascular Disease (CVD), Hypothalamic Amenorrhea

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

17beta Estradiol

Transdermal placebo patch

Progesterone

Placebo Pill

About this trial

This is an interventional treatment trial for Estrogen Deficiency focused on measuring estrogen, premenopause, menopause, amenorrhea

Eligibility Criteria

18 Years - 60 Years (Adult)FemaleAccepts Healthy Volunteers

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

Exclusion Criteria:

For premenopausal Hypo E and normal control women exclusions include:

Smoking
Hypertension
Hyperlipidemia
Diabetes
Medications including psychotropic or illicit drugs, medical, neurological
Ophthalmologic disease except acuity problems
Major Axis I disorder other than depression
Pregnancy in the last 12 months and/or lactating in the last 6 months
Current use of hormone contraceptive or any estrogen or progestin therapy

For HypoE women, exclusion criteria include:

- Allergy to adhesive or tape

For recently menopausal women exclusions also include:

Previous or current use of hormone therapy, estrogen or progestin
Surgical or chemotherapy induced menopause
Premature ovarian failure

Sites / Locations

Cedars-Sinai Barbra Streisand Women's Heart Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

17Beta Estradiol, Progesterone

Transdermal Placebo Patch, Placebo Pill

Arm Description

17Beta Estradiol (0.1mg/day) , Progesterone (100mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 100mg is a peanut based product

Placebo Transdermal Patch, Placebo Pill

Outcomes

Primary Outcome Measures

Rate of change of peripheral arterial tonometry (PAT)

PAT measured as reactive hyperemia index (RHI%)

Secondary Outcome Measures

Rate of change of pulse wave analysis

SphymoCor measured as augmentation index

Rate of change of pulse wave velocity

SphymoCor measured as meters/second

Serum Inflammatory Markers

Hormone levels

Quality of life (questionnaire)

Short-Form Health Survey 12

Depression

Patient Health Questionnaire (PHQ-9)

Sleep changes

Insomnia Severity Index

Anxiety

Overall Anxiety Severity and Impairment Scale (OASIS)

Stress

Cohen Perceived Stress Scale

DEXA Scan

dual-energy x-ray absorptiometry (DEXA) bone mass

Full Information

NCT ID

NCT03018366

First Posted

December 1, 2016

Last Updated

May 11, 2023

Sponsor

Cedars-Sinai Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03018366

Brief Title

Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

Official Title

Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

January 1, 2017 (Actual)

Primary Completion Date

February 1, 2023 (Actual)

Study Completion Date

February 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cedars-Sinai Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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.

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Estrogen Deficiency, Cardiovascular Disease (CVD), Hypothalamic Amenorrhea

Keywords

estrogen, premenopause, menopause, amenorrhea

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

17Beta Estradiol, Progesterone

Arm Type

Active Comparator

Arm Description

17Beta Estradiol (0.1mg/day) , Progesterone (100mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 100mg is a peanut based product

Arm Title

Transdermal Placebo Patch, Placebo Pill

Arm Type

Placebo Comparator

Arm Description

Placebo Transdermal Patch, Placebo Pill

Intervention Type

Drug

Intervention Name(s)

17beta Estradiol

Other Intervention Name(s)

Estradiol Transdermal Patch, Vivelle-Dot

Intervention Description

Participants will use a dose of transdermal estradiol 0.1 mg/day patch for 12 weeks +/- 1week. PAT index 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.

Intervention Type

Drug

Intervention Name(s)

Transdermal placebo patch

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Progesterone

Other Intervention Name(s)

Prometrium

Intervention Description

After 12 weeks +/- 1week of transdermal estradiol patch, participants will use estrogen patch plus progesterone for 2 additional weeks +/- 3 days. Progesterone 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.

Intervention Type

Drug

Intervention Name(s)

Placebo Pill

Other Intervention Name(s)

Placebo Oral Pill

Intervention Description

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

Primary Outcome Measure Information:

Title

Rate of change of peripheral arterial tonometry (PAT)

Description

PAT measured as reactive hyperemia index (RHI%)

Time Frame

Baseline, week 6, 12, and 14 on trial

Secondary Outcome Measure Information:

Title

Rate of change of pulse wave analysis

Description

SphymoCor measured as augmentation index

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Rate of change of pulse wave velocity

Description

SphymoCor measured as meters/second

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Serum Inflammatory Markers

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Hormone levels

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Quality of life (questionnaire)

Description

Short-Form Health Survey 12

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Depression

Description

Patient Health Questionnaire (PHQ-9)

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Sleep changes

Description

Insomnia Severity Index

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Anxiety

Description

Overall Anxiety Severity and Impairment Scale (OASIS)

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

Stress

Description

Cohen Perceived Stress Scale

Time Frame

Baseline, week 6, 12, and 14 on trial

Title

DEXA Scan

Description

dual-energy x-ray absorptiometry (DEXA) bone mass

Time Frame

Baseline

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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, 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 Exclusion Criteria: For premenopausal Hypo E and normal control women exclusions include: Smoking Hypertension Hyperlipidemia Diabetes Medications including psychotropic or illicit drugs, medical, neurological Ophthalmologic disease except acuity problems Major Axis I disorder other than depression Pregnancy in the last 12 months and/or lactating in the last 6 months Current use of hormone contraceptive or any estrogen or progestin therapy For HypoE women, exclusion criteria include: - Allergy to adhesive or tape For recently menopausal women exclusions also include: Previous or current use of hormone therapy, estrogen or progestin Surgical or chemotherapy induced menopause Premature ovarian failure

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chrisandra Shufelt, MD

Organizational Affiliation

Cedars-Sinai Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Noel Bairey-Merz, MD

Organizational Affiliation

Cedars-Sinai Medical Center

Official's Role

Study Director

Facility Information:

Facility Name

Cedars-Sinai Barbra Streisand Women's Heart Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

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