Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

Cardiovascular Disease (CVD) Clinical Trial

Official title:

Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03018366
• Other study ID #: PRO26081
• Status: Completed
• Phase: Phase 2
• Start date: January 1, 2017
• Est. completion date: February 1, 2023

Study information

• Verified date: January 2024
• Source: Cedars-Sinai Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Study Aims:

1. 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.

2. To test the hypothesis premenopausal HypoE is associated with increased immune-mediated inflammation.

3. 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 1, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Amenorrhea
• Atherosclerosis
• Cardiovascular Disease (CVD)
• Cardiovascular Diseases
• Estrogen Deficiency
• Hypothalamic Amenorrhea
• Inflammation

Intervention

Drug:
• 17beta Estradiol
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.
• 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.
• Progesterone
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.
• Placebo Pill
After 12 weeks +/- 1week of transdermal placebo patch, participants will use placebo patch plus placebo pill for 2 additional weeks +/- 3 days.

Locations

Country	Name	City	State
United States	Cedars-Sinai Barbra Streisand Women's Heart Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of change of peripheral arterial tonometry (PAT)	PAT measured as reactive hyperemia index (RHI%)	Baseline, week 6, 12, and 14 on trial
Secondary	Rate of change of pulse wave analysis	SphymoCor measured as augmentation index	Baseline, week 6, 12, and 14 on trial
Secondary	Rate of change of pulse wave velocity	SphymoCor measured as meters/second	Baseline, week 6, 12, and 14 on trial
Secondary	Serum Inflammatory Markers		Baseline, week 6, 12, and 14 on trial
Secondary	Hormone levels		Baseline, week 6, 12, and 14 on trial
Secondary	Quality of life (questionnaire)	Short-Form Health Survey 12	Baseline, week 6, 12, and 14 on trial
Secondary	Depression	Patient Health Questionnaire (PHQ-9)	Baseline, week 6, 12, and 14 on trial
Secondary	Sleep changes	Insomnia Severity Index	Baseline, week 6, 12, and 14 on trial
Secondary	Anxiety	Overall Anxiety Severity and Impairment Scale (OASIS)	Baseline, week 6, 12, and 14 on trial
Secondary	Stress	Cohen Perceived Stress Scale	Baseline, week 6, 12, and 14 on trial
Secondary	DEXA Scan	dual-energy x-ray absorptiometry (DEXA) bone mass	Baseline