Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women

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)

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