Inclusion Criteria

INCLUSION CRITERIA - General:

Healthy women, or women with RA, 18-55 year old, with a history of regular menses or who
are perimenopausal, have a BMI less than 30, able to provide informed consent to all
aspects of the study after full information is provided.

Women must have a negative pregnancy test at screening.

Study participants will be allowed to continue taking medications for chronic, stable
conditions, such as hypertension and hypercholesteremia, while in the study.

INCLUSION CRITERIA - for RA Patients:

Active RA as defined by 9 tender and 6 swollen joints; ESR greater than 35 mm/hr OR CRP
greater than 2.0 mg/dL; and, morning stiffness greater than 45 min.

Actively menstruating with a normal estrogen level or who are perimenopausal.

Women must be practicing, or willing to practice, an acceptable method of birth control
that does not involve use of prescription or OTC estrogen/progesterone preparations during
the two weeks prior to screening. Acceptable means of contraception include: abstinence,
barrier methods with spermicides, intrauterine devices (IUD's) or surgical sterilization.
(phase 2 of the study only)

Current use of nonsteroidal anti-inflammatory drugs (NSAIDs) and/or hydroxychloroquine are
permitted. Drug doses must have been stable for at least one month prior to enrollment,
and must be held constant during the study unless toxicity requires dose reduction.

Past use of a disease modifying agent (DMARD) such as methotrexate, sulfasalazine and
cyclosporine is allowed.

EXCLUSION CRITERIA - General:

Patients or control subject will be excluded if they exhibit any medical condition that
has the potential of placing the candidate at unnecessary risk during the study.
Additionally, patients with impaired renal, hepatic, cardiovascular or endocrine-metabolic
function, or any immunodeficiency syndrome including HIV infection, will be excluded

Use of systemic corticosteroids in the two weeks before screening and study entry.

Women with a history of cancer, with the exception of limited, resolved skin cancer.

Women who are menopausal. Clinical menopause is defined as the absence of spontaneous
menses during the preceding 12 months.

Pregnant women or women who are nursing.

Use of prescription or OTC estrogen/progesterone preparations during the two weeks prior
to screening

The patient or control subject has received any investigational drug within 30 days of the
start of the study.

History of autoimmune endocrinopathy.

Serious medical illnesses or abnormal laboratory values that would, in the opinion of the
P.I., preclude study participation.

EXCLUSION CRITERIA - For RA Patients:

BMI greater than or equal to 30.

Active infection or other contraindication to use of an anti-TNF agent (phase 2 of the
study only).

History of untreated tuberculosis, or of a positive PPD without completion of adequate
treatment. (phase 2 of the study only)

Live vaccinations in the 3 months prior to study (phase 2 of the study only).