GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases

Patients will be women ages 18-40 with either a severe rheumatic disease requiring
cyclophosphamide or interstitial lung disease requiring cyclophosphamide to be administered
either daily orally; monthly intravenously; or intravenously every 2 weeks for 6 doses.
Because cyclophosphamide treatment may be required urgently for some indications, study
entry may occur before either the first or second dose of cyclophosphamide for patients
receiving cyclophosphamide intravenously.

1. Female, post menarche, not menopausal

2. Ages 18-40 years inclusive at enrollment

3. Diagnosis consistent with a rheumatic or autoimmune disease requiring 3-6 months of
daily or intermittent cyclophosphamide therapy. This may include, but is not limited
to:

- Systemic lupus

- Sjogren's syndrome

- Systemic vasculitis

- Isolated vasculitis of the central nervous system

- Other autoimmune neurologic diseases requiring cyclophosphamide including
transverse myelitis, peripheral neuropathies, multiple sclerosis, neuromyelitis
optica, and retinal vasculitis

- Behcet's syndrome

- Scleroderma

- Inflammatory myositis

- Interstitial lung disease, other autoimmune pulmonary diseases requiring
cyclophosphamide

- Overlap connective tissue diseases not precisely fitting the above definitions
clearly requiring cyclophosphamide for severe immune mediated organ damage

- Rheumatoid vasculitis

4. Patients will have planned cyclophosphamide treatment according to any one of the
following regimens:

- 3 to 6 months of daily oral cyclophosphamide: Lupron/placebo must be given
within four (4) weeks of initiation of daily cyclophosphamide.

- The Eurolupus regimen consisting of 6 fortnightly biweekly boluses of 500 mg
cyclophosphamide: First dose of Lupron/placebo must be given 10 days prior to
the second dose of cyclophosphamide

- 3 to 6 monthly boluses of cyclophosphamide by the NIH regimen: First dose of
Lupron/placebo must be given 10 days prior to the second dose of
cyclophosphamide

5. A satisfactory plan for contraception consistent with cyclophosphamide administration
(when appropriate: depot progestins, IUD, combination oral contraception and/or dual
barrier contraception).

Exclusion Criteria:

1. Symptoms consistent with ovarian failure based on gynecologic evaluation and
confirmatory laboratory testing

2. Prior unilateral or bilateral oophorectomy

3. Cervical intraepithelial neoplasia (CIN 2, or more severe), that has not been
adequately evaluated or is not being adequately treated

4. Contraindications to use of GnRH-a (e.g., undiagnosed abnormal uterine bleeding)

5. Prior adverse or allergic reaction to GnRH-a

6. A history of severe psychiatric disorders, particularly severe depression that is
currently not adequately treated

7. History of significant noncompliance with medical treatment

8. Patients with major risk factors for decreased bone mineral content such as chronic
alcohol and/or tobacco use, strong family history of osteoporosis, or chronic use of
drugs that can reduce bone mass such as anticonvulsants that have not already been
addressed with appropriate measures to preserve bone mass.

9. Pregnant or breastfeeding

10. Significant thrombotic event requiring treatment that will not have received
appropriate therapy for at least 4 weeks before initiation of study drug.