Safety of Estrogens in Lupus: Hormone Replacement Therapy

Condition(s) targeted: Systemic Lupus Erythematosus

Intervention: Premarin and Provera (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Official(s) and/or principal investigator(s):
Jill Buyon, M.D., Principal Investigator, Affiliation: Hospital for Joint Diseases, Department of Rheumatology
Michelle Petri, M.D., Study Director, Affiliation: Johns Hopkins Hospital, Department of Rheumatology

Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA) is a study to test

whether postmenopausal women with systemic lupus erythematosus (SLE, or lupus) can safely use the hormone estrogen. In this part of the study, we will look at the effects of estrogen replacement therapy on the activity and severity of disease in women with SLE.

Official title: Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA): Hormone Replacement Therapy

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety/Efficacy Study

Detailed description: This study tests the effect of exogenous female hormones on disease activity and severity in women with systemic lupus erythematosus (SLE). Physicians generally do not prescribe hormone replacement therapy (HRT) to women with SLE because of the widely held view that such treatment can activate SLE. This practice is based on the greater incidence of SLE in women than in men, biologic abnormalities of estrogen metabolism, murine models of lupus, several anecdotes of patients having disease flares while receiving exogenous hormones, and a single retrospective study in patients with preexisting renal disease. By contrast, recent retrospective studies suggest that the rate of flare is not significantly increased in patients taking HRT.

We will examine, in a multicenter, randomized, double-blind, placebo-controlled trial, the effect of hormonal replacement with conjugated estrogens on disease activity in postmenopausal women with SLE. We will recruit patients from clinics and private practices that include over 4,000 women with SLE, most belonging to minority groups.

We will give patients hormones for 1 year.

NOTE: This trial has been terminated as of August 2002 upon recommendation of the Data Safety Monitoring Board (DSMB), based on the findings of the WHI Trial. Study subjects have discontinued study drug but will continue followup visits to study doctors through May 2003

Minimum age: 18 Years. Maximum age: 85 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- Female

- Unequivocal diagnosis of SLE

- Inactive disease or stable on 0. 5 mg/kg/day or less of prednisone

- Chemical evidence of menopause or have stopped periods for at least 6 months

Exclusion Criteria:

- Blood pressure >145/95 on three occasions

- Deep vein, arterial thrombosis or pulmonary embolus

- GPL >40; MPL >40; APL >50; dRVVT >37 sec

- APL antibody syndrome ever

- Gynecologic or breast cancer

- Hepatic dysfunction or liver tumors

- Diabetes mellitus (NOT due to steroids) with vascular disease

- Congenital hyperlipidemia

- Complicated migraine

- Severe disease activity (SLEDAI >12)

- Increase in SLEDAI >2 points in 3 months

- Unexplained vaginal bleeding

- Use of estrogen (HRT or OCP) for >1 month at any time after SLE diagnosis

- FSH <40

- Premenopausal myocardial infarction

UAB Medical Center, Birmingham, Alabama 35294, United States

UCLA Medical Center, Dept. of Rheumatology, Los Angeles, California 90024, United States

University of Chicago Pritzker School of Medicine, Chicago, Illinois 60637, United States

Louisiana School of Medicine, Shreveport, Louisiana 71130-3932, United States

Johns Hopkins Hospital, Baltimore, Maryland 21205, United States

Univ. of Michigan Med. Ctr., Rheumatology Div., Ann Arbor, Michigan 48109-0358, United States

Hospital for Joint Diseases, New York, New York 10003, United States

Hospital for Special Surgery, New York, New York 10021, United States

Albert Einstein College of Medicine, Jacoby Hospital, Dept. of Rheumatology, Bronx, New York 10461, United States

UNC Medical Center, Dept. of Rheumatology, Chapel Hill, North Carolina 27599-7280, United States

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, United States

Univ. of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, United States

Univ. of Pittsburgh, Dept. of Rheumatology, Pittsburgh, Pennsylvania 15213, United States

University of Texas Health Sciences Center, Houston, Texas 77030, United States

Medical College of Virginia, Ambulatory Care Center, Richmond, Virginia 23219, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

Related publications:

Petri M, Buyon J, Kim M. Classification and definition of major flares in SLE clinical trials. Lupus. 1999;8(8):685-91.

Kim MY, Buyon JP, Petri M, Skovron ML, Shore RE. Equivalence trials in SLE research: issues to consider. Lupus. 1999;8(8):620-6.

Buyon JP. Clinical trials in systemic lupus erythematosus. Curr Rheumatol Rep. 2000 Feb;2(1):11-12. Review. No abstract available.

Buyon JP. Hormone replacement therapy in postmenopausal women with systemic lupus erythematosus. J Am Med Womens Assoc. 1998 Winter;53(1):13-7. Review.

Buyon JP, Dooley MA, Meyer WR, Petri M, Licciardi F. Recommendations for exogenous estrogen to prevent glucocorticoid-induced osteoporosis in premenopausal women with oligo- or amenorrhea: comment on the American College of Rheumatology recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheum. 1997 Aug;40(8):1548-9. No abstract available.

Buyon JP, Wallace DJ. The endocrine system, use of exogenous estrogens, and the urogenital tract. In Dubois' Lupus Erythematosus, 6th edition. Wallace DJ, Hahn BH, eds. Philadelphia: Lippincott Williams & Wilkins, 2002; pp. 821-841.

Starting date: April 1996
Ending date: August 2002
Last updated: January 3, 2007