Effect of Hormone Replacement Therapy on Lupus Activity
Hypothesis, HRT does not increase the risk of lupus activity exacerbation, it is effective for the relief of menopausal symptoms and improves bone mineral density.
Double-blind, randomized, placebo controlled clinical trial.
- Determine the effect of HRT on disease activity, menopausal symptoms, bone mineral density, lipid profile, and mammographic parenchymal density in menopausal women with SLE.
- Determine the incidence rate of major side effects of HRT in menopausal women with SLE.
- Primary outcome will be global disease activity throughout the follow-up period.
- Incidence of lupus flares, time to the first flare, changes in SLEDAI values from baseline at each follow-up visit, maximum disease activity, lupus treatment, hospitalizations, thromboses, and deaths.
Menopausal symptoms and depression will be assessed utilizing the Greene Climacteric Scale questionnaire and the Beck Depression Inventory.
Bone mineral density of lumbar spine and hip will be performed with dual energy x-ray absorptiometry. In addition, blood and urine samples to measure biochemical markers of bone turnover.
Estradiol levels, lipid profile,coagulation tests, cervical cytology examinations, mammography.
Inclusion Criteria: (Any two of the following criteria)
- Amenorrhea of 6 months or more
- Serum FSH level of 30 IU/L or more
- Menopausal symptoms
- Age 48 years or older.
- Women older than 65 years
- Severe lupus activity at baseline
- Use of estrogens within 3 months of the screening visit
- Serum creatinine of 2.0 mg/dL or more
- Hypertriglyceridemia 500 mg/dL or more
- Metabolic bone diseases
- Liver disease
- Untreated hyperthyroidism
- Recent thrombosis
- Endometrial hyperplasia
- Undiagnosed uterine bleeding
- Cervical dysplasia.
Subject allocation Random assign, using a computer-generated randomization list to: Conjugated equine estrogens 0.625 mg/day plus 5 mg/day of medroxyprogesterone acetate p.o. for the first 10 days per-month, or biologically inert placebo.All women will receive 1200 mg of calcium carbonate and 800 IU of vitamin D, daily.
Follow-up procedure All patients will be evaluated by a rheumatologist and a reproductive health specialist at baseline,1,2,3,6,9,12,15,18,21, and 24 months.
- General information (baseline).
- Lupus activity (every visit).
- Medications: (every visit)
Onset of symptoms since the previous visit using a standardized questionnaire. In addition, a gynecological examination will be performed.
Criteria for early termination of the study:
A patient will be discontinued from the study whenever any of the following criteria would be present:
- Development of severe lupus activity (SLEDAI > 30).
- Development of any putative complication to hormone therapy.
- Development of any other severe complications due neither to SLE nor hormone therapy.
- Need prolonged immobilization.
Between-group comparisons of lupus activity, maximum SLEDAI, and change in SLEDAI score from baseline at each follow-up visit. Incidence-density rates of flares with relative risk and 95 percent confidence intervals.Probability of flares throughout the study using life-table analyses and log-rank test.
Climacteric symptoms as the mean value of the Green’s scale score at baseline and at each follow-up visit, between-group and intra-group. Bone mineral density as the mean value at baseline, 12 and 24 months, between and intra-group.
The proportion of patients in each group who develop secondary effects, as well as the number who quit the study during the follow-up period.
Continuous variables will be compared using Student's t-test, and categorical variables using chi-square or Fisher’s exact test. Within-group comparisons will be done using the Wilcoxon signed-rank test. P values will be two-sided. Analyses will be conducted by the intention-to-treat method.
|Systemic Lupus Erythematosus||Drug: Conjugated equine estrogens 0.625 mg/d + MPA 5 mg/d/10d||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Effect Of Hormone Replacement Therapy On Disease Activity, Menopausal Symptoms And Bone Mineral Density In Peri/Postmenopausal Women With Systemic Lupus Erythematosus.Randomized Clinical Trial|
- Global disease activity throughout the follow-up period, estimated as the area under the SLEDAI-curve
- Incidence of lupus flares
- Time to the first flare
- Changes in SLEDAI values from baseline at each follow-up visit
- Maximum disease activity
- Improvement of menopause symptoms
- Improvement in bone mineral density
- Change in mammographic breast density
- Changes in lipid profile
|Study Start Date:||November 1997|
|Estimated Study Completion Date:||December 2001|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00392093
|Principal Investigator:||Jorge Sanchez-Guerrero, MD, MS||Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran|
|Study Chair:||Maria C Cravioto, MD||Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran|