Disease Activity during the Premenopausal and Postmenopausal Periods in Women with Systemic Lupus Erythematosus Jorge Sa ´ nchez-Guerrero, MD, MS, Armando Villegas, MD, Ange ´lica Mendoza-Fuentes, MD, Juanita Romero-Dı ´az, MD, Gabriela Moreno-Coutin ˜o, MD, M. Carmen Cravioto, MD PURPOSE: Cyclophosphamide-induced ovarian failure has been reported to be protective against flares of systemic lupus erythematosus (SLE). We studied whether patients with SLE experience a decrease in disease activity after natural meno- pause. SUBJECTS AND METHODS: We studied 30 SLE patients with natural menopause who had been observed at least 2 years be- fore and after menopause and who did not receive hormone replacement therapy or danazol. Menopause was defined as the date of the last self-reported menstrual period. Disease ac- tivity was assessed retrospectively by medical chart review using standard measures (the SLE disease activity index) during the immediate premenopausal and postmenopausal periods, and 2 (n = 30 patients), 3 (n = 19), and 4 (n = 13) years before and after menopause. We also compared the use of health services and medications. RESULTS: Patients were studied for a mean ( SD) of 6.4  1.7 years (premenopausal, 3.3  0.9 years; postmenopausal, 3.2  0.9 years). During the premenopausal periods, the mean disease activity score was 2.3  2.3 (range, 0 to 9 on a 0 to 105 scale), compared with 2.3  2.9 (range, 0 to 12; P = 0.37) after menopause. The maximum disease activity score was somewhat greater in the premenopausal period (7.9  6.0 [range, 0 to 22] vs. 5.8  5.1 [range, 0 to 22]; P = 0.04). The incidence rates of flares (0.56 per year vs. 0.43 per year, P = 0.20) and severe flares (0.17 per year vs. 0.12 per year, P = 0.33) were similar in the premenopausal and postmenopausal periods. Differences in disease activity scores (mean and maximum) and the number of visits to a rheumatologist’s office were only significant when the fourth year before menopause was compared with the fourth year after menopause. CONCLUSION: Disease activity is mild during the premeno- pausal and postmenopausal periods in women with SLE. A modest decrease, especially in the maximum disease activity, is seen after natural menopause. Am J Med. 2001;111:464 – 468. 2001 by Excerpta Medica, Inc. S ystemic lupus erythematosus (SLE) is an autoim- mune disease of unknown etiology. Several studies have shown the relevance of sex hormones in the pathogenesis, course, and treatment of SLE in humans and animal models (1–14). Women during their repro- ductive years are 9 to 13 times more prone to SLE devel- opment than are men. This ratio is lower before puberty or after menopause (1). Use of oral contraceptives and postmenopausal estrogen therapy are associated with an increased risk of developing SLE (2,3). It remains contro- versial, however, whether estrogens exacerbate disease activity in patients with SLE (4 –10). In murine models of SLE, orchiectomized NZB/NZW F1 mice that are treated with estrogen have a greater mor- tality (11). Conversely, the course of the disease is delayed considerably in female NZB/NZW F1 mice by prolonged exposure to 5-dihydrotestosterone (12). Prepubertal castration of female NZB/NZW F1 mice in the absence of androgen administration does not affect the production of antibodies to DNA or mortality (13). These results suggest that sex hormones modulate immune function and that androgenic hormones are protective in murine lupus (13). In women with SLE, the reduction of estradiol to tes- tosterone ratio by the administration of cyproterone ac- etate reduces the episodes of exacerbation (14). In addi- tion, menopause affects the onset of several autoimmune diseases, including SLE (1,15,16), and cyclophospha- mide-induced ovarian failure may be protective against lupus flares (17). Given the improved progno- sis for SLE (18), more women with SLE survive to un- dergo menopause. Therefore, we analyzed activity in a cohort of 30 women with SLE before and after meno- pause. PATIENTS AND METHODS From an SLE register of 157 postmenopausal patients, 30 women were identified who fulfilled inclusion criteria: a clinical diagnosis of SLE, development of natural meno- pause, and regular follow-up at our center at least 2 years From the Departments of Immunology and Rheumatology (JSG, AMF, JRD, GMC), Department of Internal Medicine (AV), and the Department of Biology of Reproduction (MCC), Instituto Nacional de Ciencias Me ´dicas y Nutricio ´ n Salvador Zubira ´n, Me ´xico, D.F. Mexico. Supported by Grants 3367P-M and 25556-M from Consejo Nacional de Ciencia y Teconologı ´a (CONACYT) Me ´xico. Requests for reprints should be addressed to Jorge Sa ´nchez- Guerrero, MD, MS, Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Me ´dicas y Nutricio ´ n Salvador Zubira ´n, Vasco de Quiroga 15, 14000 Me ´xico, D.F. Mexico. Manuscript submitted February 9, 2001, and accepted in revised form June 26, 2001. 464 2001 by Excerpta Medica, Inc. 0002-9343/01/$–see front matter All rights reserved. PII S0002-9343(01)00885-3