Current issues of ACP Journal Club are published in Annals of Internal Medicine


Postmenopausal hormone therapy was associated with an increased risk for systemic lupus erythematosus

ACP J Club. 1995 July-Aug;123:24. doi:10.7326/ACPJC-1995-123-1-024

Source Citation

Sánchez-Guerrero J, Liang MH, Karlson EW, Hunter DJ, Colditz GA. Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus. Ann Intern Med. 1995 Mar 15;122:430-3.



To determine whether an association exists between postmenopausal hormone use and the development of systemic lupus erythematosus (SLE).


14-year cohort study of participants in the Nurses' Health Study.


11 states in the United States.


69 435 female nurses aged 30 to 55 years in 1976 who had completed menopause and did not have SLE or any connective tissue disease.

Assessment of risk factors

In 1976, women were asked by questionnaire whether they had taken hormone supplements after menopause and, if so, for how long. This information was updated every 2 years until 1990. Women were classified as never- or ever- (current and past) users of postmenopausal hormones.

Main outcome measure

Incident cases of SLE confirmed by blinded review of the medical records.

Main results

45 definite cases of SLE were confirmed. 22% of the entire cohort was classified as current users of postmenopausal hormones, 26% as past users, and 52% as never-users. Compared with never-users, ever-users had an age-adjusted relative risk (RR) for SLE of 2.1 (95% CI 1.1 to 4.0). Among ever-users, current users had an age-adjusted RR of 2.5 (CI 1.2 to 5.0), and past users had an age-adjusted RR of 1.8 (CI 0.8 to 4.1). A proportional increase in the risk for developing SLE was related to the duration of postmenopausal hormone use. Women who used hormones for 1 to 4 years had an age-adjusted RR of 1.8 (CI 0.9 to 3.8); those who used hormones for 5 to 10 years had an age-adjusted RR of 2.7 (CI 1.2 to 6.4); and those who used hormones for > 11 years had an age-adjusted RR of 3.5 (CI 1.2 to 10.9, test for trend P = 0.01).


Use of postmenopausal hormone therapy was associated with an increased risk for systemic lupus erythematosus compared with no use of postmenopausal hormones.

Source of funding: National Institutes of Health.

For article reprint: Dr. G.A. Colditz, Nurses' Health Study, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. FAX 617-731-1541.

Updated Commentary

Hormone replacement therapy (HRT) remains the treatment of choice for women with menopausal symptoms such as hot flashes and vaginal dryness. HRT is the still most effective means of preventing osteoporosis as well as being strikingly effective in treating the disorder. However, the ability of HRT to prevent coronary heart disease has been called into question, and concerns regarding thrombophlebitis, gall bladder disease, and breast cancer remain. In this article, Sanchez-Guerrero and colleagues suggest a relation between postmenopausal hormone use and the development of SLE.

Although an association between HRT and the new diagnosis of SLE was found, several cautions should be noted. The population of the Nurses' Health Study is mostly white, eliminating patient populations with a higher prevalence of SLE (i.e., African-American women). It is unclear whether a distinction was made between women using estrogen only and those using estrogen-progestin combinations. Finally, although the RR was statistically significant, the incidence of disease in postmenopausal women still makes development of SLE a rare occurrence.

Sanchez-Guerrero and colleagues refer to data suggesting that estrogens, or lack of androgens, allow the development of SLE, at least in mice (1). Their study may provide human observational data supporting this hypothesis—that estrogen permits development of SLE in women already genetically predisposed to the disease and in whom SLE might not have developed without the estrogen stimulus. The hypothesis itself remains vigorously debated (2, 3), expanding beyond the issue of induction of disease to include the question of whether hormones can be used to actually treat the disease (4). In fact, the role of estrogen as direct or adjunctive therapy in SLE is currently under clinical trial.

This study supports the epidemiologic evidence of a relation between estrogen and other diseases that predominate in women (e.g., rheumatoid arthtitis, scleroderma, multiple sclerosis). However, an important point made by the authors should not be lost: The benefit of HRT in postmenopausal women for prevention of complications of osteoporosis and possibly coronary heart disease considerably overwhelms the small risk for developing SLE. When making decisions about HRT, physicians should recognize the benefits anticipated for most of their patients.

Bruce E. Johnson, MD
University of Kansas School of MedicineKansas City, Kansas, USA


1. Laskin CA, Taurog JD, Smathers PA, Steinberg AD. Studies of defective tolerance in murine lupus. J Immunol. 1981;127:1743-7.

2. Liang MH, Karlson EW. Female hormone therapy and the risk of developing or exacerbating systemic lupus erythematosus or rheumatoid arthritis. Proceedings of the Association of American Physicians. 1996;108:25-8.

3. Yung RL. Mechanisms of lupus: the role of estrogens [Editorial]. Clin Exp Rheumatol. 1999;17:271-5.

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