SELENA: A Randomized Trial in SLE
Abstract & Commentary
By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert
Synopsis: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.
Source:Buyon JP, et al. The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med. 2005;142 (12 Pt 1):953-962.
The Safety of Estrogens in Lupus Erythematosus, National Assessment (SELENA) was composed of 2 randomized, placebo-controlled, multicenter trials—one with estrogen-progestin therapy in postmenopausal women and one comparing oral contraceptives and placebo. The trial was ended prematurely in August 2002 by the NIH in response to the publications of the Women’s Health Initiative. The results in postmenopausal women are presented for 1 year of treatment in 351 women with systemic lupus erythematosus (SLE); the results with oral contraceptives are yet to be reported. The postmenopausal treatment consisted of 0.625 mg conjugated estrogens daily with 5 mg of medroxyprogesterone acetate added for the first 12 days of each month. Severe flares were nzot increased by the treatment, and there was a slight increase in mild-to-moderate flares. The estimated relative risk for severe flares in the treated group was 1.75, but this did not achieve statistical significance and 3 of the 13 flares occurred when patients were not taking the drug.
Excluding the nonadherent patients, a very small difference existed between the treated and placebo groups. The relative risk for mild-to-moderate flares was significantly increased, RR = 1.34 (1.07-1.66). In actual numbers, 59% of treated patients had an increase compared with an increase noted in 50% of placebo patients, a small difference. There was no evidence of worsening of SLE in the treated group. Buyon and associates emphasized that the most meaningful finding clinically was the lack of an increase in the rate of severe flares.
Commentary
Successful treatment of SLE now allows many women with this condition to live beyond the menopause. The results of observational studies have been mixed regarding the administration of hormone therapy to patients with SLE. This is an important issue because it bears on the treatment of hot flushes in women with SLE, and osteoporosis is a major problem in these women because of treatment with glucocorticoids. In the Nurses’ Health Study, the use of postmenopausal estrogen was associated with approximately a 2-fold increase in SLE, an observation based on 30 cases in past and current users of estrogen.1 In a follow-up of 60 postmenopausal women with stable SLE, no adverse effects of hormone therapy could be detected.2
The results of SELENA are reassuring, but the high drop out rates in both treated (40.5%) and placebo (31.1%) groups, as well as a notable rate of patients lost to follow-up, must raise caution regarding the conclusions. Postmenopausal hormone therapy can be considered in patients with stable or inactive disease, without renal involvement and high antiphospholipid antibodies. In a 1-year study, transdermal estradiol and oral medroxyprogesterone acetate prevented bone loss with no increase in disease activity.3 Patients with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis were excluded from the SELENA study. If hormone therapy is to be provided to these patients, some form of chronic anticoagulation should be considered (such as statins or low-dose aspirin).
References
- Sanchez-Guerro J, et al. Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus. Ann Intern Med. 1995;122:430-433.
- Arden NK, et al. Safety of hormone replacement therapy (HRT) in systemic lupus erythematosus (SLE). Lupus. 1994;3:11-13.
- Bhattoa HP, et al. The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized, double-blind, placebo-controlled trial. Osteoporos Int. 2004;15:396-404.
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