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autoimmunity
June 2008 
Lupus & Hormone Therapy
Posted on Feb 29th, 2008
by 
Yogini
Yogini
A new study shows that in menopausal women with Lupus, HT does not increase blood clots. Good news! SG In postmenopausal women with lupus, no increase in vascular thrombotic events with HT use Fernandez M, Calvo-Alen J, Bertoli AM, et al, for the LUMINA Study Group. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA L II): relationship between vascular events and the use of hormone replacement therapy in postmenopausal women. J Clin Rheumatol 2007;13:261-265. Level of evidence: II-2. Menopausal hormone therapy (HT) does not predispose postmenopausal women with systemic lupus erythematosus (SLE) to vascular throm- botic events, found this substudy of LUMINA, a longitudinal, observational, multiethnic cohort study of outcome in SLE. The original cohort included women with SLE, aged 16 years or older, with disease duration of 5 years or greater. For the current study, perimenopausal women were drawn from the original cohort, excluding those with positive IgG or IgM antiphospholipid antibodies and/or the lupus anticoagulant, or vascular arterial events occurring before the use of HT. A total of 72 women were included (mean age, 53.7 y), of whom 32 were HT users and 40 were nonusers. The occurrence of vascular arterial and venous thrombotic events was compared between the two groups. available. Vascular arterial events considered in the analysis were myocardial infarction, angina, coronary artery bypass graft, stroke, inter- mittent claudication, and peripheral arterial thrombosis. Peripheral or visceral venous events were also considered. Vascular arterial events occurred more frequently in nonusers than HT users (P = 0.029). No difference was found for venous thrombotic events between the two groups (P = 0.725). Although HT use was negatively associated with vascular arterial events (odds ratio, 0.156; P = 0.021), this diminished to nonsignificance when a propen- sity score, which adjusted for baseline variables, was factored in. In women with SLE who are antiphospholipid antibody negative, with no previous thrombotic vascular events or other risk factors for such events, HT may be used in the immediate postmenopausal period, the study authors suggest. Comment. Contradictory findings exist re- garding estrogen and SLE. The Nurses’ Health Study1 demonstrated that the relative risk for SLE was increased by events that increase one’s lifetime exposure to estrogen, such as early age at menarche, oral contraceptive (OC) use, and the use of HT during perimenopause. The same study also demonstrated an increased risk for SLE with early age at menopause and surgical menopause. Like other autoimmune diseases, SLE has a varied disease course that waxes and wanes irrespective of medical therapy. Clearly there is a need for randomized controlled trials (RCTs) to evaluate the effects and safety of HT in patients with SLE. Prescribing HT to women with SLE is of particular concern because both SLE and HT have been associated with vascular events. To date, RCTs have found that neither the use of OCs nor HT leads to significant flares.2 Sanchez- Guerrero and colleagues3 performed a double- blind RCT of 106 women with SLE either in the menopause transition or in early or late postmenopause who received a continuous- sequential estrogen-progestogen regimen (n = 52) or placebo (n = 54). Disease activity remained mild and stable in both groups throughout the trial. There were no significant differences between the groups in global or maximum disease activity, incidence or probability of flares, or medication use. Thrombosis occurred in three patients who received HT and in one patient who received placebo. Thus, HT did not alter disease activity during 2 years of treatment. However, an increased risk of thrombosis was found in women with SLE who received HT. The largest RCT was conducted by Buyon and colleagues4 who evaluated the risk of 12 months of cyclic-combined HT in the Safety of Estrogens in Lupus Erythematosis National Assessment trial in 351 perimenopausal patients (mean age, 50 y) with inactive (81.5%) or stable-active (18.5%) SLE. The addition of HT was associated with a small risk for increasing the natural flare rate of mild to moderate flares of SLE although the risk for severe flare was not significantly increased compared with placebo. During the trial, they validated the Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) of ongoing, recurrent, or new activity to capture persistent activity/flares. Neither Buyon nor Sanchez-Guerrero found an increased occurrence of arterial thrombosis with HT use in women with SLE. This lack of increased risk of arterial thrombosis in selected women with SLE was confirmed in this recent study by Fernandez et al. The strengths of their multiethnic, longitudinal, nonrandomized, observational cohort trial included the use of the SLEDAI and the process of pseudo- randomization using a propensity scale to take into account the fact that subjects using HT had less severe and less active disease. The trial is limited by the lack of information about precise doses, formulations, and length of time of HT. Their findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis as these women were excluded from the trial. The indications for HT in postmenopausal women include the treatment of menopause- related symptoms and the prevention of osteoporosis. Women with SLE are more likely to have premature menopause induced by chemotherapy as well as increased risks of osteoporosis and cardiovascular disease. Recent studies2,3 have shown that HT can induce mild to moderate SLE flares as well as cardiovascular or venous thromboembolic events. Therefore, at this time, we would not recommend giving HT to women with active SLE, lupus anticoagulant, antiphospholipid antibodies, or previous thrombosis. Candidates for HT might include young women with premature ovarian failure from chemotherapy for SLE or symptomatic women with SLE for treatment of vasomotor symptoms and prevention of osteoporosis. Nonoral admin- istration may be preferable because of potential decreased effect on coagulation. The increased risk for mild to moderate flares needs to be considered on an individual basis. JoAnn V. Pinkerton, MD Professor of Obstetrics and Gynecology Vice Chair for Academic Affairs University of Virginia Charlottesville, VA President-Elect, NAMS Board of Trustees Credentialed NAMS Menopause Practitioner Dale W. Stovall, MD Professor of Obstetrics and Gynecology Division Director, Reproductive Endocrinology and Fertility University of Virginia Charlottesville, VA References: 1. Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum 2007;56:1251-1262. 2. Urowitz MB, Ibanez D, Jerome D, Gladman DD. The effect of menopause on disease activity in systemic lupus erythematosus. J Rheumatol 2006;33:2192-2198. 3. Sanchez-Guerrero J, Gonzalez-Perez M, Durand- Carbajal M, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis Rheum 2007;56:3070-3079. 4. Buyon JP, Petri MA, Kim MY, et al The effect of combined estrogen and progesterone hormone replace- ment therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med 2005;142(12 Pt 1):953-962.
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