Have We Reached an Estrogen Comfort Zone?

What is uniformly disconcerting in these trials is the risk of thrombosis, which can certainly erode confidence in choosing OCs or estrogen replacement therapy. This risk must be carefully weighed, and it seems prudent to fully evaluate patients for evidence of thrombophilia before instituting therapy. At the very least, the history of a previous venous or arterial event would be a clear-cut contraindication. The identification of a circulating lupus anticoagulant, anti-cardiolipin, or anti­–beta 2 glycoprotein I antibodies of any isotype above a modest range should be reason to dissuade a patient from considering OC or estrogen replacement therapy. While the presence of a false positive Venereal Disease Research Laboratory (VDRL) alone is unusual and likely to be identified by the obstetrician/gynecologist, it too might be reason for seeking alternatives to estrogen use. Given the rapid pace of scientific discovery, we might soon be able to identify which patients might experience flares when exposed to exogenous estrogens.

Dr. Buyon is professor of medicine in the division of rheumatology at New York University School of Medicine in New York.

References:

1. Petri M, Kim MY, Kalunian KC, et al. Combined oral contraceptives in women with systemic lupus erythematosus. New Engl J Med. 2005;353:2550-2558.
2. Buyon JP, Petri M, Kim MY, 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;142:953-962.
3. Sanchez-Guerrero J, Uribe AG, Jimenez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med. 2005;353:2539-2549.
4. Liu H, Liu Z, Chen Z, Liu D, Li L. [Estrogen receptor gene polymorphism and its association with clinicopathological manifestation of lupus nephritis.] Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2000;17:266-269.
5. Peeva E, Venkatesh J, Michael D, Diamond B. Prolactin as a modulator of B cell function: implications for SLE. Biomed Pharmacother. 2004;58:310-319.
6. Ramsey-Goldman R, Dunn JE, Huang CF, et al. Frequency of fractures in women with systemic lupus erythematosus: comparison with United States population data. Arthritis Rheum. 1999;42:882-890.
7. Sinigaglia L, Varenna M, Binelli L, et al. Determinants of bone mass in systemic lupus erythematosus: a cross sectional study on premenopausal women. J Rheumatol. 1999;26:1280-1284.
8. Gilboe IM, Kvien TK, Haugeberg G, Husby G. Bone mineral density in systemic lupus erythematosus: comparison with rheumatoid arthritis and healthy controls. Ann Rheum Dis. 2000;59:110-115.
9. Sowers MFR, Galuska DA. Epidemiology of bone mass in pre-menopausal women. Epidemiol Rev. 1993;15:374-398.
10. FDA MedWatch 2004 Safety Alert—Depo-Provera (medroxyprogesterone acetate injectable suspension). www.fda.gov/medwatch/SAFETY/2004/safety04.htm
11. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. J Am Med Assoc. 1998;280:605-613.
12. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). J Am Med Assoc. 2002;288:49-57.
13. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. J Am Med Assoc. 2002;288:321-323.
14. Morris MS, Jacques FF, Selhub J,Rosenberg IH. Total homocysteine and estrogen status indicators in the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2000;152:140-148.
15. Rosano GM, Caixeta AM, Chierchia S, et al. Short term anti ischemic effect of 17beta estradiol in postmenopausal women with coronary artery disease. Circulation. 1997;96:2837 2841.
16. McHugh NA, Solowiej A, Klabunde RE, Merrill GF. Acute coronary vascular and myocardial perfusion effects of conjugated equine estrogen in the anesthetized dog. Basic Res Cardiol. 1998;93:470 476.
17. Bellinger DA, Williams JK, Adams MR, Honore EK, Bender DE. Oral contraceptives and hormone replacement therapy do not increase the incidence of arterial thrombosis in a nonhuman primate model. Arterioscler Thromb Vasc Biol. 1998;18:92-99.
18. Kaplan JR, Adams MR, Anthony MS, Morgan TM, Manuck SB, Clarkson TB. Dominant social status and contraceptive hormone treatment inhibit atherogenesis in premenopausal monkeys. Arterioscler Thromb Vasc Biol. 1995;15:2094-2100.