Menstrual function, menopause, and hormone replacement therapy in women with systemic lupus erythematosus
- Bonnie L Bermas, MD
Bonnie L Bermas, MD
- Professor of Medicine
- UT Southwestern Medical Center
Systemic lupus erythematosus (SLE) occurs frequently in women of childbearing age. The relationships between SLE and menstrual function, menopause, and hormone replacement therapy are discussed in this topic review. Issues related to pregnancy in women with SLE,pregnancy in patients with impaired renal function, and hormonal contraception in women with SLE are presented in detail elsewhere. (See "Pregnancy in women with systemic lupus erythematosus" and "Pregnancy in women with underlying renal disease" and "Approach to contraception in women with systemic lupus erythematosus".)
Menstrual irregularities are common in women with systemic lupus erythematosus (SLE):
●Menstrual irregularity, especially oligomenorrhea, is a common clinical feature in women with SLE. As an example, among 94 women with SLE under the age of 45 without exposure to alkylating agents, oligomenorrhea occurred in 54 percent. Menstrual irregularities were associated with higher levels of prolactin, higher disease activity, and lower levels of progesterone . These observations suggest that SLE activity may result in hormonal abnormalities that may contribute to menstrual irregularity.
●Menorrhagia has been noted in 12 to 15 percent of patients [2,3]. Thrombocytopenia, antiphospholipid antibodies, and the use of glucocorticoids and/or nonsteroidal antiinflammatory drugs (NSAIDs) may contribute to the heavy menstrual flow.
●Temporary or even permanent early (or premature) amenorrhea has been noted in 17 to 24 percent of patients. Two major mechanisms have been identified: There is an association of SLE with autoimmune ovarian injury and with the administration of immunosuppressive agents (especially cyclophosphamide [CYC]) [4,5]. A retrospective review of women treated for lupus nephritis illustrated the importance of total drug exposure with CYC . Sustained early amenorrhea developed in none of 16 treated only with pulse glucocorticoids, 2 of 16 treated with seven monthly pulses of CYC, and 9 of 23 treated with 15 or more monthly pulses of CYC. Amenorrhea began within the first seven months in one-half of affected patients, occurring earlier in women over the age of 25. The amenorrhea was usually permanent, with recovery occurring only in women receiving the shorter pulse CYC regimen.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Shabanova SS, Ananieva LP, Alekberova ZS, Guzov II. Ovarian function and disease activity in patients with systemic lupus erythematosus. Clin Exp Rheumatol 2008; 26:436.
- HARVEY AM, SHULMAN LE, TUMULTY PA, et al. Systemic lupus erythematosus: review of the literature and clinical analysis of 138 cases. Medicine (Baltimore) 1954; 33:291.
- Dubois' Lupus Erythematosus, 3rd, Wallace DJ, Dubois EL (Eds), Lea and Febiger, Philadelphia 1987.
- LaBarbera AR, Miller MM, Ober C, Rebar RW. Autoimmune etiology in premature ovarian failure. Am J Reprod Immunol Microbiol 1988; 16:115.
- Boumpas DT, Austin HA 3rd, Vaughan EM, et al. Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med 1993; 119:366.
- McDermott EM, Powell RJ. Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide. Ann Rheum Dis 1996; 55:224.
- Mayorga J, Alpízar-Rodríguez D, Prieto-Padilla J, et al. Prevalence of premature ovarian failure in patients with systemic lupus erythematosus. Lupus 2016; 25:675.
- Steinberg AD, Steinberg BJ. Lupus disease activity associated with menstrual cycle. J Rheumatol 1985; 12:816.
- Lahita RG, Bradlow HL, Kunkel HG, Fishman J. Increased 16 alpha-hydroxylation of estradiol in systemic lupus erythematosus. J Clin Endocrinol Metab 1981; 53:174.
- Sánchez-Guerrero J, Villegas A, Mendoza-Fuentes A, et al. Disease activity during the premenopausal and postmenopausal periods in women with systemic lupus erythematosus. Am J Med 2001; 111:464.
- Mok CC, Lau CS, Ho CT, Wong RW. Do flares of systemic lupus erythematosus decline after menopause? Scand J Rheumatol 1999; 28:357.
- Fernández M, Calvo-Alén J, Alarcón GS, et al. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXI. Disease activity, damage accrual, and vascular events in pre- and postmenopausal women. Arthritis Rheum 2005; 52:1655.
- Urowitz MB, Ibañez D, Jerome D, Gladman DD. The effect of menopause on disease activity in systemic lupus erythematosus. J Rheumatol 2006; 33:2192.
- Petri M. Clinical features of systemic lupus erythematosus. Curr Opin Rheumatol 1995; 7:395.
- Petri M, Spence D, Bone LR, Hochberg MC. Coronary artery disease risk factors in the Johns Hopkins Lupus Cohort: prevalence, recognition by patients, and preventive practices. Medicine (Baltimore) 1992; 71:291.
- 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. JAMA 2002; 288:321.
- Sánchez-Guerrero J, González-Pérez M, Durand-Carbajal M, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis Rheum 2007; 56:3070.
- Arden NK, Lloyd ME, Spector TD, Hughes GR. Safety of hormone replacement therapy (HRT) in systemic lupus erythematosus (SLE). Lupus 1994; 3:11.
- Kreidstein S, Urowitz MB, Gladman DD, Gough J. Hormone replacement therapy in systemic lupus erythematosus. J Rheumatol 1997; 24:2149.
- Greenstein B. Hormonal aspects of lupus: therapeutic possibilities. Lupus 1993; 2:349.
- Buyon JP, Petri MA, 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.
- Sánchez-Guerrero J, Liang MH, Karlson EW, et al. Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus. Ann Intern Med 1995; 122:430.
- Rojas-Villarraga A, Torres-Gonzalez JV, Ruiz-Sternberg ÁM. Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis. PLoS One 2014; 9:e104303.