Impact of Menopause on Women With Rheumatoid Arthritis
It is well known that pregnancy and menopause can influence the disease course in women with rheumatoid arthritis (RA). Our featured expert discusses the impact of menopause on women with RA and offers insights into patient management during and after the onset of menopause.
Adjunct Clinical Professor, Division of Immunology/Rheumatology
“The disease worsens during menopause, such that there is often the need to add or adjust therapies.”
Rheumatologists recognize that menopause has a major impact on women in general and can significantly influence disease activity in those with RA. Estrogen clearly influences disease activity in RA and other arthritides and autoimmune conditions (eg, systemic lupus erythematosus [SLE]). However, we do not have a complete understanding of the role of hormones in these diseases. For instance, while women with RA often experience a partial remission during pregnancy and then flare after delivery, we frequently see worsening of SLE during pregnancy.
Nevertheless, we know that RA in postmenopausal women does not do well in the absence of some type of estrogen therapy. Mollard and colleagues reported in their recent US-wide observational study of 8189 women who developed RA prior to menopause that the premenopausal group experienced less functional decline than the postmenopausal group. Further, ever-use of hormone replacement therapy (HRT), having pregnancy, and longer length of reproductive life were linked to less functional decline in this study. There are also data suggesting that menopause is associated with the presence of anti-citrullinated protein antibodies, suggesting that an acute decline in ovarian function may contribute to the development of RA-associated autoimmunity and possibly a higher risk of RA.
In addition to their effect on RA disease activity and postmenopausal symptoms, estrogens are beneficial in terms of osteoporosis and osteopenia, and the effect is even greater in women with RA. HRT, in the form of unopposed low-dose estrogen, appears to have many benefits in postmenopausal women with RA. Although there is still some debate about the risk of estrogen-associated breast and uterine cancers, we generally believe that the benefits of unopposed low-dose estrogen therapy far outweigh the risks. The disease worsens during menopause, such that there is often the need to add or adjust therapies. For the treatment of RA in postmenopausal women, we usually try HRT first and then, perhaps, some bridging therapy, although you may have to change the underlying RA therapy in some cases. We typically refer patients to their OB-GYN or primary care physician for HRT prescriptions, but we strongly encourage them to consider estrogen therapy. There are many transdermal estrogen preparations available that can provide a low-dose maintenance effect. The vaginal estradiol inserts also have a role in the relief of urogenital symptoms.
Alpizar-Rodriguez D, Mueller RB, Möller B, et al. Female hormonal factors and the development of anti-citrullinated protein antibodies in women at risk of rheumatoid arthritis. Rheumatology (Oxford). 2017;56(9):1579-1585.
Bengtsson C, Malspeis S, Orellana C, Sparks JA, Costenbader KH, Karlson EW. Association between menopausal factors and the risk of seronegative and seropositive rheumatoid arthritis: results from the Nurses’ Health Studies. Arthritis Care Res (Hoboken). 2017;69(11):1676-1684.
Mollard E, Pedro S, Chakravarty E, Clowse M, Schumacher R, Michaud K. The impact of menopause on functional status in women with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(5):798-802.
Pikwer M, Nilsson J-A, Bergström U, Jacobsson LTH, Turesson C. Early menopause and severity of rheumatoid arthritis in women older than 45 years. Arthritis Res Ther. 2012;14(4):R190.
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