Review articleSafety of contraceptive methods for women with rheumatoid arthritis: a systematic review☆
Introduction
Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the lining of the joints, which may lead to chronic pain and disability, bone loss and increased risk of infection. RA patients are also at an increased risk for cardiovascular disease (CVD) events [1]. An estimated 1.3 million adults in the United States have RA, with women two to three times as likely to develop RA as men [2]. There is no known cause of RA, but some evidence suggests an association between sex steroids and the disease [3]. However, whether sex hormones play a causative role in development or severity of RA, or are associated through other, unknown factors, is unclear. RA patients generally have decreased androgen levels, resulting in a reduced androgen/estrogen ratio [4]. Pregnancy tends to diminish or eliminate symptoms in RA patients, although symptoms recur in 90% of women after delivery [5]. Some evidence also exists that women who have taken oral contraceptives (OCs) in the past may be protected against developing RA or more severe cases of RA [6], although other evidence suggests no such protective effect of OC use on RA development [7].
Whether certain forms of contraception affect progression of disease or increase the risk of other adverse effects in women with RA is less well studied. Determining safety of contraceptives for women with RA is important in that disease onset often occurs during the mid to late reproductive years. Additionally, certain treatments for RA, such as methotrexate, are teratogenic, necessitating highly effective contraception for sexually active women.
Women with RA and their clinicians may have unique concerns about certain methods of contraception. Many RA patients take immunosuppressive drugs. One concern is whether use of intrauterine devices (IUDs) by these women results in the possibility of an increased risk of infection, although no data to date support increased infectious complications of IUD use in women with relative states of immunosuppression from other diseases [8], [9], [10]. Another concern is the potential effect of hormonal contraceptives [e.g., depot medroxyprogesterone acetate (DMPA)] on bone, given that bone loss is a serious complication of RA. Finally, the choice of contraception for women with RA is complicated by the fact that methods of contraception requiring self-insertion, such as the vaginal ring and diaphragm, may pose problems for women with decreased manual dexterity and joint mobility.
Currently, the World Health Organization's (WHO) Medical Eligibility Criteria for Contraceptive Use (MEC) does not include RA as a medical condition [11], [12]. This systematic review was conducted in preparation for a meeting convened by the Centers for Disease Control and Prevention (CDC) in February 2009 to adapt the WHO MEC for use in the United States. Therefore, the objective of this systematic review is to assess the evidence regarding the safety of contraceptive use by women with RA, including evaluating risks of disease progression and other adverse health effects.
Section snippets
Materials and methods
We searched the MEDLINE database created by the US National Library of Medicine to identify all peer-reviewed journal articles relating to use of all methods of contraception or their component parts, such as estrogens and progestins, and progression of RA. We used a comprehensive search strategy for contraceptives and standard terms for RA and related conditions (Appendix A). Articles of interest were published in any language from MEDLINE's inception through February 2009. We reviewed
Results
A total of 250 articles were identified using the search strategy described above. Two authors (SLF and SGF) read the title and abstracts or full text of the articles and identified eight articles meeting the inclusion criteria. Six of these articles examined OC use [16], [17], [18], [19], [20], [21]. The remaining two articles provided indirect evidence of therapeutic effects of progesterone [22] and estrogen [23]. No articles assessing other forms of contraception on the progression of RA or
Discussion
Through this systematic review of the published literature, we found limited information on the safety of OCs for RA patients. Various formulations of OCs were used across the studies reviewed; several were published before 1970 and treated patients with much higher hormone doses than would be used today. Additionally, some older studies used rudimentary outcome measures of RA, yielding no consistent or comparable pattern of improvement or worsening of the disease within or between studies. One
Acknowledgments
The authors thank Dr. Beth Jonas for her expert advice and helpful comments on the manuscript.
References (33)
- et al.
Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases
Rheum Dis Clin North Am
(2000) Sex hormone adjuvant therapy in rheumatoid arthritis
Rheum Dis Clin North Am
(2000)- et al.
Is the intrauterine device appropriate contraception for HIV-1-infected women?
BJOG
(2001) - et al.
Current methods of the US Preventive Services Task Force: a review of the process
Am J Prev Med
(2001) Rheumatic complaints of women using anti-ovulatory drugs. An evaluation
J Chronic Dis
(1968)- et al.
Women's health
Rheum Dis Clin North Am
(1999) - et al.
Progestogen-only contraception and bone mineral density: a systematic review
Contraception
(2006) - et al.
Patterns of cardiovascular risk in rheumatoid arthritis
Ann Rheum Dis
(2006) - et al.
Estimates of the prevalence of arthritis and other rheumatic conditions in the United States, Part I
Arthritis Rheum
(2008) - et al.
The remission of rheumatoid arthritis during pregnancy
Semin Immunopathol
(2007)
Oral contraception and its possible protection against rheumatoid arthritis
Ann Rheum Dis
Controversy of oral contraceptives and risk of rheumatoid arthritis: meta-analysis of conflicting studies and review of conflicting meta-analyses with special emphasis on analysis of heterogeneity
Am J Epidemiol
Using an intrauterine device in immunocompromised women
Obstet Gynecol
A randomized trial of the intrauterine contraceptive device vs hormonal contraception in women who are infected with the human immunodeficiency virus
Am J Obstet Gynecol
Medical eligibility criteria for contraceptive use
Medical eligibility criteria for contraceptive use, 2008 update Geneva, Switzerland
Cited by (28)
“It Would Have Been Nice to Have a Choice”: Barriers to Contraceptive Decision-making among Women with Disabilities
2022, Women's Health IssuesCitation Excerpt :In health care settings, providing accessible resources through patient portals and showing people how to find and use them would help to ensure that pregnancy-capable individuals with disabilities have access to accurate information to guide contraceptive decisions. Additionally, there is a critical need for research on safety and effectiveness of various forms of contraceptives in people with different types of disabilities (Farr, Folger, Paulen, & Curtis, 2010; Fromson, 2021; Kaplan, 2006; Zapata et al., 2016). Such research is challenging because results may differ by diagnosis, combinations of diagnoses, extent to which diagnoses impact functioning, and other medications participants may be using (Farr et al., 2010; Kaplan, 2006; Zapata et al., 2016).
Contraception and preconception counseling in women with autoimmune disease
2020, Best Practice and Research: Clinical Obstetrics and GynaecologyCitation Excerpt :Several early studies suggested patients with RA might potentially benefit with improved disease control from treatment with estrogen-containing OCs; however, data remain inconclusive. One case–control study of 176 women with RA found a relative risk of developing severe disease with estrogen–progestin OC use for >5 years to be 0.1 (95% CI 0.01–0.6) [20]; however, a systematic review was not able to confirm any beneficial effect of estrogen–progestin OCs on RA progression [21]. Effects of the LNG IUD, etonogestrel implant, or DMPA on disease activity in AIDs including SLE have not been specifically studied, but progestins alone have not been suggested to increase disease activity in any AID.
Contraception in Patients with Rheumatic Disease
2017, Rheumatic Disease Clinics of North AmericaCitation Excerpt :Another report of an inception cohort of 132 female patients with RA followed for an average of 12 years suggested a trend for patients using COCs to have both less radiographic joint damage and a better functional level than patients not using COCs.33 However, a recent systematic review of contraceptive methods in RA did not confirm any effect of hormonal contraceptives on RA progression.34,35 Although data regarding risk of disease exacerbation with hormonal contraceptives in patients with rheumatic disease are reassuring, use of CHCs should still be restricted to those patients at low risk.
Concepts of Contraception for Adolescent and Young Adult Women with Chronic Illness and Disability
2012, Disease-a-MonthCitation Excerpt :Women seeking contraception who have the aPL syndrome should be placed on progestin-only methods, such as DMPA, which can also lead to lowering of menstrual bleeding and less anticoagulation. Research notes that the OC pill or patch neither worsens nor improves RA.254-256 Some research has shown that OCs may have a protective effect over time against severe RA.257
Health benefits of combined oral contraceptives–a narrative review
2024, European Journal of Contraception and Reproductive Health Care
- ☆
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.