Women develop rheumatoid arthritis more often than men. In fact, for each man who has RA, there are approximately three women with the disease.
RA isn’t the only autoimmune disease that’s far more prevalent in women. Thyroid disease, lupus, and Sjögren’s syndrome are just a few autoimmune conditions that affect women in far greater numbers, and as many as 78% of people who have autoimmune diseases are women.
Recent research findings are beginning to unravel why women develop autoimmune and inflammatory conditions more frequently, including specific genetic factors that may one day identify who’s at highest risk of RA or other diseases, and help scientists develop more effective therapies.
Rheumatologists, obstetrician/gynecologists (OB/GYNs) and reproductive medicine specialists are also working more closely together to help both women and men with RA manage their reproductive health throughout their lives.
New reproductive health guidelines for people with rheumatic diseases, including RA, were just released. They cover birth control, pregnancy, fertility therapy, breastfeeding, assisted reproductive technology for women who have trouble conceiving, menopause, and other topics. They’re designed to guide your physicians’ clinical decisions, but they also provide health recommendations to benefit everyone who lives day to day with RA.
Why do we need reproductive health recommendations for people with RA and other rheumatic diseases? According to the U.S. Centers for Disease Control and Prevention (CDC), more than half of pregnancies are unplanned. If you have RA, carefully planning your pregnancy is important for your health and your baby’s health. Ideally, you want to be in good health and have low disease activity when you conceive. This will improve your chances of a healthy pregnancy and healthy baby.
VGLL3: One Clue to Women’s Increased Risks?
Until recently, we didn’t know the exact reasons why women tend to get autoimmune diseases more often than men. One culprit may be VGLL3, a gene transcription factor that has a strong bias toward females. It’s a protein that turns certain genes on or off, and activates gene transcription, an important step in the process of making new proteins and cells.
One new study published in 2017 by researchers at the University of Michigan found that VGLL3 is a key player in the expression of genes related to inflammation and several autoimmune diseases, including lupus and Sjögren’s syndrome, and some inflammatory pathways found in RA.
VGLL3 is found in skin cells, and for some reason, women’s skin cells have more VGLL3 than men. The researchers found that high amounts of VGLL3 in skin cells in mice can trigger an autoimmune response, such as inflammation.
It’s too early to say if VGLL3 has the same function in people that it does in mice, but these types of breakthroughs may one day help us understand why women tend to get autoimmune, inflammatory diseases like RA .
Healthy Tips for All Ages
The new reproductive health guidelines include hundreds of recommendations for people with rheumatic diseases at every age and stage of life. We’ve included a few of the guidelines here, but the full list can be found at https://www.rheumatology.org/Portals/0/Files/Reproductive-Health-Guideline-Early-View-2020.pdf
- Safe, Effective Contraception: As we mentioned, many pregnancies in the U.S. are unplanned and may be unintended. The new guidelines strongly recommend that women with RA use effective contraceptives if they don’t want to conceive. They also conditionally recommend highly effective intrauterine devices (IUDs) and subdermal progestin implants, which are placed under the skin, as safe, effective options for women who want to prevent pregnancy.
- Meds for Men: Men are strongly recommended not to take the medications cyclophosphamide or thalidomide before they attempt to conceive with their partners. In addition, cyclophosphamide can cause infertility in men. The guidelines strongly recommend that guys discuss fertility preservation options with their doctors, like freezing their sperm for later use, before they start the drug.
- Plan for Pregnancy: If you have RA and are considering pregnancy soon, the guidelines suggest that you plan your pregnancy for when your disease activity is low. Work with your rheumatologist to be sure that your RA is well controlled as you get ready to conceive with your partner. While some RA drugs are safe to take during pregnancy according to the guidelines, others may not be safe for an unborn baby, so you may have to switch medications. Your rheumatologist will create a tailored treatment plan to keep your disease activity low during pregnancy and after you deliver your baby—when you will have more than enough to handle!
- Breastfeeding: The guidelines suggest that women with RA who want to breastfeed should do so for the health benefits to their baby, but recommend that nursing moms not take cyclophosphamide, leflunomide, mycophenolate mofetil, or thalidomide, as well as methotrexate during this time.
- Address Hot Flashes: Women with RA who are in menopause may experience unpleasant vasomotor symptoms, also known as hot flashes or night sweats, just like other women. Can they safely take hormone replacement therapy (HRT) to find relief? Yes, they can. The new guidelines strongly suggest that HRT is OK for women with rheumatic diseases, as long as they don’t have any other contraindications, lupus, or a positive test for antiphospholipid antibodies. Whew!
Disease Activity and Inflammation: Track It with Your Vectra® Score. Vectra is an advanced blood test that objectively measures inflammation caused by RA. Your Vectra Score is a number from 1-100 that reveals the severity of your RA, how well your current treatment is working, and is the best predictor of future joint damage. Your Vectra Score tells you if your RA is in low, moderate, or high disease activity. This number can reassure you that your treatment plan is working or alert you that it may be time to make some changes.
 Van Vollenhoven RF. “Sex differences in rheumatoid arthritis: more than meets the eye.” BMC Med. 2009;7:12.  Fairweather D and Rose NR. “Women and Autoimmune Diseases.” Emerg Infect Dis. 2004 Nov;10(11):2005-2011.  Sammaritano LR, Bermas BL, Chakravarty EE, et al. “2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases.” Arthritis Rheumatol. 2020 Jan;0(0):1-28.  U.S. Centers for Disease Control and Prevention. “Unplanned Pregnancy.”  Liang Y, Tsoi LC, Xing X, et al. “A gene network regulated by the transcription factor VGLL3 as a promoter of sex-biased autoimmune diseases.” Nat Immunol. 2017;18(2):152–160.