APS and Contraception Choice

Co-author: Dr. Angela Weyand, Clinical Associate Professor of Pediatrics, Pediatric Hematology/Oncology. Dr. Weyand is a co-chair of the International Society for Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee on Women's Health, a member of the ISTH guidance and guidelines committee, and a section lead for the Lancet Haematology Commission on Women’s Health.

Today, we’ll be reviewing how the choice of contraceptive therapy is a little more complex in patients with APS. One important aspect of APS treatment is ensuring our patients don’t have other risk factors for clots, or, if they do, finding ways to reduce those risks. One of these potential risk factors is the use of systemic estrogen therapy, most commonly in oral contraceptive pills (OCPs). There are other times estrogen treatment is considered, especially in menopause, and I hope to address this topic in a future post, but today’s post is all about hormonal and other contraceptive choices. This post is co-written by our friend and colleague in Pediatric Hematology, Dr. Angela Weyand, who, in addition to treating and studying APS, also has a particular interest in women’s health.

Oral Contraceptive Pills

Hormone therapies like OCPs are used for a variety of reasons, including heavy menstrual periods, acne, and contraception. The problem for patients with antiphospholipid antibodies (even those without a prior clot) is that the combined OCPs, which contain estrogen (called combined OCPs because they contain both estrogen and progesterone), lead to a greater risk of blood clots. In fact, we have a number of patients who weren’t diagnosed with APS until after they were put on an OCP and then developed a blood clot! Only then were the antiphospholipid antibodies identified, leading to their APS diagnosis.

So, what OCPs can be used when you have APS? There are OCPs that contain progesterone only, and these are relatively safe for patients with antiphospholipid antibodies¹. The progesterone-only OCPs are also sometimes called the “Mini Pill,” and they are even available over the counter. One particular aspect of their use is that they work best when taken at exactly the same time every day (set that phone alarm when the dose is due!). The Mini Pill is considered effective, just like other OCP’s, but with typical (not perfect) use, there is a 6-9% risk of pregnancy each year².

Other Contraceptives to Avoid in APS

There are other contraceptives that are effective (6-9% risk of pregnancy per year) but best avoided in people with antiphospholipid antibodies. These include depot medroxyprogesterone acetate (aka DMPA or DepoProvera, injections every 3 months), vaginal rings (such as NuvaRing), and transdermal patches (applied to the skin). The ring and the patch contain estrogen at high enough doses that they should be avoided in APS. Depo (DMPA) is a progestin-only contraceptive, but in some studies, users had an increased risk of clotting (perhaps double)^3,4. These studies could not perfectly capture whether there is a definite risk or exactly how high it may be, or if there is a risk specifically related to antiphospholipid antibodies; perhaps the only people enrolling were already avoiding estrogen because they already had an increased clotting risk. Still, because of the finding, we advise our patients with APS or other risk factors for clots to avoid DMPA injections.

Highly Effective Contraceptive Options in APS

There are several options that are considered highly effective (<1% pregnancy risk each year) for contraception, meaning they are more effective than the Mini Pill. There are multiple types of IUDs (intrauterine devices), and all are considered safe for patients with APS¹. IUDs may be particularly useful to women who are not planning on pregnancy in the near future because they last 3-10 years before needing replacement, depending on the specific device chosen. The hormonal (levonorgestrel) IUDs have the lowest rates of pregnancy (0.07% per year), and the hormone included is a tiny amount of progestin, not estrogen. Some example brand names include Mirena and Kyleena. Copper IUDs also have very low rates of pregnancy (0.63% per year) and contain no hormone. The downside is that for women on anticoagulation, they can experience heavy menstrual bleeding on copper IUDs. Cyclic menstrual bleeding often stops in users of hormonal IUDs. Hormonal IUDs can also be used to reduce dysmenorrhea and endometriosis-related pelvic pain.

Another highly effective option is the implant (for example, Nexplanon), which contains only progestin. An implant looks like a tiny plastic rod that is placed under the skin and lasts for 5 years before it is replaced. Are there clotting risks, perhaps similar to Depo? Although the American College of Rheumatology in its last reproductive health guidelines in 2020 advised caution because there were not yet a lot of studies on the topic, additional studies have been done since then, and the 2024 conclusion from the CDC is that the progestin implants are a reasonable choice for women with a history of clotting, similar to progestin-only pills⁵. One other downside for women on anticoagulation, though, is that some women can have irregular menstrual bleeding.

Less effective, but low-risk contraception choices in APS

There are other contraceptive options which pose no clotting risk, but they are not nearly as effective as the options above: condoms, diaphragms, sponges, cervical caps, spermicide, and fertility awareness (calendar methods). In these options, there is a 10-25% risk of pregnancy per year with typical use.

Emergency Contraception

Emergency contraception (which prevents ovulation, thus preventing pregnancy) is also safe for women with APS. There are 2 oral emergency contraceptive methods available in the United States (ulipristal acetate and levonorgestrel, which is available over the counter as Plan B), and neither contains estrogen. IUD placement can also work as emergency contraception.

What is the best choice for me?

The best choice for an individual is highly personal and depends on preferences and specific medical history. Talk about your options with your rheumatologist, hematologist, obstetrician/gynecologist, and/or primary care physician. Because pregnancy is high-risk for patients with APS, the choice of contraception is very important. There are multiple choices, but you do need to be thoughtful about which are safe and which might be best for you. 

Safety grading: 1=no restriction, 2=advantages outweigh risks, 3=risks outweigh advantages, 4=unacceptable health risk. Effectiveness category: highly effective indicates <1% pregnant each year, effective indicates 6-9% pregnant each year, and ineffective indicates 10-25% pregnant each year.

Additional information: This linked handout was made specifically for lupus patients, but many of the same principles apply to APS, and it notes particular areas that apply to people with antiphospholipid antibody positivity. The first page addresses pregnancy planning, and the second goes through birth control options. Check it out! 

1. Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, Marder W, Guyatt G, Branch DW, Buyon J, Christopher-Stine L, Crow-Hercher R, Cush J, Druzin M, Kavanaugh A, Laskin CA, Plante L, Salmon J, Simard J, Somers EC, Steen V, Tedeschi SK, Vinet E, White CW, Yazdany J, Barbhaiya M, Bettendorf B, Eudy A, Jayatilleke A, Shah AA, Sullivan N, Tarter LL, Birru Talabi M, Turgunbaev M, Turner A, D'Anci KE. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol. 2020 Apr;72(4):529-556. doi: 10.1002/art.41191. Epub 2020 Feb 23. PMID: 32090480.

2. https://lupuspregnancy.org/wp-content/uploads/2021/09/HOP-STEP-OB-GYN-MFM-Handouts_Pregnancy-Planning-and-Contraception_Sept-1-2021.pdf

3. Bergendal A, Persson I, Odeberg J, Sundström A, Holmström M, Schulman S, Björgell O, Kieler H. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol. 2014 Sep;124(3):600-609. doi: 10.1097/AOG.0000000000000411. Erratum in: Obstet Gynecol. 2015 Feb;125(2):495. PMID: 25162263.

4. Cockrum RH, Soo J, Ham SA, Cohen KS, Snow SG. Association of Progestogens and Venous Thromboembolism Among Women of Reproductive Age. Obstet Gynecol. 2022 Sep 1;140(3):477-487. doi: 10.1097/AOG.0000000000004896. Epub 2022 Aug 3. PMID: 35926206; PMCID: PMC9669089.

5. https://www.cdc.gov/contraception/media/pdfs/2024/07/us-mec-summary-chart-color-508.pdf