Contraception represents an important area of reproductive health for patients with rheumatic diseases given the potential pregnancy risks associated with active disease, teratogenic medications, and severe disease-related damage. A high proportion of patients with rheumatic disease do not use effective contraception. Long-acting contraceptives are most effective. Antiphospholipid-negative patients with stable systemic lupus erythematosus may use oral combined contraceptives. Antiphospholipid-positive patients, or patients with rheumatic disease with other risk factors for thrombosis, should avoid estrogen-containing contraceptives. Contraceptive methods should be addressed by both the rheumatologist and gynecologist to determine the safest, most effective, and most convenient form for each patient.
Key points
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Contraception is an important area of reproductive health for patients with rheumatic diseases given the potential pregnancy risks associated with active disease, teratogenic medications, and severe disease-related damage.
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Long-acting reversible contraceptives, such as intrauterine devices and progestin implants, are most effective and should be encouraged even for nulliparous or adolescent patients who do not have contraindications.
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Antiphospholipid-negative patients with stable systemic lupus erythematosus may use oral combined contraceptives.
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Antiphospholipid-positive patients, or patients with rheumatic disease with other risk factors for thrombosis, should not use estrogen-containing contraceptives.
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Contraceptive methods should be discussed by both the rheumatologist and gynecologist to determine the safest, most effective, and most convenient form for each individual patient.
Introduction
Counseling patients to plan for pregnancy is an important aspect of care for reproductive-aged patients, especially in the presence of active rheumatic disease, teratogenic medications, or severe disease-related damage. Prepregnancy planning may promote optimal pregnancy outcomes for patients with rheumatic disease, but minimizing unplanned pregnancies relies on the critical assumption that patients use safe and effective contraception. As a result, a basic knowledge of currently available contraceptive methods is essential for both rheumatologists and patients with rheumatic disease.
Effective Contraception
Effectiveness of contraceptive methods varies widely, and counseling for patients must include both the necessity of contraceptive use and also guidance on the safest, most effective methods for that particular patient. Effectiveness is reported in 2 ways: as perfect use (ie, when used exactly as prescribed), and typical use, reflecting real-world use. Perfect use and typical use effectiveness are closest for those methods not directly related to the act of intercourse, and are nearly identical for long-acting reversible contraceptives (LARC) that require no effort on the part of the patient, such as the intrauterine device (IUD) and subdermal implant.
Reversible contraception includes barrier methods, IUDs, and various forms of hormonal contraceptives. Natural or fertility awareness methods are least effective and are not recommended for patients with rheumatic disease for whom unintended pregnancy may have adverse health consequences. Effectiveness rates for commonly used contraceptive methods are summarized in Table 1 .
| Method | Effectiveness (%) a | |
|---|---|---|
| Perfect Use | Typical Use | |
| None | 85 | 85 |
| Barrier Methods: | ||
| Condom | 2 | 15 |
| Diaphragm | 6 | 16 |
| IUDs: | ||
| Copper IUD | 0.6 | 0.8 |
| LNG-IUD | 0.2 | 0.2 |
| Progesterone Only: | ||
| Progesterone pill | 0.5 | 8 |
| Etonogestrel implant | 0.05 | 0.05 |
| DMPA IM | 0.3 | 3 |
| Combined Hormonal Contraceptives: | ||
| Oral | 0.3 | 9 |
| Transdermal patch | 0.3 | 9 |
| Vaginal ring | 0.3 | 9 |
a Percentage of women experiencing pregnancy during first year of use.
LARC methods are clearly most effective: a prospective study of 9256 women showed superior efficacy of LARC (IUD or implant) compared with other contraceptives (including oral contraceptive pills, patch, and vaginal ring). The contraceptive failure rate was 4.55 (per 100 participant-years) for oral, patch, and vaginal ring contraceptives versus 0.27 (per 100 participant-years) for LARC methods. Despite the demonstrated greater efficacy for LARC, the most common contraceptive methods used by women of child-bearing age in the United States are the combined oral contraceptive pill (27%) and female sterilization (28%). Rate of IUD use is about 7%.
Introduction
Counseling patients to plan for pregnancy is an important aspect of care for reproductive-aged patients, especially in the presence of active rheumatic disease, teratogenic medications, or severe disease-related damage. Prepregnancy planning may promote optimal pregnancy outcomes for patients with rheumatic disease, but minimizing unplanned pregnancies relies on the critical assumption that patients use safe and effective contraception. As a result, a basic knowledge of currently available contraceptive methods is essential for both rheumatologists and patients with rheumatic disease.
Effective Contraception
Effectiveness of contraceptive methods varies widely, and counseling for patients must include both the necessity of contraceptive use and also guidance on the safest, most effective methods for that particular patient. Effectiveness is reported in 2 ways: as perfect use (ie, when used exactly as prescribed), and typical use, reflecting real-world use. Perfect use and typical use effectiveness are closest for those methods not directly related to the act of intercourse, and are nearly identical for long-acting reversible contraceptives (LARC) that require no effort on the part of the patient, such as the intrauterine device (IUD) and subdermal implant.
Reversible contraception includes barrier methods, IUDs, and various forms of hormonal contraceptives. Natural or fertility awareness methods are least effective and are not recommended for patients with rheumatic disease for whom unintended pregnancy may have adverse health consequences. Effectiveness rates for commonly used contraceptive methods are summarized in Table 1 .
| Method | Effectiveness (%) a | |
|---|---|---|
| Perfect Use | Typical Use | |
| None | 85 | 85 |
| Barrier Methods: | ||
| Condom | 2 | 15 |
| Diaphragm | 6 | 16 |
| IUDs: | ||
| Copper IUD | 0.6 | 0.8 |
| LNG-IUD | 0.2 | 0.2 |
| Progesterone Only: | ||
| Progesterone pill | 0.5 | 8 |
| Etonogestrel implant | 0.05 | 0.05 |
| DMPA IM | 0.3 | 3 |
| Combined Hormonal Contraceptives: | ||
| Oral | 0.3 | 9 |
| Transdermal patch | 0.3 | 9 |
| Vaginal ring | 0.3 | 9 |
a Percentage of women experiencing pregnancy during first year of use.
LARC methods are clearly most effective: a prospective study of 9256 women showed superior efficacy of LARC (IUD or implant) compared with other contraceptives (including oral contraceptive pills, patch, and vaginal ring). The contraceptive failure rate was 4.55 (per 100 participant-years) for oral, patch, and vaginal ring contraceptives versus 0.27 (per 100 participant-years) for LARC methods. Despite the demonstrated greater efficacy for LARC, the most common contraceptive methods used by women of child-bearing age in the United States are the combined oral contraceptive pill (27%) and female sterilization (28%). Rate of IUD use is about 7%.
Underuse of effective contraception
Effective contraceptive methods are underused by patients with rheumatic disease. In general, patients with rheumatic disease at risk for unplanned pregnancy do not consistently use contraception, and, when they do, they often use a less effective method (usually condoms).
Recent survey studies confirm a lower-than-expected rate of contraception use in patients with rheumatic disease. One report of contraceptive use among women with systemic lupus erythematosus (SLE) aged 8 to 50 years surveyed 97 women at risk for unplanned pregnancy during the previous 3 months: 55% reported unprotected sex at least once, and 23% reported unprotected sex most of the time. In another study of 86 patients with SLE, 22% reported inconsistent contraceptive use, and 55% used barrier methods. Even more concerning, women on teratogenic medications were no more likely than other women to have used effective contraception. Patients with inflammatory arthritis show similar trends: in another survey, 27% of 94 women at risk for unintended pregnancy who were on the potentially teratogenic drugs methotrexate or leflunomide were not using any form of contraception, although most patients indicated that they were aware of the medications’ potential teratogenicity.
Analyses of health care claims databases also show decreased use of effective contraception for women with chronic illnesses, including SLE and rheumatoid arthritis (RA). DeNoble and colleagues analyzed prescription contraceptive use for 11,649 women in 1 large health care database, 1869 of whom had a chronic condition, defined as SLE, RA, inflammatory bowel disease, hypertension, asthma, obesity, or hypothyroidism. Over a 3-year period, only 33.5% of women with a chronic condition (vs 41.1% of healthy controls) received prescription contraception ( P <.001). Significantly, rates of contraception prescriptions were lowest for the groups with SLE and RA: 21.7% and 20.0% respectively.
Poor use of effective contraception is likely multifactorial. Management of a serious illness may overshadow usual health maintenance issues, and rheumatologists may assume contraceptive counseling is being provided by other physicians. Time allotted for patient visits may also limit discussion. Screening for sexual activity in pediatric rheumatology patients was evaluated in one study of 178 adolescents : rates of screening were low, and physicians reported that limited time was the major barrier, although other factors cited included logistical problems, discomfort with the subject area, and ambivalence about the rheumatologist’s role. Other socioeconomic factors may also play a role. Ferguson and colleagues found that one-third of their adult SLE cohort (n = 68) did not receive contraceptive counseling when starting a new medication. Older age, white race, depressive symptoms, and higher SLE disease activity were independently associated with not receiving contraceptive counseling.
Types of contraceptives
Contraceptives vary in terms of effectiveness, but they also vary in terms of availability, convenience of use, and safety. Safety issues are of particular concern for women with rheumatic diseases.
Barrier Contraception
Barrier methods of contraception, most commonly the condom, have significantly lower typical use effectiveness than do hormonal methods or IUDs: 15 out of 100 women using condoms become pregnant during 1 year of use. Despite lower effectiveness, condoms offer the advantages of easy availability and protection against sexually transmitted diseases. Efficacy of barrier contraception is increased if 2 methods are used; for example, condom and spermicide. As a result, this should be a standard recommendation for patients who use barrier protection.
Intrauterine Devices
Although not as commonly used in the United States, the IUD is the most commonly used form of reversible contraception worldwide. IUDs are extremely effective and may be recommended for use even in adolescents and nulliparous women. The most commonly used IUDs contain either copper or the second-generation progesterone levonorgestrel (LNG; 14 or 20 μg/24 h). Copper-containing IUDs remain in place for 10 years, but are often associated with heavier menses and dysmenorrhea. LNG-containing IUDs remain in place for 3 to 5 years. The LNG-IUDs generally reduce dysmenorrhea and menstrual bleeding, with complete amenorrhea in up to 50% of patients by 24 months. The progestin effect of the LNG-IUD is primarily local, although a small proportion of patients report systemic side effects; fertility quickly returns to normal with removal.
Complications associated with IUD use include risk of expulsion (5% over 5 years) and a very low risk of pelvic inflammatory disease (1.6 infections per 1000 women-years) in the 20 days following insertion. Risk of IUD-associated infection in patients on immunosuppressive medications has not been studied, but reports in immunocompromised women infected with HIV show no increased risk of infection. In addition to specific contraindications related to gynecologic disorders, IUD use is discouraged in women at high risk for sexually transmitted diseases; that is, those with multiple sexual partners.
Hormonal Contraception
Hormonal contraceptives include combined estrogen-progesterone and progestin-only preparations. Dose and type of hormone, as well as route of administration, affect both efficacy and risk of side effects.
Combined hormonal contraceptives
The first available birth control pill had 3 to 5 times the estrogen content of current combined oral contraceptives (COCs). Current COCs contain a low dose of synthetic estrogen (ethinyl estradiol or mestranol, 20–50 μg) and a progestin (17-α ethinyl analogues of 19-nortestosterone). The 19-nortestosterones are termed second-generation progestins and include norethindrone and LNG. Third-generation progestins were developed to decrease androgenic side effects and include norgestimate and desogestrel. Drospirenone, an analogue of spironolactone, shows progestational, antiandrogenic, and antimineralocorticoid activity and is considered a fourth-generation progestin. Potential side effects differ according to generation.
Newer formulations of combined (ie, estrogen-progestin) hormonal contraceptives (CHCs) with novel (nonoral) administration methods include the transdermal patch and the intravaginal ring. The transdermal patch is applied weekly for 3 out of 4 weeks, and delivers 20 μg of ethinyl estradiol and 150 μg of norelgestromin every 24 hours. Efficacy is similar to the pill; however, overall estrogen exposure may be increased. The intravaginal ring is kept in place for 3 of 4 weeks and releases 15 μg of ethinyl estradiol and 120 μg of etonogestrel every 24 hours.
Occurrence of serious complications is low and may be limited with careful assessment to exclude patients at greatest risk. Serious complications are usually vascular, including venous thromboembolism (VTE), stroke, and myocardial infarction (MI). There is an increased risk of cervical cancer and a slightly increased risk of breast cancer in current (but not past) users. Effects on the hemostatic system involve multiple mechanisms with an overall net effect that is prothrombotic. The overall risk of VTE in women on current CHCs is increased by a factor of 3 to 5 from the baseline annual risk in healthy women of 1 in 10,000. Nonoral preparations may confer higher risk than do some of the oral preparations.
Both estrogen and progestin contribute to increased VTE risk. Relative risk was increased by a factor of 10 with the earliest COCs, but reducing estrogen content has reduced the risk of oral preparations. At present, variation in type of progestin now accounts for most variability in VTE risk among different CHCs. Third-generation progestins confer greater risk than do second-generation progestins because of greater activated protein C resistance. Relative risks for VTE with selected CHCs are shown in Table 2 .
| Contraceptive | VTE Risk per Year (%) | Adjusted Odds Ratio (95% CI) |
|---|---|---|
| No contraception | 0.020 | 1.00 |
| Combined Oral: 30–40 μg Ethinyl Estradiol Plus | ||
| LNG (second generation) | 0.055 | 2.92 (2.23–3.81) |
| Desogestrel (third generation) | 0.099 | 6.61 (5.60–7.80) |
| Drospirenone (fourth generation) | 0.068 | 6.37 (5.43–7.47) |
| Transdermal patch | 0.097 | 7.90 (3.54–17.65) |
| Vaginal ring | 0.078 | 6.48 (4.69–8.94) |
CHC-associated risk of VTE is further increased in the presence of genetic or acquired thrombophilia, including antiphospholipid antibody (aPL), and is also increased with smoking (>10 cigarettes a day), age greater than 35 years, and obesity (body mass index ≥25 kg/m 2 ). Arterial thrombosis risk is also increased with CHC use. Stroke risk is increased 2-fold and depends on the presence of additional risk factors, including hypertension, migraine, smoking, and older age (>35 years). The likelihood of stroke associated with use of third-generation progestins is no higher than that associated with second-generation progestins, and may be slightly lower. Myocardial infarction risk is also increased, with greatest risk associated with traditional risk factors, including older age, smoking, hypertension, diabetes mellitus, hyperlipidemia, and obesity.
Progestin-only contraceptives
Progestin-only contraceptives (POCs) (including the most effective, LARC) present an alternative option for patients who cannot take estrogen. Oral POCs contain norethindrone or norgestrel: they are less popular than COCs because they have more frequent side effects, particularly irregular vaginal bleeding. It is also important to take the progestin-only pill at the same time each day to ensure stability in serum level.
Other progestin contraceptives confer more stable serum levels through different methods of delivery. Depot medroxyprogesterone acetate (DMPA) is administered as an intramuscular or subcutaneous injection every 3 months. Unlike other progestin methods, it suppresses ovulation. As a result, unlike the progesterone-only pill or LNG-IUD, DMPA may cause reversible bone loss: reduction in bone density in healthy women is 5.7% to 7.5% after 2 years of use. History of fragility fracture, known osteoporosis, or strong risk factors for osteoporosis (such as corticosteroid use or diagnosis of RA) are generally considered contraindications to use of DMPA. An additional disadvantage is a delayed return to fertility: it is not recommended for patients who plan pregnancy within the next year.
The single-rod etonogestrel subdermal implant is placed in the inner upper arm and releases hormone over a 3-year period. It may inhibit ovulation initially following insertion, but does not consistently inhibit ovulation throughout the 3 years, although other mechanisms remain intact.
Noncontraceptive benefits of POCs are occasionally the primary reason for use and include decreased menstrual bleeding and amelioration of endometriosis symptoms. Minor side effects are common, including irregular breakthrough bleeding (the most common cause of discontinuation) and weight gain. Unpredictable bleeding is greatest within the first 3 months of use and diminishes significantly with time. The risk for thromboembolism with POCs is clearly lower than for CHCs, but the precise degree of risk is debated and is discussed in detail later.
Emergency Contraception
Emergency contraception to prevent pregnancy after unprotected intercourse is widely available. Options include placement of a copper IUD, prescription-only oral selective progesterone receptor modulators (ulipristal or mifepristone), and nonprescription oral LNG. Rheumatic disease, cardiovascular disease, and thrombophilia are not contraindications to the use of emergency contraception.
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