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Approach to contraception in women with systemic lupus erythematosus

Approach to contraception in women with systemic lupus erythematosus
Literature review current through: Jan 2024.
This topic last updated: Jul 18, 2023.

INTRODUCTION — Family planning is an important clinical consideration in women with systemic lupus erythematosus (SLE), given that the peak incidence of this disorder is in women of reproductive age and that approximately 50 percent of pregnancies in the United States are unintended. Pregnancies in SLE patients during periods of high disease activity (particularly nephritis) or with significant disease-related damage (such as pulmonary hypertension and cardiovascular disease) are associated with high maternal morbidity and mortality and poor fetal outcomes. Furthermore, many of the medications used for the management of SLE and antiphospholipid syndrome (APS), such as mycophenolate mofetil, cyclophosphamide, methotrexate, and warfarin, are contraindicated during pregnancy. (See "Pregnancy in women with systemic lupus erythematosus".)

Contraceptive choice varies for patients with SLE and APS, and depends upon clinical history including the presence or absence of antiphospholipid antibodies (aPL); current disease activity; the patient's age, reproductive history, and desires; and religious and cultural factors.

Recommendations for individualizing the contraceptive decision for patients with SLE and/or APS will be discussed here. Rheumatologists and gynecologists each have specific expertise to contribute toward making the final decision with the patient. An overview of contraception as well as more detailed information regarding the various contraceptive methods can be found in separate topics. (See "Contraception: Counseling and selection" and "Intrauterine contraception: Candidates and device selection" and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use" and "Combined estrogen-progestin contraception: Side effects and health concerns" and "Contraception: Progestin-only pills (POPs)" and "Contraception: Etonogestrel implant" and "Contraception: Transdermal contraceptive patches".)

UNDERUTILIZATION — Despite the risks of unintended pregnancy in the setting of systemic lupus erythematosus (SLE), many women with SLE do not adequately use effective birth control. Survey studies examining the likelihood of unintended pregnancy and the use of effective contraception in reproductive-aged sexually active women with SLE have found that almost one-quarter have inconsistent or no use of contraception [1,2]. Women on teratogenic medications were no more likely than others to use effective contraception. An administrative database study indicates low rates of prescription contraception use by patients with rheumatic disease including SLE; in one institution, 32.1 percent of patients used prescription contraception and only 7.9 percent used highly effective methods despite a 70 percent rate of teratogenic medication use (figure 1) [3].

The inconsistent use of contraception in patients with SLE may partly reflect limited screening, counseling, and gynecology referral by rheumatology clinicians. One prospective study of 178 adolescents from a rheumatology practice evaluated clinician performance of behavioral screening, including screening for sexual activity, and demonstrated low rates of screening by rheumatologists (12.4 percent) [4]. The major reported barrier to addressing contraception was limited time during the clinic visit. Other factors identified by rheumatologists included logistical issues, their discomfort with the subject area, and ambivalence about their role in behavior screening. Other studies have found that approximately one-half of adult reproductive-aged women with SLE do not receive documented contraceptive counseling [5,6]. Additionally, older age, depressive symptoms, more active disease, and being from a White population have been associated with reduced rates of contraceptive counseling [7]. Racial disparities in family planning also likely play a role in contraceptive use patterns. An analysis of Medicaid claims data found that Asian American and Hispanic women had lower odds of contraception dispensing and Black women had lower odds of highly effective contraception use [8].

Use of pregnancy intention screening tools or structured documentation fields within the electronic medical record has been suggested to guide reproductive health discussions about contraception, but adoption by clinicians has been low [9]. For example, contraception documentation within the Rheumatology Informatics System for Effectiveness (RISE) registry was 7.9 percent for women of childbearing age with SLE and was no higher for women on teratogenic medications compared with women not taking such medications [10].

Additional factors likely contribute to underutilization of contraception among women with SLE. Clinicians may advise against estrogen-containing contraceptives due to concerns regarding risk of disease flare or thrombosis and may be unfamiliar with alternative long-acting reversible contraceptive methods that do not contain estrogen. Estrogen-progestin contraceptives continue to be underused in this population in spite of good data that these methods are safe in SLE patients with stable, mild disease and without the presence of antiphospholipid antibodies (aPL).

Awareness of contraception and reproductive health among women with SLE is increasing. Both the European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism) and the American College of Rheumatology (ACR) have published guidance documents regarding selection of safe and effective contraception for women with SLE [11,12].

In addition, in the United States, the US Food and Drug Administration (FDA) mandates appropriate patient education regarding necessity of contraceptive use when initiating therapy with mycophenolate mofetil [13].

FACTORS TO CONSIDER — The choice of the optimal method of birth control for women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) depends upon multiple factors, including patient values and preferences, efficacy and side effects of contraceptive methods, underlying disease activity, thromboembolic risk, and medication interactions. The rheumatologist and gynecologist both contribute to identifying these factors and ultimately making recommendations to the patient.

Efficacy of contraception — The effectiveness of a contraceptive method is expressed as both theoretical or "perfect use" and actual or "typical use," with the actual effectiveness typically being lower due to inconsistent or incorrect use. Effectiveness should be taken into account when choosing a contraceptive method. Long-acting reversible contraceptives (LARCs), which traditionally include intrauterine devices (IUDs) and progesterone implants, are considered the most effective form of contraception (figure 1). By contrast, barrier methods, which include condoms, diaphragms, and spermicides, have low rates of typical use effectiveness. (See "Contraception: Counseling and selection", section on 'Discuss method characteristics'.)

Disease activity — The choice of contraceptive agent should take into account the underlying disease activity and severity of SLE. As an example, SLE patients with high disease activity are advised against the use of estrogen-containing contraceptives given the limited data on thromboembolic risk and risk of disease flare in patients with active disease. (See 'Risk of lupus flare' below and "Overview of the management and prognosis of systemic lupus erythematosus in adults", section on 'Issues with specific therapies'.)

Comorbidities — Comorbidities such as hypertension and migraine with aura should also be considered when choosing a contraceptive agent. In a cohort study that included premenopausal women with SLE, 55 percent of women using estrogen-containing contraceptives had a contraindication to combined hormonal contraceptives [14]. (See "Contraception: Counseling and selection", section on 'Document medical history/potential contraindications'.)

Thromboembolic risk — A number of comorbidities associated with increased risk of thromboembolism are more prevalent in SLE patients, including a history of thrombosis or the presence of antiphospholipid antibodies (aPLs; eg, lupus anticoagulant [LA], immunoglobulin G [IgG] and IgM anticardiolipin [aCL] antibodies, and IgG and IgM anti-beta2-glycoprotein I [anti-beta-2GPI]), uncontrolled hypertension or other cardiac risk factors, known cardiovascular disease, migraine with aura, stroke, and complicated or longstanding diabetes. Thus, a careful assessment of thromboembolic risk is necessary to exclude patients at greatest risk when using some of the hormonal contraceptive methods. (See "Diagnosis of antiphospholipid syndrome" and "Combined estrogen-progestin contraception: Side effects and health concerns".)

Medication interactions — Interactions of hormonal contraceptives with other medications used to treat SLE may lead to decreased efficacy of either the contraceptive or the alternative medication. Medications commonly used in SLE that have potential interactions with estrogen-containing contraceptives include warfarin, mycophenolate, corticosteroids, cyclosporine, and anticonvulsants (table 1) [15,16]. Since SLE patients are often on multiple medications, checking for pharmacologic interactions before advising hormonal contraception is recommended.

CHOOSING A METHOD OF CONTRACEPTION — Our approach to helping a woman with systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS) decide upon a contraceptive method includes counseling on the necessity for planning when it will be ideal to be pregnant, and explaining the increased risks associated with an unintended pregnancy. Family planning takes into account achieving good disease control prior to pregnancy, and using the most effective method of contraception particularly for those with severe disease-related damage, high levels of disease activity, or use of teratogenic medications. We also provide patients with guidance regarding effective and safe methods for the given clinical situation, while taking into account their specific values and preferences. Any risk associated with a contraceptive method must be weighed against the risk of unintended pregnancy for that particular patient. (See "Pregnancy in women with systemic lupus erythematosus", section on 'Preconception evaluation'.)

Our overall approach — When helping a woman with SLE and APS initiate contraception, we suggest the following (table 2) [17]:

For patients who want to use a long-acting reversible contraceptive (LARC), the levonorgestrel (LNg)-containing intrauterine device (IUD) is a safe and effective option for most patients with SLE and/or positive antiphospholipid antibodies (aPLs). The risk of pelvic infection in patients on immunosuppressive medication is unknown, but an increased risk of infection has not been reported in other immunocompromised patient groups. (See 'Intrauterine devices' below.)

While other LARCs may also be safe and effective for SLE and patients with aPLs, we prefer the LNg-IUD because it has not been shown to increase thrombosis risk or have a detectable impact on bone density. By contrast, the effect of the etonogestrel-releasing contraceptive implant on bone density and thrombosis risk is uncertain. Another advantage of the LNg-IUD is that it reduces menstrual blood loss, which many women consider a benefit and is particularly helpful for patients on anticoagulation. The copper IUD, on the other hand, may worsen menstrual cramps and may cause heavier bleeding when compared with the LNg-IUD, although most women do not discontinue this IUD because of bleeding. (See 'Long-acting reversible contraception' below and 'Thromboembolic risk and progestin' below.)

For patients who want to use an oral hormonal contraceptive, the estrogen-progestin contraceptives with ethinyl estradiol doses of 30 mcg or lower (dose used in the clinical trials) may be used in patients with stable low disease activity and documented negative aPLs. We suggest avoiding the transdermal patch as an alternative contraceptive due to the potentially higher estrogen exposure. The vaginal ring is suggested to provide serum estrogen levels comparable to those seen with estrogen-progestin pills, but there are no data on its use in SLE patients. (See 'Thromboembolic risk and estrogen' below.)

The data are limited on the safety of estrogen-containing contraceptives in women with high disease activity; thus, alternative methods such as progestin-only contraceptives and IUDs are preferable in these patients. (See 'Progestin-only contraceptives' below.)

The use of estrogen-progestin contraceptives are contraindicated in women with aPLs with or without SLE, due to the increased risk for thrombosis. The safety of estrogen-progestin contraceptive use in patients with fluctuating aPL titers or positive aPL on anticoagulation is unknown. Given this, we do not recommend estrogen-progestin contraceptives in these patient groups. Similarly, we discourage the use of estrogen-progestin hormonal contraceptives in patients with prolonged immobility, such as in the postoperative setting. (See 'Estrogen-progestin contraceptives' below.)

For SLE patients who do not want to use an IUD and have high disease activity, a positive aPL, or other contraindications to the use of estrogen, we suggest progestin-only contraceptives such as the progestin-only pill. While the etonogestrel implant is likely to be low-risk and effective as well, it is a third-generation progestin and has not been well studied in these patients or in other patients with prothrombotic risk factors. Depomedroxyprogesterone acetate (DMPA), an injectable progestin-only contraceptive, is not a good long-term option for patients with osteoporosis or long-term glucocorticoid use due to risk of decreased bone density. Importantly, progestin-only contraceptives have higher rates of discontinuation due to unscheduled bleeding, so women will need to be counseled about this ahead of time. (See 'Progestin-only contraceptives' below.)

Women taking medications that increase serum potassium or alter renal function (such as angiotensin-converting enzyme [ACE] inhibitors), or women with renal insufficiency, require careful monitoring of serum potassium if taking drospirenone-containing oral contraceptives. (See 'Estrogen-progestin contraceptives' below.)

Pericoital and barrier methods are the least effective contraceptive method, and should be reserved for situations when hormone-containing contraceptives or IUDs must be avoided or are unacceptable to the woman (figure 1). (See 'Barrier and pericoital contraceptives' below.)

The above recommendations differ from those of Center for Disease Control (CDC) and Prevention medical eligibility criteria (MEC) for contraceptive use in regard to the use of progestin-based contraceptives (eg, LNg-IUD, progestin-only pill, and DMPA) in patients with SLE and positive aPLs. The CDC categorizes the use of all progestin-based contraceptives in SLE patients with positive aPLs as a "3," which is meant to indicate that the theoretical or proven risks usually outweigh the advantages (more information can be found in the Centers for Disease Control and Prevention United States Medical Eligibility Criteria for Contraceptive Use). By comparison, the authors feel that in some scenarios the progestin-based contraceptives may be used based upon the advantages outlined above, the known risks of unintended pregnancy in certain SLE patients, and the fact that the increased thromboembolic risk of progestins is largely theoretical with limited clinical data, which is discussed further in detail below. (See 'Thromboembolic risk and progestin' below.)

Contraceptive options — Reversible contraception options for women include IUDs, contraceptive implants, progestin-only or estrogen-progestin hormonal contraceptives, pericoital methods, and barrier methods. We present a summary of the salient points for several types of contraceptive methods as related specifically to SLE and APS, including those patients with positive aPLs. We discuss family planning desires and contraceptive needs with all women of reproductive potential.

Long-acting reversible contraception — LARCs such as IUDs and contraceptive implants are considered the most effective form of contraception and are generally safe for women with SLE and APS. LARCs should be discussed with all women seeking contraception who are appropriate candidates for these methods. This is consistent with guidelines of the CDC which suggest that an unintended pregnancy in women with SLE may pose an unacceptable health risk, and favor long-acting, highly effective contraceptive methods over behavior-based and barrier methods [18]. (See "Intrauterine contraception: Candidates and device selection" and "Contraception: Etonogestrel implant" and "Contraception: Issues specific to adolescents", section on 'Long-acting reversible methods'.)

Intrauterine devices — IUDs are safe and effective for most women with SLE and aPLs, including adolescents and nulliparous women [18]. IUDs available in the United States release either copper or the synthetic progestin LNg. The primary mechanisms of action of both devices prevent fertilization. The copper-containing IUD may be used for at least 10 years and may be associated with heavier menses and dysmenorrhea.

We prefer the LNg-containing IUD, which may remain in place for at least six to eight years and significantly reduces dysmenorrhea and menstrual bleeding [19]. Complete amenorrhea occurs in up to 50 percent of patients by 24 months [20], which is a significant benefit for patients who require long-term anticoagulation. Our preference for the use of LNg-containing IUD in women with aPLs differs from that of the CDC, which favors the copper IUD. We feel that benefit of reduced menstrual bleeding associated with the LNg-containing IUD in women who are frequently anticoagulated outweighs the potential increased risk of thrombosis associated with this exposure to progestin, particularly given that there are insufficient data on this point. (See "Intrauterine contraception: Candidates and device selection", section on 'Anticoagulation/bleeding diathesis' and 'Thromboembolic risk and progestin' below and "Intrauterine contraception: Management of side effects and complications".)

While data on IUD use in patients treated with immunosuppressive medications are limited, no increased infection risk is found in immunocompromised HIV-infected women [21] or in women on immunosuppressive therapy following solid organ transplant [22]. Guidelines developed by professional organizations do not consider immunosuppressive therapy a contraindication to IUD use [18], and most experts agree that the minimal risk of infection with IUD use is outweighed by the risks associated with unintended pregnancy in women with active inflammatory disease on potentially teratogenic medications [23]. Several studies have reported successful use of the copper IUD in SLE patient groups [24-26]. Although numbers are small, there were no reported pelvic infections. A single case report has described failure of the copper IUD in two renal transplant patients on immunosuppressive therapies [27].

Thrombocytopenia does not preclude placement of an IUD. Caution is advised, however, if patients have significant thrombocytopenia that would preclude minor surgical procedures. In such cases, placement of any IUD should be avoided until the count improves in order to minimize risk of bleeding during the procedure.

Contraceptive implants — Contraceptive implants are an alternative option to IUDs for women with SLE or aPLs who want an effective LARC and cannot take estrogen-containing preparations. The implant most commonly used in the United States is a single rod subdermal implant that is placed in the inner upper arm and releases etonogestrel (a third-generation progestin) over a three-year period. An LNg (a second-generation progestin) implant is also available in many countries but not the United States. (See "Contraception: Etonogestrel implant".)

The risk for thromboembolism with progestin-only contraception is low, and is discussed in further detail below; however, third-generation progestins do have a slightly higher risk of venous thromboembolism than do the second-generation progestins (see 'Thromboembolic risk and progestin' below). In addition, safety data on use of the etonogestrel implant in patients with APS are not available. Given the slightly greater risk of venous thrombosis associated with third-generation progestins, and the lack of data for use in aPL-positive patients, we prefer use of the LNg-containing IUD over contraceptive implants in aPL-positive women. Progestin-only contraceptives are not associated with an increased risk of SLE flare. (See 'Risk of lupus flare' below.)

Unscheduled bleeding is a common side effect of contraceptive implants, and is a common cause of discontinuation of this form of contraception. Thus, the patient needs to be well counseled about what to expect. (See "Contraception: Etonogestrel implant", section on 'Counseling points'.)

Hormonal contraception — Hormonal contraception is moderately effective and includes estrogen-progestin preparations (eg, pill, patch, ring) and progestin-only preparations (eg, pill, injection, IUD, implant) (figure 1). (See "Contraception: Counseling and selection", section on 'The shared decision-making process' and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)

Estrogen-progestin contraceptives — Estrogen-progestin contraceptives may be used in SLE patients with stable low disease activity and documented negative aPLs. Avoiding estrogen-progestin contraceptive methods with higher estrogen exposures than those that have been studied in women with SLE is suggested to minimize the risk of thrombosis [25,28]. The data are also limited on the safety of estrogen-containing contraceptives in SLE patients with high disease activity; thus, alternative methods such as the progestin-only pill and IUDs are preferable in such patients. (See 'Intrauterine devices' above and 'Progestin-only contraceptives' below.)

Estrogen-progestin oral contraceptive preparations contain both synthetic estrogen (usually ethinyl estradiol, 20 to 35 mcg) and a progestin, one of multiple 17-alpha ethinyl analogs of 19-nortestosterone. The 19-nortestosterones, also termed second-generation progestins, include norethindrone, LNg, and others (table 3). The third-generation progestins, developed to reduce androgenic side effects, include norgestimate and desogestrel (and its active metabolite etonogestrel). A fourth-generation progestin, drospirenone, is a spironolactone analog with progestational, anti-androgenic, and anti-mineralocorticoid activity. The potential side effects of progestins differ according to their generation, which is pertinent for evaluation of suitability for SLE patients. All progestins can cause irregular bleeding. Second-generation progestins are associated with more androgenic side effects such as acne, hirsutism, and weight gain than are third-generation progestins; however, third-generation agents are associated with a slightly higher risk of venous thrombosis. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Hormone components'.)

Other estrogen-progestin contraceptive hormone administration methods enhance convenience, and include a transdermal patch and an intravaginal ring. The efficacy for these is similar to that of the estrogen-progestin pill, but the overall estrogen exposure appears to be increased with the patch [29]. Thus, we suggest that women with SLE avoid using the transdermal patch.

Thromboembolic risk and estrogen — Serious complications associated with estrogen-progestin hormonal contraceptives are usually vascular in nature, including venous thromboembolism, stroke, and myocardial infarction. The use of estrogen-progestin hormonal contraceptives is contraindicated in women with aPL with or without SLE due to an increased risk of thrombosis. The safety of use in patients with fluctuating aPL titers or positive aPL on anticoagulation is unknown, and thus their use is not recommended. In addition to the absolute and relative contraindications to the use of oral contraceptives for the general population, a number of comorbidities that present concern for increased cardiovascular risk are more prevalent in SLE patients, including prothrombotic factors (generally aPL) or history of thrombosis, uncontrolled hypertension or other cardiac risk factors, known cardiovascular disease, migraine with aura, stroke, and complicated or longstanding diabetes. (See "Combined estrogen-progestin contraception: Side effects and health concerns".)

A reduction in estrogen content in birth control pills has markedly decreased the high thrombosis risk associated with the earliest birth control pills. As described above, differences in the type of progestin used in estrogen-progestin hormonal contraceptives account for some variability in venous thrombosis risk among preparations. Third-generation progestins confer greater venous thrombosis risk than do second-generation progestins due to greater activated protein C resistance, while the lowest risk of venous thromboembolism is found in estrogen-progestin contraceptives containing LNg [30]. Other factors such as genetic or acquired thrombophilia, smoking, age over 35 years, and obesity likewise increase the risk of venous thromboembolism in those taking hormonal contraceptives. (See "Combined estrogen-progestin contraception: Side effects and health concerns".)

aPLs are significant risk factors for thrombosis and pregnancy morbidity in patients with SLE as well as primary APS, and multiple case reports suggest an association of oral contraceptive use with increased risk of thrombosis in aPL-positive patients [31-34]. A large case-control study evaluating oral contraceptives and risk of arterial thrombosis in the general population found an increased risk for both stroke and myocardial infarction in patients using oral contraceptives, which was further increased in the presence of a positive lupus anticoagulant (LA) [35]. The diagnosis of APS is discussed in detail separately, but is generally defined as presence of one clinical and one laboratory criterion. Clinical criteria include thrombosis (arterial, venous, or small vessel thrombosis) and obstetric morbidity (three or more early losses, one or more fetal losses, or delivery prior to 34 weeks due to severe preeclampsia or placental insufficiency). Laboratory criteria include persistent positive LA, moderate-high titer immunoglobulin G (IgG) or IgM anticardiolipin (aCL) antibody , or moderate-high titer IgG or IgM anti-beta2-glycoprotein I (anti-beta-2GPI) antibody. The risk of thrombosis associated with lower titers of aCL or anti-beta-2GPI is controversial. Thus, we generally avoid estrogen-containing contraceptives in the presence of any positive aPLs. (See "Diagnosis of antiphospholipid syndrome".)

SLE patients with stable low-level disease and without aPLs do not appear to be at increased risk for thrombosis when taking oral hormonal contraceptives. The Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) trial randomized 183 lupus patients with inactive or stable-active disease to either oral contraceptive (triphasic ethinyl estradiol 35 mcg / norethindrone 0.5 to 1 mg) or placebo for 12 28-day cycles [28]. The study design specifically excluded high-risk patients with history of thrombosis as well as those with presence of moderate- to high-titer aCL or positive LA in the absence of thrombosis. Although the trial was designed to assess the risk of disease flare, there was no increase in thrombotic complications in the oral contraceptive group versus the placebo group. Some patients in both treatment and placebo groups presumably had low-titer aCLs (not reported). In another trial of SLE patients, treatment with either estrogen-progestin (ethinyl estradiol 30 mcg / LNg 150 mcg/day) or progestin-only (LNg 0.3 mg/day) oral contraceptives resulted in similar low rates of thrombosis, 2 of 54 patients per group [25]. Among the four patients with thrombosis, all were reported to be aPL-positive [25].

Risk of lupus flare — Despite the common, long-held belief that estrogens provoke lupus disease activity, estrogen-progestin hormonal contraceptives are generally a safe form of contraception for stable aPL-negative SLE patients with mild-moderate disease activity.

The randomized trials described above also found no significant increase in risk of flare from combination hormonal contraceptives in well-defined lupus populations with stable disease activity [25,28]. In the SELENA trial, severe flare rates at one year did not differ between treatment and placebo groups (0.084 vs. 0.087, respectively). Mild-moderate flares were also equivalent, and there was no difference in overall combined flare rates. Another trial similarly evaluated the risk of flare associated with the use of estrogen-progestin oral contraceptive compared with a progestin-only oral contraceptive and a copper IUD, and found no significant differences in disease activity among the three groups [25].

Progestin-only contraceptives — Progestin-only contraceptives present an alternative option for SLE patients who cannot take estrogen-containing preparations. This includes patients with active disease and those with positive aPLs, as well as those with other general contraindications. Oral progestin-only contraceptives usually contain norethindrone or norgestrel and have greater rates of side effects when compared with combination pills. (See "Contraception: Progestin-only pills (POPs)".)

The progestin-only contraceptive depomedroxyprogesterone acetate (DMPA) is administered as an intramuscular or subcutaneous injection, is more convenient than the pills, and has improved efficacy due to its suppression of ovulation. (See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

Progestin-only preparations are more likely to cause irregular, "break-through" bleeding, and this is the most common cause of discontinuation, but unpredictable bleeding is greatest within the first three months of use and diminishes significantly with time [36].

DMPA, but not the progesterone-only pill or LNg IUD, may cause reversible bone loss due to inhibition of ovulation. Bone density in healthy women is reduced by 5.7 to 7.5 percent after two years of use [37]. A history of fragility fracture, known osteoporosis, or strong risk factors for osteoporosis (such as corticosteroid use) are generally considered contraindications to use of DMPA. The stability of bone density with use of the etonogestrel subdermal implant is uncertain [38]. An additional disadvantage of DMPA in contrast to the LNg IUD and subdermal system is that there may be a delayed return to fertility. Thus, it is not recommended for patients who plan pregnancy within the next year. (See "Contraception: Etonogestrel implant", section on 'Counseling points'.)

Thromboembolic risk and progestin — The risk for thromboembolism with progestin-only contraception is very low, and they are generally safe for most SLE patients with or without positive aPLs. A meta-analysis including eight observational studies, two of which were in populations at elevated risk for thrombosis, found that the use of progestin-only contraceptive methods was not associated with any increased risk of thromboembolism compared with non-users [39]. A subgroup analysis confirmed this finding for progestin-only pills and LNg IUDs, but the relative risk was significantly elevated for injectable progestins such as DMPA. However, the significance of this finding is uncertain due to the low number of DMPA users. There are no good data on the etonogestrel subdermal implant in SLE or APS patients, although thrombosis risk might theoretically be slightly higher than with levonorgestrel-containing preparations due to the inclusion of a third-generation progestin.

Guidelines from national and international organizations suggest that progestin-only methods are generally safe for use, with the benefits outweighing the risks [40-42]. Discrepancies in recommendations have been a source of some confusion among clinicians and patients, as progestin-containing product package inserts often list a history of venous thromboembolism as a contraindication to use.

Specific recommendations for progestin-only contraceptives for rheumatologic conditions are listed in the medical eligibility for contraceptive use (MECC) guidelines of the Centers for Disease Control and Prevention (CDC) [18]. Progestin-only contraceptives in woman with SLE and positive (or unknown) aPL are categorized as a "3" (where the risk of use may exceed the benefits). By contrast, the American College of Obstetricians and Gynecologists (ACOG) guidelines for contraceptive use in women with chronic medical conditions specifically suggest that progestin-only contraceptives may be safer alternatives than estrogen-progestin contraceptives for women with SLE with aPL, active nephritis, and vascular disease [42]. (See "Contraception: Counseling and selection", section on 'Special populations'.)

Risk of lupus flare — Progestin-only contraceptives have not been observed to increase risk of lupus flare [25,43-45]. The oral pregnane progestins chlormadinone acetate and cyproterone acetate (anti-androgenic, anti-estrogenic weak progestins unavailable at present in the United States) have been studied as potential contraceptive alternatives for SLE patients in Europe. In one study, there was a significant decrease in disease activity as well as a low incidence of thrombosis (3 out of 187) in SLE patients treated for a mean period of 46 months [46].

Barrier and pericoital contraceptives — Barrier (female and male condoms) and pericoital (diaphragm, cervical cap, and spermicidal sponge) methods of contraception have low rates of typical use effectiveness (figure 1). Since highly effective methods are preferred to avoid unintended pregnancy, barrier methods are not appropriate first-line methods. However, reliance on barrier methods may be necessary during periods of acute illness, including acute thrombosis, when other methods may be contraindicated, or as an interim method until more effective methods can be safely instituted. An additional consideration is that condoms are effective for reducing the risk of transmission of sexually transmitted diseases. Also, they may be used in combination with oral hormonal contraceptives as dual contraception when patients are on mycophenolate-containing medications that may interfere with efficacy of hormonal contraception. (See "Pericoital (on demand) contraception: Diaphragm, cervical cap, spermicides, and sponge" and "Contraception: Counseling and selection", section on 'Discuss method characteristics'.)

Emergency contraception — Emergency contraception is an option for all patients with SLE, including those with positive antiphospholipid antibodies (aPLs). Patients should be informed about the use and nonprescription availability of emergency contraception. (See "Emergency contraception".)

RESOURCES FOR PATIENTS AND CLINICIANS

bedsider.org: A free website developed by the National Campaign to Prevent Teen and Unplanned Pregnancy, a private nonprofit group

The Family Planning National Training Center: The website for federally funded contraceptive resources developed with the support of the Office of Population Affairs

Center for Young Women's Health: A free website run by Boston Children's Hospital that addresses reproductive health needs of teens and young adults

Beyond the Pill: A free website run by the University of California San Francisco

SexualityandU.ca: An educational site run by the Society of Obstetricians and Gynaecologists of Canada that includes descriptions of various methods and a tool to help with selection of birth control

Planned Parenthood: A nonprofit organization dedicated to reproductive health with resources for patients and clinicians

ACOG Contraceptive FAQs: American College of Obstetricians and Gynecologists addresses frequently asked questions (FAQs) about contraception

ACOG LARC Program: American College of Obstetricians and Gynecologists Long-Acting Reversible Contraception Program

United States Medical Eligibility Criteria for Contraceptive Use

United States Selected Practice Recommendations for Contraceptive Use

World Health Organization Medical Eligibility Criteria for Contraceptive Use

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Systemic lupus erythematosus".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Lupus and pregnancy (The Basics)")

Beyond the Basics topic (see "Patient education: Systemic lupus erythematosus and pregnancy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Contraception selection – The choice of the optimal method of birth control for women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS) depends upon multiple factors, including patient values and preferences, efficacy and side effects of contraceptive methods, underlying disease activity, other comorbidities, thromboembolic risk, and medication interactions. In addition, any risk associated with a contraceptive method must be weighed against the risk of unintended pregnancy for that particular patient. (See 'Factors to consider' above.)

Considerations for specific methods – When helping a woman with SLE and APS initiate contraception, we suggest the following (table 2) (see 'Our overall approach' above):

People who prefer LARC – For patients who want to use a long-acting reversible contraceptive (LARC), we suggest the levonorgestrel (LNg)-containing intrauterine device (IUD) over other LARC options (Grade 2C). The LNg IUD is a safe and effective option for most patients with SLE and/or positive antiphospholipid antibodies (aPLs). Moreover, it has not been shown to increase thrombosis risk or worsen bone density, and it may reduce menstrual blood loss. (See 'Intrauterine devices' above and 'Long-acting reversible contraception' above and 'Thromboembolic risk and progestin' above.)

People who prefer oral hormonal contraception – For patients with stable low disease activity and documented negative aPLs who want to use an oral hormonal contraceptive, we suggest the estrogen-progestin contraceptives (Grade 2C). We suggest avoiding the transdermal patch and estrogen-progestin contraceptive methods with higher estrogen exposures to minimize thromboembolic and cardiovascular risk (Grade 2C). The vaginal ring is suggested to provide serum estrogen levels comparable to those seen with estrogen-progestin pills, but there are no data on its use in SLE patients. (See 'Thromboembolic risk and estrogen' above.)

For patients with high disease activity, apL antibodies, or prolonged immobility (eg, following surgery), we suggest progestin-only contraceptives and IUDs (Grade 2C). Importantly, progestin-only contraceptives have higher rates of discontinuation due to unscheduled bleeding, so women will need to be counseled about this ahead of time. (See 'Progestin-only contraceptives' above.)

We suggest avoiding estrogen-progestin contraceptives in patients with an increased risk for thrombosis.

Women taking medications that increase serum potassium or alter kidney function (such as angiotensin-converting enzyme [ACE] inhibitors), or women with renal insufficiency, require careful monitoring of serum potassium if taking drospirenone-containing oral contraceptives. (See 'Estrogen-progestin contraceptives' above.)

Barrier method – Barrier methods are the least effective contraceptive method and should be reserved for situations when hormone-containing contraceptives or IUDs must be avoided or are unacceptable to the woman. (See 'Barrier and pericoital contraceptives' above.)

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References

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