1. A PPROACH TO CONTRACEPTION IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS Dr Movahed

2. FACTORS TO CONSIDER The choice of the optimal method of birth control for women with SLE and/or APS depends upon multiple factors:  patient values and preferences  efficacy and side effects of contraceptive methods  underlying disease activity  thromboembolic risk  medication interactions In addition, any risk associated with a contraceptive method must be weighed against the risk of unplanned pregnancy for that particular patient.

3. CHOOSING A METHOD OF CONTRACEPTION Reversible contraception options for women:  Barrier methods  IUDs  Contraceptive implants  Progestin-only  Estrogen-progestin hormonal contraceptives

4. L ONG - 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.

5. I NTRAUTERINE DEVICES IUDs are safe and effective for most women with SLE and aPLs, including adolescents and nulliparous women. IUDs available in the United States release either copper or the synthetic progestin LNg. The copper-containing IUD may be used for at least 10 years and may be associated with heavier menses and dysmenorrhea. The LNg-containing IUD which may remain in place for at least three to five years and significantly reduces dysmenorrhea and menstrual bleeding. Complete amenorrhea occurs in up to 50 percent of patients by 24 months, which is a significant benefit for patients who require long-term anticoagulation.

6. I NTRAUTERINE DEVICES While data on IUD use in patients treated with immunosuppressive medications are limited, no increased infection risk is found in HIV-infected women. Guidelines developed by professional organizations do not consider immunosuppressive therapy a contraindication to IUD use. 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. Thrombophilia 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.

7. C ONTRACEPTIVE 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. A LNg (a second-generation progestin) implant is also available. The risk for thromboembolism with progestin-only contraception is low, third-generation progestins do have a slightly higher risk of venous thromboembolism than do the second-generation progestins.

8. C ONTRACEPTIVE IMPLANTS In addition, safety data on use of the etonogestrel implant in patients with APS are not available.etonogestrel implant 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.

9. H ORMONAL CONTRACEPTION Hormonal contraception includes:  Estrogen-progestin preparations(eg, pill, patch, ring)  Progestin-only preparations (eg, pill, injection, IUD, implant).

10. E STROGEN - PROGESTIN CONTRACEPTIVES Estrogen-progestin contraceptives may be used in SLE patients with stable low disease activity and documented negative aPLs. 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.

11. T HROMBOEMBOLIC RISK AND ESTROGEN Serious complications 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 their use is not recommended. SLE patients without aPLs do not appear to be at increased risk for thrombosis when taking oral hormonal contraceptives.

12. R ISK 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. A clinical trial 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

13. P ROGESTIN - 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. DMPA is more convenient than the pills, and has improved efficacy due to its suppression of ovulation. 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

14. P ROGESTIN - ONLY CONTRACEPTIVES Also, DMPA, may cause reversible bone loss due to inhibition of ovulation. 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. 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.

15. T HROMBOEMBOLIC 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. GuidelinesGuidelines of the CDC: 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 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

16. R ISK OF LUPUS FLARE Progestin-only contraceptives have not been observed to increase risk of lupus flare.

17. B ARRIER METHODS Barrier methods of contraception, which include condoms, diaphragms, and spermicides, have low rates of typical use effectiveness. 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.

18. E MERGENCY CONTRACEPTION Emergency contraception is an option for all patients with SLE, including those with positive antiphospholipid antibodies (aPLs).

19. SUMMARY AND RECOMMENDATIONS

20. F OR PATIENTS WHO WANT TO USE A LONG - ACTING REVERSIBLE CONTRACEPTIVE The levonorgestrel (LNg)-containing intrauterine device (IUD) is a safe and effective option for most patients with SLE and/or positive antiphospholipid antibodies (aPLs).

21. F OR PATIENTS WHO WANT TO USE AN ORAL HORMONAL CONTRACEPTIVE The OCP may be used in patients with stable low disease activity and documented negative aPLs. In women with high disease activity; alternative methods such as progestin-only contraceptives and IUDs are preferable. The use of OCP are contraindicated in women with aPLs with or without SLE, due to the increased risk for thrombosis. The safety of OCP use in patients with fluctuating aPL titers or positive aPL on anticoagulation is unknown and is not recommended.

22. F OR SLE PATIENTS WHO DO NOT WANT TO USE AN IUD AND HAVE HIGH DISEASE ACTIVITY, A POSITIVE A PL We suggest progestin-only contraceptives such as the progestin-only pill. Barrier methods are the least effective contraceptive method, and should be reserved for situations when hormone-containing contraceptives or IUDs must be avoided.

23. R HEUMATOID ARTHRITIS AND CONTRACEPTION The data on the effect of oral contraceptives on RA are conflicting:  A case-control study that reviewed the records of 229 women with RA and 458 controls reported no association between RA and the use of oral contraceptives.  Two other reports noted a decreased risk of RA among current users of oral contraceptives, as well as a lower risk among women who had used oral contraceptives in the past.  The Nurses’ Health Study found that the risk of RA was not altered by a history of oral contraceptive use but reported that a modest protective effect of current users could not be excluded.

24. R HEUMATOID ARTHRITIS AND CONTRACEPTION In summary, data do not support the concept that oral contraceptives protect against the development of RA, at least among women who have used these medications in the past. The use of oral contraceptives appears neither to worsen nor to improve disease activity.