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Contraception Corner

Contraception in the Lupus Patient

Thomas E. Nolan, MD, MBA

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder that primarily affects reproductive-aged women and often presents after puberty. ¹ With the exception of barrier methods, prescribing safe and appropriate contraception in women with SLE often presents a challenge to the practitioner involved in female health care as exogenous estrogen is believed to cause flare-ups in SLE activity as well as exacerbate hypercoagulability. ² This is especially a concern and relative contraindication in those patients who also suffer from antiphospholipid antibody syndrome (APS).

SAFETY OF ESTROGEN IN LUPUS ERYTHEMATOSUS NATIONAL ASSESSMENT TRIAL

The Safety of Estrogen in Lupus Erythematosus National Assessment (SELENA) trial, funded by the National Institutes of Health, was announced in 1996 as the first randomized, double-blind placebo-controlled multi-center clinical trial to study the safety of exogenous use of estrogen in women with SLE. The purpose of this study was to determine the effects of both oral contraceptive (OC) use and estrogen use in hormone replacement therapy (HRT) on SLE disease activity and severity. ³

This study, however, was recently halted due to lack of patient enrollment in the OC arm of the study as well as the July findings of the Women’s Health Initiative concerning use of HRT. In a personal communication with Lisa Sigler, research manager to Michelle M. Petri, MD, director of the Johns Hopkins Lupus Center, the patients enrolled in both the HRT and OC arms of the trial are still following up with this research facility, and this center anticipates publication of findings by the end of 2003.

ORAL CONTRACEPTIVES

While there is no definite proof that combination OCs exacerbate SLE, it does appear that some women with SLE may be more likely to suffer adverse events from use. In addition, there is concern that OC use can increase the risk of, and induce thromboses in women with SLE who also suffer from APS. ⁴ It does appear best to avoid combination OCs in SLE patients with high levels of antiphospholipid antibodies, and it is contraindicated for use in patients with active lupus nephritis. ⁵ However, recent data suggest that OC use may be safe for some groups of women with SLE.

Lakasing and Khamashta conducted a questionnaire-based study to determine contraceptive practices of women with SLE and/or APS to establish incidence of complications related to use of different types of contraceptives. This study comprised of 86 women with SLE and/or APS. ⁶

One of the 19 (5%) women with SLE who used OCs at the time of diagnosis reported a severe lupus flare; seven of 32 (22%) of the women with APS using OCs suffered from thromboses during OC use; and there were no reported problems specific to patients with SLE and/or APS who reported using other forms of contraception. ⁶ Based on these results, the authors concluded that there was no clinically significant association between OC use and lupus flare. However, there was a higher incidence of thromboses in women with APS who used OCs containing second or third generation progestogens, which suggests that women with this condition should be advised against OC use. ⁶

In 1999, Rampone et al conducted a study to assess the relationship between OC use in women with SLE. ⁷ In this study, 20 reproductive-aged women with SLE who specifically suffered from cutaneous manifestations were studied for 1 year of use. ⁷ All participants in this group were prescribed gestodene at a dose of 0.075 mg and etinilestrdiol at a dose of 0.02 mg per day. These patients were compared with a similar control group of women with SLE not using OCs. ⁷

In the results, 5 out of the 20 patients were required to stop OC use 4 or 5 months into the study; this discontinuation was due to SLE relapse. The remaining 15 patients did not suffer from relapse of SLE. Based on these findings, the authors concluded that use of newer estrogen-protestogen OCs does not constantly cause exacerbation of SLE in women. ⁷ However, the authors do recommend strict follow-up and management of all patients with SLE using hormonal contraceptives. ⁷

PROGESTOGENS

In addition to studies on combination OC use in patients with SLE, research has also been conducted to determine the safety and efficacy of progestogen-only use in women with SLE as a safer alternative to combination OCs. While progestogen-only contraception can cause side-effects in patients with SLE, it does not appear to activate the condition. ⁸ In its July 2000 practice bulletin, The American College of Obstetricians and Gynecologists recommends use of injectable forms of contraception or implants as safer alternatives to combination OCs in women with one or more conditions such as lupus, sickle cell anemia, migraine headaches, and hypertension or diabetes with vascular disease, or older than age 35 years. ⁹

Mintz et al tested the effectiveness and tolerance of progestogens as an alternative to combination OC use for women with SLE. ¹⁰ In this study, 10 patients with SLE were administered 200 mg intramuscular norethisterone enanthate, and 15 patients with SLE received 0.03 mg/day of oral levonorgestrel. Both groups were compared with a control group of 18 patients. ¹⁰ In the norethisterone enanthate group, 4 episodes of active SLE occurred in 48 patient-months; in the levonorgestrel group, six episodes of active SLE occurred in 122 patient-months; and 9 episodes of active disease occurred in the control group in 298 patient-months. ¹⁰ There was a discontinuation of medication in 30% of patients due to intermenstrual bleeding, and no pregnancies occurred in any of the groups studied. ¹⁰ These results, therefore, suggest that progestogen use in patients with SLE may be a safe contraception method for some patients with SLE.

In addition to the above mentioned progestogens, a long-acting progestogen such as depot medroxyprogesterone acetate (DMPA) also may provide a safe alternative to estrogen-containing contraceptives for women with SLE. ¹¹ Also, chlormadinone acetate (a 17-OH progesterone derivative) has also proved safe and effective for use in women with SLE as it has shown no metabolic or vascular side effects in these patients. ¹²

INTRAUTERINE DEVICES

In addition to barrier methods, women with SLE who are not severely immunocompromised may safely use intrauterine devices (IUDs) as a nonhormonal form of contraception. ²

Julkunen et al performed a cross-sectional study of real contraceptive practices in a group of reproductive-aged Finnish women with SLE. ¹³ Part of this study assessed the side effects of both OC and IUD use. The risk of deep venous thrombosis of patients using estrogen-containing OCs was slightly increased (relative risk 2.3, 95% confidence interval 0.5 to 10.3). ¹³ Twenty-five (78%) of the 32 patients who had used progestogen-only contraceptives discontinued use due to side effects from the medication; however, no major bleeding or pelvic infection occurred in any patients who used IUDs. ¹³

CONCLUSION

Women with SLE should be carefully evaluated and assessed before administration of any exogenous hormones containing estrogen. To avoid hypercoagulability, particular care should be taken prior to prescribing any estrogen therapy to SLE patients who also suffer from APS, and use of combination OCs is contraindicated in patients with active lupus nephritis. Recent studies have shown safety and efficacy of progestogen-only contraceptives in SLE patients, and the use of an IUD has also been proved safe for use in SLE patients who are not severely immunocompromised. Regardless of form or regimen, all SLE patients receiving any hormonal contraceptive therapy should be carefully followed and monitored for any signs of complications or flares.

REFERENCES

1. Petri M. Systemic Lupus Erythematosus: Pathogenesis, Diagnosis, and Treatment. The Female Patient. 2003; 28(3):25-28;31.
2. Petri M. Pregnancy in the Lupus Patient. The Female Patient. 2003;28 (3):12-15.
3. National Institute on Arthritis and Musculoskeletal and Skin Diseases. NIAMS Launches Two Research Initiatives in Systemic Lupus Erythematosus. Available at: http://www.nia ms.nih.gov/ne/press/1996/01_15.htm.
4. Lockshin M. Lupus in the Female Patient. The Female Patient. 2000;9 (25):36-47.
5. Julkunen H. Pregnancy and lupus nephritis. Scand J Urol Nephrol. 2001; 35(4):319-327.
6. Lakasing L, Khamashta M. Contraceptive practices in women with systemic lupus erythematosus and/or antiphospholipid syndrome: what advice should we give them? J Fam Reprod Health Care. 2001;27(1)7-12.
7. Rampone A, Rampone B, Tirabasso S, et al. Contraception with the latest estroprogestagens in women suffering from systemic lupus erythematosus. Minerva Ginecol. 2001;53(1 Suppl 1):75-77.
8. Julkunen HA. Oral contraceptives in systemic lupus erythematosus: side-effects and influence on the activity of SLE. Scand J Rheumatol. 1991;20 (6):427-433.
9. Kaunitz AM. ACOG Practice Bulletin. The use of hormonal contraception in women with coexisting medical conditions. Number 18, July 2000. Int J Gynaecol Obstet. 2001;75(1):93-106.
10. Mintz G, Gutierrez G, Deleze M, Rodriguez E. Contraception with progestagens in systemic lupus erythematosus. Contraception. 1984;30(1): 29-38.
11. Frederiksen MC. Depot medroxyprogesterone acetate contraception in women with medical problems. J. Reprod Med. 1996;41(5 Suppl): 414-418.
12. Jungers P, Liote F, Dehaine V, et al. Hormonal contraception and lupus. Ann M ed Interne (Paris). 1990;141 (3):253-256.
13. Julkunen HA, Kaaja R, Friman C. Contraceptive practice in women with systemic lupus erythematosus. Br J Rheumatol. 1993;32(3):227-230.

About ARHP
ARHP is a nonprofit, national medical organization that has been educating front line providers and their patients since 1963. The organization and members are dedicated to educating physicians and health care providers, and the public about important reproductive health issues including contraception, sexually transmitted diseases, menopause, abortion, sexuality, and infertility. ARHP contact information: 2401 Pennsylvania Ave, N.W., Suite 350, Washington DC 20037-1718; ph: (202) 466-3825; fax: (202) 466-3826; e-mail: arhp@arhp.org; Web: www.arhp.org.

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