TABLE 1.
List of studies on the risk of disease onset or flares in patients with systemic lupus erythematosus using oral contraceptives.
| Study design | Study population | Oral contraceptives, dose | Main findings | References |
| SLE Flares | ||||
| Case report | 23-year-old female | COC, 3 mg norethisterone + 50 μg ethinyl estradiol | Flare (high fever, arthritis, malar rash) in 1 week | (115) |
| Case report | Two cases | POC, Mestranol 100 μg POC, Mestranol 80 μg |
Flare (arthritis) in 10 days Flare (skin rash) in 3 months |
(116) |
| Retrospective study | 26 Lupus nephritis | COC, 50 μg (14 patients) and 30 μg (7 patients) ethinyl estradiol POC (11 patients) |
- Incidence of flare: 43% in COC groups within 3 months - No flare in POC group |
(117) |
| Case report | 16-year-old female | 30 μg ethinyl estradiol + 150 μg levonorgestrel | Pulmonary hypertension in 7 months later | (118) |
| Retrospective study | 85 SLE | COC (31 patients), 30 μg ethinyl estradiol + 150 μg levonorgestrel/75 μg gestodene POC (32 patients) Other unspecified |
- Incidence of flare: 4 (13%) during the first 6 months - Incidence of flare was similar as in patients not using OCPs |
(119) |
| Retrospective questionnaire study | 55 SLE | OCP unspecified | Incidence of flare: 7 (13%) reported an exacerbation of disease activity, mostly musculoskeletal system | (120) |
| RCT, single blind, non-placebo, follow-up 12 months | 162 SLE (≤ 40 years old, with mild or stable disease) |
COC, 35 μg ethinyl estradiol + 150 μg levonorgestrel POC, 30 μg levonorgestrel IUD (TCu 380A copper device) |
No difference among groups in mean activity, incidence of flares or time to first flare | (131) |
| RCT, double blind placebo-controlled, follow-up 12 months | 183 stable or inactive SLE (91 OCP vs. 92 placebo) |
Triphasic ethinyl estradiol 35μg + norethisterone at a dose of 0.5−1 mg for 12 cycles of 28 days | No differences between groups in occurrence of flares of any type (Severe lupus flare occurred in 7.7% of OCP group vs. 7.6% in the placebo group) | (132) |
| SLE onset | ||||
| Case report | False positive serological test for syphilis | COC, 1 mg norethisterone + 50 μg ethinyl estradiol | Developed SLE 3 weeks after the start of OCP | (122) |
| Case report | False positive serologic prenuptial syphilis test | 1 mg ethynodiol diacetate + 50 μg ethinyl estradiol | Developed SLE 4 weeks after the start of OCP and improved with withdrawal of OCP | (123) |
| Case report | 22-year-old female | 30 μg ethinyl estradiol + 250 μg levonorgestrel | Developed pulmonary hypertension related to SLE in 9 months | (121) |
| Case control study | 109 SLE and 109 controls | OCP unspecified | No association between OCPs and SLE | (126) |
| Case report | 24-year-old female | 30 μg ethinyl estradiol | Developed malignant hypertension who has incomplete SLE with DNA antibodies and high levels of antiphospholipid antibodies | (119) |
| Case control study | 195 SLE and 143 controls | OCP unspecified | No association between OCPs and SLE | (127) |
| Prospective cohort study | 99 SLE confirmed among NHS cohort 121,645 women | Use of OCPs based on self-report | - Past users vs. never users: RR 1.9 (95% CI 1.1−3.3) - No relationship with duration of OCP use |
(131) |
| Case control study | 85 SLE and 205 controls | Use of OCPs containing estrogen based on self-report | No association between OCPs and SLE | (128) |
| Population-based case control study | 240 SLE 240 and 321 controls | OCP unspecified | No association between OCPs and SLE | (129) |
| Prospective cohort study | 262 SLE confirmed among NHS cohort 238,308 women | Use of OCPs based on self-report | - Ever use of OCPs: RR 1.5 (95% CI 1.1–2.1) - Highest risk with short duration (< 2 years) of OCPs: (RR 1.9, 95% CI 1.3–2.8) |
(125) |
| Population based nested case control-study | 786 SLE and 7,817 controls | COC exposure First- and second-generation (ethinyl estradiol combined with the progestatives norethisterone, levonorgestrel, and norgestrel) vs. third-generation (ethinyl estradiol and either gestodene, desogestrel, or norgestimate) |
- Any use of OCPs: RR 1.19 (95% IC: 0.98–1.45) - Current use of OCPs: RR 1.54 (95% IC: 1.14–5.57) - Risk was higher in current users who recently started (RR 2.52, 95% CI: 1.14–5.57), first or second-generation OC (RR 1.65, 95% CI 1.20–2.26), and increase with dose of ethinyl estradiol (RR 1.42, 1.63, and 2.92 for ≤ 30 μg, 31−49 μg, and ≥ 50 μg, respectively) |
(10) |
SLE, systemic lupus erythematosus; COC, combined oral contraceptives; POC, progestin-only oral contraceptives; OCP, oral contraceptives; NHS, nurses’ health study; RR, relative risk; CI, confidence interval.