Original research articlePregnane progestin contraception in systemic lupus erythematosus: a longitudinal study of 187 patients☆
Introduction
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects young women. The severity of SLE flares can be life-threatening, and the deleterious effect of pregnancy on the course of the disease is well established, especially in the case of kidney involvement [1], [2]. Thus, effective contraception is crucial in these patients but remains the object of debate [3].
The use of ethinylestradiol-containing contraceptive pills in SLE patients is controversial since estrogens can increase the incidence and severity of the disease [3], [4], [5], [6]. Furthermore, the risk of arterial and venous thrombosis is increased both in SLE patients without any hormonal therapy [7], [8] and in healthy women using combined estrogen–progestin contraceptive (COC) pills [9], [10], [11]. Alternative effective contraception means are thus mandatory in SLE patients even if recent data suggest that COC can be used in nonsevere patients without history of thrombosis [12], [13]. Low-dose progestin-only pills (POPs; low-dose Continuous 19-nortestosterone-derived progestin compounds administered orally or as implants) do not increase the risk of thrombosis episodes and are widely used in SLE patients [14]. However, their low effectiveness and the poor compliance observed in some series suggest the need for other contraceptive methods [14]. The contraceptive efficacy of progestin agents is improved by increasing the dose, which provides additional antigonadotropic efficacy. Injectable depo-medroxyprogesterone acetate (DMPA) is not used in France except for patients with extreme compliance difficulties related to psychiatric disorders. Norethisterone derivatives used at 10 mg/day are effective but may cause thrombosis [15], [16]. Thus, they cannot be used in women with SLE who have a high baseline risk of venous thromboembolism (VTE). The use of copper intrauterine devices (IUD) is frequently challenged in SLE patients due to the potential risk of infection soon after insertion [17]. The levonorgestrel-releasing intrauterine system, which may carry a lower risk for infection [18], has been only recently easily available on the French market.
For the present study, we used two pregnane progestin (PP) compounds, cyproterone acetate (CPA) and chlormadinone acetate (CMA), in women with SLE who wanted to use hormonal contraception. Cyproterone acetate is a potent antigonadotropic agent, which induces a hypoestrogenic environment. It is most commonly used in women in combination with 17β-estradiol to treat hirsutism [19]. Chlormadinone acetate is a weaker antigonadotropic agent than CPA [20]. Both compounds have been reported not to alter lipid fractions, glucose metabolism or haemostatic parameters, at least in healthy women [20], [21].
One hundred eighty-seven SLE patients using PP for contraception were followed up prospectively in a real-life cohort study. This cohort was derived from an initial prospective randomized study comparing CMA and CPA in 100 women with SLE that has not been published. Forty of the women in the follow-up cohort were initially included in the prospective study. Follow-up rules from the randomized study were applied in the subsequent cohort follow-up, providing homogeneous and systematic data. We thus found it would be interesting to report on our experience of the use of CMA and CPA for contraception in SLE women. The purpose of this article is to report on gynecological tolerability, vascular safety and SLE disease activity in women using CMA and CPA for contraception.
Section snippets
Patients
One hundred eighty-seven consecutive premenopausal women requesting contraception and willing to use hormonal contraception were followed up in the Gynecology Unit of the Necker Hospital and then the Hôtel-Dieu Hospital between 1981 and 2004. All of the patients fulfilled the diagnostic criteria for SLE as defined by the American Rheumatism Association [22]. The study was performed according to French law on clinical trials and informed consent was obtained from each patient. It was initiated
Results
One hundred eighty-seven patients were followed up in this cohort study. The mean age at the beginning of the follow-up was 31±7.1 years (mean±S.E.; range, 16–54 years). The mean±S.E. time since diagnosis of SLE at the beginning of PP contraception use was 57.6±46.5 months. Systemic lupus erythematosus treatments at the time of inclusion were prednisone in 67 (35.8%) patients and immunosuppressive drugs in 28 (14.9%) patients. Ninety-four women had received previous COC.
In terms of the main SLE
Discussion
Different types of progestins can be used for contraception [29] in women with specific vascular risk [21], [30], [31]. Progestins at a low-dose regimen, either POP given orally or through implants, are considered safe to use in these women. However, they have incomplete antigonadotropic activity and thus may cause spotting and breakthrough bleeding and have limited compliance [14], [31], [32]. Progestin can also be used in a high-dose regimen with additional antigonadotropic effects [21]. The
Conclusions
Pregnane progestins offer a safe and effective contraception in SLE patients, even with history of DVT and a high risk of thrombosis. The gynecological acceptability is satisfactory. Thus, this contraceptive may provide an excellent and safe alternative to COC or low-dose POP contraception in aPL/SLE patients.
Acknowledgments
We gratefully acknowledge the collaboration of the following clinicians P Godeau (APHP, Hôpital La Pitié Salpêtrière) J-P Clauvel and E Oksenhendler (APHP, Hôpital Saint-Louis), L Guillevin (APHP, Hôpital Cochin), A-M Piette (Hôpital Foch), F Martinez (APHP, Hôpital Necker), O Chosidow (APHP, Hôpital Tenon), T Papo (APHP, Hôpital Bichat), J-C Roujeau (APHP, Hôpital Henri-Mondor), N Galezowsky (Hôpital Saint-Joseph), C Larroche (Hôpital Avicenne), L Capron (APHP, Hôpital EGP) and E Gainer
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Authors contributions: NCB acquired the data, drafted the paper and actively contributed to the intellectual content, ZA contributed to acquisition of data and to draft and revision of the paper, CF, LG,BW and OB contributed to conception of the study, follow-up of the patients and revision of the paper, DPL contributed to conception and drafting of the paper, PYS contributed to data analysis, drafting of the paper, JCP contributed to the conception, follow-up of the patients, interpretation of data, draft, AG was in charge of the study, followed up all the patients and contributed to drafting the paper.
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Current address: Université Pierre et Marie Curie, APHP, Service de Gynécologie, Hôpital Tenon, 4, rue de la Chine, 75970 Paris Cedex 20, France.