The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case–control study

• Published in: Human reproduction (Oxford) 2003-03, Vol.18 (3), p.522-526
• Main Authors: Seaman, H.E., Vries, C.S.de, Farmer, R.D.T.
• Format: Article
• Language: English
• Subjects: Acne Vulgaris - drug therapy; Adult; Androgen Antagonists - adverse effects; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Cohort Studies; Contraceptives, Oral, Combined - adverse effects; Cyproterone Acetate - adverse effects; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Estradiol Congeners - adverse effects; Ethinyl Estradiol - adverse effects; Female; Genital system. Reproduction; Hirsutism - drug therapy; Humans; Key words: acne/cyproterone acetate/ethinyl estradiol/polycystic ovary syndrome/venous thrombosis; Medical sciences; Odds Ratio; Pharmacology. Drug treatments; Polycystic Ovary Syndrome - drug therapy; Risk Factors; Thromboembolism - chemically induced; Venous Thrombosis - chemically induced
• ISSN: 0268-1161; 1460-2350; 1460-2350
• DOI: 10.1093/humrep/deg120

BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case–control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age‐adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35–3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case–control analysis gave an adjusted odds ratio (ORadj) of 7.44 (95% CI 3.67–15.08) for CPA/EE use compared with an ORadj of 2.58 (95% CI 1.60–4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.