The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.
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 (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) 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.
Seaman
H E
HE
Pharmacoepidemiology Unit, Postgraduate Medical School (University of Surrey), Stirling House, Stirling Road, Surrey Research Park, Guildford, Surrey GU2 7DJ, UK. h.seaman@surrey.ac.uk
de Vries
C S
CS
Farmer
R D T
RD
D000152:Acne Vulgaris / Q000188:drug therapy; D000328:Adult; D000726:Androgen Antagonists / Q000009:adverse effects*; D016022:Case-Control Studies; D015331:Cohort Studies; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D017373:Cyproterone Acetate / Q000009:adverse effects*; D045166:Estradiol Congeners / Q000009:adverse effects*; D004997:Ethinyl Estradiol / Q000009:adverse effects*; D005260:Female; D006628:Hirsutism / Q000188:drug therapy; D006801:Humans; D016017:Odds Ratio; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy; D012307:Risk Factors; D013923:Thromboembolism / Q000139:chemically induced*; D020246:Venous Thrombosis / Q000139:chemically induced*
D000726:Androgen Antagonists; D003277:Contraceptives, Oral, Combined; D045166:Estradiol Congeners; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate