Eric Wooltorton1 has written a balanced article in response to the warning on Diane-35 and the risk of venous thromboembolism issued by Health Canada.
Caution is always required in prescribing estrogen–progestin combinations, whether for contraception, postmenopausal hormone replacement or treatment of acne. However, the risk attributed to preparations containing cyproterone acetate in comparison with other preparations may have been exaggerated by not taking first-time use into account. This effect has been estimated2 to increase the risk of venous thromboembolism 10-fold in the first year of oral contraceptive use, regardless of preparation. The research letter of Vasilakis-Scaramozza and Jick,3 which was used by Health Canada to support the increased risk, provided adjusted odds ratios for venous thromboembolism, but no reference is made to first-time use as a potential factor. That report described a total of 128 subjects (cases and controls) who had used levonorgestrel-containing preparations and 42 subjects (cases and controls) who had used preparations containing cyproterone acetate. In the first group, only 9 (7%) had used the preparation for 6 months or less, whereas in the second group, a much larger proportion (12 or 29%) had used the drug for 6 months or less. Among patients with this short duration of use, there is a greater probability of first-time use. Thus, the proportion of women using an estrogen–progestin combination for the first time appears to have been higher in the group receiving preparations containing cyproterone acetate, which might account for some or all of the greater risk of venous thromboembolism in that group.
Timothy C. Rowe Gynaecologist and Associate Professor University of British Columbia Vancouver, BC