Thrombotic stroke and myocardial infarction with hormonal contraception.
BACKGROUND
Although several studies have assessed the risk of venous thromboembolism with newer hormonal contraception, few have examined thrombotic stroke and myocardial infarction, and results have been conflicting.


METHODS
In this 15-year Danish historical cohort study, we followed nonpregnant women, 15 to 49 years old, with no history of cardiovascular disease or cancer. Data on use of hormonal contraception, clinical end points, and potential confounders were obtained from four national registries.


RESULTS
A total of 1,626,158 women contributed 14,251,063 person-years of observation, during which 3311 thrombotic strokes (21.4 per 100,000 person-years) and 1725 myocardial infarctions (10.1 per 100,000 person-years) occurred. As compared with nonuse, current use of oral contraceptives that included ethinyl estradiol at a dose of 30 to 40 μg was associated with the following relative risks (and 95% confidence intervals) for thrombotic stroke and myocardial infarction, according to progestin type: norethindrone, 2.2 (1.5 to 3.2) and 2.3 (1.3 to 3.9); levonorgestrel, 1.7 (1.4 to 2.0) and 2.0 (1.6 to 2.5); norgestimate, 1.5 (1.2 to 1.9) and 1.3 (0.9 to 1.9); desogestrel, 2.2 (1.8 to 2.7) and 2.1 (1.5 to 2.8); gestodene, 1.8 (1.6 to 2.0) and 1.9 (1.6 to 2.3); and drospirenone, 1.6 (1.2 to 2.2) and 1.7 (1.0 to 2.6), respectively. With ethinyl estradiol at a dose of 20 μg, the corresponding relative risks according to progestin type were as follows: desogestrel, 1.5 (1.3 to 1.9) and 1.6 (1.1 to 2.1); gestodene, 1.7 (1.4 to 2.1) and 1.2 (0.8 to 1.9); and drospirenone, 0.9 (0.2 to 3.5) and 0.0. For transdermal patches, the corresponding relative risks were 3.2 (0.8 to 12.6) and 0.0, and for a vaginal ring, 2.5 (1.4 to 4.4) and 2.1 (0.7 to 6.5).


CONCLUSIONS
Although the absolute risks of thrombotic stroke and myocardial infarction associated with the use of hormonal contraception were low, the risk was increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 μg and by a factor of 1.3 to 2.3 with those that included ethinyl estradiol at a dose of 30 to 40 μg, with relatively small differences in risk according to progestin type. (Funded by the Danish Heart Association.).
Gynecologic Clinic 4232, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. lidegaard@rh.regionh.dk
Øjvind
Ø
Lidegaard
Ellen
E
Løkkegaard
Aksel
A
Jensen
Charlotte Wessel
CW
Skovlund
Niels
N
Keiding
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003270:Contraceptive Agents / Q000009:adverse effects*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects; D004522:Educational Status; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D020767:Intracranial Thrombosis / Q000139:chemically induced / Q000453:epidemiology; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects*; D012044:Regression Analysis; D012306:Risk; D012907:Smoking / Q000009:adverse effects; D020521:Stroke / Q000139:chemically induced* / Q000453:epidemiology; D013927:Thrombosis; D055815:Young Adult
D003270:Contraceptive Agents; D003277:Contraceptives, Oral, Combined; D011372:Progestins; D004958:Estradiol