Editor—Mayor reports the Department of Health’s change of view on the use of third generation oral contraceptives.1 The department now proposes that women may be prescribed these newer oral contraceptives provided that they are “fully informed.” It is reported that the new package insert will include a statement that the risk of deep venous thrombosis is 15 per 100 000 among women using second generation pills and 25 per 100 000 among users of third generation products. The source of the data that formed the basis of the Department of Health’s estimates has not been revealed. Using an evidence based approach to this issue, we conducted a search on Medline and Embase using several terms: contraceptives, oral (oral contraceptive agents); thromboembolism; thrombophlebitis; venous thrombosis (vein thrombosis/deep vein thrombosis); pulmonary embolism (lung embolism); and incidence or cohort studies (cohort analysis). The search was restricted to studies published from 1985 onwards in order to focus on studies involving the newer low dose oral contraceptives. We found six relevant papers. From each of these we abstracted the crude population incidences of venous thromboembolic events (deep venous thrombosis and pulmonary embolism) (table). Rates vary between 8 and 62 per 100 000 exposed woman years and result in a pooled estimate of 36.5 per 100 000. The only studies with rates of less than 25 per 100 000—the rate that the Department of Health states is associated with the newer third generation combined oral contraceptives—are those of Jick et al (1995)4 and Porter et al (1985),7 Porter et al’s estimate being based on three exposed cases.
We recently completed a further study on the general practice research database, in which we identified 320 cases of venous thromboembolism in users of combined oral contraceptives between 1992 and 1997. We found an incidence in women using combined oral contraceptives containing less than 50 μg oestrogen of 38 per 100 000. We believe that this is likely to be closer to the true incidence of venous thromboembolism in users of low oestrogen combined oral contraceptives. It is interesting that the Department of Health quotes a rate based on only one study when a body of evidence is available.
Table.
Incidence of venous thromboembolism (number of cases per 100 000) among all users of combined oral contraceptives in six studies
| Study | Incidence | No of cases: No of woman years |
|---|---|---|
| Farmer et al 19972 | 41 | 83:202 517 |
| Pini et al, 19963 | 62 | 37:59 603 |
| Jick et al, 19954 | 23.2 | 75:323 888 |
| Gerstman et al, 19905 | 5 | 94:177 607 |
| Vessey et al, 19866 | 39 | 3:7606 |
| Porter et al, 19857 | 8 | 3:37 807 |
References
- 1.Mayor S. Department of Health changes advice on third generation pills. BMJ. 1999;318:1026. doi: 10.1136/bmj.318.7190.1026a. . (17 April.) [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Farmer RD, Lawrenson RA, Thompson CR, Kennedy JG, Hambleton IR. Population-based study of risk of venous thromboembolism association with various oral contraceptives. Lancet. 1997;349:83–88. doi: 10.1016/s0140-6736(96)07496-x. [DOI] [PubMed] [Google Scholar]
- 3.Pini M, Scoditti U, Caliumi F, Manotti C, Quitavalla R, Pattacini C, et al. Risk of venous thromboembolism and stroke associated with oral contraceptives. Recent Prog Med. 1996;87:331–337. [PubMed] [Google Scholar]
- 4.Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet. 1995;346:1589–1593. doi: 10.1016/s0140-6736(95)91928-7. [DOI] [PubMed] [Google Scholar]
- 5.Gerstman BB, Piper JM, Freiman JP, Tomita DK, Kennedy DL, Ferguson WJ, et al. Oral contraceptive oestrogen and progestin potencies and the incidence of deep vein thromboembolism. Int Epidemiol. 1990;19:931–936. doi: 10.1093/ije/19.4.931. [DOI] [PubMed] [Google Scholar]
- 6.Vessey M, Mant D, Smith A, Yeates D. Oral contraceptives and venous thromboembolism: finding in a large prospective study. BMJ. 1986;292:526. doi: 10.1136/bmj.292.6519.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Porter JB, Hunter JR, Jick H, Stergachis A. Oral contraceptives and nonfatal vascular disease. Obstet Gynecol. 1985;66:1–4. [PubMed] [Google Scholar]