The following is a summary of the most important data on the risk of thromboembolism (occlusion of a blood vessel by a detached thrombus (blood clot )) under hormonal contraception (contraception with hormones). WHO has indicated four categories of risk constellations to facilitate the problem, and these are regularly revised and supplemented as necessary.
| Categories | Description |
| 1 | Unrestricted use of COCs (combined oral contraceptives);benefit outweighs risk without restriction |
| 2 | Benefit > Risk |
| 3 | Risk ≥ benefit (relative contraindications); only after detailed explanation and absence of alternatives |
| 4 | Contraindication (contraindications) due to high health risks. |
Venous thromboembolism risk with COCs (oral, nonoral (vaginal ring, patch).
- Recent evaluations confirm the previous assessment that the risk of venous thromboembolism (VTE; (occlusion of a vein by a dislodged blood clot)) is low among all low-dose CHCs (ethinyl estradiol content <50 μg).
- There is clear evidence that, depending on the progestin contained, there are differences in VTE risk between CHDs. Currently available data suggest that combined hormonal contraceptives (CHCs; combined hormone contraception) containing the progestogens levonorgestrel, norethisterone, or norgestimate have the lowest VTE risk among combined hormonal contraceptives (see Table 1 below).
- When prescribing CHD, the risk factors of each individual woman/user-particularly those for VTE-as well as the differences that exist between preparations in terms of VTE risk should be considered.
- There is no need to discontinue the preparation if there have been no previous problems with the use of the combined hormonal contraceptive.
- There is no evidence that there are differences in the risk of arterial thromboembolism (ATE) with low-dose CHD (ethinyl estradiol content <50 μg).
- In most women, the benefits associated with the use of CHD far outweigh the risk for the occurrence of serious adverse events. The focus now is on the importance of individual woman/user risk factors and the need to reassess risk factors on a regular basis. In addition, awareness of the signs and symptoms of VTE or ATE should be raised. These signs and symptoms should be described to users who are prescribed CHDs.
- The possibility of CHD-related thromboembolism should always be considered when a user presents with appropriate symptoms.
1 CHD containing ethinylestradiol or estradiol plus chlormadinone, desogestrel, dienogest, drospirenone, etonogestrel, gestodene, nomegestrol, norelgestromin, or norgestimate.VTE risk with combined hormonal contraceptives.
| Progestin contained in CHD(combined with ethinyl estradiol unless otherwise specified). | Relative risk compared with levonorgestrel. | Estimated incidence(per 10 000 women and year of use) |
| Nonpregnant nonusers | – | 2 |
| Levonorgestrel | Reference | 5-7 |
| Norgestimate/Norethisterone | 1,0 | 5-7 |
| Dienogest | 1,6 | 8-11 |
| Gestodene/desogrestrel/drospirenone | 1,5-2,0 | 9-12 |
| Etonogestrel/norelgestromin | 1,0-2,0 | 6-12 |
| Chlormadinone acetate/nomegestrol acetate (estradiol) | To be confirmed1 | To be confirmed1 |
1Further studies are being conducted or are planned to collect meaningful data for the risk of these preparations. Further notes
- Non-oral combined hormonal contraceptives, e.g., contraceptive patches, vaginal ring have, like oral combined contraceptives, a sometimes significantly increased risk of thrombosis between (2-7 fold) compared with levonorgestrel [S3 guideline].
- Thromboembolic risk with progestin monotherapy (oral, intrauterine, intramuscular): oral and intrauterine progestin monotherapy does not result in an increased risk of thromboembolic events [4, guideline]. This is not true for intramuscular three-month injection with depot medroxyprogesterone acetate. It has a 6.5-fold increased risk of thrombosis [5 guideline].
Thromboembolic recurrence risk with anticoagulation (anticoagulation)
Although oral contraceptives should be automatically discontinued by most professional societies after a thromboembolic event, this is now increasingly controversial because the prothrombotic hormone effects (procoagulant hormone effects) are compensated by anticoagulation.To date, there is only one study on this topic. The authors found no differences in the rate of recurrent VTE under anticoagulation and different hormone doses in 18 88 women. The risk of thromboembolic complications and was higher under therapy with rivaroxaban or warfarin in patients
- Without hormone exposure 4.7%/year (N = 1413).
- Estrogen-containing preparations 3.7%/year (N = 306).
- Progestogen monopreparations 3.8%/year (N = 217).
Although further valid data do not exist, according to expert opinion, the following procedure (modality) can be discussed:
- Combined contraceptives should be discontinued because of a health risk that is not yet clear
- Progestogen monopreparations are predominantly considered unproblematic because the expected benefit exceeds the potential risk, exception: three-month injection: depot medroxyprogesterone acetate)
- Progestogen monopreparations are also after termination of anticoagulation means of choice for anticonception (exception: three-month injection: depot medroxyprogesterone acetate).
- unplanned pregnancy is a high risk for patients on anticoagulants due to
- Renewed thromboembolic complications as a result of pregnancy-related increased clotting activity
- Both warfarin and NOAKs (new oral anticoagulants) have an increased risk of embryotoxicity
Thromboembolic recurrence risk without anticoagulation
- The use of hormonal combined contraceptives (oral, transdermal (“through the skin“), vaginal) in patients after an acute or previous thromboembolic event is contraindicated (not indicated).
- For anticonception (contraception), progestin monotherapy (oral, intrauterine) should be used because the benefit outweighs any potential hazard that has not yet been demonstrated
- The use of depot medroxyprogesterone acetate (three-month injection) is not recommended, as there are no data on it.
Thromboembolism risk in predisposing factors (obesity, hyperlipidemia/dyslipidemia, hypertension/high blood pressure, nicotine) (guideline).
The study evidence for the above risk factors is poor and inconclusive. If at all, these risk constellations seem to have only a minor influence on the risk of thromboembolism. There appears to be no risk with progestin monotherapy, with studies also poor. Arterial thromboembolism risk (ATE) (guideline).
Arterial thromboembolic risk refers to myocardial infarction (heart attack) and ischemic cerebral infarction, two factors associated with high mortality (death rate). The most important risk factor, which, however, cannot be influenced, is the age-dependent frequency of increase. In addition, there are congenital and acquired risk factors that increase the risk, e.g. angina pectoris (“chest tightness”; sudden pain in the heart area), diabetes mellitus, lipometabolic disorders, hypertension (high blood pressure), smoking and migraine. Data are insufficient because of the rarity of the events in the age groups of women using contraceptive measuresFollowing recommendations are made:
- Combined hormonal contraceptives (CHC) should be avoided because of the increased risk of myocardial infarction and ischemic cerebral infarction from estrogen use on the coagulation system. The risk depends on the ethinyl estradiol dose. The relative risk for myocardial infarction with COCs is 1.6, and the relative risk for stroke is 1.7.
- Oral progestin monopreparations have no effect on ATE.
- Progestin implants and progestin-containing intrauterine devices have no effect on ATE.
- the three-month injection should be avoided, because high-dose progestins have a negative impact on blood lipids (blood lipid levels).
