Age, obesity (overweight), diabetes mellitus, epilepsy, hypertension (high blood pressure), headaches/migraines, surgery, and smoking are the main risks that, individually or in various combinations, can make the choice of safe contraception (birth control) difficult for health reasons. This is particularly true for combined oral contraceptives (COCs; contraceptives containing an estrogen and a progestin). 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. |
Age
WHO Assignment for KOK:
- Age without risks
- Up to 40 + years of age: category → 1
- > 40 years: Category → 2
- Age + risks, e.g. obesity (overweight), familial thromboembolic predisposition (thromboembolism = blood clot (thrombus) detaches from the wall of a blood vessel and is transported further within the bloodstream), hypertension (high blood pressure), etc.
- Recommendation: if possible abandonment of KOK.
- Alternative: progestogen monotherapy (oral, implant (hormone implant; contraceptive sticks), intrauterine device (IUD; coil)), copper IUD.
Obesity
WHO Assignment for KOK:
- Age without risks (which is rare): category → 2.
- Obesity (overweight) + risks, e.g. diabetes mellitus, dyslipidemia, hypertension (high blood pressure): category → 3
- Recommendation:
- No KOK
- Progestin monotherapy (oral, implant, intrauterine device (IUD; coil)), copper IUD: No depot medroxyprogesterone (DMPA; progestin-type hormonal preparation used for contraception and as part of menopausal hormone therapy) because of the potential side effects (increased risk of thrombosis (formation of a blood clot (thrombus)), glucose metabolism disorders, which are often present in obesity, and can be exacerbated by DMPA).
- Recommendation:
- Obesity + risk of myocardial infarction (heart attack) or apoplexy (stroke): currently, the risk cannot be estimated because there are conflicting results [2,3,4].
Diabetes mellitus [1, LL 1]
Diabetics frequently have cardiovascular disease. About 75% of type II diabetics die from myocardial infarction (heart attack) or apoplexy (stroke). Contraceptive choice is important because pregnancy in a diabetic woman is associated with a high risk of complications. WHO Assignment for COCs:
- Diabetes I and II:
- Category → 1, up to 35 years, if secondary vascular damage is excluded.
- Category → 2, > 35 years, if secondary vascular damage is excluded.
- Diabetes I and II + vascular disease or other risk factors: category → 4caused by diabetes or other diseases e.g. obesity, epilepsy, dyslipidemia, hypertension (high blood pressure), migraine, smoking, KOK are contraindicated (not applicable).
- Recommendation:
- Progestin monotherapy (oral, implant, IUD), except for the three-month injection (depot medroxyprogesterone acetate), because it may be combined with an increase in the rate of thrombosis (vascular occlusion by a thrombus (blood clot)), glucose metabolism disorder, and decrease in bone density with long-term exposure.
- Copper IUD
Epilepsy
- COCs do not cause an increase in seizure frequency or seizure incidence.
- However, antiepileptic drugs (drug used to treat or prevent epileptic seizures, such as tonic-clonic seizures) may reduce the efficacy of COCs and oral or parenteral (“bypassing the intestine”) progestin monopreparations by enzyme induction in the liver or activation of the metabolism of ethinyl estradiol.This may affect the contraceptive safety (protection against conception).The contraceptive safety is with the following preparations.
- Assured: no enzyme induction (WHO category → 1):
- Not warranted: Enzyme induction (WHO category → 3):
- The substances belonging to category 3 also refer to oral progestogen monotherapy.
- The three-month injection (depot medroxyprogesterone acetate and the progestogen-containing IUD are assigned to group → 1
- The implant is assigned to group → 2
- No data are available for: Brivaracetam, potassium bromide, mesuximide, perampanel, stiripentol, sultiam.
- For emergency contraception with levonorgestrel (1.5 mg), double dosage, 2 x 1.5 mg 12 hours apart, is advised for enzyme-inducing preparations. No information is available on Ulipristal. Alternative: intrauterine device (IUD; coil) within five days.
- Recommendation: KOK in the long cycle, or as a long-term use in premenstrual epileptic seizures.
Hypertension (high blood pressure)
WHO assignment for COCs:
- A hypertension is classified by WHO for KOK as.
- Category → 3 (relative contraindication/counterindications), even if the hypertension is well controlled with medication
- Category → 4 (absolute contraindication), if risk factors exist in addition to a well-controlled hypertension, e.g. obesity, diabetes mellitus, dyslipidemia, smoking. They increase the risk of arterial thromboembolic complications.
- Category → 4 (absolute contraindication) in hypertension values >160/100 mm/Hg.
- Category → 2, following hypertension during pregnancy. These women are considered high-risk patients. In the setting, the estrogen dose should be chosen as low as possible, preferably 20 µg ethinylestradiol. In addition, regular blood pressure monitoring is necessary.
Recommendation: progestogen monopreparations (oral, implant, intramuscular, intrauterine).
Headache/migraine
Headache
WHO assignment for COCs:
- Category → 1 [6, LL 1]
- Preference is given to application as long-term use or in a long cycle. Particularly benefits the group suffering from premenstrual or menstrual headaches (headaches that occur before menstruation or with menstruation).
- Alternative: progestogen monopreparations (oral, implant, IUD, three-month injection).
- Cave: if headaches occur again after symptom improvement, a detailed diagnosis must be performed
for this group of women, however, there is little data from the point of view of ischemic stroke.
Migraine
Migraine is hormone-dependent to a high degree. The prevalence (disease frequency) is most common in the period from puberty to menopause. It increases particularly frequently between the ages of 35-45. Migraine attacks often occur shortly before or during menstruation (menstruation-associated migraine) as a result of the drop in estrogen.Basically, migraine is associated with an increased risk of apoplexy (strokes), less frequently myocardial infarction (heart attack) and thrombosis (vascular occlusion by a thrombus (blood clot)). These risks apply mainly to patients with migraine with aura. However, the absolute risk for these complications in young, otherwise healthy women without other vascular risk factors, is considered to be very low [LL1]. As there are different attitudes in scientific publications and also in daily practice, especially between gynecologists and neurologists, the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC) clearly pointed out in 2016, after searching the available studies, that there are not enough data available for a more precise differentiation and risk assessment of the different forms of migraine and that further investigations are necessary. This is because the risk of stroke is not solely dependent on the diagnosis, but in particular on the subtype of migraine z.B. Initial manifestation, duration of the disease, frequency of attacks, frequency of attacks with or without aura.This panel also clearly states that migraine with aura has the highest risk of stroke without hormonal contraception with a sixfold increase under hormonal contraception see Table : 1. Table1: Absolute risk of ischemic stroke in women aged 20-40 with and without aura, with and without hormonal contraception.
| Contraception | No migraine | Migraine without aura | Migraine with aura |
| Without hormonal contraception | 2,5/100.000 | 4,0/100.000 | 5,9/100.000 |
| With hormonal contraception | 6,3/100.000 | 25,4/100.000 | 36,0/100.000 |
WHO assignment for KOK:WHO also differentiates between migraine patients with and without aura from a KOK point of view: according to current doctrine, migraine may be
- Patients without aura are
- Assigned to group 2 if they are <35 years old
- Assigned to group 3 if they are > 35 years old
- The WHO distinction by age is not made in the guideline.female patients without aura are assigned to category → 2
- Patients with aura are assigned to group 4 and are considered an absolute contraindication (contraindication) for KOK.
- Alternative are all progestin monopreparations. They are assigned to category → 2 according to WHO (oral, intramuscular, implant, intrauterine).
Progestogen monopreparations can also be used if there are additional risk factors to migraine with aura e.g. obesity, hypertension (high blood pressure), cardiovascular disease, deep vein thrombosis (DVT), pulmonary embolism (LE), cigarette smoking. (Exception: depot medroxyprogesterone acetate, because of additional risk for thromboembolic events and glucose metabolism disorders).
Women with migraine with or without aura who require emergency contraception may use the usual emergency contraceptive measures of levonorgestrel 1.5 mg orally, ulipristal acetate 30 mg orally, or an intrauterine device. When standard prophylactic measures are not effective, many patients with migraine benefit
- Without aura from continuous use of COCs (long-term use, long-cycle).
- With aura from a continuous progestogen application (oral, intramuscular, implant, intrauterine).
- If seizures occur more frequently or auras occur for the first time during hormone therapy (COCs or progestin monotherapy), discontinue the preparations. Alternative: copper IUD
Operations
The criterion for risk stratification in surgery is the thromboembolic risk due to the size of the operation and the length of time of immobilization or partial immobilization. According to the WHO and the recommendations of the Red Hand Letter, discontinuation of COCs is recommended when the risk of thrombosis is high. This is in contrast to recent guideline statements, which no longer recommend discontinuation of COCs because thromboprophylaxis is given anyway, providing adequate protection against partial risk (see below for details). WHO Assignment for COCs:
- Minor surgery: Category → 1
- large operations:
- With long immobilization: category → 4, especially orthopedic surgery, major abdominal visceral surgery (abdominal surgery) , cardiopulmonary surgery (heart-lung surgery), and carcinoma surgery (surgery for cancer).
- With short immobilization: category → 2, this includes most gynecological procedures (exception: carcinoma operations).
Recommendation:
- For major surgery, especially with long immobilization, COCs should be discontinued 4-6 weeks beforehand.
- Restart: about 2 weeks after full mobilization.
Alternatives to COCs: progestin monotherapy (oral, implant, IUD). Exception: depot medroxyprogesterone acetate, because it can increase the risk of thrombosis. Current guideline recommendations have a different assessment of COCs and thrombosis risk or discontinuation during major surgery [LL1].
Citation p. 42 of the guideline:
The risk of unplanned pregnancy when oral contraceptives are discontinued before surgery should be weighed in terms of reducing the risk of thrombosis. Interruption of contraception is not recommended.Users of hormonal contraceptives should receive drug thromboprophylaxis anyway during major surgical procedures with a medium or high risk of thrombosis and are thus adequately protected.
Smoking
Overall, there are few meaningful hazard studies on venous thromboembolism (VTE) risk and arterial thromboembolism (ATE) risk. Venous thromboembolism (VTE) risk.
Smoking has a low to moderate risk of VTE (1.3-4-fold). It depends on the nicotine dose.
- 1-10 cigarettes/day: OR (odds ratio) 1.3.
- 11-20 cigarettes/day: OR 1.7
- > 20 cigarettes/day: OR 1.9
Guideline recommendations:
- If age > 35 years and/or > 15 cigarettes/day, COCs should be avoided.
- Progestin monopreparations have no effect on VTE risk. Exception: depot medroxyprogesterone acetate, it can increase the risk of thrombosis.
Arterial thromboembolism (ATE) risk.
The risk of myocardial infarction (heart attack) and apoplexy (stroke) is only slightly increased in women under 40 who smoke. However, cigarette consumption significantly increases this risk. Exact figures are not available [LL 1].
- WHO Assignment for KOK:
- Classification → 3, for women > 35 years of age.
- + Cigarette consumption up to 15/day.
- Classification → 4, in women > 35 years.
- + cigarette consumption > 15/day.
- Classification → 3, for women > 35 years of age.
Liver tumors
Because of the rarity of liver tumors (hepatic hemangioma, focal nodular hyperplasia (FNH), hepatocellular adenoma, hepatocellular carcinoma (HCC)/liver carcinoma/liver cancer), they will be discussed only in passing. WHO assignment for COCs:
- Liver hemangioma: → 1 category.
- Focal nodular hyperplasia (FNH): category → 2
- Hepatocellular adenoma: category → 3
- Hepatocellular carcinoma (HCC): category → 3
Condition after breast carcinoma: see article: “Hormonal contraceptives and carcinoma risk“.