Questions and Answers

As part of the examination, the physician will need to rule out possible individual risk factors.

For example, the physician might ask the following questions:

• How tall are you?
• How much do you weigh?
• Do you smoke?
• What diseases have you had up to now in your life? Have you ever had breast or abdominal surgery?
• Do you take any medications on a regular basis and, if so, which ones?
• Do your parents have – or have they had in the past – any serious diseases, e.g. circulatory disorders, heart attacks, strokes, thromboses, and was this when they were young?
• Do you currently have any symptoms and, if so, which?

Questions on the most suitable contraceptive method should be discussed with a physician.

In general, women should take the combined pill regularly at the same time of day. Please note that some drugs, such as antibiotics or psychopharmaceuticals, can impair the Pill’s contraceptive effect.

Women should also be especially careful if they suffer from severe diarrhea or vomiting within three to four hours after taking the Pill. Usually it takes this long for the combined pill’s active ingredients to be entirely absorbed by the body. This situation is comparable to forgetting to take the combined pill. The package insert contains information on what action to take in the above-mentioned cases. Further questions should be discussed with a physician.

Low-dose combined pills with the ingredients estrogen and progestin are well tolerated by most women. Minor side effects can include headaches, breast tenderness, intermenstrual bleeding or weight increase. Venous and arterial thrombosis and thromboembolism are rare, but serious, known complications that can occur in connection with the combined pill.

This is why it is important for every woman to discuss her individual risk of thrombosis and other possible side effects with a physician.

Thrombosis is the medical term for the formation of a blood clot in the arteries or veins. It is a vascular disease (disease of the blood vessels) in which a blood clot (thrombus) forms in a vein or artery and blocks it (thromboembolism).

This clotting may be due to a damaged blood-vessel lining, a disruption to the body's clotting system or blood-circulation problems. Thrombosis can occur in any blood vessel in the human body, especially in the deep veins of the legs or pelvis.

The danger is increased if the clot breaks free in the deep vein system, flows with the bloodstream through the heart and into the arteries leading to the lungs and clogs these arteries. This causes pulmonary embolism, which is a potentially life-threatening situation. Arterial thromboses are even rarer than venous thromboses.

There are many symptoms. Possible indications of venous thrombosis/thromboembolism can include:

swelling of the leg a feeling of heaviness in the leg pain on pressure on the inside of a foot

shortness of breath and difficulty in breathing coughing (combined with coughing up blood)

Possible indications of arterial thrombosis can include:

sudden pain in the area of the heart a loss of feeling and movement control, sometimes combined with a severe headache

pain, paleness, coldness and lack of pulse in the arm or leg loss of the ability to see or speak

You should consult a physician if you have severe symptoms, especially if they are acute and there is no other evident cause.

If diagnosed early enough, there is a good chance of successfully treating thrombosis/thromboembolism. This is done, for example, by immediately administering a medication which inhibits clotting of the blood so that the blood clot is dissolved and secondary damage is prevented or reduced.

Thrombosis is a rare side effect of all combined hormonal contraceptives (e.g. Pill, ring, patch) that contain estrogens and progestins:

• Out of 10,000 women of childbearing age who do not use a combined contraceptive pill, three to 4.5 suffer from venous thrombosis/thromboembolism per year (Dinger et al., in: Contraception 2007).
• Out of 10,000 women who take a combined contraceptive pill, eight to ten suffer from venous thrombosis/thromboembolism per year (Dinger et al., in: Contraception 2007).
• The risk is higher, however, for women during pregnancy and in the weeks following childbirth. Studies have determined that in this case between 20 and 30 out of 10,000 women suffer from venous thrombosis/thromboembolism (John A. Heit, in: Annals of Internal Medicine 2005).

Since the risk of thrombosis varies from one woman to the other, the personal risk profile can only be assessed on the basis of an individual consultation with a physician.

Before prescribing a hormonal contraceptive the physician will ask a woman about her individual risk factors and those of her family, so as to assess the danger as well as possible and to give her the best possible advice.

In most cases in which women who are taking combined preparations suffer venous thrombosis/thromboembolism, at least one or more of the following personal risk factors is usually present:

a personal or family predisposition for thrombosis diseases overweight

long-term immobilization (e.g. surgery, accident, long-haul flights) advanced age.

Personal risk factors for arterial thrombosis include:

advanced age smoking fat metabolism disorders diabetes high blood pressure

migraine with aura overweight personal or family predisposition valvular heart disease atrial fibrillation

In general, every combined hormonal contraceptive method (e.g. combined pill, patch or ring) increases the risk of thrombosis, regardless of its brand or ingredients. It is also recognized that with all oral contraceptives the risk of venous thrombosis/thromboembolism is highest during the first year of use.

A personal consultation with the physician will help a woman find out which method of contraception is most suitable for her.
Furthermore, the package inserts of combined pills also provide information on side effects and risks. Any unanswered questions should be discussed with a physician.

The safety, tolerability and efficacy of a drug as proven in clinical studies is a prerequisite for its marketing authorization by the relevant regulatory authorities. Following the market launch of recently approved low-dose combined pills, additional studies on their safety were conducted.

For example, two epidemiological studies commissioned and sponsored by Bayer (EURAS and Ingenix), which were carried out by independent investigators, specifically examined the cardiovascular safety profile of various combined pills containing different progestins. The design of these studies was extensively discussed and aligned in advance with the health authorities in Europe and the United States. The size and methodology of both studies were chosen to make it possible to assess differences between different combined pills with regard to the risk of thrombosis.

The EURAS study controlled for potentially confounding factors such as body weight (body mass index, BMI) or an individual predisposition for thrombosis; the Ingenix study used a recognized epidemiological method (propensity score matching) to achieve a balance between the different cohorts studied.

The currently available results of these studies which involved more than 120,000 women confirm that:

• venous thrombosis and thromboembolism are rare among women who take low-dose combined pills
• the risk of a venous thrombosis and thromboembolism in women who take low-dose combined pills is lower than the risk associated with pregnancy and following childbirth
• the EURAS and Ingenix studies demonstrate that the risk of a venous thrombosis or thromboembolism is comparable for all the combined pills with different progestins, including levonorgestrel and drospirenone, that were studied