MEDICAL MATTERS:In a significant first under new rules for drug safety, France has asked the European Medicines Agency (EMA) to review third- and fourth-generation oral contraceptives to see if their use should be restricted across the European Union. The agency's pharmacovigilance risk assessment committee will reassess the safety of newer contraceptive pills taken by thousands of Irish women.
It’s part of a general crackdown on medication safety by France, which has one of the highest rates of medicine consumption in Europe.
Last week the focus turned to a drug marketed as Diana in France and as Dianette here. The active ingredients are cyproterone acetate and ethinylestradiol, and the drug is used for the treatment of severe acne in women. But it also acts as an oral contraceptive, although doctors must use it only as a contraceptive in women with severe acne.
Blood clots
It is well established that combined contraceptives carry a rare risk of blood clots, known as venous thromboembolism. The absolute risk is very small at between 20 and 40 cases per 100,000 women in one year of use but this risk differs between different generations of combined contraceptives (pills containing oestrogen and progesterone). There is a higher risk for third- and fourth-generation contraceptives compared with first- and second-generation ones.
Deep venous thrombosis (DVT) is a form of venous thromboembolism, as is a condition called pulmonary embolus (PE). DVT refers to the formation of a blood clot in the deep- lying veins of the leg; and PE occurs when a piece of this clot breaks off and travels from the leg, through the heart, and lodges in the lung.
A large clot can block one or more of the pulmonary arteries so that blood cannot travel from the right side of the heart to the lungs, rapidly causing death.
Processes
Thromboembolism is precipitated by three distinct processes: pooling of blood in the veins such as may occur with long-distance air travel; damage to the wall of the vessel; and the presence of any substance that increases the tendency for blood to coagulate, such as oestrogen.
But the increased risk of DVT/PE associated with oral contraceptive use is low in absolute terms. This additional risk generally manifests itself by the fourth month of pill use and disappears about three months after stopping a combined contraceptive pill.
A Dutch study published in the British Medical Journal in 2009 found that, overall, taking the pill was associated with a five-fold increased risk of experiencing a clot.
However, on closer analysis, a variation in risk emerged: women taking pills containing a progestogen called levonorgestrel (for example, Microgynon) had the lowest risk of thrombosis at four times that of women not on the pill; those on contraceptives containing desogestrel (for example, Mercilon or Marvelon) had the highest risk, at seven times that of those not taking the pill; and women taking a pill with norgestimate (for example, Cilest) had an almost sixfold extra risk as did those on drospirenone (for example, Yasmin).
Additional risk
Interestingly, those taking the acne-cum-contraceptive drug Dianette had an almost sevenfold additional risk of venous thromboembolism. Cyproterone acetate, which is a progestogen derivative, works an anti-androgen. Androgens are male hormones and are produced by women as well as men. However, if your body produces too much androgen, this can cause the sebaceous glands in the skin to become blocked, resulting in infection, inflammation and acne spots. The androgens may also cause excessive growth of hair on the face and body (hirsutism).
What to do
So what should women on the pill do? Do not abruptly stop taking your contraceptive. Should you wish to change to an older generation pill, discuss this with your doctor. And if you are taking any combined contraceptive pill or Dianette and notice leg pain, swelling or redness of the calf, or chest pain or breathlessness, you should be assessed medically to check for evidence of a DVT or PE.