Editorial (Debating the Evidence: Oral Contraceptives Containing Drospirenone and Risk of Blood Clots)

Skepticism is an essential quality in science. We doubt, re-examine and demand the highest quality of evidence. However, sometimes this puts us in an awkward situation. How much evidence do we need before we act? This dilemma is a constant problem in drug safety. Treatment decisions are always a balance of risks and benefits and there may be a paucity of evidence about rare or very rare adverse events. Recently, two important nested case-control studies have been published that have brought drug safety once again into the spotlight of the global media. A study using the UK general practice research database [1] and a study using a US database of claims paid by managed care plans [2], with both studies concluding that oral contraceptives containing drospirenone had an increased risk of venous thromboembolism (VTE) compared to earlier generation oral contraceptives. Earlier studies from Denmark and the Netherlands that reached similar conclusions had been criticised for methodological concerns [3]. Other studies have not found an increase in VTE with drospirenone containing oral contraceptives compared to other oral contraceptives [4]. It has been argued that estrogen independent of progestogen is the cause of VTE associated with oral contraceptives [3]. Previous generations of oral contraceptives are also associated with an increased risk of VTE and reports of this increase risk resulted in changes in prescription patterns, which may have led to fewer cases of VTE [5]. To add to this dilemma, risk of VTE is compounded by other risk factors, including age, obesity and smoking [6]. Given the evidence, our strategy as always is to balance the risks and benefits of treatment. Regulatory bodies at a population level, clinicians and their patients at an individual level. The risk of VTE associated with drospirenone containing oral contraceptive use is very low, however it is a serious and sometimes fatal adverse effect. The benefits of oral contraceptives on an individual's lifestyle may be enormous, as has been the impact of oral contraception on societal change. However, these are not health benefits and attempting to balance them against a health risk requires assigning a subjective value to them. Additionally, many other forms of contraception are available, including earlier and possibly safer forms of oral contraception. Then there are inter-individual differences, where for some people substituting one form of contraception for another is simple, whereas for others it is unimaginable. Given the level of complexity, most people will quite rightly turn to the regulatory authorities and leading scientists and academics for guidance. The U.S. Food and Drug Administration (FDA) issued a communication giving useful advice, but not taking a firm stand one way or the other with regards to the safety of these drugs. They are waiting for the results of their own review [7]. Recent guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC) firmly conclude that there is no increased risk of VTE with drospirenone containing oral contraceptive and suggest that concerns over safety are a media driven “pill scare” [8], however, these guidelines were written prior to the publication of the two recent studies that have caused the latest controversy.....