Drospirenone detected in postmortem blood of a young woman with pulmonary thromboembolism: A case report and review of the literature

Abstract

Progestin/estrogen oral contraceptives have some side effects, including venous thromboembolism. To alleviate side effects, improvements have been made to low-dose oral contraceptives, including reductions in the amount of estrogen and/or changes the type of progestin. A compound drug containing 3mg drospirenone and 20μg ethinylestradiol (DRSP/EE20, YAZ®) was released in overseas markets in 2006, and in Japan in 2010 as a newly developed low-dose medicines. This drug is expected to have lower side effects. We received a medicolegal autopsy case of a young woman who had been prescribed YAZ for dysmenorrhea for 17months. The autopsy revealed a blood clot in her pulmonary artery bifurcation. Blood screening by ultra-performance liquid chromatography-mass spectrometry analysis did not detect any medicinal toxicants. However, from police investigations, it is strongly believed that she had been taking YAZ. Therefore we performed a single ion resolution mode assay and detected DRSP. A quantitative analysis revealed 32.3ng/mL of DRSP. As no other cause of the pulmonary thromboembolism was evident, we consider YAZ as the likely cause of the pulmonary thromboembolism. Recent reports from the past few years suggest a higher risk of venous thromboembolism with DRSP/EE20 than earlier progestin/estrogen oral contraceptives. Comparing the risk associated with DRSP/EE20 and DRSP/EE30, one report found no differences and another report showed DRSP/EE20 was associated with a higher risk than DRSP/EE30. No cases of thrombosis caused by progestin alone have been reported. But comparing the risk between DRSP/EE20 and other progestins/EE20, two studies reported DRSP/EE20 had a higher risk than other progestins/EE20. The incidence of venous thromboembolism is highest in the first year of use and decreases thereafter. Because DRSP/EE20 has been on the market for only a couple of years, it is necessary for clinicians to use the drug carefully and accumulate more side-effect data. It is important for forensic scientists to confirm all of the prescribed drugs in autopsy cases, search the risks of identified drugs, particularly new drugs, and provide relevant case information in a timely manner.

Keywords: Drospirenone; Ethinylestradiol; Oral contraceptive; Pulmonary thromboembolism; Ultra-performance liquid chromatography–mass spectrometry; YAZ.