Drosperinone is a hormone that is included in the most recent generation of birth control pills such as Yaz and Yasmin. While birth control pills that contain drospirenone are effective for preventing unwanted pregnancies, they have been shown to increase the risk of blood clots. This increased risk of blood clots associated with their use has received attention from regulatory agencies such as the European Medicines Agency, Health Canada, and the US Food and Drug Administration, who issued warnings regarding this potential drug side effect in 2011. This is not the first time that regulatory agencies issued warnings regarding the risk of blood clots with birth control pills. In the 1990’s, warnings were issued regarding the blood clot risk of third generation birth control pills, which resulted in several women stopping their birth control pills during the so-called ‘pill scare’. Previous studies have shown that the ‘pill scare’ of the 1990s resulted in an increase in the number of pregnancies and induced abortions. However, little is known about the impact of the drospirenone safety concerns on the number of pregnancies or the number of induced abortions in the United Kingdom. To address this issue, we will use an analytical approach called interrupted time series analysis that will examine the number of pregnancies and induced abortions in the United Kingdom before and after this most recent pill scare, comparing the observed numbers to those that would have been expected to occur in the absence of this most recent pill scare.
Fourth generation combined oral contraceptives (COCs) entered the market in the early 2000’s and contain the progestin drosperinone. Drosperinone-containing COCs have been shown to be effective for the prevention of unwanted pregnancies and for the treatment of acne. However, they have also been associated with an increased risk of venous thromboembolism (VTE), including pulmonary embolism and deep vein thrombosis, relative to second generation (levonorgestrel) COCs. Regulatory agencies such as the European Medicines Agency (EMA), Health Canada, and the U.S. Food and Drug Administration issued warnings regarding this increased VTE risk in 2011. This was not the first time that regulatory agencies issued warnings regarding the VTE risk of COCs; concerns regarding the safety of third generation COCs resulted in the ‘pill scare’ of the 1990s, during which thousands of women discontinued their COCs due to concerns regarding the VTE risk. As a result of this discontinuation, there was a large number of pregnancies and induced abortions. However, the impact of the drospirenone-containing COC pill scare on the rates of pregnancy and induced abortions in the United Kingdom remain poorly delineated. We will use the Clinical Practice Research Datalink (CPRD) Gold and its Pregnancy Register to conduct a retrospective cohort study with interrupted time series analysis to describe the impact of the EMA warning regarding the VTE risk of drosperinone-containing COCs on: 1) rates of pregnancy and induced abortion; and 2) prescription rates of COCs overall and by generation. Inclusion will be restricted to all women aged 15 to 45 years in the CPRD, and the study period will be 2000 to 2019. Prescription rates will be defined by quarter, and the impact of the regulatory warnings will be assessed using interrupted time series analyses. We will conduct extensive sensitivity analyses to assess the robustness of the results
• Rate of pregnancy
• Rate of induced abortion
• Prescription rates of COCs overall and by generation (drospirenone-containing COCs; other fourth generation COCs, third generation COCs, second generation COCs, first generation COCs, progestin only COCs, and hormone coated intrauterine devices).
• Rate of urinary tract infections
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Reem Masarwa - Collaborator - PPD North America
Robert Platt - Collaborator - McGill University
Samuel Igweokpala - Collaborator - McGill University
Reem Masarwa - Collaborator - McGill University
Pregnancy Register