This paper reviews the risk of thrombosis with use of different types of hormonal contraception in women of different ages. AREAS COVERED: Combined hormonal contraceptives with desogestrel, gestodene, drospirenone or cyproterone acetate (high-risk products) confer a sixfold increased risk of venous thromboembolism as compared with nonusers, and about twice the risk as compared with users of products with norethisterone, levonorgestrel or norgestimate (low-risk products). Transdermal patches and vaginal ring belong to high-risk products. The risk of thrombotic stroke and myocardial infarction is increased 50 - 100% with use of combined products, with little difference in risk between different progestins. Progestin-only products do not confer any increased risk of venous or arterial thrombosis, except for progestin depot, which may double the risk of venous thrombosis. EXPERT Opinion: First choice in women below 35 years should be a combined low-risk pill, that is, with a second-generation progestin, with the lowest compliable dose of estrogen. Young women with risk factors of thrombosis such as age above 35 years, genetic predispositions, adiposity, polycystic ovary syndrome, diabetes, smoking, hypertension or migraine with aura should not use high-risk products, but should primarily consider progestin-only products, and be careful to use low-risk combined products.
Farris M et al., 2025·Expert review of clinical pharmacology
Pincus and his group's initial research on hormonal contraception focused on progesterone. However, the natural compound could not be utilized in clinical practice because of the high incidence of breakthrough bleeding and its low oral availability. This led to the introduction of orally active progestins. The estrogen was added to ensure proper cycle control. Concern about side effects of combined oral contraceptive pills (COC) and specifically the increased occurrence of thromboembolism was raised at the very early stages of clinical use. These were attributed to the estrogenic component, ethinyl estradiol (EE). The first pill scare followed the publication in 1977 of evidence of thromboembolism-related mortality in COC users. This and subsequent alarming publications acted as the engine for a successful attempt to substantially decrease the daily content of EE in a COC. Over time, adverse events were also reported for the newer progestins compared to levonorgestrel. Attempts have been made to utilize natural estrogens in COC based on the assumption that this will reduce adverse effects. The wide range of progestins available for use in COC renders comparisons between preparations more challenging. Each progestin has its own androgenic, antiandrogenic, antiestrogenic, and mineralocorticoid activity and, consequently, a unique risk and benefit profile.
Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and cerebral VT. To provide a current comprehensive overview of the risk of objectively confirmed VT with HC in healthy women compared to nonusers. Methods: PubMed was searched from inception to April 2018 for eligible studies in the English language, with hand searching from past systematic reviews.
We selected original research evaluating risk of objectively confirmed VT in healthy women taking oral or nonoral HC compared with nonusers. The primary outcome of interest was a fatal or nonfatal VT in users of HC compared to nonusers or past users. Studies with at least twenty events were eligible. Adjusted relative risks with 95 percent confidence intervals were reported. Three independent reviewers extracted data from selected studies. 1,962 publications were retrieved through the search strategy, with 15 publications included. Users of oral contraception with levonorgesterol had increased risk of VT by a range of 2.79-4.07, while other oral hormonal preparations increased risk by 4.0-48.6. Levonorgestrel intrauterine devices did not increase risk. Etonogestrel/ethinyl estradiol vaginal rings increased the risk of VT by 6.5. Norelgestromin/ethinyl estradiol patches increased risk of VT by 7.9. Etonogestrel subcutaneous implants by 1.4 and depot-medroxyprogesterone by 3.6. The risk of fatal VT was increased in women aged fifteen to twenty-four by 18.8-fold. Users of HC have a significant increased risk of VT compared to nonusers. Current risks would project at least 300-400 healthy young women dying yearly in the United States due to HC. Women should be informed of these risks and offered education in fertility-awareness-based methods with comparable efficacy for family planning.
HC is widely used throughout the world and has been associated with blood clots in the legs and lungs. We searched the literature and found the risks of currently used forms of birth control increased between threeand ninefold for blood clots for healthy women. The risks found would project 300-400 women dying from using HC each year in the United States.
The "International Active Surveillance Study of Women Taking Oral Contraceptives" investigated the risks of shortand long-term use of an extended 24-day regimen of drospirenone and ethinylestradiol (DRSP24d) compared to established oral contraceptives (OCs) in a routine clinical setting. Prospective, controlled, noninterventional cohort study conducted in the United States and six European countries new users of DRSP24d, DRSP21d (21-day regimens of DRSP-containing OCs), and non-DRSP (OCs without DRSP). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious clinical outcomes, in particular venous thromboembolism (VTE). Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models. Primary statistical variable was the VTE hazard ratio (HR) for DRSP24d vs. non-DRSP. A total of 2285 study centers enrolled 85,109 women. Study participants were followed for 2 to 6 years, which generated 206,296 woman-years (WY) of observation. A low loss to follow-up of 3.3% was achieved. DRSP24d, DRSP21d, non-DRSP and levonorgestrel-containing OCs (LNG) showed similar incidence rates of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events. VTE incidence rates for DRSP24d, DRSP21d, non-DRSP and LNG were 7.2, 9.4, 9.6 and 9.8 VTE/10,000 WY, respectively. Adjusted HRs for DRSP24d vs. non-DRSP and DRSP24d vs. LNG were 0.8 [95% confidence interval (CI), 0.5-1.3] and 0.8 (95% CI, 0.4-1.5). DRSP24d, DRSP21d, non-DRSP and LNG use was associated with similar risks of serious adverse events, and particularly VTE, during routine clinical use. The 24-day regimen of drospirenone-containing combined OCs is associated with similar risks of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events compared to 21-day regimens of drospirenone-containing combined OCs, OCs without drospirenone and LNGs.