Risks of venous thromboembolic complications in related to combined oral contraceptives

Hormonal contraception is the most popular and effective reversible method for preventing unwanted pregnancy exerting multiple prophylactic and therapeutic effect along with contraceptive activity. The main adverse coupled to combined oral contraceptives (COCs) is its impact on the hemostasis and increased risk of venous thromboembolic complications. A great evolutionary path has been travelled after beginning application of hormonal contraception to reduce dose of its estrogen component and improving quality of gestagen component. Nevertheless, thrombotic complications related to COCs use still remain a pressing issue not only due to disease severity and high mortality rate from pulmonary embolism (PE), but also due to the difficulties in its timely diagnostics. Here we describe a clinical case of a 19-year-old patient suffering from vena cava inferior thrombosis complicated by PE after using COCs.

Observational Study for Adverse Effects and Discontinuation with Long-Term Post-Operative Hormonal Treatment for Endometriosis in Real-World Practice

Objectives: To evaluate the side effects and causes of discontinuation of either combined oral contraceptives or dienogest (DNG) used to prevent recurrence in patients with surgically confirmed endometriosis.Methods: We retrospectively analyzed the medical records of 213 women with endometriosis who had been treated with combined oral contraceptives (ethinyl estradiol 0.02 mg/drospirenone 3 mg [EE/DRSP]) or DNG 2 mg for 12 months or more. The side effects reported by the patients, laboratory parameters, causes of discontinuation of medication, and recurrence rates were evaluated one, two, three, four, and five years after starting medication (Y1, Y2, Y3, Y4, and Y5).Results: EE/DRSP were administered to 59 patients, while DNG was administered to 154 patients. The mean durations of postoperative use of EE/DRSP and DNG were 44.5 ± 22.6 months and 23.6 ± 13.5 months, respectively. The prevalence of side effects was 27.1%, 19.0%, 10.0%, 10.5%, and 7.4% in the EE/DRSP group and 29.2%, 15.7%, 14.0%, 23.1%, and 0.0% in the DNG group at Y1, Y2, Y3, Y4, and Y5, respectively. The discontinuation rates were 1.7%, 1.7%, 4.0%, 0.0%, and 7.4% at Y1, Y2, Y3, Y4, and Y5, respectively, in the EE/DRSP group and 10.4%, 3.3%, 4.0%, 3.8%, and 0.0% at the same times in the DNG group. The recurrence rates were less than 4% in both the groups.Conclusions: The side effects of commonly prescribed postoperative hormone treatments were relatively mild, and the occurrence of side effects decreased with continuous administration. Further, the long-term use of postoperative hormone treatments is likely to prevent recurrence of endometriosis after surgery.

Consulting a Patient on Hormonal Contraception: A Clinical Case of Vulvar Vestibulitis

This article presents a clinical case of a 23-year-old female who developed vulvodynia and dyspareunia while taking combined oral contraceptives (OCs). The case study shows that physicians should not recommend any combination of OCs over another to reduce weight gain, headache, breast tenderness, breakthrough bleeding, sexual dysfunction, dyspareunia, and decreased libido. Hormonal contraception counseling should be based on known, evidence-based recommendations and not be limited to the unnecessary substitution of one drug for another.

Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk

Many factors must be considered and discussed with women when initiating a contraceptive method and the risk of venous thromboembolism (VTE) is one of them. In this review, we discuss the numerous strategies that have been implemented to reduce the thrombotic risk associated with combined oral contraceptives (COCs) from their arrival on the market until today. Evidences suggesting that COCs were associated with an increased risk of VTE appeared rapidly after their marketing. Identified as the main contributor of this risk, the dosage of the estrogen, i.e., ethinylestradiol (EE), was significantly reduced. New progestins were also synthetized (e.g., desogestrel or gestodene) but their weak androgenic activity did not permit to counterbalance the effect of EE as did the initial progestins such as levonorgestrel. Numerous studies assessed the impact of estroprogestative combinations on hemostasis and demonstrated that women under COC suffered from resistance towards activated protein C (APC). Subsequently, the European Medicines Agency updated its guidelines on clinical investigation of steroid contraceptives in which they recommended to assess this biological marker. In 2009, estradiol-containing COCs were marketed and the use of this natural form of estrogen was found to exert a weaker effect on the synthesis of hepatic proteins compared to EE. In this year 2021, a novel COC based on a native estrogen, i.e., estetrol, will be introduced on the market. Associated with drospirenone, this preparation demonstrated minor effects on coagulation proteins as compared with other drospirenone-containing COCs. At the present time, the standard of care when starting a contraception, consists of identifying the presence of hereditary thrombophilia solely on the basis of familial history of VTE. This strategy has however been reported as poorly predictive of hereditary thrombophilia. One rationale and affordable perspective which has already been considered in the past could be the implementation of a baseline screening of the prothrombotic state to provide health care professionals with objective data to support the prescription of the more appropriate contraceptive method. While this strategy was judged too expensive due to limited laboratory solutions, the endogenous thrombin potential-based APC resistance assay could now represent an interesting alternative.

Polycystic Ovary Syndrome, Combined Oral Contraceptives, and the Risk of Dysglycemia: A Population-Based Cohort Study With a Nested Pharmacoepidemiological Case-Control Study

<b>Objectives: </b>Irregular menstrual cycles are associated with increased cardiovascular mortality. Polycystic ovary syndrome (PCOS) is characterized by androgen excess and irregular menses; androgens are drivers of increased metabolic risk in women with PCOS. Combined oral contraceptives (COCPs) are used in PCOS both for cycle regulation and to reduce the biologically active androgen fraction. We examined COCP use and risk of dysglycemia (pre-diabetes and type 2 diabetes) in women with PCOS. <p><b>Research Design and Methods: </b>Utilizing a large UK primary care database (The Health Improvement Network, THIN; 3.7 million patients from 787 practices), we carried out a retrospective population-based cohort study to determine dysglycemia risk (64,051 women with PCOS, 123,545 matched controls), as well as a nested pharmaco-epidemiological case-control study to investigate COCP use in relation to dysglycemia risk (2407 women with PCOS with [=cases] and without [=controls] a diagnosis of dysglycemia during follow-up).<b> </b>Cox models were used to estimate the unadjusted and adjusted hazard ratio and conditional logistic regression was used to obtain adjusted odds ratios (aORs). </p> <p><b>Results: </b>The adjusted hazard ratio for dysglycemia in women with PCOS was 1.87 (95% CI 1.78-1.97, p<0.001; adjustment for age, social deprivation, BMI, ethnicity, and smoking), with increased rates of dysglycemia in all BMI subgroups. Women with PCOS and COCP use had a reduced dysglycemia risk (aOR 0.72, 95% CI 0.59 to 0.87).</p> <p><b>Conclusions: </b>In this study limited by its retrospective nature and the use of routinely collected electronic general practice record data, which does not allow to exclude the impact of prescription-by-indication bias, women<b> </b>with PCOS exposed to COCPs had a reduced risk of dysglycemia across all BMI subgroups. Future prospective studies should be considered to further understand these observations and potential causality. </p>