Hormone-dependent gynaecological disorders and contraceptive modalities in women with a history of venous thromboembolic event: The THROMBOGYN study.

Hormone-dependent gynaecological disorders, such as polycystic ovary syndrome (PCOS) or endometriosis, have been recently discussed as potential risk factors for venous thromboembolism (VTE). Combined hormonal contraceptive (CHC) therapy, which is a well-known risk factor for VTE, is usually used to alleviate symptoms related to these gynaecological disorders. Nevertheless, prevalence of hormone-dependent gynaecological disorders at the time of VTE event and the management of hormonal contraceptives are not well known. To assess retrospectively the prevalence of hormone-dependent gynaecological disorders in patients with VTE event and the hormonal therapy at the time of VTE event and at the time of inclusion in the present study. Women aged between 18 to 50-year-old who were hospitalized at Saint-Joseph Hospital (Paris) for a VTE event from January 1st, 2016 to December 31st, 2020 were included in this retrospective observational study. In total, 125 women were included. At the time of VTE event, mean age was 39-years-old (±8) and mean body mass index (BMI) 26kg/m2 (±8). Pulmonary embolism represented more than two third (68%) of VTE events. Fourteen women (11%) had PCOS and among them, 6 (43%) were using CHC. Eleven women (9%) had endometriosis and among them, 1 (9%) was using CHC. Women with PCOS appeared to be younger at the time of VTE compared to non-PCOS women (mean age 32 years (±6.0) vs. 40 years (±8.0), respectively, P<0.001), whereas women with endometriosis were older with a mean age of 43-year-old (±7.8), which did not differ significantly from women without endometriosis. Among PCOS women, 1 (7%) VTE event was idiopathic, whereas among those with endometriosis, 5 (46%) VTE events were idiopathic. Regarding contraceptive use at the time of inclusion, with a mean delay between VTE event and inclusion of 3 years (±1), 1 woman pursued CHC, 35 (28%) used non-hormonal contraceptive. Seventy-three women (58%) were aware of hormonal contraindications due to VTE event. The present study, including 125 young women with a mean age of 39 years, allowed a description of gynecological pathologies and history of contraceptive use potentially involved in VTE events.

Mottais-Cosnefroy V ，Pecourt M ，Yannoutsos A ，Fels A ，Beaussier H ，Alran S ，Priollet P ，Hugon-Rodin J ... -  《-》

Hormonal contraceptive use after a first venous thrombotic event and the risk of recurrence in premenopausal women.

Extensive evidence is available on hormonal contraceptive (HC) use and the risk of a first venous thromboembolism (VTE) event. Despite recommendations to discontinue combined HC (CHC) use, some women continue or start its use after a first VTE. We aimed to evaluate the VTE recurrence risk associated with HC use in premenopausal women. Premenopausal women with a first VTE included in the Multiple Environmental and Genetic Assessment of Venous Thrombosis study between 1999 and 2004 were followed for a recurrence until 2010. Data on HC use were available through linkage to the Dutch Foundation for Pharmaceutical Statistics. The risk of recurrence was assessed 1) during anticoagulant therapy and 2) after cessation of anticoagulant therapy. Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs adjusted for age and body mass index at baseline and thromboprophylaxis use during follow-up. Six hundred fifty women were uniquely linked and followed for a total of 3538 person-years (median, 6.1 years), during which 57 VTE recurrences occurred. Five occurred (8.8%) during anticoagulation treatment, with no clear risk difference for CHC use vs nonuse (HR, 0.8; 95% CI, 0.1-8.2). After anticoagulation cessation, CHC use was associated with a 2.4-fold higher risk of recurrence (HR, 2.4; 95% CI, 1.2-5.0) compared with nonuse. Recurrence risk for levonorgestrel-releasing intrauterine device use was similar to that for nonuse (HR, 0.9; 95% CI, 0.3-3.1). CHC use after a first VTE is safe during anticoagulant use but substantially increases the risk of a recurrent VTE event in absence of anticoagulant use. This study adds to the evidence regarding the use of a levonorgestrel-releasing intrauterine device as a safe alternative.

Verlaan JPL ，Stegeman BH ，Timp JF ，Scheres LJJ ，Flinterman LE ，Helmerhorst FM ，Rosendaal FR ，Cannegieter SC ，van Hylckama Vlieg A ... -  《-》

Population-based study of risk of venous thromboembolism associated with various oral contraceptives.

Farmer RD ，Lawrenson RA ，Thompson CR ，Kennedy JG ，Hambleton IR ... -  《LANCET》

Type of Combined Contraceptives, Factor V Leiden Mutation and Risk of Venous Thromboembolism.

This article estimates the interaction between types of combined hormonal contraception (CHC) and factor V Leiden (FVL) mutation on the risk of venous thrombosis event (VTE). All premenopausal women with first incident VTE who were referred to our unit (Paris, France) between 2000 and 2009 were included in this case-only study. Differences in interactions by progestin type were assessed on a multiplicative scale, assuming the independence of genotype and prescription of type of CHC. Among 2,613 women with VTE, 15.9% had a FVL and 69% used CHC. The interaction between CHC use and presence of FVL on VTE risk was statistically significant (1.37, 1.06-1.77 95% confidence interval [CI]). This interaction appeared higher for drospirenone 1.99 (1.18-3.38 95% CI) (n = 98) or cyproterone acetate users 1.71 (1.20-2.45 95% CI) (n = 326), but not significant for 1st or 2nd or norgestimate CHC users. The results were similar when excluding women with a family history of VTE or with provoked VTE. In this sub-group of women, these interactions appeared higher for third generation, cyproterone acetate and drospirenone CHC users as compared with 1st or 2nd or norgestimate CHC users (odds ratio [OR], 1.68 [1.04-2.70; 95% CI], 2.91 [1.71-4.95 95% CI], 3.22 [1.54-6.73 95% CI], respectively). Our results show that the interaction between FVL and CHC use differ by progestin type, which is higher in CHC containing third-generation progestin, drospirenone or cyproterone acetate, compared with second generation. Further studies are needed to assess the cost-effectiveness of biological thrombophilia screening (FVL) when such prescription of CHC is planned.

Hugon-Rodin J ，Horellou MH ，Conard J ，Gompel A ，Plu-Bureau G ... -  《-》

Combined hormonal contraceptive use among obese women and risk for cardiovascular events: A systematic review.

Combined hormonal contraceptive (CHC) use may modify the risk of cardiovascular events in obese [body mass index (BMI) ≥30kg/m2] women. The objective was to evaluate from the literature whether CHC use modifies the risk of acute myocardial infarction (AMI), stroke, cerebral venous thrombosis (CVT) and venous thromboembolism (VTE) in obese women and to evaluate evidence for a dose-response relationship between BMI and VTE. We searched PubMed for all articles published between database inception and February 2016 providing direct evidence on BMI, CHCs, and cardiovascular outcomes. We also searched for indirect evidence related to a dose-response relationship between BMI and risk of VTE in the general population, as these data were lacking for CHC users. The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. The direct evidence search yielded 3 pooled analyses, 11 case-control studies and 1 cohort study. There was conflicting evidence about the risk of AMI or stroke among obese combined oral contraceptive (COC) users compared to obese nonusers, with one study finding no increased risk for AMI or stroke for COC users overall or stratified by BMI. A second study found significantly increased risk of AMI and stroke for COC users, with the highest risk estimates for high-BMI COC users. A single study suggested that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. For VTE, obese COC users consistently had a risk that was 5 to 8 times that of obese nonusers and approximately 10 times that of nonobese nonusers. Five prospective cohort studies were identified as indirect evidence, and all found increased risk for VTE as BMI increased, suggesting a dose-response relationship between BMI and risk for VTE. No studies on the contraceptive patch or vaginal ring were identified that met the inclusion criteria. Limited evidence of Level II-2, fair quality, concerning whether CHC use modifies the risk of AMI and stroke in obese women is inconclusive, while a single study of Level II-2, poor quality, found that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. Both COC use and higher BMI increase risk for VTE, and the greatest relative risks are for those with both risk factors based on a body of evidence graded as Level II-2, fair to poor quality. It is not possible to estimate absolute risk of VTE among women with both of these risk factors; however, the absolute risk of VTE in healthy women of reproductive age is small.

Horton LG ，Simmons KB ，Curtis KM 《-》