Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives.

ABSTRACT: The persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHCs), after their cessation, is unknown but important to guide clinical practice. The objective of this prospective cohort study was to define the time until normalization of estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18 to 50 years who had decided to stop their CHC, excluding those with a personal history of VTE, anticoagulation, or pregnancy. The study started before cessation of CHC, with 6 visits afterwards (at 1, 2, 4, 6, and 12 weeks after cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone-binding globulin (SHBG) as a secondary end point. We also included control women without CHC. Among 66 CHC users, from baseline until 12 weeks, average levels of nAPCsr, nTMsr, and SHBG decreased from 4.11 (standard deviation [SD], 2.06), 2.53 (SD, 1.03), and 167 nmol/L (SD, 103) to 1.27 (SD, 0.82), 1.11 (SD, 0.58), and 55.4 nmol/L (SD, 26.7), respectively. On a relative scale, 85.8%, 81.3%, and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks and 86.7%, 85.5%, and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to 4 weeks of cessation before planned major surgery or withdrawal of anticoagulants in patients with VTE appears sufficient for the majority of women. The trial is registered at www.clinicaltrials.gov as #NCT03949985.

Obstetrical complications in hereditary fibrinogen disorders: the Fibrinogest study.

BACKGROUND: Women with hereditary fibrinogen disorders (HFDs) seem to be at an increased risk of adverse obstetrical outcomes, but epidemiologic data are limited. OBJECTIVES: We aimed to determine the prevalence of pregnancy complications; the modalities and management of delivery; and the postpartum events in women with hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. METHODS: We conducted a retrospective and prospective multicentric international study. RESULTS: A total of 425 pregnancies were investigated from 159 women (49, 95, and 15 cases of hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia, respectively). Overall, only 55 (12.9%) pregnancies resulted in an early miscarriage, 3 (0.7%) resulted in a late miscarriage, and 4 (0.9%) resulted in an intrauterine fetal death. The prevalence of live birth was similar among the types of HFDs (P = .31). Obstetrical complications were observed in 54 (17.3%) live birth pregnancies, including vaginal bleeding (14, 4.4%), retroplacental hematoma (13, 4.1%), and thrombosis (4, 1.3%). Most deliveries were spontaneous (218, 74.1%) with a vaginal noninstrumental delivery (195, 63.3%). A neuraxial anesthesia was performed in 116 (40.4%) pregnancies, whereas general or no anesthesia was performed in 71 (16.6%) and 129 (44.9%) pregnancies, respectively. A fibrinogen infusion was administered in 28 (8.9%) deliveries. Postpartum hemorrhages were observed in 62 (19.9%) pregnancies. Postpartum venous thrombotic events occurred in 5 (1.6%) pregnancies. Women with hypofibrinogenemia were at an increased risk of bleeding during the pregnancy (P = .04). CONCLUSION: Compared with European epidemiologic data, we did not observe a greater frequency of miscarriage, while retroplacental hematoma, postpartum hemorrhage, and thrombosis were more frequent. Delivery was often performed without locoregional anesthesia. Our findings highlight the urgent need for guidance on the management of pregnancy in HFDs.

Prothrombotic biomarkers during controlled ovarian stimulation for assisted reproductive technology.

OBJECTIVE: To assess the impact of 3 different ovarian stimulation protocols on surrogate biomarkers of coagulation. DESIGN: Observational multicenter cohort study. SETTING: The study was conducted in assisted reproductive technology (ART) units. PATIENTS: Infertile women undergoing ART in 2017-2019 were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Our primary outcome was the endogenous thrombin potential (ETP) assessed by the calibrated automated thrombogram. The ETP was measured at baseline (T1), on the day of ovulation triggering (T2), and 7 days after triggering (T3). Three protocols were prescribed according to the standards used and without hormonal before treatment: agonist protocol with human chorionic gonadotropin (hCG) trigger (ag-hCG), antagonist protocol with hCG trigger (atg-hCG), or GnRH agonist trigger. The evolution of ETP was compared among groups using a mixed-effects linear regression model. RESULT(S): Sixty-four women with a mean age of 37.8 years participated in the study: of which 24, 16, 24 received ag-hCG, atg-hCG, and GnRH agonist triggers, respectively. As expected, the mean serum estradiol levels in GnRH agonist trigger were statistically higher at T2 and lower at T3 than that for both ag-hCG and atg-hCG. Overall, the ETP evolution over time was statistically different between the groups. Values were similar between groups at T1 and increased at T2 in each group. The greatest difference occurred between T2 and T3 in each group. The ETP continued to increase at T3 in ag-hCG (+110 nM/L × min) and atg-hCG (+171 nM/L × min), but it remained stable in GnRH agonist trigger (-2 nM/L × min). Sex hormone-binding globulin showed persistent increase at T3 despite the fall in estradiol levels, particularly in the GnRH agonist trigger group. CONCLUSION(S): The ag-hCG and atg-hCG groups were associated with a higher hypercoagulable state at T3 than the GnRH agonist trigger group. However, our results show the persistence of a hypercoagulable state after the GnRH agonist triggering despite a sharp drop in estradiol levels. These findings may support the use of GnRH agonist trigger protocol in patients with high thrombotic risk and gives new insight into the fact that coagulation parameters could be disturbed for long time periods. CLINICAL TRIAL REGISTRATION NUMBER: NCT04188444.

[News on progestatives in gynaecology]. / Actualités sur les progestatifs en gynécologie.

Progesterone (P4), a steroid primarily secreted by the corpus luteum, placenta and adrenal glands, plays an essential role on female reproductive function. Progestins (PS) are synthetic analogues of P4 with specific steroid receptor affinities. A progestin-only-pill (POP) with an antimineralocorticoid effect was recently marketed with a tolerance and safety profile superior to existing POPs. In contrast, PS with antiandrogenic properties used at high doses for the treatment of hirsutism have been associated with an increased meningioma risk. New clinical and fundamental data open paths for research into the therapeutic use of P4 in cognition, neuroprotection and bone.

La progestérone (P4), stéroïde sécrété principalement par le corps jaune, le placenta et les glandes surrénales, joue un rôle essentiel dans le contrôle de la fonction reproductive de la femme. Les progestatifs de synthèse (PS) sont des analogues avec des affinités spécifiques sur les divers récepteurs stéroïdiens. Une pilule progestative (POP) aux effets antiminéralocorticoïdes a récemment été commercialisée avec un profil de tolérance et de sécurité supérieur aux POP existants. En revanche, des PS aux propriétés antiandrogènes utilisés en forte dose pour le traitement de l'hirsutisme ont été associés à un risque accru de méningiome. De nouvelles données cliniques et fondamentales ouvrent de nouvelles voies de recherche sur l'utilisation thérapeutique de la P4 dans les champs de la cognition, de la neuroprotection et de l'os.

Position statement on the diagnosis and management of premature/primary ovarian insufficiency (except Turner Syndrome).

Premature ovarian insufficiency (POI) is a rare pathology affecting 1-2% of under-40 year-old women, 1 in 1000 under-30 year-olds and 1 in 10,000 under-20 year-olds. There are multiple etiologies, which can be classified as primary (chromosomal, genetic, auto-immune) and secondary or iatrogenic (surgical, or secondary to chemotherapy and/or radiotherapy). Despite important progress in genetics, more than 60% of cases of primary POI still have no identifiable etiology; these cases are known as idiopathic POI. POI is defined by the association of 1 clinical and 1 biological criterion: primary or secondary amenorrhea or spaniomenorrhea of>4 months with onset before 40 year of age, and elevated follicle-stimulating hormone (FSH)>25IU/L on 2 assays at>4 weeks' interval. Estradiol level is low, and anti-Müllerian hormone (AMH) levels have usually collapsed. Initial etiological work-up comprises auto-immune assessment, karyotype, FMR1 premutation screening and gene-panel study. If all of these are normal, the patient and parents may be offered genome-wide analysis under the "France Génomique" project. The term ovarian insufficiency suggests that the dysfunction is not necessarily definitive. In some cases, ovarian function may fluctuate, and spontaneous pregnancy is possible in around 6% of cases. In confirmed POI, hormone replacement therapy is to be recommended at least up to the physiological menopause age of 51 years. Management in a rare diseases center may be proposed.

Next Generation Sequencing Should Be Proposed to Every Woman With "Idiopathic" Primary Ovarian Insufficiency.

CONTEXT: Primary ovarian insufficiency (POI) affects 1% of women under 40 years of age. POI is idiopathic in more than 70% of cases. Though many candidate genes have been identified in recent years, the prevalence and pathogenicity of abnormalities are still difficult to establish. OBJECTIVE: Our primary objective was to evaluate the prevalence of gene variations in a large prospective multicentric POI cohort. Our secondary objective was to evaluate the correlation between phenotype and genotype. METHODS: Two hundred and sixty-nine well-phenotyped POI patients were screened for variants of 18 known POI genes (BMP15, DMC1, EIF2S2, FIGLA, FOXL2, FSHR, GDF9, GPR3, HFM1, LHX8, MSH5, NOBOX, NR5A1, PGRMC1, STAG3, XPNPEP2, BHLB, and FSHB) by next generation sequencing (NGS). Abnormalities were classified as "variant" or "variant of unknown signification" (VUS) according to available functional tests or algorithms (SIFT, Polyphen-2, MutationTaster). RESULTS: One hundred and two patients (38%) were identified as having at least 1 genetic abnormality. Sixty-seven patients (25%) presented at least 1 variant. Forty-eight patients presented at least 1 VUS (18%). Thirteen patients (5%) had combined abnormalities. NOBOX variants were the most common gene variants involved in POI (9%). Interestingly, we saw no significant differences in the previous family history of POI, ethnic origin, age at onset of POI, primary amenorrhea, or secondary menstrual disturbances between the different genotypes. CONCLUSION: In our study, a high percentage of patients presented gene variants detected by NGS analysis (38%). Every POI patient should undergo NGS analysis to improve medical cares of the patients.

[Contraception and venous thromboembolism]. / Contraception et maladie thromboembolique veineuse.

Combined oral contraceptives remain in 2020 the most used contraceptive method in Switzerland and Europe, and are found in about half of venous thromboembolism (VTE) occurring in women aged up to 50 years. In this narrative review, we describe the determinants of the VTE risk, related to the types of oral contraceptives and to genetic or acquired risk factors of users, while summarizing several current recommendations of prescription for contraceptives. The complex management of contraception at the time of VTE should be discussed with patients, in order to minimize the risks of undesired pregnancy, abnormal uterine bleeding and recurrent VTE.

En 2020, la contraception orale combinée reste la méthode contraceptive la plus utilisée en Suisse et en Europe, et son usage est retrouvé dans environ la moitié des événements de maladie thromboembolique veineuse (MTEV) des femmes de moins de 50 ans. Dans cette revue narrative, nous décrivons les déterminants du risque de MTEV en fonction du type de contraceptif et des facteurs de risque acquis ou génétiques des utilisatrices, en se basant sur les recommandations actuelles de prescription. La gestion de la contraception lors d'un événement de MTEV reste complexe et doit alors être discutée avec la patiente, afin de minimiser les problèmes de grossesse non désirée, de ménorragies et de récidive thromboembolique.

The effect of mind-body interventions on psychological and pregnancy outcomes in infertile women: a systematic review.

Preliminary evidence suggests that mind-body interventions, including mindfulness-based interventions and yoga, may be effective in reducing mental health difficulties and psychological distress in infertile patients undergoing fertility treatments. We systematically reviewed and synthesized current medical literature of the effectiveness of mind-body interventions in reducing the severity of psychological distress and improving marital function and pregnancy outcomes in infertile women/couple. Databases including PsychINFO, PubMed, EMBASE, and the Cochrane Library were searched for relevant studies. Manual searches were conducted in relevant articles. We included 12 studies that met the inclusion criteria. Four studies were randomized controlled trials (RCT), 4 non-randomized controlled trial (NRCT), and 4 uncontrolled studies (UCT). Participation in a mind-body intervention was associated with reduced anxiety trait and depression scores. The reduction was of low or moderate amplitude in most studies. Our review offers evidence for the effectiveness of mind-body interventions in reducing anxiety state and depression in infertile women and a possible improvement in pregnancy rate. Further RCTs with a precise timing of intervention are needed.

Migraine in relation with endometriosis phenotypes: Results from a French case-control study.

BACKGROUND: Studies have shown a significant association between migraine and endometriosis, but no study has explored the relationship between migraine and endometriosis phenotypes: Superficial peritoneal endometriosis, ovarian endometrioma, and deep infiltrating endometriosis. METHODS: We conducted a case-control study using data collected from 314 women aged 18 to 42 years who had undergone surgery for benign gynecological conditions between January 2013 and December 2015. All women completed a self-administered headache questionnaire according to the IHS classification. Cases (n = 182) are women with histologically proven endometriosis and controls are women (n = 132) without endometriosis. Occurrence of migraine was studied according to endometriosis phenotypes. RESULTS: Migraine prevalence in cases was significantly higher compared with controls (35.2% vs. 17.4%, p = 0.003). The risk of endometriosis was significantly higher in migrainous women (OR = 2.62; 95% CI = 1.43-4.79). When we take into account endometriosis phenotypes, the risk of ovarian endometrioma and deep infiltrating endometriosis were significant (OR = 2.78; 95% CI = 1.11-6.98 and OR = 2.51; 95% CI = 1.25-5.07, respectively). In women with endometriosis, the intensity of chronic non-cyclical pelvic pain was significantly greater for those with migraine (visual analogic scale (VAS) = 3.6 ± 2.9) compared with the women without headache (VAS = 2.3 ± 2.8, p = 0.0065). CONCLUSION: Our study shows a significant association between migraine and endometriosis. In clinical practice, women of reproductive age who suffer from migraine should be screened for endometriosis criteria in order to optimise the medical and therapeutic care of this condition.

Association between polycystic ovary syndrome and venous thromboembolism: A systematic review and meta-analysis.

AIMS: Polycystic ovary syndrome (PCOS) is very prevalent and commonly treated with prothrombotic combined oral contraceptives (COC). Our aim was to systematically review the available evidence to evaluate the risk of venous thromboembolism (VTE) associated with PCOS, and whether observed increased risks may be explained by a higher prevalence of obesity and hormonal treatments. METHOD: For this systematic review and meta-analysis, two authors independently searched MEDLINE, EMBASE and conference proceedings (ISTH, WHITH) from inception through 4.2019 for studies reporting the association of PCOS with VTE risk. Study quality was assessed and relative risk estimates were pooled through random effect models. RESULTS: We identified 5 large observational studies published between 2004 and 2018, most commonly using administrative data, set in Denmark, the USA or the United Kingdom. Compared with participants without PCOS, participants with PCOS had greater risks of VTE in unadjusted analyses (pooled OR 1.70, 95%CI 1.42-2.04, I2 67%). In three studies reporting analyses adjusted for at least obesity and hormonal treatments, PCOS was still associated with greater risks of VTE (pooled OR 1.89, 95%CI 1.60-2.24, I2 27%). CONCLUSIONS: PCOS appears to be a risk factor for VTE, independently of its associated excess weight and greater use of combined oral contraceptives. This should be taken into account in the pharmacological management of PCOS.

[Hypertension and contraception]. / Hypertension artérielle et contraception.

Hypertension is a major risk factor for cardiovascular diseases. Because of the high frequency of hormonal contraceptives use, assessing their side effects is an important public health issue. In this perspective, we conducted a review of the risk of hypertension associated with the use of hormonal contraceptives, either combined estrogen-progestin or only progestin. The use of combined hormonal contraceptives, regardless of its type and route of administration, is associated with a slight increase in blood pressure, both systolic and diastolic blood pressures. The frequency of onset of hypertension in women who use combined hormonal contraception is between 0.6% and 8.5%. Progestin-only contraception seems safe with respect to the risk of hypertension. It is therefore important to remember that the use of combined hormonal contraception is contra-indicated in hypertensive women, even well controlled. Finally, we propose a prescription assistance algorithm according to the recommendations of an expert panel. It should be remembered that taking blood pressure at each contraceptive consultation (initial and follow-up) is essential.

Obstetrical and postpartum complications in women with hereditary fibrinogen disorders: A systematic literature review.

INTRODUCTION: Hereditary fibrinogen disorders (HFD) are rare quantitative or qualitative fibrinogen anomalies, including afibrinogenaemia (A), hypofibrinogenaemia (H), dysfibrinogenaemia (D) and hypodysfibrinogenaemia (HD). As fibrinogen plays an essential role in pregnancy, we addressed the issue of obstetrical and postpartum complications in women with HFD. METHODS: A systematic literature review, restricted to English manuscripts, was conducted according to the PRISMA guidelines. We searched through the MEDLINE database for English articles, published from January 1985 until November 2018, focusing on pregnancy in A, H, D and HD. A total of 198 articles were identified, 15 articles were added from other sources. Overall, 213 articles were screened and 54 were included in the final analysis. RESULTS: A total of 188 pregnancies from 70 women were analysed. About half of pregnancies resulted in miscarriage; more specifically in 15 (42.9%), 36 (46.8%), 27 (42.9%) and 4 (30.8%) of A, H, D and HD patients, respectively. Preterm complications were also frequent (33.5%). Metrorrhagia, mainly in the first trimester, was observed in 21.7% of the pregnancies. Placenta abruption was reported in 5 (14.3%), 4 (5.2%), 5 (7.9%) and 1 (7.7%) of A, H, D and HD, respectively. A total of 24 (12.7%) deliveries were complicated by postpartum thrombotic events (3.2%) or postpartum haemorrhage (9.6%). A fibrinogen replacement therapy was introduced in 30% of pregnancies, as prophylaxis (81.1%) or on demand (18.9%). CONCLUSION: These results suggest that women with HFD are at high risk of obstetrical and postpartum complications. Prospective international registries may allow to identify more precisely the incidence of obstetrical and postpartum adverse outcomes and their management.

Shedding light on the fertility preservation debate in women with endometriosis: a swot analysis.

Endometriosis, a hormone-dependant condition affecting around 10% of women in their reproductive years, has frequent consequences on fertility. Indeed, a proportion of women will require assisted reproductive techniques or surgery in order to achieve pregnancy. Recent refining of stimulation protocols and vitrification techniques has created new possibilities in the field of fertility preservation. As a consequence, oocyte vitrification is now discussed not only in oncologic situations, but also in other conditions at risk of altered ovarian reserve and poor fertility outcome. In endometriosis, various mechanisms can impair ovarian function and diminish ovarian, particularly bilateral or repeated cystectomy. Fertility preservation could represent an option for women with endometriosis but still remains controversial. In order to shed some light on this complex subject and to outline different issues at stake we conducted a SWOT analysis highlighting strengths, weaknesses, opportunities and threats of oocyte vitrification in women with endometriosis.

Complete Kisspeptin Receptor Inactivation Does Not Impede Exogenous GnRH-Induced LH Surge in Humans.

Context: Mutations in the kisspeptin receptor (KISS1R) gene have been reported in a few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). Objectives: To describe a female patient with nCHH and a novel homozygous KISS1R mutation and to assess the role of kisspeptin pathway to induce an ovulation by GnRH pulse therapy. Design, Setting, and Intervention: Observational study of a patient including genetic and kisspeptin receptor functions and treatment efficiency using a GnRH pump. Main Outcome Measure: Response to pulsatile GnRH therapy. Results: A partial isolated gonadotropic deficiency was diagnosed in a 28-year-old woman with primary amenorrhea and no breast development. A novel homozygous c.953T>C variant was identified in KISS1R. This mutation led to substitution of leucine 318 for proline (p.Leu318Pro) in the seventh transmembrane domain of KISS1R. Signaling via the mutated receptor was profoundly impaired in HEK293-transfected cells. The mutated receptor was not detected on the membrane of HEK293-transfected cells. After several pulsatile GnRH therapy cycles, an LH surge with ovulation and pregnancy was obtained. Conclusion: GnRH pulsatile therapy can induce an LH surge in a woman with a mutated KISS1R, which was previously thought to be completely inactivated in vivo.

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

OBJECTIVE: 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). SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Hormonal contraception and vascular risk]. / Contraception hormonale et risque vasculaire.

Hormonal contraception and vascular risk. Since the early 1960, it has been well documented that combined hormonal contraceptives (CHC) increase the risk of venous thromboembolism diseases (VTE) and arterial diseases, even if it is an uncommon disease before menopause. Vascular risk is the most important determinant of the benefit/ risk profile of hormonal contraceptive. The most recent pills are associated with a higher risk of VTE than second- generation pill. CHC increase the risk of arterial disease (myocardial infarction or ischemic stroke), especially in women at high vascular risk. This increase does not depend on the generation of CHC. A meticulous research of vascular risk factors, including familial history of VTE, is recommended before prescription. It allows to adapt the contraceptive strategy for every woman according to the bene- fit/risk profile. In context of high vascular risk, low doses of both oral progestin contraceptives and intrauterine levonorgestrel could be safe with respect to VTE risk.

Contraception hormonale et risque vasculaire. La contraception hormonale demeure la contraception la plus utilisée en France. Les événements vasculaires représentent les principaux effets délétères de la contraception estroprogestative ou contraception hormonale combinée. De très nombreuses études épidémiologiques ont analysé le lien entre l'utilisation d'une contraception hormonale et le risque vasculaire. Les pilules les plus récentes sont associées à un risque de thrombose veineuse plus important que les pilules dites de 2e génération, contenant du lévonorgestrel. La contraception hormonale combinée, quel qu'en soit le type, augmente le risque d'accident artériel. Une recherche minutieuse des facteurs de risque, notamment des antécédents familiaux de thrombose, est recommandée avant toute prescription mais aussi lors du suivi. Une stratégie contraceptive doit être proposée et adaptée à chaque situation clinique afin d'en optimiser la balance béné- fice-risque. La contraception combinée est contre-indiquée formellement chez les femmes à haut risque vasculaire quelle que soit la voie d'administration et quel que soit le type d'estrogène ou de progestatif combiné. Dans ce contexte, les contraceptions progestatives - en dehors la contraception injectable - sont, dans la plupart des cas, autorisées.

Combined Hormonal Contraceptives and First Venous Thrombosis in Young French Women: Impact of Thrombotic Family History.

CONTEXT: In UK and French, but not World Health Organization (WHO), guidelines for combined hormonal contraception (CHC), family history of a venous thromboembolism (VTE) is a condition for which the theoretical risks usually outweigh the advantages of using CHC. OBJECTIVE: We estimated the prevalence of inappropriate prescriptions of CHC according to several international guidelines and their impact on VTE. DESIGN: A single-center observational study. SETTING: Hemostasis unit outpatient clinic (Paris, France). POPULATION: A total of 2088 French CHC users of childbearing age with a first documented VTE who were referred to our unit between 2000 and 2009. METHODS: Data were collected by a standardized questionnaire during a medical consultation. Family history of VTE was analyzed according to definitions from international recommendations (VTE before age 45 years, United Kingdom; before age 50 years, France). A CHC prescription was considered inappropriate for women with vascular contraindications and/or a family history of VTE. Cross-sectional analysis of the clinical and biological characteristics was performed. MAIN OUTCOME MEASURES: Prevalence of inappropriate prescription of CHC and potentially preventable events were estimated. RESULTS: According to the WHO, UK, or French guidelines, 8.8%, 18.9%, and 25.9%, respectively, of CHC prescriptions were considered inappropriate. Compliance with these guidelines could reduce the corresponding number of VTEs by 6.3%, 13.5%, and 18.5%, respectively. Characteristics of the women were similar. CONCLUSION: Our results suggest inappropriate CHC prescriptions are prevalent among CHC users with first VTE. The appropriate way to take family history of VTE into account should be further clarified.

[Hormonal treatments and venous thrombosis in women]. / Traitements hormonaux et risque de thrombose veineuse chez la femme.

Venous thromboembolism is frequently associated with hormonal factors in women. A thorough medical history taking of vascular risks and an individual evaluation of the risk-benefit ratio should precede any prescription of hormonal therapies. In contrary to progestin-only-pills, estroprogestative contraceptives increase 3-6 times the risk of venous thrombosis. In assisted reproductive techniques, venous thrombosis is frequently associated with the occurrence of a severe ovarian hyperstimulation syndrome. Antagonist ovarian stimulation protocols lower the risk of hyperstimulation and should therefore be preferred. Finally, at menopause, hormonal treatments combining transdermal estradiol and micronized progesterone do not seem to increment the risk of thrombosis.

La maladie veineuse thromboembolique est fréquemment associée aux facteurs hormonaux chez la femme. La prescription de toute thérapeutique hormonale sera précédée d'un interrogatoire minutieux à la recherche de facteurs de risque vasculaires et d'une évaluation individuelle de la balance bénéfice-risque. Contrairement à la contraception micro-progestative, la contraception œstroprogestative augmente le risque de thrombose veineuse de 3 à 6 fois. En procréation médicalement assistée, la thrombose veineuse est fréquemment associée à la survenue d'un syndrome d'hyperstimulation ovarienne sévère. Les protocoles de stimulation antagonistes minimisant le risque d'hyperstimulation ovarienne sont donc à privilégier. Enfin, après la ménopause, le traitement hormonal associant de l'œstradiol par voie percutanée et de la progestérone micronisée ne semble pas augmenter le risque de thrombose veineuse.

First venous thromboembolism and hormonal contraceptives in young French women.

Information on the clinical and biological characteristics of combined hormonal contraceptives (CHC) users experiencing a venous thromboembolism (VTE) event is scarce. Better knowledge of factors determining the VTE risk in CHC users could help identify women at high risk.Data were obtained from a large cohort of consecutive women with the first documented VTE event. Cross-sectional analysis of clinical and biological characteristics of the women was performed.Of the 3009 women with the first VTE included, 31% were nonusers and 69% CHC users at time of VTE. CHC users were significantly younger (29.0 ±â€Š7.2) than nonusers (31.6 ±â€Š7.1) (P < .001). No difference in VTE familial history was observed between the 2 groups. Compared with nonusers, the CHC users experienced more frequently pulmonary embolism: odds ratio (OR) = 1.28 (1.06-1.55; 95% confidence interval [CI]), factor V Leiden mutations were more frequent in this group (OR = 1.41 [1.11-1.80; 95% CI]). Venous sclerotherapy and travel were associated with VTE in CHC users, whereas surgery and bed rest were significantly associated with VTE in nonusers. Finally, 2/3 of CHC users with VTE had additional VTE risk factors.CHC users experiencing the first VTE differ from nonusers with respect to clinical and genetic background. Better understanding of the characteristics of VTE and associated risk factors could allow more appropriate management of these women and contribute to more accurate benefit-risk assessment before prescribing a CHC.