Emergency contraception: potential role of ulipristal acetate

Unintended pregnancy is a global reproductive health problem. Emergency contraception (EC) provides women with a safe means of preventing unwanted pregnancies after having unprotected intercourse. While 1.5 mg of levonorgestrel (LNG) as a single dose or in 2 doses with 12 hours apart is the currently gold standard EC regimen, a single dose of 30 mg ulipristal acetate (UPA) has recently been proposed for EC use up to 120 hours of unprotected intercourse with similar side effect profiles as LNG. The main mechanism of action of both LNG and UPA for EC is delaying or inhibiting ovulation. However, the ‘window of effect’ for LNG EC seems to be rather narrow, beginning after selection of the dominant follicular and ending when luteinizing hormone peak begins to rise, whereas UPA appears to have a direct inhibitory effect on follicular rupture which allows it to be also effective even when administered shortly before ovulation, a time period when use of LNG is no longer effective. These experimental findings are in line with results from a series of clinical trials conducted recently which demonstrate that UPA seems to have higher EC efficacy compared to LNG. This review summarizes some of the data available on UPA used after unprotected intercourse with the purpose to provide evidence that UPA, a new type of second-generation progesterone receptor modulator, represents a new evolutionary step in EC treatment

Emergency contraception -mechanisms of action

Abstract Concerns regarding the mechanisms of action of emergency contraception (EC) create major barriers to widespread use and could also lead to incorrect use of EC and overestimation of its effectiveness. While the copper intrauterine device (Cu-IUD) is the most effective method available for EC, the hormonal methods are frequently considered to be more convenient and acceptable. Today, the most commonly used method for hormonal EC is levonorgestrel (LNG). More recently, the progesterone receptor modulator ulipristal acetate (UPA) has been shown to be more effective than LNG to prevent an unwanted pregnancy. The main mechanism of action of both LNG and UPA for EC is delaying or inhibiting ovulation. However, UPA appears to have a direct inhibitory effect on follicular rupture which allows it to be effective even when administered shortly before ovulation, a time period when use of LNG is no longer effective. The main mechanism of action of the Cu-IUD is to prevent fertilization through the effect of Cu ions on sperm function. In addition, if fertilization has already occurred, Cu ions influence the female reproductive tract and prevent endometrial receptivity. Based on this review of the published literature, it can be concluded that existing methods used today for EC act mainly through inhibition of ovulation or prevention of fertilization. An additional effect on the endometrium as occurs for the Cu-IUD, but not for the hormonal alternatives, seems to increase the efficacy of the method

Thirty years of mirena : A story of innovation and change in women's healthcare

Since its introduction in 1990, the levonorgestrel-releasing intrauterine system (LNG-IUS) has played a key role in shaping the healthcare landscape of women. Here we explore the development of the first LNG-IUS (Mirena (R)) and the early clinical trials that demonstrated its potential. We highlight the contraceptive and therapeutic benefits of Mirena (R), and discuss how clinical practice has been changed since the introduction of LNG-IUS and other long-acting reversible contraceptive methods. The history of Mirena (R) is rich in innovation and has also paved the way to the development of smaller intrauterine systems with lower hormone doses. Along with Mirena (R), these newer LNG-IUS contribute to improving contraceptive choices for women, allowing them to select the option that is right for them and that meets their needs no matter their age, parity or circumstances.Non peer reviewe

Le modèle de 'l'État-stratège':Genèse d'une forme organisationnelle dans l'administration française

Cet article retrace la genèse d'une nouvelle forme d'organisation du système administratif en France, désignée sous le nom d'« État-stratège », qui redessine, dans les années 1990, les relations entre administrations centrales et services territoriaux de l'État. La séparation entre les fonctions stratégiques de pilotage et de contrôle de l'État et les fonctions opérationnelles d'exécution et de mise en œuvre des politiques publiques est au cœur de ce changement. Cette transformation suit deux processus. D'un côté, l'adoption de mesures concrètes de « gouvernement à distance » fait l'objet de luttes de pouvoir entre trois acteurs ministériels majeurs (ministère de l'Intérieur, du Budget et de la Fonction publique). De l'autre, est produite une nouvelle « catégorisation » légitime de l'État, portée par des hauts fonctionnaires généralistes, dans le cadre de grandes commissions de réforme, et inspirée des idées du New Public Management. La fabrique d'une nouvelle forme d'organisation étatique renvoie ainsi à deux dynamiques et deux dimensions, politique et idéelle. — Numéro spécial : Les nouveaux formats de l'institution.Since the 1990s, a new organisational form of the administrative system in France has been steadily redefining relations between central administrations and local state units. Labelled “the steering state” or the “managerial state”, this new paradigm hinges on separating the strategic functions of steering and controlling the state from the operational functions of execution and policy implementation. The making of this new form of state organization involves two parallel processes: political and cognitive. For one thing, the adoption of concrete measures for “government at distance” results from power struggles between three major ministries (Home Office, Budget and Civil Service). For another, a new legitimate “categorization of the state” is being formed in the major committees involved in the reform process of the 1990s; it is borne by top civil servants and inspired by the ideas of New Public Management. — Special issue: New patterns of institutions

More than just contraception : the impact of the levonorgestrel-releasing intrauterine system on public health over 30 years

Universal access to sexual and reproductive health services is essential to facilitate the empowerment of women and achievement of gender equality. Increasing access to modern methods of contraception can reduce the incidence of unplanned pregnancy and decrease maternal mortality. Long-acting reversible contraceptives (LARCs) offer high contraceptive efficacy as well as cost-efficacy, providing benefits for both women and healthcare systems. The levonorgestrel-releasing intrauterine system (LNG-IUS) first became available in 1990 with the introduction of Mirena (LNG-IUS 20), a highly effective contraceptive which can reduce menstrual blood loss and provide other therapeutic benefits. The impact of the LNG-IUS on society has been wide ranging, including decreasing the need for abortion, reducing the number of surgical sterilisation procedures performed, as well as reducing the number of hysterectomies carried out for issues such as heavy menstrual bleeding (HMB). In the context of the COVID-19 pandemic, Mirena can provide a treatment option for women with gynaecological issues such as HMB without organic pathology, minimising exposure to the hospital environment and reducing waiting times for surgical appointments. Looking to the future, research and development in the field of the LNG-IUS continues to expand our understanding of these contraceptives in clinical practice and offers the potential to further expand the choices available to women, allowing them to select the option that best meets their needs.Non peer reviewe

The benefits of estetrol addition to drospirenone for contraception

Ethinylestradiol and drospirenone combined oral contraceptive formulations have been marketed for >20 years. Drospirenone has antimineralocorticoid and anti-androgenic effects that may offer several health benefits. Recently, 2 new drospirenone-containing oral contraceptives entered the market, 1 as a progestin-only pill containing 4 mg drospirenone and the other as a combined oral contraceptive containing 15 mg estetrol and 3 mg drospirenone. Estetrol has a unique differential effect on nuclear and membrane estrogen α-receptors when compared with other estrogens, leading to low impact on the liver, breast, and hemostasis parameters and a beneficial effect on the endometrium, vagina, cardiovascular system, bone, and brain. Phase 3 clinical studies demonstrated that the Pearl Index (pregnancies per 100-woman-years) for drospirenone alone is 4.0 in the United States and 0.93 in the European Union and for the estetrol-drospirenone combination it is 2.65 and 0.44, respectively. Drospirenone alone demonstrates high rates of unscheduled bleeding and low rates of scheduled bleeding, whereas the estetrol-drospirenone combination demonstrates a predictable and regular bleeding profile for most users with a high stable rate of scheduled bleeding and a low rate of unscheduled bleeding, reported primarily as spotting only. The adverse event profiles and discontinuation rates owing to adverse events are comparable, and no clinically significant effects were observed on metabolic parameters with either product. Hemostatic assays for drospirenone do not fully evaluate all parameters although the testing that is available suggests negligible effects, whereas validated hemostatic assays demonstrate that the estetrol-drospirenone combination has limited impact on hemostasis. The introduction of 4 mg drospirenone and 15 mg estetrol with 3 mg drospirenone are valuable additions to the contraceptive market. Adding estetrol to 3 mg drospirenone provides advantages of contraceptive efficacy and a regular, predictable bleeding profile with minimal impact on hemostasis parameters

Reproductive changes among women in their 40s : A cross-sectional study

Introduction: The aim was to describe and compare changes in the reproductive pattern of women in their 40s observed over a decade in Scandinavia. Material and Methods: Cross-sectional study using the total population of women aged 40-49 years between 2008-2018 in Denmark, Norway and Sweden (on average n = 1.5 million). Aggregated data concerning birth and induced abortion rate were collected and analyzed from national health registers. National data on redeemed prescriptions of hormonal contraceptives in the three countries were collected from prescription registers. Births after spontaneous and assisted conceptions were identified by using cross-linked data on deliveries from the Medical Birth Registers and National Registers of Assisted Reproduction in the three countries. Results: Use of hormonal contraception increased among women aged 40-44 years in Denmark from 24% to 31%, in Sweden from 27% to 30%, and in Norway from 22% to 24%. The levonorgestrel-releasing intrauterine device was the most frequently used method in all countries. Birth rates among women 40-44 years increased continuously from 9.5 to 12/1000 women in Denmark and from 11.7 to 14.3/1000 in Sweden, but remained stable in Norway at similar to 11/1000 women. There was a doubling of assisted conceptions in Denmark from 0.71 to 1.71/1000 women, Sweden from 0.43 to 0.81/1000 and Norway from 0.25 to 0.53/1000 women 40-49 years of age. Sweden had the highest induced abortion rate (7.7 to 8.1/1000 women) in women aged 40-49 years during the study period. Conclusions: From 2008 to 2018, birth rates continuously increased among women aged 40-49 years in Denmark and Sweden and births resulting from assisted reproductive technology doubled in all three countries.Peer reviewe

Phenotype-genotype correlations for clinical variants caused by CYLD mutations

Background Studies evaluating acceptability of simplified follow-up after medical abortion have focused on high-resource or urban settings where telephones, road connections, and modes of transport are available and where women have formal education. Objective To investigate women’s acceptability of home-assessment of abortion and whether acceptability of medical abortion differs by in-clinic or home-assessment of abortion outcome in a low-resource setting in India. Design Secondary outcome of a randomised, controlled, non-inferiority trial. Setting Outpatient primary health care clinics in rural and urban Rajasthan, India. Population Women were eligible if they sought abortion with a gestation up to 9 weeks, lived within defined study area and agreed to follow-up. Women were ineligible if they had known contraindications to medical abortion, haemoglobin < 85mg/l and were below 18 years. Methods Abortion outcome assessment through routine clinic follow-up by a doctor was compared with home-assessment using a low-sensitivity pregnancy test and a pictorial instruction sheet. A computerized random number generator generated the randomisation sequence (1:1) in blocks of six. Research assistants randomly allocated eligible women who opted for medical abortion (mifepristone and misoprostol), using opaque sealed envelopes. Blinding during outcome assessment was not possible. Main Outcome Measures Women’s acceptability of home-assessment was measured as future preference of follow-up. Overall satisfaction, expectations, and comparison with previous abortion experiences were compared between study groups. Results 731 women were randomized to the clinic follow-up group (n = 353) or home-assessment group (n = 378). 623 (85%) women were successfully followed up, of those 597 (96%) were satisfied and 592 (95%) found the abortion better or as expected, with no difference between study groups. The majority, 355 (57%) women, preferred home-assessment in the event of a future abortion. Significantly more women, 284 (82%), in the home-assessment group preferred home-assessment in the future, as compared with 188 (70%) of women in the clinic follow-up group, who preferred clinic follow-up in the future (p < 0.001). Conclusion Home-assessment is highly acceptable among women in low-resource, and rural, settings. The choice to follow-up an early medical abortion according to women’s preference should be offered to foster women’s reproductive autonomy