Estetrol and the possibilities of its clinical use

Summary Combined hormonal contraceptive methods are one of the most commonly used methods of planned parenthood. They show high contraceptive effectiveness, reasonable cycle control and bring several non-contraceptive benefits. A limitation of the widespread use of combined hormonal contraception is the risk of cardiovascular complications in individuals with specific risk factors. The risk of cardiovascular complications is related to the used estrogen component. Currently, the most common use of estrogen in combined hormonal contraception is ethinyl estradiol and estradiol valerate. The good estrogenic part of combined oral contraceptives is estetrol, a hormone produced exclusively by the fetal liver. Estetrol exhibits a tissue-selective receptor activity. Unlike previously used estrogens, it does not negatively affect the production of liver proteins and blood clotting parameters. Estetrol is not a perspective for combined hormonal contraception only. It is also promising for treating and preventing osteoporosis, hormonal therapy of menopausal syndrome, and vulvovaginal atrophy syndrome.

The postcoital test in the development of new vaginal contraceptives†

Postcoital tests (PCTs) have been used for over a century in the clinical evaluation of infertile couples, and for nearly 70 years in the evaluation of new vaginal contraceptive products. PCTs have been largely replaced by more modern methods in the study of infertility, but they remain the most useful way to obtain preliminary data on the effectiveness of vaginal contraceptive products. The World Health Organization has described important aspects of the procedure. It involves collection of cervical mucus at a certain time point after intercourse and the counting and characterization of sperm found in the mucus. A wide range of progressively motile sperm (PMS) has been associated with pregnancy rates in infertility studies. Eligibility for contraceptive trials includes the requirement that couples achieve a certain threshold number of PMS per high power field at midcycle in a baseline cycle without the test product. The primary endpoint, or definition of a satisfactory result in test cycles, is predefined. A literature review identified 10 PCT studies of vaginal contraceptives involving nine test products. Phase II trials of vaginal contraceptives have not been deemed feasible in the development of any vaginal contraceptive to date. A PCT study of a test product can be predictive of contraceptive efficacy, although ultimate contraceptive effectiveness is influenced by the ease of use of the product, along with patient compliance. PCT results similar to results seen with products that later showed satisfactory performance in efficacy trials is the best indicator of likely success of a test product.

FRI0510 THE FREQUENCY OF CONTRACEPTION DOCUMENTATION IN WOMEN ON AND OFF TERATOGENIC ANTI-RHEUMATIC MEDICATIONS IN THE RISE REGISTRY

Background:Several of the most commonly prescribed medications for women with rheumatic disease are teratogens, posing a risk for pregnancy loss and birth defects if taken in pregnancy. To prevent these life-altering complications, it is important that all women taking teratogenic medications avoid pregnancy through abstinence or contraception.Objectives:We sought to understand the accessibility to contraceptive data within the RISE Registry and to test whether, compared to other women, those prescribed a teratogen would be more likely to have documentation of contraceptive.Methods:Data were derived from Rheumatology Informatics System for Effectiveness (RISE), a national EHR-enabled rheumatology registry that passively collects data on all patients seen by participating practices. As of 2018, RISE held validated data from 1,113 clinicians in 226 practices, representing an estimated 32% of the U.S. clinical rheumatology workforce. Female patients between the ages 18-45 with an anti-rheumatic medication prescribed within the RISE system in 2018 were stratified into one of 3 groups: 1) Any teratogen (methotrexate, mycophenolate, mycophenolic acid, cyclophosphamide, leflunomide, thalidomide, lenalidomide); 2) Only pregnancy-compatible medications (hydroxychloroquine, azathioprine, or a TNF-α inhibitors [TNFi]); and 3) Any medication with unknown teratogenicity (non-TNF biologics and new small molecule medications). We identified the most recent contraceptive medication or device reported in 2018 using structured fields in the EHR. Contraceptive effectiveness was classified as ‘highly effective’ (IUD, Nexplanon, and surgical) and ‘effective’ (oral contraceptives, depo-provera, patch, ring), and unknown (type not reported). Statistical significance was assessed using Stata SE 15.1.Results:In 2018, 110,359 women between the ages of 18-45 were prescribed an anti-rheumatic medication within the RISE Registry. Of these, 11,569 (10.5%) had a contraceptive documented at the last visit. The frequency of contraception documentation varied between practices, ranging from 0% to 28.7% (median 9.2%).Contraception was documented slightly less often in women receiving teratogens (9.8%) compared to women receiving only pregnancy-compatible medications (10.4%, p=0.04) and medications with unknown pregnancy risks (10.0%, p=0.67).The frequency of contraceptive documentation in women prescribed a teratogen varied significantly by race with white women having the highest rate (11.0%) compared to African-American women (7.4%, p<0.001), Hispanic women (5.5%, p<0.001), and Asian women (8.4%, p=0.08).The type of contraceptive documented did not vary significantly between medication group. Highly effective contraception was rarely documented (1.4-1.6%) and moderately-effective hormonal contraceptives were more frequently documented (6.3-8.2%).Conclusion:This study is limited to the analysis of structured fields within the RISE Registry, thereby missing contraceptive documentation within the clinician notes. Increased uniformity in documentation and/or analysis of visit notes will be essential to use the RISE Registry to study the implementation of published contraceptive guidelines. While the documentation of contraception identified in this analysis of the RISE Registry likely under-estimates actual contraceptive use, it reveals important gaps in care. Contrary to what was expected, women prescribed a teratogen were not more likely than other women to have a documented contraceptive. Additionally, important racial disparities in contraception documentation suggest that rheumatologists may not addressing reproductive health needs equally across patient populations.Acknowledgments Disclaimer:This data was supported by the ACR’s RISE Registry. However, the views expressed represent those of the authors, not necessarily those of the ACRDisclosure of Interests:Megan Clowse Grant/research support from: GSK, Pfizer, Consultant of: UCB, Astra-Zeneca, Speakers bureau: UCB, Jing Li: None declared, Mehret Birru Talabi: None declared, Amanda Eudy: None declared, Gabriela Schmajuk Grant/research support from: Pfizer

Mechanisms involved in the contraceptive effects of ulipristal acetate

The use of emergency contraception (EC) methods is increasing worldwide as it constitutes an effective way to prevent unplanned pregnancy after unprotected sexual intercourse. During the last decade, ulipristal acetate (UPA), a selective progesterone receptor modulator, has emerged as the most effective EC pill, and it is now recommended as first-line hormonal treatment for EC in several countries. Its principal mechanism of action involves inhibition or delay of follicular rupture, but only when administered during the follicular phase before the luteinizing hormone (LH) peak. However, considering the high efficacy of UPA, it is possible that it also exerts contraceptive effects besides ovulation. In the present review, we summarize and discuss the existing evidence obtained on the effect of UPA on sperm function and post-ovulatory events as potential additional mechanisms to prevent pregnancy. The bulk of evidence collected so far indicates that UPA would not affect gamete function; however, it could impair embryo–uterine interaction. Thus, besides the described effects on ovarian function, UPA contraceptive effectiveness might also be attributed to post-ovulatory effects, depending on the moment of the female cycle in which the drug is administered.