contraceptives--postcoital and ulipristal-acetate

The emergency contraceptive drugs (EC), levonorgestrel (LNG) and ulipristal acetate (UPA), are sensitive substrates of cytochrome P450 3A4 (CYP3A4). In 2016, the label of LNG was updated based on a drug-drug interaction (DDI) study showing a significant decrease in LNG exposure when co-administered with efavirenz, a known CYP3A4 inducer. DDI between UPA and CYP3A4 inducers are poorly characterized. The aims of this study were to review quantitative data from the literature on DDI with EC, to provide quantitative predictions of DDI between UPA and CYP3A4 inducers, and to identify moderate and severe DDI that may require a dose adjustment. A literature search was performed on pharmacokinetic DDI of LNG and UPA. Quantitative prediction of DDI with UPA was carried out by using the in vivo mechanistic static model (IMSM). Limited information was available on DDI with emergency contraception drugs. For LNG, data from eleven studies were retrieved, including five known CYP3A4 inducers that confirmed a risk of underexposure to LNG when co-administered with inducers. For UPA, only three studies were identified, including only one CYP3A4 inducer. The IMSM approach indicated that UPA is a sensitive substrate of CYP3A4, with an estimated contribution of 86% of CYP3A4 to oral clearance. Moderate to severe DDI were predicted in 17 cases with CYP3A4 inducers, and dosage adjustments were suggested. This study illustrates the ability of the IMSM approach to inform about the DDI profile of old and new drugs.

Topics: Contraceptive Agents, Hormonal; Contraceptives, Postcoital; Cytochrome P-450 CYP3A; Drug Interactions; Humans; Norpregnadienes

Ulipristal acetate (UPA) 30 mg (ella®, HRA-Pharma, Paris, France) acts as an emergency contraceptive (EC) by delaying ovulation. Because it is a selective progesterone receptor modulator, an additional effect on interfering with implantation has been suggested.. This review discusses the evidence for, and against, an anti-implantation effect of UPA-EC.. Primary research on the effect of UPA, at a relevant dose, on endometrium, implantation, efficacy and pregnancy outcome.. UPA-EC does not appear to have a direct effect on the embryo. Changes in endometrial histology are small and not consistent, varying among studies. While UPA-EC affects the profile of gene expression in human endometrium, the findings vary between studies, and it is not clear that these changes affect endometrial receptivity or prevent implantation. UPA at pharmacological concentrations does not appear to have any inhibitory effect on embryo attachment in in vitro systems of human endometrium. UPA-EC is not more effective at preventing pregnancy than chance alone if used after ovulation and does not increase miscarriage rates.. An anti-implantation effect of UPA is highly unlikely at the dose used for EC. Maintaining the warning on the FDA-approved label that "it may also work by preventing implantation to the uterus" might deter some women from using EC, leaving them no option to prevent unwanted pregnancy after unprotected sexual intercourse.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Embryo Implantation; Endometrium; Female; Humans; Norpregnadienes; Ovulation; Pregnancy

This review discusses the development of selective progestin receptor modulators (SPRMs) for use in women's health and specifically the use of ulipristal acetate (UPA) as emergency contraception (EC) and as a treatment for symptomatic fibroids in women who want to preserve their fertility or avoid a hysterectomy. As an EC, UPA 30 mg should be recommended for women, within 102 h of unprotected intercourse. As a treatment of fibroids, UPA (5 mg daily dose) should be administered for periods of three months as a pre-surgical strategy, reducing bleeding and fibroid size and facilitating surgery. A proportion of these patients may even avoid surgery. Future developments will demonstrate whether UPA can be used for other indications such as endometriosis and breast cancer prevention or treatment.

Topics: Contraception, Postcoital; Contraceptive Agents, Female; Contraceptives, Postcoital; Female; Humans; Leiomyoma; Norpregnadienes; Receptors, Progesterone; Uterine Neoplasms

Emergency contraception (EC) is a way to significantly reduce the chance of becoming pregnant after an episode of unprotected intercourse. Considerable data support the safety of all available and emerging options for EC. Areas covered: This review presents a comprehensive summary of the literature regarding the safety of EC as well as directions for further study. PubMed was searched for all relevant studies published prior to June 2017. Expertopinion: All available methods of EC (i.e., ulipristal acetate pills, levonorgestrel pills, and the copper-IUD), carry only mild side effects and serious adverse events are essentially unknown. The copper IUD has the highest efficacy of EC methods. Given the excellent safety profiles of mifepristone and the levonorgestrel IUD, research is ongoing related to use of these products for EC.

Topics: Animals; Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Norpregnadienes; Pregnancy

Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. This is an update of a review previously published in 2009 and 2012.. To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.. In February 2017 we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, Popline and PubMed, The Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database. We also searched ICTRP and ClinicalTrials.gov as well as contacting content experts and pharmaceutical companies, and searching reference lists of appropriate papers.. Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible.. We used standard methodological procedures recommended by Cochrane. The primary review outcome was observed number of pregnancies. Side effects and changes of menses were secondary outcomes.. We included 115 trials with 60,479 women in this review. The quality of the evidence for the primary outcome ranged from moderate to high, and for other outcomes ranged from very low to high. The main limitations were risk of bias (associated with poor reporting of methods), imprecision and inconsistency. Comparative effectiveness of different emergency contraceptive pills (ECP)Levonorgestrel was associated with fewer pregnancies than Yuzpe (estradiol-levonorgestrel combination) (RR 0.57, 95% CI 0.39 to 0.84, 6 RCTs, n = 4750, I. Levonorgestrel and mid-dose mifepristone (25 mg to 50 mg) were more effective than Yuzpe regimen. Both mid-dose (25 mg to 50 mg) and low-dose mifepristone(less than 25 mg) were probably more effective than levonorgestrel (1.5 mg). Mifepristone low dose (less than 25 mg) was less effective than mid-dose mifepristone. UPA was more effective than levonorgestrel.Levonorgestrel users had fewer side effects than Yuzpe users, and appeared to be more likely to have a menstrual return before the expected date. UPA users were probably more likely to have a menstrual return after the expected date. Menstrual delay was probably the main adverse effect of mifepristone and seemed to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than ECPs.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Drug Administration Schedule; Estradiol; Female; Humans; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Mifepristone; Norpregnadienes; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Unsafe Sex

The World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) provide recommendations for use of emergency contraceptive pills (ECPs), including levonorgestrel (LNG) and combined oral contraceptives (COCs). A new ECP formulation, ulipristal acetate (UPA), is now available worldwide. To determine whether LNG, UPA or COC (Yuzpe) ECPs are safe for women with certain characteristics or medical conditions, we searched the PubMed and Cochrane databases for articles published from date of inception until May 2015 pertaining to the safety of LNG, UPA or Yuzpe ECP use. For direct evidence, we considered studies that looked at safety outcomes among women with certain medical conditions or characteristics taking ECPs compared with women not taking ECPs. For indirect evidence, we considered studies that reported pharmacokinetic (PK) data for ECP use among women with certain medical conditions or characteristics and studies that reported safety outcomes among healthy women taking ECPs. Five studies provided direct evidence; of these five studies, four examined LNG or Yuzpe use among pregnant or breastfeeding women, and one reported risk of ectopic pregnancy among women repeatedly using LNG ECPs. Poor pregnancy outcomes were rare among pregnant women who used LNG or Yuzpe ECPs during the conception cycle or early pregnancy. Breastfeeding outcomes did not differ between women exposed to LNG ECP and those unexposed, and there was no increased risk of ectopic pregnancy versus intrauterine pregnancy after repeated use of LNG ECPs compared with nonuse. Forty-five studies provided indirect evidence. One PK study demonstrated that LNG passes into breastmilk but in minimal quantities. In addition, nine studies examined pregnancy outcomes following ECP failure among healthy women, and 35 articles reported adverse events. Studies suggest that serious adverse events are rare among women taking any of these ECP formulations.. Evidence on safety of ECPs among women with characteristics or medical conditions listed within WHO and CDC family planning guidance is limited. However, both direct and indirect evidence for our study question did not suggest any special safety concerns for the use of ECPs among women with particular medical conditions or personal characteristics, such as pregnancy, lactation or frequent ECP use.

Topics: Breast Feeding; Contraception, Postcoital; Contraceptives, Oral, Combined; Contraceptives, Postcoital; Female; Humans; Lactation; Levonorgestrel; Norpregnadienes; Pregnancy; Pregnancy Outcome; Treatment Failure

Emergency contraception (EC) may help prevent pregnancy in various circumstances, such as contraceptive method failure, unprotected sexual intercourse, or sexual assault, yet it remains underused. There are 4 approved EC options in the United States. Although ulipristal acetate requires a provider's prescription, oral levonorgestrel (LNG) is available over the counter for women of all ages. The most effective method of EC is the copper intrauterine device, which can be left in place for up to 10 years for efficacious, cost-effective, hormone-free, and convenient long-term primary contraception. Ulipristal acetate tends to be more efficacious in pregnancy prevention than is LNG, especially when taken later than 72 hours postcoitus. The mechanism of action of oral EC is delay of ovulation, and current evidence reveals that it is ineffective postovulation. Women who weigh more than 75 kg or have a body mass index greater than 25 kg/m(2) may have a higher risk of unintended pregnancy when using oral LNG EC; therefore, ulipristal acetate or copper intrauterine devices are preferable in this setting. Providers are often unaware of the range of EC options or are unsure of how to counsel patients regarding the access and use of EC. This article critically reviews current EC literature, summarizes recommendations, and provides guidance for counseling women about EC. Useful tips for health care providers are provided, with a focus on special populations, including breast-feeding women and those transitioning to long-term contraception after EC use. When treating women of reproductive age, clinicians should be prepared to counsel them about EC options, provide EC appropriately, and, if needed, refer for EC in a timely manner.

Topics: Administration, Oral; Attitude of Health Personnel; Body Mass Index; Breast Feeding; Contraception, Postcoital; Contraceptive Agents, Female; Contraceptives, Postcoital; Female; Health Knowledge, Attitudes, Practice; Humans; Intrauterine Devices, Copper; Levonorgestrel; Nonprescription Drugs; Norpregnadienes; Ovulation; Patient Education as Topic; Pregnancy; Prescription Drugs

Emergency contraception provides a critical and time-sensitive opportunity for women to prevent undesired pregnancy after intercourse. Both access and available options for emergency contraception have changed over the last several years.. Emergency contraceptive pills can be less effective in obese women. The maximum achieved serum concentration of levonorgestrel (LNG) is lower in obese women than women of normal BMI, and doubling the dose of LNG (3 mg) increases its concentration maximum, approximating the level in normal BMI women receiving one dose of LNG. Repeated use of both LNG and ulipristal acetate (UPA) is well tolerated. Hormonal contraception can be immediately started following LNG use, but should be delayed for 5 days after UPA use to avoid dampening the efficacy of UPA. The copper intrauterine device (IUD) is the only IUD approved for emergency contraception (and the most effective method of emergency contraception), but use of LNG IUD as emergency contraception is currently being investigated. Accurate knowledge about emergency contraception remains low both for patients and healthcare providers.. Emergency contraception is an important yet underutilized tool available to women to prevent pregnancy. Current options including copper IUD and emergency contraceptive pills are safe and well tolerated. Significant gaps in knowledge of emergency contraception on both the provider and user level exist, as do barriers to expedient access of emergency contraception.

Topics: Adult; Contraception; Contraception, Postcoital; Contraceptive Agents, Female; Contraceptives, Postcoital; Female; Health Services Accessibility; Humans; Intrauterine Devices, Copper; Levonorgestrel; Norpregnadienes; Obesity; Pregnancy

The most used treatment in the world for emergency contraception is the levonorgestrel (LNG) pill. However, its efficacy decreases if it is administered 3 days after unprotected sexual intercourse, whereas the ulipristal acetate (UPA) pill is effective up until 5 days afterwards. Pooled clinical data show that UPA is more effective than LNG when taken very shortly after intercourse (within 24h) or, conversely, between 72 and 120 h after intercourse. UPA is also more effective than LNG in inhibiting follicular rupture when administered near the time of ovulation. We show here why overall UPA is more effective than LNG in reducing the rate of unwanted pregnancies by demonstrating the effect of each product depending on the follicular size at the time of an unprotected sexual intercourse We also explain the difference between UPA and LNG in the maximum time to administration simply by the shift in ovulation and the fact that UPA has an effect on larger follicles than LNG does (18 mm vs. 14 mm), without postulating a hypothetical endometrial effect. We also explain why UPA and LNG remain emergency contraceptives and should not be used for daily contraception.

Topics: Coitus; Contraception, Postcoital; Contraceptive Agents, Female; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Norpregnadienes; Organ Size; Ovarian Follicle; Ovulation; Pregnancy; Time Factors; Unsafe Sex

Several selective progesterone receptor modulators (SPRMs) show promise in several areas of medicine and this work has been summarized by us in 2008.. Since the publication of our reviews, several developments have taken place in the field of reproductive medicine. The first is emergency contraception (EC). Two SPRMs are clinically utilized today: mifepristone (MFP) and ulipristal acetate (UPA). MFP is available for EC in up to 120 h following unprotected intercourse. A dose of 10 mg is significantly more effective than levonorgestrel (LNG). In a metanalysis of the use of UPA versus LNG up to 72 h after unprotected intercourse, failure rates of 1.4 versus 2.2% were reported. The second is contraception. A daily dose of 2 mg MFP can block ovulation and several MFP regimens are being tested, including a vaginal ring releasing MFP. The third is the preoperative administration in women harboring leiomyomas, where clinical testing of several SPRM has shown that they can decrease uterine leiomyomas' size and substantially reduce uterine bleeding. SPRM can induce unusual, specific endometrial appearances. Many believe that these changes should not cause concern, but the issue remains controversial.. SPRMs are very effective in EC and for the preoperative treatment of uterine leiomyomas.

Topics: Adenomyosis; Animals; Clinical Trials as Topic; Contraception, Postcoital; Contraceptive Agents, Female; Contraceptives, Postcoital; Endometriosis; Estrenes; Female; Hormone Antagonists; Humans; Leiomyoma; Levonorgestrel; Mifepristone; Norpregnadienes; Oximes; Receptors, Progesterone; Uterine Neoplasms

Review of recent data from clinical trials and descriptions of endometrial morphology with administration of selective progesterone receptor modulators (SPRMs).. Recent reports concerning administration of SPRMs, specifically the efficacy of ulipristal acetate in reducing fibroid size and rapid control of menstrual blood loss, have renewed clinical interest in this class of compound. Histological data from studies with SPRMs report that this class of drugs is associated with progesterone receptor modulator-associated endometrial changes. Data on mechanisms of action are lacking. The antagonistic progesterone effect of SPRMs has shown promising results in animal studies with endometriosis. Sex steroid receptor effects of PRMs outside the reproductive tract raise the potential for use in neurology and oncology, and although there are several randomized trials in these areas, there are limited small studies published to date.. The SPRM ulipristal acetate is an effective treatment for preoperative treatment of fibroids and a reliable emergency contraceptive. This class of compounds holds the potential for long-term effective medical management of fibroids and may have utility in the management of other sex steroid-dependent conditions.

Topics: Breast Neoplasms; Contraceptives, Postcoital; Endometriosis; Female; Hormone Antagonists; Humans; Leiomyoma; Menorrhagia; Norpregnadienes; Quality of Life; Receptors, Progesterone; Uterine Neoplasms

Several options for emergency contraception are available in the United States. This article describes each method, including efficacy, mode of action, safety, side effect profile, and availability. The most effective emergency contraceptive is the copper intrauterine device (IUD), followed by ulipristal acetate and levonorgestrel pills. Levonorgestrel is available for sale without restrictions, whereas ulipristal acetate is available with prescription only, and the copper IUD must be inserted by a clinician. Although EC pills have not been shown to reduce pregnancy or abortion rates at the population level, they are an important option for individual women seeking to prevent pregnancy after sex.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Evidence-Based Medicine; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Norpregnadienes; Practice Guidelines as Topic

Emergency contraceptives (EC) are forms of contraception that women can use after intercourse to prevent pregnancy. EC use is safe for women of all ages, and there are no medical contraindications to its use. There are two types of emergency contraceptive pills currently available: ulipristal acetate (UPA) and levonorgestrel. UPA is the most effective oral option for EC. In the United States, levonorgestrel containing ECPs are available without prescription to women and men without age restrictions. However, the more effective UPA pills require a prescription. ECPs do not cause abortion or harm an established pregnancy. Placement of a copper intrauterine device (IUD) is more effective EC than either UPA or levonorgestrel, and requires a timely visit with a trained clinician. EC pills are less effective for women who are overweight or obese, therefore such women should be offered a copper IUD or ulipristal rather than levonorgestrel pills. Any woman requesting EC after unprotected intercourse should be offered treatment within 120 hours of intercourse, as should all women who are victims of sexual assault. Women requesting EC should be offered information and services for ongoing contraception. Although levonorgestrel EC is now available over-the-counter, ongoing need exists to educate women about emergency contraception to encourage prompt use of EC when it is needed.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Male; Nonprescription Drugs; Norpregnadienes; Patient Education as Topic; Pregnancy

Emergency contraception (EC) is used to prevent unintended pregnancies. The current gold standard for oral EC is levonorgestrel (LNG) administered as a single 1.5-mg dose or in 2 doses of 0.75 mg separated by 12 hours. LNG has shown to be effective up to 72 hours after coitus. Ulipristal acetate (UPA) is a selective progesterone receptor modulator approved for EC use in the United States in August 2010. UPA is administered as a one-time, 30-mg dose within 120 hours of intercourse.. The goal of this review was to provide a summary of the available literature on the use of UPA for EC.. PubMed, Cochrane Library, ClinicalTrials.gov, International Pharmaceutical Abstracts, EBSCO, and Iowa Drug Information Service were searched from February 2011 through September 2011 to identify relevant articles. Search terms included ulipristal acetate, CDB-2914, VA 2914, and emergency contraception.. In an open-label study, UPA was effective in preventing pregnancy in 1241 women who presented for EC up to 120 hours (5 days) after unprotected intercourse, with an observed pregnancy rate of 2.1% (95% CI, 1.4%-3.1%) versus 5.5% (ie, the expected pregnancy rate without EC). The efficacy of UPA did not decrease significantly (P = 0.44) over time, with pregnancy rates at intervals between >48 and 72 hours at 2.3% (95% CI, 1.4%-3.8%), >72 and 96 hours at 2.1% (95% CI, 1.0%-4.1%), and >96 and 120 hours at 1.3% (95% CI, 0.1%-4.8%). In a single-blind, comparative noninferiority study of 1696 women, UPA was at least as effective as LNG when used within 72 hours for EC, with 15 pregnancies in the UPA group and 22 pregnancies in the LNG group (odds ratio = 0.68 [95% CI, 0.35-1.31]). In addition, UPA prevented significantly (P = 0.037) more pregnancies than LNG when used between 72 and 120 hours after unprotected intercourse, with 0 pregnancies in the UPA group and 3 pregnancies in the LNG group. In a meta-analysis, UPA prevented a greater percentage of pregnancies than LNG at intervals up to 24 hours (0.9% UPA vs 2.5% LNG; P = 0.035), up to 72 hours (1.4% UPA vs 2.2% LNG; P = 0.046), and up to 120 hours (1.3% UPA vs 2.2% LNG; P = 0.025). The most commonly (>10%) reported adverse events included headache, nausea, and abdominal pain. In addition, UPA delayed onset of menstruation by a mean of 2.1 to 2.8 days.. Based on clinical trials, UPA seems to be a reasonably tolerable and effective method of EC when used within 120 hours of intercourse. UPA is at least as effective as LNG when used within the first 72 hours after unprotected intercourse. However, UPA may be more effective than LNG when used between 72 to 120 hours after unprotected intercourse, extending the window of opportunity for EC. UPA may provide a new option for women who require EC up to 5 days after unprotected intercourse.

Topics: Administration, Oral; Animals; Contraception, Postcoital; Contraceptives, Postcoital; Drug Administration Schedule; Drug Costs; Female; Humans; Norpregnadienes; Pregnancy; Time Factors; Treatment Outcome; Unsafe Sex

Emergency contraceptive agents play a crucial role in preventing unplanned pregnancy. These agents and devices have been studied since the 1960s and have had varied results in terms of side effects and efficacy. A new oral tablet for emergency contraception (EC), ulipristal acetate (UPA) , is a selective progesterone receptor modulator and can be used up to 120 h following unprotected intercourse, without an increase in adverse effects or a decrease in efficacy.. This article reviews studies that evaluate the pharmacodynamics, pharmacokinetics, clinical efficacy, and safety profile of UPA as an emergency contraceptive agent.. UPA, a selective progesterone receptor modulator, is administered as a single 30 mg dose for EC. This agent provides a comparable, if not better, efficacy and side effect profile than seen with levonorgestrel or mifepristone. Because it has both agonistic and antagonistic effects on the progesterone receptor, ongoing clinical trials are documenting UPA's use for patients with endometriosis and as an extended use contraceptive.

Topics: Administration, Oral; Animals; Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Mifepristone; Norpregnadienes; Receptors, Progesterone; Time Factors

Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve.. To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.. The search included the Cochrane Controlled Trials Register, Popline, MEDLINE, PubMed, Biosis/EMBASE, Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (July 2011). Content experts and pharmaceutical companies were contacted.. Randomised controlled trials and controlled clinical trials including women attending services for EC following a single act of unprotected intercourse were eligible.. Data on outcomes and trial characteristics were extracted in duplicate and independently by two review authors. Quality assessment was also done by two review authors independently. Meta-analysis results are expressed as risk ratio (RR) using a fixed-effect model with 95% confidence interval (CI). In the presence of statistically significant heterogeneity a random-effects model was applied.. One hundred trials with 55,666 women were included. Most trials were conducted in China (86/100). Meta-analysis indicated that mid-dose mifepristone (25-50 mg) (20 trials; RR 0.64; 95% CI 0.45 to 0.92) or low-dose mifepristone (< 25 mg) (11 trials; RR 0.70; 95% CI 0.50 to 0.97) were significantly more effective than levonorgestrel (LNG), but the significance was marginal when only high-quality studies were included (4 trials; RR 0.70; 95% CI 0.49 to 1.01). Low-dose mifepristone was less effective than mid-dose mifepristone (25 trials; RR 0.73; 95% CI 0.55 to 0.97). This difference was not statistically significant when only high-quality trials were considered (6 trials; RR 0.75; 95% CI 0.50 to 1.10). Ulipristal acetate (UPA) appeared more effective (2 trials; RR 0.63) than LNG at a marginal level (P = 0.09) within 72 hours of intercourse.Regarding effectiveness in relation to the time of administration, women who took LNG within 72 hours of intercourse were significantly less likely to be pregnant than those who took it after 72 hours (4 trials; RR 0.51; 95% CI 0.31 to 0.84). It was not evident that the coitus-treatment time affected the effectiveness of mifepristone and UPA.Single-dose LNG (1.5 mg) showed similar effectiveness as the standard two-dose regimen (0.75 mg 12 h apart) (3 trials; RR 0.84; 95% CI 0.53 to 1.33). This conclusion was not modified by the time elapsed from intercourse to treatment administration.Mifepristone (all doses) (3 trials; RR 0.14; 95% CI 0.05 to 0.41) and LNG (5 trials; RR 0.54; 95% CI 0.36 to 0.80) were more effective than the Yuzpe regimen in preventing pregnancy. One trial compared gestrinone with mifepristone. No significant difference of effectiveness was identified in this trial (996 women; RR 0.75; 95% CI 0.32 to 1.76).All methods of EC were safe. Nausea and vomiting occurred with oestrogen-containing EC methods and progestogen and anti-progestogen methods caused changes in subsequent menses. LNG users were more likely to have a menstrual return before the expected date, but UPA users were more likely to have a menstrual return after the expected date. Menstrual delay was the main adverse effect of mifepristone and seemed to be dose-related.. Intermediate-dose mifepristone (25-50 mg) was superior to LNG and Yuzpe regimens. Mifepristone low dose (< 25 mg) may be more effective than LNG (0.75 mg two doses), but this was not conclusive. UPA may be more effective than LNG. LNG proved to be more effective than the Yuzpe regimen. The copper IUD was the most effective EC method and was the only EC method to provide ongoing contraception if left in situ.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Drug Administration Schedule; Female; Humans; Levonorgestrel; Mifepristone; Norpregnadienes; Randomized Controlled Trials as Topic

To review the pharmacology, pharmacokinetics, efficacy, and safety of data of ulipristal acetate, a new emergency contraceptive approved for use up to 120 hours after unprotected intercourse.. Articles pertaining to the topic were identified and reviewed through searches of PubMed (1994-March 2011) and clinicaltrials.gov, using the key terms ulipristal and CDB-2914. Ella approval documents were obtained and reviewed from Drugs@FDA on the Food and Drug Administration (FDA) Web site.. All published data and FDA approval documents examining pharmacologic, pharmacokinetic, and clinical studies related to ulipristal acetate as an emergency contraceptive were evaluated. Selected studies included 3 randomized trials and 1 meta-analysis.. Ulipristal acetate is a progesterone agonist/antagonist emergency contraceptive approved for the prevention of pregnancy to be taken as soon as possible, within 120 hours after unprotected intercourse or a known or suspected contraceptive failure. Based upon results of the Phase 3 clinical trials used to obtain approval, ulipristal acetate administration was at least as effective as levonorgestrel in the reduction of pregnancy rate when studied alone after unprotected intercourse and when taken up to 120 hours after unprotected intercourse. Commonly reported adverse effects associated with ulipristal acetate in trials included headache, breast tenderness, nausea, and abdominal pain.. Ulipristal acetate is effective as an emergency contraceptive for up to 120 hours after unprotected intercourse. Because ulipristal is available only via prescription, it may be covered by insurance. However, the additional factors of travel expenses and time to make and attend a physician appointment must be taken into account when considering use of ulipristal as an emergency contraceptive. Due to the similarity of its structure to mifepristone, controversy regarding ulipristal's mechanism of action has arisen.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Norpregnadienes; Time Factors

This review presents the most up-to-date information regarding available methods, safety, efficacy, and availability of emergency contraception for adolescents.. Recent reanalysis suggests that previously reported efficacy rates for the levonorgestrel-only method emergency contraception were probably overestimated. A newer and more efficacious method of emergency contraception, ulipristal acetate, was FDA approved in August 2010.. Emergency contraception provides young women with an opportunity to prevent pregnancy in the event of unprotected sexual intercourse. Several dedicated products are available commercially in the USA with varying efficacy rates. Barriers, including cost and accessing emergency contraception within the designated time frame, often prevent use among young women.

Topics: Adolescent; Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Norpregnadienes; Time Factors; United States; United States Food and Drug Administration; Young Adult

Ulipristal acetate (UPA) is a newly developed emergency contraceptive currently available in the USA and Europe. It is approved as a 30 mg one-time dose taken within 120 h (5 days) of unprotected intercourse or failed contraception. This selective progesterone receptor modulator appears to be more effective than the levonorgestrel-containing emergency contraceptive, which must be taken within 72 h of unprotected intercourse. According to pharmacodynamic trials, UPA delays follicular maturation and ovulation. In addition, UPA may modulate the endometrium. Both Phase III clinical trials found that UPA does not lose efficacy within the 120-h dosing interval. Throughout all phases of clinical studies, UPA was shown to be well tolerated with only minimal adverse drug reactions, all of which are similar to competitor therapies.

Topics: Animals; Clinical Trials as Topic; Contraceptive Agents; Contraceptives, Postcoital; Drug Interactions; Female; Food-Drug Interactions; Humans; Norpregnadienes; Receptors, Progesterone; Unsafe Sex

A major barrier to the widespread acceptability and use of emergency contraception (EC) are concerns regarding the mechanisms of action of EC methods. Today, levonorgestrel (LNG) in a single dose of 1.5 mg taken within 120 h of an unprotected intercourse is the most widely used EC method worldwide. It has been demonstrated that LNG-EC acts through an effect on follicular development to delay or inhibit ovulation but has no effect once luteinizing hormone has started to increase. Thereafter, LNG-EC cannot prevent ovulation and it does not prevent fertilization or affect the human fallopian tube. LNG-EC has no effect on endometrial development or function. In an in vitro model, it was demonstrated that LNG did not interfere with blastocyst function or implantation.

Topics: Adolescent; Adult; Animals; Contraception, Postcoital; Contraceptives, Postcoital; Female; Genitalia, Female; Humans; Levonorgestrel; Male; Norpregnadienes; Ovarian Follicle; Ovulation; Receptors, Progesterone; Reproduction; Young Adult

To describe ovulation inhibition and safety of daily oral ulipristal acetate (UPA) over 84 days.. This multi-center phase 1 and/or 2 trial randomized participants to use oral ulipristal 10 mg or 5 mg daily or a 3 cycle regimen of 5 mg for 24 days followed by four placebo days. We stratified randomization by body mass index (BMI) <32 or 32-40 kg/m. Oral ulipristal acetate over 12 weeks did not reliably suppress ovulation, particularly in the 5 mg cyclic-dose group. Ovulation inhibition and endometrial changes were dose dependent. Reversible endometrial changes occurred during treatment.. Progesterone-receptor modulators have been suggested for daily oral contraception. Since progesterone concentrations suggest that ovulation occurred during treatment, further studies would be necessary to assess whether these were functional ovulations and to evaluate other possible mechanisms of contraception.

Topics: Contraceptives, Postcoital; Female; Humans; Norpregnadienes; Ovulation; Ovulation Inhibition; Progesterone

Topics: Adolescent; Adult; Contraception, Postcoital; Contraceptive Agents, Hormonal; Contraceptives, Postcoital; Desogestrel; Drug Implants; Female; Humans; Levonorgestrel; Norpregnadienes; Pregnancy; Pregnancy Tests; Risk Assessment; Time Factors; Unsafe Sex; Young Adult

Background Oral emergency contraceptives containing levonorgestrel or ulipristal acetate are available without prescription and only in pharmacies in Germany since March 2015. Due to this change community pharmacists are responsible for evaluating whether the product is appropriate and to educate women on proper use. Objective To measure the utilization of emergency contraceptives without a prescription and describe potential concerns and safety issues identified by community pharmacists in Germany. Setting The Drug Commission of German Pharmacists' nationwide network of reference pharmacies which includes 860 community pharmacies. Methods Reference community pharmacies were asked to participate in the eleven-questions online survey. Respondents were asked to recall their experiences with oral emergency contraceptives in the past 3 months. Data were collected between January 8 and February 19, 2018. Main outcome measure The survey focused on the utilization of emergency contraceptives without a prescription in Germany, and on the pharmacists' experiences with (potential) problems and concerns regarding safe use. Results In total, 555 community pharmacies (64.5%) participated. Overall 38.2% of community pharmacists stated they dispensed six to ten courses of emergency contraceptives within the past 3 months. In addition, 54.3% of the pharmacists estimated they dispensed emergency contraceptives exclusively without prescription and 35.9% dispensed more than 30% of emergency contraceptives during night-time and emergency services. Moreover, 82.8% of pharmacists stated that emergency contraceptives were requested not by the women concerned but a third person and 44.3% identified uncertainties in woman's self-diagnosis. Three out of four pharmacists had concerns about the effective and safe use of emergency contraceptives. In situations suggesting sexually transmitted diseases, or suspicion for use of force, 59.5% and 55.8% of the pharmacists, respectively, dispensed emergency contraceptives. In cases of acute health impairment or chronic disease, or (potentially) relevant drug/drug interaction, the vast majority (91.0% and 90.5%) did not. Here, most pharmacists referred to gynecologists. Conclusion Pharmacists had safety concerns when dispensing emergency contraceptives. Professional expertise in evaluating the need for oral emergency contraceptives and the proper use is needed.

Topics: Community Pharmacy Services; Contraceptives, Oral; Contraceptives, Postcoital; Female; Germany; Health Care Surveys; Humans; Levonorgestrel; Norpregnadienes; Pharmacists; Professional Role; Referral and Consultation

To estimate the cost-effectiveness of ulipristal acetate (UPA) and levonorgestrel (LNG) emergency contraception (EC) on pregnancy prevention among combined oral contraceptive (COC) pill users with an extended pill-free interval. We accounted for the potential interaction of COCs and obesity on EC efficacy.. We built a decision-analytic model using TreeAge software to evaluate the optimal oral EC strategy in a hypothetical cohort of 100,000 twenty-five-year-old women midcycle with a prolonged "missed" pill episode (8-14 days). We used a 5-year time horizon and 3% discount rate. From a healthcare perspective, we obtained probabilities, utilities and costs inflated to 2018 dollars from the literature. We set the threshold for cost-effectiveness at a standard $100,000 per quality-adjusted life-year. We included the following clinical outcomes: number of protected cycles, unintended pregnancies, abortions, deliveries and costs.. We found that UPA was the optimal method of oral EC, as it resulted in 720 fewer unintended pregnancies, 736 fewer abortions and 80 fewer deliveries at a total cost savings of $50,323 and 79 additional adjusted life-years. UPA continued to be the optimal strategy even in the case of obesity or COCs impacting UPA efficacy, in which a COC interaction would have to change efficacy of UPA by 160% before LNG was the dominant strategy.. Our models found that UPA was the dominant choice of oral EC among COC users with a prolonged "missed" pill episode, regardless of body mass index or an adverse interaction of COCs on UPA.. Ulipristal acetate is the dominant choice of oral emergency contraception among combined oral contraceptive users.

Topics: Adult; Body Mass Index; Contraceptives, Oral, Combined; Contraceptives, Postcoital; Cost-Benefit Analysis; Female; Humans; Levonorgestrel; Models, Theoretical; Norpregnadienes; Obesity; Pregnancy; Pregnancy, Unplanned; United States; Young Adult

Ulipristal acetate (UPA) is a prescription emergency contraceptive pill (ECP). Despite the potential for UPA to reduce the risk of unintended pregnancies, a recent study in Hawaii demonstrated less than 3% of pharmacies stocked UPA and less than 23% reported the ability to order it. The primary outcome of our study was to assess the availability of UPA in a sample of large cities nationwide.. We conducted a telephone-based secret shopper study of 533 retail pharmacies sampled proportionally from 10 large cities in five geographic regions across the US. Callers represented themselves as uninsured 18-year-old women attempting to fill prescriptions for UPA between February and May 2016. Using a semi-structured questionnaire, callers inquired regarding availability and use of UPA.. Less than 10% (33/344; 95% CI: 6.5-12.7%) of pharmacies indicated the ability to immediately fill a UPA prescription, while 72% (224/311; 95% CI: 65.0-77.0%) of pharmacies without immediate availability reported the ability to order UPA, with the median predicted wait time of 24 h (IQR: 21.5 to 26.0 h).. Despite evidence for increased efficacy of UPA over levonorgestrel (LNG) ECPs, the availability of UPA in a sample of US major cities is extremely limited. Given that ECPs should be taken as soon as possible after unprotected sex, the long wait times when ordering UPA present an access barrier. Efforts to improve the availability of UPA are important to optimize the potential of ECPs to decrease unintended pregnancy following unprotected sex.. Interventions are needed to address barriers to obtaining UPA from retail pharmacies nationwide.

Topics: Adolescent; Adult; Cities; Contraception, Postcoital; Contraceptives, Postcoital; Female; Health Services Accessibility; Humans; Norpregnadienes; Pharmaceutical Services; Pharmacies; Pregnancy; Pregnancy, Unplanned; Prescriptions; United States; Unsafe Sex; Young Adult

Ulipristal acetate (UPA) is a selective progesterone receptor modulator (PRM), which is used as an emergency contraceptive in women. Recent studies demonstrated the efficacy of an UPA contraceptive vaginal ring (UPA-CVR) as a blocker of ovulation. However, the endometrium of women exposed to UPA over a 6-month period display glandular changes, termed PRM-associated endometrial changes (PAECs). We, therefore, investigated whether UPA-induced PAECs are associated with altered expression of the transcription factor heart- and neural crest derivatives-expressed protein 2 (HAND2) whose downregulation is observed in endometrial epithelial hyperplasia and cancer. Our results showed that while exposure to mifepristone, a well-known PRM, leads to suppression of endometrial HAND2 expression, long-term exposure to UPA-CVR did not cause downregulation of this marker. Further studies, using human primary endometrial stromal cells, confirmed that whereas mifepristone-mediated suppression of HAND2 elevated the levels of its downstream target fibroblast growth factor 18, UPA did not significantly alter the expression of this growth factor. A rationale for the differential regulation of HAND2 by these PRMs was provided by our observation that mifepristone-bound progesterone receptors turn over at a faster rate than those bound to UPA. Collectively, these results support the selective effects of different PRMs and indicate that chronic exposure to UPA does not alter the HAND2 pathway whose dysregulation is linked to complex atypical endometrial hyperplasia and cancer. The results from this study involving a limited number of clinical samples should pave the way for a larger study to determine the safety of UPA for long-term use.

Topics: Basic Helix-Loop-Helix Transcription Factors; Contraceptives, Postcoital; Endometrium; Female; Hormone Antagonists; Humans; Mifepristone; Norpregnadienes; Receptors, Progesterone; Stromal Cells

The case concerns a 31 year-old woman with no previous history who consulted due to decreased vision in both eyes. She mentioned taking 1 pill of ulipristal acetate (30mg) as an emergency contraceptive four days before the visual symptoms appeared. In the examination, a better corrected visual acuity of 0.6 was found in the right eye and 0.8 in left eye (by Snellen chart), and bilateral macular serous detachment. It was decided to observe, and 15 days later she showed a functional and anatomical improvement.. Ulipristal acetate could lead to serous central chorioretinopathy due to its activity on the progesterone receptors present in choroidal and retinal pigment epithelium.

Topics: Adult; Central Serous Chorioretinopathy; Contraceptive Agents, Female; Contraceptives, Postcoital; Female; Humans; Norpregnadienes

To determine if a combined oral contraceptive (COC) initiated shortly after ulipristal acetate (UPA) administration interferes with its mechanism of action.. Healthy, reproductive-age women of normal BMI with proven ovulation (serum progesterone >3 ng/ml) were enrolled for three cycles (Cycle 1, UPA only; Cycle 2 washout; Cycle 3 UPA plus COC). During Cycles 1 and 3, subjects were monitored with transvaginal ultrasound and blood sampling for progesterone and LH every other day until a dominant follicle measuring >15 mm was visualized. In both treatment cycles, subjects received UPA (30mg) and were followed daily with similar monitoring for up to 7 days. In Cycle 3 only, subjects initiated a daily COC (0.15 mg levonorgestrel/30 μg ethinyl estradiol) 2 days after UPA. The study had 80% power to detect a 15% difference in the proportion of cycles with at least a 5-day delay in follicle rupture. We assessed follicle rupture as >50% decrease in mean size and adjudicated unclear outcomes with serum hormones.. A total of 36 women enrolled and 33 completed all study procedures [age 28.4 years (SD 3.9); BMI 23.4 (SD 2.4)]. Compared to Cycle 1, more subjects demonstrated evidence of follicle rupture in <5 days in Cycle 3 [1/33 (3%) vs. 9/33 (27%), p = .008]. We also included data from 2 subjects who experienced rupture prior to COC dosing in the analysis.. UPA's effectiveness is significantly reduced by administering COCs 2 days later.. This study demonstrates that UPA's efficacy as an emergency contraceptive is reduced with early exposure to COCs.

Topics: Adult; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Contraceptives, Postcoital; Drug Combinations; Drug Interactions; Ethinyl Estradiol; Female; Healthy Volunteers; Humans; Levonorgestrel; Luteinizing Hormone; Norpregnadienes; Ovarian Follicle; Ovulation; Progesterone; Prospective Studies; Ultrasonography

To assess the accessibility of ulipristal acetate (UPA) and copper intrauterine devices (IUDs) for emergency contraception (EC) in reproductive health centers in the Kansas City metropolitan area.. Using a secret shopper method, two female investigators called the reproductive health centers listed as EC providers on the nonprofit website bedsider.org that were located within 25 miles of the University of Kansas Medical Center. We categorized clinics as Title X providers vs. not according to the grantee list from the Office of Population Affairs. Investigators inquired about obtaining a UPA prescription by phone, the availability of the copper IUD for EC and time to first available appointment for EC. We evaluated correlates of EC access and provision with Fisher's Exact Tests.. We identified 40 clinics as potential EC providers. Some clinics reported that UPA could be prescribed by phone to existing patients (13/40, 32%), while others reported that women must meet with a provider first (15/40, 38%). Few clinics offered copper IUDs as EC (3/40, 8%). Title X clinic status did not predict provision of UPA by phone or copper IUDs as EC. The average time to next available appointment was 9±9 days to discuss EC and 13±9 days for a copper IUD.. Accessing the most efficacious forms of EC in a timely fashion presents many logistic challenges for women.. Healthcare systems should streamline protocols, train providers and improve rapid-access referral networks to facilitate timely provision of UPA and copper IUDs for EC.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Cross-Sectional Studies; Female; Health Services Accessibility; Humans; Intrauterine Devices, Copper; Kansas; Norpregnadienes; Reproductive Health Services; Surveys and Questionnaires; Time-to-Treatment

Emergency contraceptive pills (ECPs) are medications used after unprotected intercourse, underprotected intercourse, or sexual assault to decrease the risk of pregnancy. Availability of ECPs in Hawai'i's retail pharmacies was last assessed in 2007, following over-the-counter access to levonorgestrel ECPs (LNG-ECP) for women age 18 years or older and prior to U.S. Food and Drug Administration (FDA) approval of prescription-only ulipristal acetate (UPA). We conducted a county-by-county subanalysis from a larger observational population-based study on statewide availability of ECPs in Hawai'i's pharmacies. In the original study, researchers called all 198 unique retail pharmacies in Hawai'i between December 2013 and June 2014. Only 3% of pharmacies had UPA immediately available on-site in the state, with UPA available on Kaua'i and O'ahu only. At least one form of LNG-ECPs was available in 82% of pharmacies in 2013-2014, roughly the same as 2007 (81%) (P=0.9) when Lana'i and Moloka'i lacked access. Currently, only Moloka'i lacks retail pharmacy access to ECPs. When controlling for general inflation, the 2013-2014 mean price for name brand LNG-ECP fell within the reported range of 2007 prices. Generic LNG-ECPs were substantially lower in price than name brand LNG-ECPs in 2007 and 2013-2014. Availability of UPA is limited and significantly lower compared to LNG-ECPs. Availability of LNG-ECPs statewide has remained stable and the arrival of generics has decreased prices.

Topics: Adolescent; Contraceptives, Postcoital; Female; Hawaii; Health Expenditures; Health Services Accessibility; Humans; Nonprescription Drugs; Norpregnadienes; Pharmacy; Pregnancy; Telephone

This study describes women's reasons for seeking ulipristal acetate (UPA) for emergency contraception (EC) through the only authorized online retailer for UPA EC in the US.. Women aged 14 to 59 years, living in states that allow prescription medications to be shipped from out-of-state, accessed the KwikMed online pharmacy between January 2011 and December 2015. After completing a medical eligibility screener, women answered optional multiple-choice questions. To obtain UPA through KwikMed, individuals must be female, 50 years of age or younger, not currently pregnant or breastfeeding and not attempting to order UPA more than once within 30 days or more than four times per year.. Over the 5-year period, KwikMed provided 8019 prescriptions for UPA, and the number of women using this service more than tripled over time. Among women who responded to the survey questions (n=7133; response rate = 89%), most sought EC because of a condom failure (45.3%) or because they did not use regular contraception (41.2%). More than half (53.5%) of women reported that they chose UPA because of its effectiveness compared to levonorgestrel EC pills, and 58.9% preferred ordering UPA online because they found it easier than getting it from a doctor, clinic or pharmacy.. This study documents the importance of providing confidential services for acquiring EC online. Benefits of online access include convenience, less embarrassment, avoiding situations in which a provider might refuse to provide EC because of their own ideological belief and more reliable availability for this time-sensitive contraceptive.. Though physical, logistical and societal barriers can restrict women's access to EC, this study demonstrates that providing access to UPA online empowers women to obtain EC when they need it.

Topics: Adolescent; Adult; Attitude of Health Personnel; Contraceptives, Postcoital; Female; Health Services Accessibility; Humans; Norpregnadienes; Pharmaceutical Services, Online; Prescriptions; Privacy; Surveys and Questionnaires; United States; Young Adult

Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Contraceptives, Postcoital; Drug Interactions; Enterohepatic Circulation; Female; Humans; Levonorgestrel; Norpregnadienes; Pregnancy; Rifampin; Risk Factors

To determine pharmacy availability of ulipristal acetate (UPA) and compare to availability of levonorgestrel-containing emergency contraceptive pills (LNG-ECPs).. We conducted an observational population-based study utilizing a telephone-based secret shopper methodology. Researchers called all 198 unique retail pharmacies in Hawaii on December 2013-June 2014, representing themselves as patients and physicians.. Only 2.6% of pharmacies had UPA immediately available, though 22.8% reported ability to order UPA. In contrast, 82.4% reported immediate availability of LNG-ECPs. No significant difference in availability was reported to patients and physicians.. Availability of UPA is limited and significantly lower compared to LNG-ECPs. The study period did overlap with a change in distributor for UPA, likely capturing some disruption of the supply chain.. Systems-based interventions are needed to address barriers to obtaining UPA.

Topics: Chi-Square Distribution; Contraceptive Agents; Contraceptives, Postcoital; Female; Hawaii; Health Services Accessibility; Humans; Levonorgestrel; Norpregnadienes; Pharmacies; Surveys and Questionnaires

The copper intrauterine contraceptive (IUC) is the most effective method of emergency contraception (EC), yet it is underutilized. The objective was to evaluate a pilot project integrating the copper IUC into EC care.. Single-group evaluation study. Nine geographically diverse reproductive health centers implemented 6-month pilot interventions. All interventions included staff education and inclusion of the IUC in EC patient counseling; some sites developed patient education materials. Health center staff completed manual monthly tracking forms of the number of EC patients receiving oral levonorgestrel, ulipristal acetate or the copper IUC. Sites also tracked and reported the number of patients returning for removal during the 6-month pilot period and for 5 subsequent months. Main study outcomes included the number of IUC for EC insertions, the proportion that were same-day insertions and the proportion of patients receiving each EC type during the pilot period. A secondary outcome was the number of patients who had returned for removal at 5 months postpilot.. There were 101 IUC insertions for EC during the pilot period. Seventy-seven percent were same-day insertions; the remainder returned for insertion within 5 days of unprotected intercourse. The percentage of EC patients choosing the IUC varied by site from 1 to 16% (overall=7%). At 5 months postpilot, 20 patients (20%) had returned for removal.. Some women will be interested in the copper IUC for EC, and therefore, all women should be offered this option. Results suggest that the large majority continued to use the IUC for ongoing contraception.. Copper IUCs are a viable option for women in need of EC. All women should be offered the most effective EC option.

Topics: Choice Behavior; Contraception, Postcoital; Contraceptives, Postcoital; Counseling; Device Removal; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Norpregnadienes; Pilot Projects; United States

In November 2014, the European Medicines Agency (EMA) recommended switching the emergency contraceptive (EMC) ulipristal acetate to non-prescription status. This study's objective is to assess the current legal status of the two EMCs ulipristal acetate and levonorgestrel in Europe and to report on the development of sales figures for EMCs since they were made freely available.. Health authorities were contacted in autumn 2015 and asked about the current status of EMCs and whether the sales figures had changed after a switch to non-prescription status. Additionally, data on consumption were collected in 18 German community pharmacies.. As of November 2015, most countries in the European Union (EU) have followed the EMA recommendation. Hungary kept the prescription-only status. In Malta, EMC drugs are not authorized. Germany and Croatia switched levonorgestrel to non-prescription status as well. Of the EU candidate and European Free Trade Association countries, ulipristal acetate is available without prescription in Norway and Bosnia and Herzegovina only. Several countries reported an increase in EMC sales since the switch.. An EMA recommendation can strongly contribute to the harmonization of a drug's legal status in the EU. In most European countries, ulipristal acetate and/or levonorgestrel are now freely available.

Topics: Contraceptives, Postcoital; Drug Prescriptions; Europe; European Union; Female; Health Services Accessibility; Humans; Legislation, Drug; Levonorgestrel; Nonprescription Drugs; Norpregnadienes

Does ulipristal acetate (UPA) used for emergency contraception (EC) interfere with the human embryo implantation process?. UPA, at the dosage used for EC, does not affect human embryo implantation process, in vitro.. A single pre-ovulatory dose of UPA (30 mg) acts by delaying or inhibiting ovulation and is recommended as first choice among emergency contraceptive pills due to its efficacy. The compound has also been demonstrated to have a dose-dependent effect on the endometrium, which theoretically could impair endometrial receptivity but its direct action on human embryo implantation has not yet been studied.. Effect of UPA on embryo implantation process was studied in an in vitro endometrial construct. Human embryos were randomly added to the cultures and cultured for 5 more days with UPA (n = 10) or with vehicle alone (n = 10) to record the attachment of embryos.. Endometrial biopsies were obtained from healthy, fertile women on cycle day LH+4 and stromal and epithelial cells were isolated. A three-dimensional in vitro endometrial co-culture system was constructed by mixing stromal cells with collagen covered with a layer of epithelial cells and cultured in progesterone containing medium until confluence. The treatment group received 200 ng/ml of UPA. Healthy, viable human embryos were placed on both control and treatment cultures. Five days later the cultures were tested for the attachment of embryos and the 3D endometrial constructs were analysed for endometrial receptivity markers by real-time PCR.. There was no significant difference in the embryo attachment rate between the UPA treated group and the control group as 5 out of 10 human embryos exposed to UPA and 7 out of 10 embryos in the control group attached to the endometrial cell surface (P = 0.650). Out of 17 known receptivity genes studied here, only 2 genes, HBEGF (P = 0.009) and IL6 (P = 0.025) had a significant up-regulation and 4 genes, namely HAND2 (P = 0.003), OPN (P = 0.003), CALCR (P = 0.016) and FGF2 (P = 0.023) were down-regulated with the exposure of UPA, compared with control group.. This proof of concept study was conducted with a few human embryos, as their availability was limited. Although the 3D model used for this study is well established and the artificial endometrial luminal epithelium shown to express progesterone regulated markers of endometrial receptivity it is still an in vitro model, lacking all cell types that constitute the receptive endometrium in vivo.. This study provides new insights on the mechanism of action of UPA on human embryo implantation, demonstrating that UPA in a dosage used for EC does not affect embryo viability and the implantation process of embryo. Progesterone receptor modulators (PRMs) hold the potential to be attractive estrogen- and gestagen-free contraceptives and thus may be made available to a larger proportion of women globally due to these findings.. Swedish Research Council (K2010-54X-14212-09-3) and support provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska University Hospital.

Topics: Adult; Biopsy; Blastocyst; Coculture Techniques; Contraception, Postcoital; Contraceptive Agents; Contraceptives, Postcoital; Embryo Culture Techniques; Embryo Implantation; Endometrium; Female; Gene Expression Regulation; Healthy Volunteers; Humans; Norpregnadienes; Ovulation; Tissue Culture Techniques; Young Adult

Ulipristal acetate (UPA) is a new selective progesterone receptor (PR) modulator used for emergency contraception. However, our understanding of its mechanisms of action on oviductal cilia is limited. The present study focused on the in vitro effects of UPA (0.1, 1, and 10 μmol/L) on the cilia and steroid receptors of human fallopian tubes. The ciliary beat frequency (CBF), the ultrastructure of cilia, and the levels of steroid receptors were measured. The effects of UPA on the progesterone-induced CBF reduction were also studied. Our results show that UPA dose dependently antagonizes the progesterone-induced CBF decrease, but it does not affect the CBF or the ultrastructure of the cilia. The UPA also upregulates the expression levels of the estrogen receptor α and the PR in the fallopian tubes. The results enable us to better understand the mechanisms by which UPA works as an emergency contraceptive and provides a scientific basis for its clinical application.

Topics: Cilia; Contraceptives, Postcoital; Dose-Response Relationship, Drug; Epithelial Cells; Estrogen Receptor alpha; Fallopian Tubes; Female; Hormone Antagonists; Humans; Immunohistochemistry; Microscopy, Electron, Transmission; Movement; Norpregnadienes; Progesterone; Real-Time Polymerase Chain Reaction; Receptors, Progesterone; Stromal Cells; Tissue Culture Techniques; Up-Regulation

There have been numerous attempts to control fertility after unprotected sexual intercourse (UPSI). From very bizarre methods like the vaginal application of Coca Cola to the more serious attempts using calcium antagonists influencing fertility parameters in sperm to hormonal methods or intrauterine devices. So far, hormonal methods preventing or delaying ovulation have proved to be the most popular starting with the combination of ethinyl estradiol and levonorgestrel (LNG), known as the Yuzpe regimen. The first dose had to be taken within 72 hours of UPSI, a second one 12 hours later. Later on, LNG alone, at first in a regimen similar to the Yuzpe method (2 × 0.75 mg 12 hours apart) showed to be more successful, eventually resulting in the development of a 1.5 mg LNG pill that combined good efficacy with a high ease of use. Several efficacious and easy to use methods for emergency contraception (EC) are available on the market today with the most widely spread being LNG in a single dose of 1.5 mg (given as one tablet of 1.5 mg or 2 tablets of 0.75 mg each) for administration up to 3 days (according to WHO up to 5 days) after UPSI. Its limitations are the non-optimal efficacy which is decreasing the later the drug is taken and the fact that it is only approved for up to 72 hours after UPSI. This regimen has no effect on the endometrium, corpus luteum function and implantation, is not abortive and don't harm the fetus if accidentally taken in early pregnancy. It has no impact on the rate of ectopic pregnancies. It has become the standard method used up to this day in most countries. Since the mid 1970s copper IUDs have been used for EC, which show a high efficacy. Their disadvantages lie in the fact that EC is considered an off label use for most IUDs (not for the GynFix copper IUD in the European Union) and that they might not be acceptable for every patient. Furthermore IUD-insertion is an invasive procedure and it is required trained providers and sterilized facilities. Mifepristone in the dosages of 10 or 25 mg is used with good results as an emergency contraceptive in China for up to 120 hours after UPSI, but has never received any significant consideration in Western countries. While high doses of mifepristone has an effect on endometrial receptivity and will inhibit ovulation if given in the follicular phase and prevent implantation if given in the early luteal phase, low doses such as 10 mg has no impact on the endometrium. Mifepristone does not in

Topics: China; Contraception, Postcoital; Contraceptive Agents; Contraceptives, Postcoital; Contraceptives, Postcoital, Synthetic; Ethinyl Estradiol; European Union; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Mifepristone; Norpregnadienes; Ovulation; Pregnancy; Pregnancy, Ectopic; Receptors, Progesterone; Time Factors

This emergency contraception update and telephone triage guide can help ensure that your patients get the help they need, when they need it.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Directive Counseling; Estrogens; Female; Health Services Accessibility; Humans; Intrauterine Devices, Copper; Levonorgestrel; Norpregnadienes; Progestins; Triage

The use of selective progesterone modulators (SRMs) has been investigated extensively over the last few years. Ulipristal acetate (UPA) is an selective progesterone receptor modulator (SPRM) which has been in use since 2010 as an effective alternative emergency contraception (EC) regimen to Levonorgestrel (LNG). It acts by inhibiting ovulation and delaying implantation. Its effectiveness is active up to 120 h after sexual intercourse. UPA is safe and has a good tolerability profile. Health care practitioners should inform women of all reproductive ages that UPA is an effective alternative agent for those who are dissatisfied with other means of EC, and its activity of up to 120 h after sexual intercourse should also be highlighted.

Topics: Animals; Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Norpregnadienes

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Intrauterine Devices; Levonorgestrel; Luteinizing Hormone; Norpregnadienes; Risk Factors

This month, we focus on current research in contraception. Dr. Grimes discusses four recent publications, and each is concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.

Topics: Clinical Trials, Phase III as Topic; Contraception; Contraceptive Agents, Female; Contraceptives, Postcoital; Female; Humans; Norpregnadienes

Ulipristal acetate (UPA), a selective progesterone receptor modulator, when taken as a single 30-mg dose, is safe and effective for emergency contraception up to 5 days (120 h) following unprotected intercourse. This indication has been approved in Europe since May 2009 and was approved by the US FDA in August 2010. The older progesterone-only emergency contraceptive, levonorgestrel (LNG), is approved only up to 72 h after unprotected intercourse. UPA is effective in delaying or inhibiting ovulation, even if taken 24 to 48 h prior to expected ovulation, a time when LNG is no longer effective. A recent meta-analysis of two randomized clinical trials showed UPA to have a pregnancy risk 42% lower than LNG up to 72 h, and 65% lower in the first 24 h following unprotected intercourse. In a randomized trial enrolling women up to 5 days after unprotected intercourse, significantly more pregnancies were prevented with UPA than with LNG when taken beyond 72 h.

Topics: Clinical Trials as Topic; Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Norpregnadienes; Ovulation Inhibition; Pregnancy; Time Factors; Treatment Outcome

Topics: Clinical Trials as Topic; Contraceptives, Postcoital; Drug Interactions; Female; Humans; Levonorgestrel; Norpregnadienes

Topics: Contraceptive Agents, Female; Contraceptives, Oral; Contraceptives, Postcoital; Cost-Benefit Analysis; Female; Humans; Meta-Analysis as Topic; Norpregnadienes; Pregnancy; Pregnancy, Unplanned; Randomized Controlled Trials as Topic

Topics: Benzimidazoles; Contraceptives, Postcoital; Dabigatran; Drug Therapy; Fibrinolytic Agents; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Norpregnadienes; Pharmaceutical Preparations; Propylene Glycols; Pyridines; Sphingosine

Ulipristal acetate is the first selective progesterone receptor modulator approved for postcoital contraception in the US. It appears to be significantly more effective in inhibition of ovulation than other forms of emergency contraception. However, ulipristal acetate is structurally similar to mifepristone, and several lines of evidence suggest that a postfertilization mechanism of action is also operative. This mechanism of action is considered to be contragestive versus contraceptive. Ulipristal acetate administration is contraindicated in a known or suspected pregnancy; however, it could quite possibly be used as an effective abortifacient. Health-care providers should inform patients of the possibility of both mechanisms of action with use of this drug.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Contraindications; Drug Approval; Female; Humans; Norpregnadienes; Pregnancy; Receptors, Progesterone; United States

Topics: Abortion, Induced; Adolescent; Adult; Australia; Contraception Behavior; Contraceptives, Postcoital; Female; Forecasting; Health Services Accessibility; Humans; Levonorgestrel; Nonprescription Drugs; Norpregnadienes; Pregnancy; Pregnancy in Adolescence; Pregnancy, Unwanted; Public Opinion; Young Adult

Emergency contraception is a second chance for prevention of pregnancy after unprotected intercourse. Hormonal emergency contraception with levonorgestrel 1.5 mg, only provides an effective contraception from 0 to 72 hours after intercourse with decreasing effectiveness as time elapses. It was accordingly mandatory to develop an alternative approach with a stable contraceptive efficacy and good tolerance for 5 days, knowing additionally that the estimated lifespan of sperm in the female genital tract is about 5 days. In comparative studies bearing on more than 3000 young women, the progesterone receptor modulator (PRM) ulipristal acetate, a progesterone antagonist (taken in a single dose of 30 mg), or levonorgestrel (1.5 mg) were administered. Results indicated that the PRM was as effective as levonorgestrel, or even more, kept a stable efficacy for 120 hours after an unprotected intercourse, and was well tolerated. This establishes ulipristal acetate as the new standard for hormonal emergency contraception.

Topics: Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Norpregnadienes