Drug interactions between emergency contraceptive drugs and cytochrome inducers: literature review and quantitative prediction.

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.

Use of effective contraception following provision of the progestogen-only pill for women presenting to community pharmacies for emergency contraception (Bridge-It): a pragmatic cluster-randomised crossover trial.

BACKGROUND: Unless women start effective contraception after oral emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies. We hypothesised that pharmacist provision of the progestogen-only pill as a bridging interim method of contraception with emergency contraception plus an invitation to a sexual and reproductive health clinic, in which all methods of contraception are available, would result in increased subsequent use of effective contraception. METHODS: We did a pragmatic cluster-randomised crossover trial in 29 UK pharmacies among women receiving levonorgestrel emergency contraception. Women aged 16 years or older, not already using hormonal contraception, not on medication that could interfere with the progestogen-only pill, and willing to give contact details for follow-up were invited to participate. In the intervention group, women received a 3-month supply of the progestogen-only pill (75 µg desogestrel) plus a rapid access card to a participating sexual and reproductive health clinic. In the control group, pharmacists advised women to attend their usual contraceptive provider. The order in which each pharmacy provided the intervention or control was randomly assigned using a computer software algorithm. The primary outcome was the use of effective contraception (hormonal or intrauterine) at 4 months. This study is registered, ISRCTN70616901 (complete). FINDINGS: Between Dec 19, 2017, and June 26, 2019, 636 women were recruited to the intervention group (316 [49·6%], mean age 22·7 years [SD 5·7]) or the control group (320 [50·3%], 22·6 years [5·1]). Three women (one in the intervention group and two in the control group) were excluded after randomisation. 4-month follow-up data were available for 406 (64%) participants, 25 were lost to follow-up, and two participants no longer wanted to participate in the study. The proportion of women using effective contraception was 20·1% greater (95% CI 5·2-35·0) in the intervention group (mean 58·4%, 48·6-68·2), than in the control group (mean 40·5%, 29·7-51·3 [adjusted for recruitment period, treatment group, and centre]; p=0·011).The difference remained significant after adjusting for age, current sexual relationship, and history of effective contraception use, and was robust to the effect of missing data (assuming missingness at random). No serious adverse events occurred. INTERPRETATION: Provision of a supply of the progestogen-only pill with emergency contraception from a community pharmacist, along with an invitation to a sexual and reproductive health clinic, results in a clinically meaningful increase in subsequent use of effective contraception. Widely implemented, this practice could prevent unintended pregnancies after use of emergency contraception. FUNDING: National Institute for Health Research (Health Technology Assessment Programme project 15/113/01).

The use of emergency contraceptive pills in India: A meta-analysis.

BACKGROUND: Unplanned pregnancies are a major public health concern. In India, 33% of an estimated 48.1 million pregnancies end in induced abortions. Emergency contraceptive pills (ECPs) can prevent pregnancy after sexual intercourse, have been part of India's family planning program since 2002-2003 and are available as over-the-counter drugs. While there are concerns about the overuse of ECPs, the pattern of use of ECPs in India is unknown. OBJECTIVES: The objective is to determine the proportion of women who have ever used ECPs and repeatedly used ECPs and also to assess the reasons for use and nonuse of EC pills along with factors associated with the use. METHODS: A systematic review of ECP use in India was conducted by electronically searching three databases-PubMed, Popline, and Google Scholar. All studies were published between 2001 and 2017, and the electronic search was last conducted in July 2018. The proportion of use was calculated using meta-analysis, and the other factors were assessed by narratively synthesizing the findings. Thirty-three articles met the inclusion criteria. RESULTS: The pooled proportion of women who ever used ECPs was 6% (95% confidence interval, 0.03-0.10). The proportion of repeat use ranged from 12% to 69%. Five studies reported reasons for not using ECPs, and the most common reasons were religious/cultural beliefs followed by fear of side effects and inadequate knowledge. Studies to understand sociodemographic and other factors affecting the use of ECPs in India are lacking. There are significant concerns about the quality of the studies. The definition of repeat use of ECPs is inconsistent across papers. Furthermore, judgmental attitudes of health-care providers were apparent in some papers. CONCLUSION: The review highlights important research and program gaps.

A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive.

INTRODUCTION: The levonorgestrel oral emergency contraceptive is well tolerated and effective, however its use is still limited, mainly due to safety concerns. OBJECTIVE: This systematic review and meta-analysis aimed to summarize current evidence regarding the adverse events, and their prevalence, reported during the use of oral levonorgestrel emergency contraceptives. METHODS: Four electronic databases and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched. Studies that reported or investigated safety outcomes or adverse reactions during the use of levonorgestrel as an emergency oral contraceptive were included. Data on study design, demographics of levonorgestrel and the control cohort, and reported adverse effects were extracted. RESULTS: A total of 47 articles were included in this systematic review, from which it was shown that most of the adverse reactions were common and not serious. Uncommon adverse reactions identified included anorexia, ectopic pregnancy, exanthema, chloasma, miscarriage, and weight gain. Multiple serious adverse events, including convulsion, ectopic pregnancy, febrile neutropenia, stroke, abdominal hernia, anaphylaxis, cancer, ovarian cyst rupture, serious infections, and suicidal ideation, were reported. In addition, the prevalence of adverse events after a levonorgestrel 0.75 mg two-dose regimen and a levonorgestrel 1.5 mg single-dose regimen were not statistically different (p > 0.05). CONCLUSIONS: The most common adverse effects of levonorgestrel were not serious. This systematic review shows that data regarding the adverse reactions of repeated use of levonorgestrel are scarce. Studies on the multiple uses of levonorgestrel emergency contraception are still required to ensure its safety.

Papel actual del acetato de ulipristal en el tratamiento de los síntomas asociados a los miomas uterinos / Current role of ulipristal acetate in the management of uterine fibroids

No disponible

TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating.

Previous studies revealed the increasing risk of tubal pregnancy following failure of levonorgestrel (LNG)-induced emergency contraception, which was attributed to the reduced ciliary motility in response to LNG. However, understanding of the mechanism of LNG-induced reduction in the ciliary beat frequency (CBF) is limited. The transient receptor potential vanilloid (TRPV) 4 channel is located widely in the female reproductive tract and generates an influx of Ca2+ following its activation under normal physiological conditions, which regulates the CBF. The present study aimed to explore whether LNG reduced the CBF in the Fallopian tubes by modulating TRPV4 channels, leading to embryo retention in the Fallopian tubes and subsequent tubal pregnancy. The study provided evidence that the expression of TRPV4 was downregulated in the Fallopian tubes among patients with tubal pregnancy and negatively correlated with the serum level of progesterone. LNG downregulated the expression of TRPV4, limiting the calcium influx to reduce the CBF in mouse oviducts. Furthermore, the distribution of ciliated cells and the morphology of cilia did not change following the administration of LNG. LNG-induced reduction in the CBF and embryo retention in the Fallopian tubes and in mouse oviducts were partially reversed by the progesterone receptor antagonist RU486 or the TRPV4 agonist 4α-phorbol 12,13-didecanoate (4α-PDD). The results indicated that LNG could downregulate the expression of TRPV4 to reduce the CBF in both humans and mice, suggesting the possible mechanism of tubal pregnancy. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Interventions for emergency contraception.

BACKGROUND: 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. OBJECTIVES: To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy. SEARCH METHODS: 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. SELECTION CRITERIA: Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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, I2 = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I2 = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence).Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence).Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence).Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence). AUTHORS' CONCLUSIONS: 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 may be 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.

Acute bilateral serous central chorioretinopathy after emergency contraceptive therapy with ulipristal acetate. / Coriorretinopatía serosa central aguda bilateral tras terapia anticonceptiva de urgencia con acetato de ulipristal.

CASE REPORT: 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. DISCUSSION: Ulipristal acetate could lead to serous central chorioretinopathy due to its activity on the progesterone receptors present in choroidal and retinal pigment epithelium.

Levonorgestrel only emergency contraceptive use and risk of ectopic pregnancy in Eldoret Kenya: a case-control study.

INTRODUCTION: ectopic pregnancy is one of the causes of maternal morbidity and mortality in sub-Saharan Africa. Levonorgestrel (LNG) only emergency contraceptive pill is a well-established emergency contraceptive pill that is administered within 72 hours after unprotected intercourse. This study aimed at determining whether or not there is a significant association between levonorgestrel emergency contraceptive use and the occurrence of ectopic pregnancy. METHODS: case-control (1:3) study among 79 women with ectopic pregnancy (cases) matched against 237 women without (controls) at Moi Teaching and Referral Hospital in Eldoret, Kenya; Sociodemographic and clinical data were collected using a questionnaire. Association between ectopic pregnancy and LNG-EC was assessed using Pearson chi-square test. The relationship between outcome and exposure (while adjusting for confounders) was assessed using logistic regression model. RESULTS: The mean age was 27.15 years. Both cases and controls were similar by age (p = 0.990), educational level (p = 0.850), marital status (p = 0.559), employment status (p = 0.186) and parity (p = 0.999). Seventy-eight (24.7%) participants had a history of miscarriage. A higher proportion of the cases had history of using LNG-EC compared to the controls (32.9% vs. 7.2%, p < 0.001). The use of LNG-EC portended more than nine times increased odds of ectopic pregnancy compared to other contraceptive methods {OR = 9.34 (95% CI: 3.9 - 16.0)}. CONCLUSION: levonorgestrel only emergency contraceptive use was associated with ectopic pregnancy. One of the limitations of this study is that we could not control for all confounders of ectopic pregnancy.

Are oral emergency contraceptives a safe and effective form of long-term birth control?

Yes, but not as effective as some other methods. Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%; menstrual irregularity is the most common adverse effect (strength of recommendation [SOR]: B, Cochrane review of lower-quality trials). In women younger than 35 years who have sexual intercourse 6 or fewer times per month, correct and consistent use of pericoital levonorgestrel 1.5 mg results in an annual pregnancy rate of 11% (SOR: B, one large prospective, open-label trial). Pericoital contraception is less effective than long-acting reversible contraceptives (annual pregnancy rates of 0.05%-0.8%) or perfect use of combined oral contraceptives (0.3% annual pregnancy rate), but similar to, or better than, typical use of combined oral contraception (9%) and condoms (18%).

Interventions for emergency contraception.

BACKGROUND: 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. OBJECTIVES: To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy. SEARCH METHODS: 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. SELECTION CRITERIA: Randomised controlled trials including women attending services for EC following a single act of unprotected intercourse were eligible. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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, I2 = 23%, high-quality evidence). This suggests that if the chance of pregnancy using Yuzpe is assumed to be 29 women per 1000, the chance of pregnancy using levonorgestrel would be between 11 and 24 women per 1000.Mifepristone (all doses) was associated with fewer pregnancies than Yuzpe (RR 0.14, 95% CI 0.05 to 0.41, 3 RCTs, n = 2144, I2 = 0%, high-quality evidence). This suggests that if the chance of pregnancy following Yuzpe is assumed to be 25 women per 1000 women, the chance following mifepristone would be between 1 and 10 women per 1000.Both low-dose mifepristone (less than 25 mg) and mid-dose mifepristone (25 mg to 50 mg) were probably associated with fewer pregnancies than levonorgestrel (RR 0.72, 95% CI 0.52 to 0.99, 14 RCTs, n = 8752, I2 = 0%, high-quality evidence; RR 0.61, 95% CI 0.45 to 0.83, 27 RCTs, n = 6052, I2 = 0%, moderate-quality evidence; respectively). This suggests that if the chance of pregnancy following levonorgestrel is assumed to be 20 women per 1000, the chance of pregnancy following low-dose mifepristone would be between 10 and 20 women per 1000; and that if the chance of pregnancy following levonorgestrel is assumed to be 35 women per 1000, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1000.Ulipristal acetate (UPA) was associated with fewer pregnancies than levonorgestrel (RR 0.59; 95% CI 0.35 to 0.99, 2 RCTs, n = 3448, I2 = 0%, high-quality evidence). Comparative effectiveness of different ECP dosesIt was unclear whether there was any difference in pregnancy rate between single-dose levonorgestrel (1.5 mg) and the standard two-dose regimen (0.75 mg 12 hours apart) (RR 0.84, 95% CI 0.53 to 1.33, 3 RCTs, n = 6653, I2 = 0%, moderate-quality evidence).Mid-dose mifepristone was associated with fewer pregnancies than low-dose mifepristone (RR 0.73; 95% CI 0.55 to 0.97, 25 RCTs, n = 11,914, I2 = 0%, high-quality evidence). Comparative effectiveness of Cu-IUD versus mifepristoneThere was no conclusive evidence of a difference in the risk of pregnancy between the Cu-IUD and mifepristone (RR 0.33, 95% CI 0.04 to 2.74, 2 RCTs, n = 395, low-quality evidence). Adverse effectsNausea and vomiting were the main adverse effects associated with emergency contraception. There is probably a lower risk of nausea (RR 0.63, 95% CI 0.53 to 0.76, 3 RCTs, n = 2186 , I2 = 59%, moderate-quality evidence) or vomiting (RR 0.12, 95% CI 0.07 to 0.20, 3 RCTs, n = 2186, I2 = 0%, high-quality evidence) associated with mifepristone than with Yuzpe. levonorgestrel is probably associated with a lower risk of nausea (RR 0.40, 95% CI 0.36 to 0.44, 6 RCTs, n = 4750, I2 = 82%, moderate-quality evidence), or vomiting (RR 0.29, 95% CI 0.24 to 0.35, 5 RCTs, n = 3640, I2 = 78%, moderate-quality evidence) than Yuzpe. Levonorgestrel users were less likely to have any side effects than Yuzpe users (RR 0.80, 95% CI 0.75 to 0.86; 1 RCT, n = 1955, high-quality evidence). UPA users were more likely than levonorgestrel users to have resumption of menstruation after the expected date (RR 1.65, 95% CI 1.42 to 1.92, 2 RCTs, n = 3593, I2 = 0%, high-quality evidence). Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related. Cu-IUD may be associated with higher risks of abdominal pain than mifepristone (18 events in 95 women using Cu-IUD versus no events in 190 women using mifepristone, low-quality evidence). AUTHORS' CONCLUSIONS: 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.

The safety of available and emerging options for emergency contraception.

INTRODUCTION: 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.

["Hormone bomb": risks of emergency contraception from the perspective of pharmacy attendants in Rio de Janeiro, Brazil]. / "Bomba hormonal": os riscos da contracepção de emergência na perspectiva dos balconistas de farmácias no Rio de Janeiro, Brasil.

This study focused on views towards emergency contraception among pharmacy attendants in Greater Metropolitan Rio de Janeiro, Brazil. The empirical material came from a socio-anthropological study with 20 semi-structured interviews of pharmacy attendants of both sexes (8 females and 12 males). The interviews showed negative views of emergency contraception, emphasizing its potential health risks. Interviews considered emergency contraception a "hormone bomb" that can harm the female reproductive organs and other organ systems. The pharmacy attendants highlighted the risks of "uncontrolled" or "indiscriminate" use, especially by adolescents and young women. Since they considered it "dangerous" to women's bodies, they assigned the responsibility for orientation and counseling on use of the method to gynecologists rather than to pharmacists. The article discusses the need to expand the public debate on emergency contraception in Brazil to include pharmacists and pharmacy attendants, in addition to health professionals in general and teachers.

Emergency Contraception.

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.

Emergency contraception: which is the best?

INTRODUCTION: Emergency contraception is a safe and effective method to prevent an unwanted pregnancy after an unprotected or inadequately protected sexual intercourse. Several methods for emergency contraception (EC) are currently registered in many countries for use in an emergency to prevent a pregnancy following an unprotected, possibly fertile intercourse or after a contraceptive accident like condom rupture. Different methods have varying modes of action, time frame of efficacy, dosage schedule and unwanted effects. Since several methods are available it is important to decide the best method. EVIDENCE ACQUISITION: In this article the available literature on emergency contraception has been reviewed and an attempt has been made to discuss the need for emergency contraception and compare different options for emergency contraception in terms of their efficacy in pregnancy prevention, their safety profile and unwanted side effects. EC repeated use and initiating a regular method after EC use are also discussed. EVIDENCE SYNTHESIS: Emergency contraceptive methods include copper Intra-uterine devices (IUD) and different types of pills like estrogen progestin combination pill (Yuzpe Regimen), Progestin only pill (LNG), antiprogestin pill (Mifepristone), and progesterone modulator Uripristal Acetate (UPA). There is a marginal difference in the mechanism of action, efficacy including time frame and ability to protect from pregnancy with regular doses in obese women, drug interactions and side effects. These are discussed in detail. CONCLUSIONS: Copper IUD is the most effective emergency contraceptive with advantage of providing continued contraception. However, it cannot be used universally due to lack of infrastructure and a trained provider as well as not being suitable option for women at risk of sexually transmitted infections. Amongst different pills LNG is more effective with fewer side effects than Yuzpe regimen. LNG and UPA are comparable with similar efficacy and side effect profile. UPA has a wider window of efficacy, in LNG efficacy declines after 72 hours. UPA is more suitable for obese women. Mifepristone is effective but is registered as EC pill only in few countries and use is limited as it is also used as an abortion pill. Yuzpe regimen is the least effective of all contraceptive pills as EC, and works only till 72 hours of unprotected sex, but is useful in places where dedicated methods are not available, as it is easily accessible. Any combined pill can be used in this regimen except triphasic pill.

Safety data for levonorgestrel, ulipristal acetate and Yuzpe regimens for emergency contraception.

UNLABELLED: 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. IMPLICATIONS: 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.

"Bomba hormonal": os riscos da contracepção de emergência na perspectiva dos balconistas de farmácias no Rio de Janeiro, Brasil / "Hormone bomb": risks of emergency contraception from the perspective of pharmacy attendants in Rio de Janeiro, Brazil / "Bomba hormonal": los riesgos de la anticoncepción de emergencia desde la perspectiva de los auxiliares de farmacias en Río de Janeiro, Brasil

Resumo: A pesquisa objetivou conhecer a perspectiva dos balconistas de farmácias sobre a contracepção de emergência na Região Metropolitana do Rio de Janeiro, Brasil. O material empírico advém de pesquisa socioantropológica com vinte entrevistas semiestruturadas com balconistas dos sexos feminino (8) e masculino (12). Os entrevistados apresentam concepções negativas sobre a contracepção de emergência, enfatizando os riscos que ela pode provocar à saúde. O medicamento é considerado uma "bomba hormonal" que pode causar danos aos órgãos reprodutivos femininos e outros sistemas do corpo. Eles destacam os riscos do uso "descontrolado" ou "indiscriminado", especialmente por adolescentes e mulheres jovens. Por ser considerado "perigoso" aos corpos femininos, eles atribuem a responsabilidade de orientação e aconselhamento sobre o uso do método aos médicos ginecologistas e não aos farmacêuticos. Discute-se a necessidade de ampliação do debate público sobre contracepção de emergência no Brasil, incluindo-se os farmacêuticos e balconistas de farmácia, além dos profissionais de saúde e educadores.

Abstract: This study focused on views towards emergency contraception among pharmacy attendants in Greater Metropolitan Rio de Janeiro, Brazil. The empirical material came from a socio-anthropological study with 20 semi-structured interviews of pharmacy attendants of both sexes (8 females and 12 males). The interviews showed negative views of emergency contraception, emphasizing its potential health risks. Interviews considered emergency contraception a "hormone bomb" that can harm the female reproductive organs and other organ systems. The pharmacy attendants highlighted the risks of "uncontrolled" or "indiscriminate" use, especially by adolescents and young women. Since they considered it "dangerous" to women's bodies, they assigned the responsibility for orientation and counseling on use of the method to gynecologists rather than to pharmacists. The article discusses the need to expand the public debate on emergency contraception in Brazil to include pharmacists and pharmacy attendants, in addition to health professionals in general and teachers.

Resumen: La investigación tuvo como objetivo conocer la perspectiva de los auxiliares de farmacias sobre los contraceptivos de emergencia en la Región Metropolitana de Río de Janeiro, Brasil. El material empírico proviene de una investigación socioantropológica con 20 entrevistas semiestructuradas con auxiliares de sexo femenino (8) y masculino (12). Los entrevistados presentan concepciones negativas sobre la anticoncepción de emergencia, enfatizando los riesgos que puede provocar en la salud. El medicamento es considerado una "bomba hormonal" que puede causar daños a los órganos reproductivos femeninos y otros sistemas del cuerpo. Ellos destacan los riesgos del uso "descontrolado" o "indiscriminado", especialmente por adolescentes y mujeres jóvenes. Por ser considerado "peligroso" para el cuerpo femenino, ellos atribuyen la responsabilidad de la orientación y asesoría sobre el uso de este método anticonceptivo a los médicos ginecólogos, y no a los farmacéuticos. Se discute la necesidad de la ampliación del debate público sobre la anticoncepción de emergencia en Brasil, incluyéndose a farmacéuticos y auxiliares de farmacia, además de los profesionales de salud y educadores.

Emergency contraceptive pill safety profile. Comparison of the results of a follow-up study to those coming from spontaneous reporting.

BACKGROUND: The emergency contraceptive pill (ECP) containing levonorgestrel is dispensed without a prescription in Spain since 2009. An easy access could diminish unwanted pregnancies; however, there is a risk of misuse and, in any case, of developing some adverse events. The aim of the present study is to further learn the adverse effects of this ECP. METHODS: An ad hoc follow-up study was carried out in three community pharmacies in a city of Central Spain; the sample was composed of those women asking for the ECP; they were interviewed by telephone after at least a month since the last menses. We completed the safety profile obtained with that coming from spontaneous reporting in Spain. RESULTS: Out of 139 women surveyed, 113 developed any adverse event--two considered as severe; the most frequently reported events were menstrual disturbances, which accounted for 21% of all events. Through spontaneous reporting, 36 cases of whatever adverse events related to levonorgestrel as ECP were identified. Twenty-five cases were considered as severe. Both types of reaction and severity were significantly different in the follow-up study and in the spontaneous reporting. Some of the reactions identified, such as miscarriage, febrile neutropenia, and porphyria, are not included in the Summary of Product Characteristics. CONCLUSIONS: Levonorgestrel as an ECP is mostly safe. Attention should be paid to some severe events and particularly to those risk factors for them to appear. Combining spontaneous reporting with an ad hoc follow-up study, the whole safety profile of a given medication can be obtained.

Repeated use of pre- and postcoital hormonal contraception for prevention of pregnancy.

BACKGROUND: Repeated use of postcoital hormonal contraception is not currently recommended due to the higher risk of side effects and lower contraceptive effectiveness compared to other modern methods of contraception. However, emerging evidence indicates renewed interest in a regular coitally-dependent method of oral contraception. We evaluated the existing data on safety and effectiveness of pericoital use of levonorgestrel and other hormonal drugs to prevent pregnancy. OBJECTIVES: To determine the effectiveness and safety of repeated use of pre- and postcoital hormonal contraception for pregnancy prevention. SEARCH METHODS: We searched until 1 September 2014 for trials that tested repeated pre- and postcoital use of hormonal drugs for pregnancy prevention. Databases included CENTRAL, MEDLINE, and POPLINE. We searched for current trials via ClinicalTrials.gov and ICTRP. For the initial review, we also searched EMBASE, CINAHL, and LILACS, and wrote to researchers to identify other trials. SELECTION CRITERIA: We considered published and unpublished studies of repeated postcoital or immediately precoital use of hormonal drugs for contraception with pregnancy as an outcome. DATA COLLECTION AND ANALYSIS: Two authors independently confirmed eligibility and extracted data from the included studies. We calculated confidence intervals (CI) around individual study Pearl indices using a Poisson distribution. We presented individual study estimates and pooled estimates and their 95% CI, where appropriate. MAIN RESULTS: We found 22 trials that evaluated pericoital use of LNG and other hormonal drugs on a regular basis to prevent pregnancy. The studies included a total of 12,400 participants, and were conducted in Europe, Asia, and the Americas. The drugs and doses evaluated included levonorgestrel (LNG) 0.75 mg (11 studies), LNG in doses other than 0.75 mg (4 trials), and hormones other than LNG (7 trials). Outcomes included pregnancy rates, discontinuation, side effects, and acceptability.Pericoital levonorgestrel was reasonably efficacious and safe. The pooled Pearl Index for the 0.75 mg dose of LNG was 5.4 per 100 woman-years (95% CI 4.1 to 7.0). The pooled Pearl Index for all doses of LNG was 5.0 per 100 woman-years (95% CI 4.4 to 5.6). Other hormonal drugs appeared promising but most of them were not studied extensively. Menstrual irregularities were the most common side effects reported. However, the studies provided no consistent evidence of a relationship between bleeding abnormalities and either frequency of pill intake or total dose of the drug. Non-menstrual side effects were reportedly mild and not tabulated in most studies. Most women liked the pericoital method in spite of frequent menstrual irregularities. AUTHORS' CONCLUSIONS: The studies of pericoital LNG regimens provided promising results but many had serious methodological issues. Most reports were decades old and provided limited information. However, we considered the evidence to be moderate quality because of the large number of participants from diverse populations, the low pregnancy rates, and the consistent results across studies. Rigorous research is still needed to confirm the efficacy and safety of pericoital use of LNG as a primary means of contraception among women with infrequent intercourse. If the method is shown to be efficacious, safe and acceptable, the results may warrant revision of the current World Health Organization recommendations and marketing strategies.

Consequences of emergency contraceptives: the adverse effects.

INTRODUCTION: Emergency contraception (EC) offers women an important strategy to prevent unintended pregnancy following intercourse. Despite the constant improvement of availability of different molecules and techniques already existing (Yuzpe regimen, levonorgestrel, intrauterine device) and the emergence of ulipristal acetate, the numbers of unintended pregnancies and unplanned births could still be reduced. AREAS COVERED: This review will evaluate all the information about the potential adverse effects and tolerability of each method of EC by putting them in balance with their safety and effectiveness. A literature search until December 2013 was performed to identify all trials studying the safety data available concerning EC. EXPERT OPINION: Different means of EC have been demonstrated to be generally safe and well tolerated. These data support women information in order to improve use and efficacy of EC.