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Chmaj-Wierzchowska K, Wszołek K, Tomczyk K, Wilczak M. Safety of Progestogen Hormonal Contraceptive Methods during Lactation: An Overview. Clin Pract 2024; 14:1054-1064. [PMID: 38921261 PMCID: PMC11203090 DOI: 10.3390/clinpract14030083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 05/11/2024] [Accepted: 05/29/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Breastfeeding is a process for not only nourishing infants but also for building a unique emotional bond between mother and child. Therefore, the ideal contraception during lactation should not affect lactation (milk composition, milk volume) and offspring development. OBJECTIVES This study aims to analyze the literature on the safety of progestogen hormonal contraceptive methods during lactation. METHODS We conducted a thorough search across various databases, including the National Library of Medicine (PubMed), and the Cochrane Database, Drugs and Lactation Database (LactMed). Our search utilized specific phrases such as: "lactation" and "breastfeeding" and "oral contraception" with "drospirenone" or "desogestrel", with "subcutaneous etonogestrel implant" or "etonogestrel implant", with "levonorgestrel-releasing intrauterine system", and "emergency contraception", with "levonorgestrel" or "ulipristal acetate". CONCLUSIONS Based on published scientific reports, progestogen hormonal contraceptives can be considered a relatively safe solution for women desiring to continue feeding their infant with their milk while using hormonal contraception. It is important to seek guidance on selecting the best contraception method based on the latest medical knowledge, tailored to the individual needs and clinical circumstances of each woman and place of residence. A woman should always be informed of the potential risks of such a treatment and then allowed to make her own decision based on the knowledge received from a specialist.
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Caruso S, Caruso G, Bruno MT, Minona P, Di Guardo F, Palumbo M. Effects of Drospirenone only pill contraception on postpartum mood disorders: A prospective, comparative pilot study. Eur J Obstet Gynecol Reprod Biol 2023; 288:73-77. [PMID: 37453345 DOI: 10.1016/j.ejogrb.2023.06.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/19/2023] [Accepted: 06/26/2023] [Indexed: 07/18/2023]
Abstract
OBJECTIVE The aim of this non-randomized control study was to assess the effect of Drospirenone (DRSP) only pill (DOP) 4 mg, in a 24 active/4 placebo regimen, on the mood of postpartum women who wanted to use a hormonal contraceptive. STUDY DESIGN Seventy-one women in the study group, and 78 in the control group, were included in intention-to-treat analyses. The depression score was assessed using the self-administrated Edinburgh Postnatal Depression Scale (EPDS) at the childbirth preparation course (T0), and at 2 (T1), 12 (T2), and 24 (T3) weeks postpartum follow-ups. RESULTS From T0 to T1 an increase in the scores was observed in both groups: in the study group from 9.2 ± 2.5 to 10.1 ± 2.4 (p = 0.02), and in the control group from 8.7 ± 2.7 to 10.3 ± 2.2 (p < 0.001). At the T2 follow-up, the EPDS score reduction was statistically significant in the study group (p < 0.001) but not in the control group (p = 0.16). Similarly, at the T3 follow-up, the score was statistically reduced in the study (p < 0.01), but not in the control group (p = 0.35). The intergroup statistical analysis showed no differences between groups at T0 (p = 0.19) and at T1 (p = 0.55). Instead, they were statistically significant at T2 and T3 (p < 0.001). EPDS scores had no significant correlation with the mode of delivery (r = 0.2; p > 0.05) and with the mode of breastfeeding (r = 0.3; p > 0.05). On the other hand, EPDS scores demonstrated a positive correlation with the social status of single (r = 0.99; p < 0.002) and low education level (r = 0.82; p < 0.004). CONCLUSION Postpartum mood disorders may have persistent effects that compromise the mother's health and newborn development. DRSP, used as DOP, could modulate mood disorders of the postpartum period in women with individual sensitivity to steroid levels.
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Affiliation(s)
- Salvatore Caruso
- Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic, Research Group for Sexology, University of Catania, Via Santa Sofia 78, PC 95123, Catania, Italy.
| | - Giuseppe Caruso
- Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic, Research Group for Sexology, University of Catania, Via Santa Sofia 78, PC 95123, Catania, Italy
| | - Maria Teresa Bruno
- Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic, Research Group for Sexology, University of Catania, Via Santa Sofia 78, PC 95123, Catania, Italy
| | - Patrizia Minona
- Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic, Research Group for Sexology, University of Catania, Via Santa Sofia 78, PC 95123, Catania, Italy
| | - Federica Di Guardo
- Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic, Research Group for Sexology, University of Catania, Via Santa Sofia 78, PC 95123, Catania, Italy
| | - Marco Palumbo
- Department of General Surgery and Medical Surgical Specialties, Gynecological Clinic, Research Group for Sexology, University of Catania, Via Santa Sofia 78, PC 95123, Catania, Italy
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Sausjord IK, Acton LW, White KO, O'Connor SK, Lerner NM. Breastfeeding and Hormonal Contraception: A Scoping Review of Clinical Guidelines, Professional Association Recommendations, and the Literature. Breastfeed Med 2023; 18:645-665. [PMID: 37672571 DOI: 10.1089/bfm.2023.0118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/08/2023]
Abstract
Background: Postpartum contraceptive use can help prevent short-interval pregnancies, which have been associated with adverse neonatal and maternal health outcomes. Many contraceptive methods are safe for postpartum use, but patients and providers may be confused as to what impact hormonal contraception has on lactation. We performed a scoping review of the most recent U.S.-based guidelines regarding hormonal contraception on lactation to provide synthesis and recommendations to aid providers in counseling their patients. Methods: We conducted a scoping review by identifying the most recent clinical recommendations and guidelines from the Centers for Disease Control and Prevention (CDC) and three maternal and child health professional associations (American College of Obstetricians and Gynecologists [ACOG], Society for Maternal-Fetal Medicine [SMFM], and Academy of Breastfeeding Medicine [ABM]). We also reviewed the citations in these guidelines used in their development. We then conducted an updated literature review to capture studies published since the most recent systematic reviews were conducted. Results: We reviewed 1 clinical guideline from the CDC and 2 systematic reviews cited in its references, 6 professional association recommendations, and 28 publications identified through the updated literature review. Progestin-only contraceptive methods continue to demonstrate safety in breastfeeding patients, while low-quality evidence supports concerns of decreased milk supply with combined hormonal contraception. Discussion: Organizations should consider updating counseling recommendations regarding progestin-only contraceptives and lactation. Further research is needed to examine new contraceptive methods as well as the effect of hormonal contraception on lactation in the setting of preterm birth.
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Affiliation(s)
- Isabel K Sausjord
- University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA
| | - Lillian W Acton
- Boston University SchooI of Medicine, Boston, Massachusetts, USA
- Boston Medical Center, Boston, Massachusetts, USA
| | - Katharine O White
- Boston University SchooI of Medicine, Boston, Massachusetts, USA
- Boston Medical Center, Boston, Massachusetts, USA
| | - Sarah K O'Connor
- Boston University SchooI of Medicine, Boston, Massachusetts, USA
- Boston Medical Center, Boston, Massachusetts, USA
| | - Natasha M Lerner
- Boston University SchooI of Medicine, Boston, Massachusetts, USA
- Boston Medical Center, Boston, Massachusetts, USA
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Melka D, Kask K, Colli E, Regidor PA. A single-arm study to evaluate the transfer of drospirenone to breast milk after reaching steady state, following oral administration of 4 mg drospirenone in healthy lactating female volunteers. ACTA ACUST UNITED AC 2020; 16:1745506520957192. [PMID: 32903172 PMCID: PMC7485149 DOI: 10.1177/1745506520957192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Objective: The primary objective of this trial was to assess the transfer of
drospirenone to breast milk after daily administration of an oral test
preparation containing 4 mg of drospirenone at the steady state. The
secondary objective of the trial was to assess safety based on clinical and
laboratory measurements and reporting of adverse events and/or adverse drug
reactions. Patients and Methods: This was an open label, non-comparative single-center study. Drospirenone
4 mg per day was the first postpartum contraceptive for the study
participants who were no longer breastfeeding yet were still lactating. It
was administered for 7 days to achieve steady-state concentration. All
participants were volunteers who planned to use oral contraceptives as their
family planning method in the future. Results: Twelve volunteers completed the trial according to the protocol, and the
samples of all 12 study completers were analyzed. The average
concentration–time curve of drospirenone in plasma 24 h after the
administration of the last dose (area under the curve (0–24 h)) was
635.33 ng h/mL and 120 h after the single repeated dose administration (area
under the curve (0–120 h)) was 1180.57 ng h/mL, respectively. The average
Cmax was 48.64 ng/mL. The average concentration–time curve of drospirenone in milk 24 h after the
administration of the last dose (area under the curve (0–24 h)) was
134.35 ng h/mL and 120 h after the single repeated dose administration (area
under the curve (0–120 h)) was 227.17 ng h/mL, respectively. The average
Cmax was 10.34 ng/mL. Conclusion: On average, 18.13% of plasma drospirenone made it to breast milk and the
highest concentration of drospirenone in breast milk was 17.55% of that in
plasma. The total quantity of drospirenone passing to breast milk is on
average 4478 ng during a 24-h period representing 0.11% of the maternal
daily dose. Thus, at the recommended doses, no effects on breastfed
newborns/infants are anticipated with drospirenone 4 mg.
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Affiliation(s)
| | - Kalev Kask
- EGeen International Corporation, Mountain View, CA, USA
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A Systematic Review and Meta-analysis of the Adverse Effects of Levonorgestrel Emergency Oral Contraceptive. Clin Drug Investig 2020; 40:395-420. [PMID: 32162237 DOI: 10.1007/s40261-020-00901-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
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.
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Shaaban OM, Abbas AM, Mahmoud HR, Yones EM, Mahmoud A, Zakherah MS. Levonorgestrel emergency contraceptive pills use during breastfeeding; effect on infants' health and development. J Matern Fetal Neonatal Med 2019; 32:2524-2528. [PMID: 29463142 DOI: 10.1080/14767058.2018.1439470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 02/07/2018] [Accepted: 02/07/2018] [Indexed: 10/18/2022]
Abstract
OBJECTIVE The current study aims to evaluate the effect of the use of single packet of levonorgestrel emergency contraceptive pills (LNG-ECPs) during breastfeeding on the health and development of the nursing infant. MATERIALS AND METHODS The current study was an ancillary observational cohort study carried out in a university hospital. We counseled all women delivered and planning birth-space and breastfeed for at least 1 year for participation during postpartum hospital stay. Eligible participants for inclusion in the randomized controlled trial (NCT01111929) were allocated to receive adequate Lactational Amenorrhea Method (LAM) counseling (LAM-only group) or the LAM counseling in addition to counseling about LNG-ECPs use (LAM + emergency contraception (EC) group). These pills were to be used once if unprotected intercourse did occur after expiry of any of the LAM prerequisites and before the couples started to use a reliable method of contraception. We included the first 100 women in the LAM + EC who did use the pills and the first 100 women in the control group who completed the follow-up visits for 6 months to draw the infants' outcome. The primary outcome was the difference of anthropometric measurements of the infants at 3 and 6 months postpartum. Secondary outcome was the difference in the Psycho-social, fine and gross motor, and language development using Denver development screening test. RESULTS There were no statistical significant differences between both the groups regarding the infants' weight, length, head circumference, chest circumference, and mid-arm circumference at each visit (p > .05). Additionally, there were no statistically significant differences regarding all items (psycho-social, fine and gross motor, and language) of Denver development screening test between the infants in LAM-only and LAM + EC groups (p = .081). CONCLUSIONS The use of single packet of LNG-ECPs during breastfeeding not objectively affects health and development of nursing infants or subjectively affects the quantity of breast milk.
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Affiliation(s)
- Omar M Shaaban
- a Department of Obstetrics and Gynecology , Faculty of Medicine, Assiut University , Assiut , Egypt
| | - Ahmed M Abbas
- a Department of Obstetrics and Gynecology , Faculty of Medicine, Assiut University , Assiut , Egypt
| | - Hanaa R Mahmoud
- b Department of Obstetric and Gynecological Nursing , Faculty of Nursing, Assiut University , Assiut , Egypt
| | - Entsar M Yones
- b Department of Obstetric and Gynecological Nursing , Faculty of Nursing, Assiut University , Assiut , Egypt
| | - Ahmed Mahmoud
- c Department of Pediatrics, Faculty of Medicine , Assiut University , Assiut , Egypt
| | - Mahmoud S Zakherah
- a Department of Obstetrics and Gynecology , Faculty of Medicine, Assiut University , Assiut , Egypt
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Shen J, Che Y, Showell E, Chen K, Cheng L, Cochrane Fertility Regulation Group. Interventions for emergency contraception. Cochrane Database Syst Rev 2019; 1:CD001324. [PMID: 30661244 PMCID: PMC7055045 DOI: 10.1002/14651858.cd001324.pub6] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
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.
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Affiliation(s)
- Jie Shen
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
| | - Yan Che
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
| | | | - Ke Chen
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
| | - Linan Cheng
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
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Abstract
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.
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Key Words
- female
- humans
- pregnancy
- contraception, postcoital
- contraception, postcoital/adverse effects
- contraception, postcoital/methods
- contraceptives, postcoital
- contraceptives, postcoital/administration & dosage
- contraceptives, postcoital/adverse effects
- drug administration schedule
- estradiol
- estradiol/administration & dosage
- estradiol/adverse effects
- intrauterine devices, copper
- intrauterine devices, copper/adverse effects
- intrauterine devices, medicated
- intrauterine devices, medicated/adverse effects
- levonorgestrel
- levonorgestrel/administration & dosage
- levonorgestrel/adverse effects
- mifepristone
- mifepristone/administration & dosage
- mifepristone/adverse effects
- norpregnadienes
- norpregnadienes/administration & dosage
- norpregnadienes/adverse effects
- pregnancy rate
- randomized controlled trials as topic
- unsafe sex
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Affiliation(s)
- Jie Shen
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
| | - Yan Che
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
| | | | - Ke Chen
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
| | - Linan Cheng
- Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan UniversityCentre for Clinical Research and Training2140 Xie Tu RoadShanghaiChina
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9
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Lee JK, Schwarz EB. The safety of available and emerging options for emergency contraception. Expert Opin Drug Saf 2017; 16:1163-1171. [PMID: 28730840 DOI: 10.1080/14740338.2017.1354985] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
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.
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Affiliation(s)
- Jessica K Lee
- a Department of Obstetrics and Gynecology , Johns Hopkins University , Baltimore , MD , USA
| | - Eleanor Bimla Schwarz
- b Department of General Internal Medicine , UC Davis, Division of General Internal Medicine , Sacramento , CA , USA
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10
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Kelekci S, Aydogmus S. Emergency contraception: What is new? World J Obstet Gynecol 2015; 4:95-101. [DOI: 10.5317/wjog.v4.i4.95] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Revised: 07/19/2015] [Accepted: 09/08/2015] [Indexed: 02/05/2023] Open
Abstract
Unintended pregnancy rates remain high throughout the World and increase the risk of poor maternal and infant outcomes. Most of unintended pregnancies occur in women who were not using contraception or who became pregnant despite the reported use of contraception. Women who have had recent unprotected intercourse including those who have had another form of contraception fail are potential candidates for this intervention. Currently used emergency contraceptive methods are pills that contain combined estrogen-progesterone, only progestin, antiprogestins and copper intrauterine devices. The most common form of this type of contraception is oral progestin-only pills (levonorgestrel). The most effective method is copper intrauterine devices followed by anti-progestins and oral progestin-only pills. The major pathogenesis of oral emergency contraceptives is the prevention or delay of ovulation. Although conception is possible on only a few days of the cycle, emergency contraception is offered when indicated without regard to the timing of the menstrual cycle because of uncertainty in the timing of the ovulation. Levonorgestrel and E/P regimes are most effective as soon as possible after unprotected sexual intercourse. A linear relationship has been shown between effectiveness and the time of dose. The effectiveness continues for 120 h, but it is recommended to be used within 72 h after intercourse. Intrauterine devices may prevent pregnancy when 5 d after ovulation.
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11
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Safety data for levonorgestrel, ulipristal acetate and Yuzpe regimens for emergency contraception. Contraception 2015; 93:93-112. [PMID: 26546020 DOI: 10.1016/j.contraception.2015.11.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Revised: 10/23/2015] [Accepted: 11/01/2015] [Indexed: 12/30/2022]
Abstract
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.
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12
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Abstract
A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.
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Affiliation(s)
- Pamela Berens
- 1 Department of Obstetrics and Gynecology, University of Texas , Houston, Texas
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13
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Carvajal A, Sáinz M, Velasco V, García Ortega P, Treceño C, Martín Arias LH, Pellón M, García Sevillano L. Emergency contraceptive pill safety profile. Comparison of the results of a follow-up study to those coming from spontaneous reporting. Pharmacoepidemiol Drug Saf 2014; 24:93-7. [PMID: 25408302 DOI: 10.1002/pds.3725] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 08/02/2014] [Accepted: 09/22/2014] [Indexed: 02/05/2023]
Abstract
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.
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Affiliation(s)
- Alfonso Carvajal
- Centro de Estudios sobre la Seguridad de los Medicamentos (CESME), Universidad de Valladolid, Valladolid, Spain
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14
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Li HWR, Lo SST, Ho PC. Emergency contraception. Best Pract Res Clin Obstet Gynaecol 2014; 28:835-44. [DOI: 10.1016/j.bpobgyn.2014.04.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Revised: 04/23/2014] [Accepted: 04/25/2014] [Indexed: 12/30/2022]
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