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Mayo Clinic Proceedings Jun 2016Emergency contraception (EC) may help prevent pregnancy in various circumstances, such as contraceptive method failure, unprotected sexual intercourse, or sexual... (Review)
Review
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
PubMed: 27261868
DOI: 10.1016/j.mayocp.2016.02.018 -
The New England Journal of Medicine Jan 2021In the United States, more intrauterine device (IUD) users select levonorgestrel IUDs than copper IUDs for long-term contraception. Currently, clinicians offer only... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
In the United States, more intrauterine device (IUD) users select levonorgestrel IUDs than copper IUDs for long-term contraception. Currently, clinicians offer only copper IUDs for emergency contraception because data are lacking on the efficacy of the levonorgestrel IUD for this purpose.
METHODS
This randomized noninferiority trial, in which participants were unaware of the group assignments, was conducted at six clinics in Utah and included women who sought emergency contraception after at least one episode of unprotected intercourse within 5 days before presentation and agreed to placement of an IUD. We randomly assigned participants in a 1:1 ratio to receive a levonorgestrel 52-mg IUD or a copper T380A IUD. The primary outcome was a positive urine pregnancy test 1 month after IUD insertion. When a 1-month urine pregnancy test was unavailable, we used survey and health record data to determine pregnancy status. The prespecified noninferiority margin was 2.5 percentage points.
RESULTS
Among the 355 participants randomly assigned to receive levonorgestrel IUDs and 356 assigned to receive copper IUDs, 317 and 321, respectively, received the interventions and provided 1-month outcome data. Of these, 290 in the levonorgestrel group and 300 in the copper IUD group had a 1-month urine pregnancy test. In the modified intention-to-treat and per-protocol analyses, pregnancy rates were 1 in 317 (0.3%; 95% confidence interval [CI], 0.01 to 1.7) in the levonorgestrel group and 0 in 321 (0%; 95% CI, 0 to 1.1) in the copper IUD group; the between-group absolute difference in both analyses was 0.3 percentage points (95% CI, -0.9 to 1.8), consistent with the noninferiority of the levonorgestrel IUD to the copper IUD. Adverse events resulting in participants seeking medical care in the first month after IUD placement occurred in 5.2% of participants in the levonorgestrel IUD group and 4.9% of those in the copper IUD group.
CONCLUSIONS
The levonorgestrel IUD was noninferior to the copper IUD for emergency contraception. (Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT02175030.).
Topics: Adolescent; Adult; Contraception, Postcoital; Female; Follow-Up Studies; Humans; Intention to Treat Analysis; Intrauterine Devices, Copper; Intrauterine Devices, Medicated; Levonorgestrel; Pregnancy; Pregnancy Rate; Pregnancy Tests; Unsafe Sex; Young Adult
PubMed: 33503342
DOI: 10.1056/NEJMoa2022141 -
Contraception Sep 2018The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent...
The recent Danish cohort study reported a 20% increased risk of breast cancer among current and recent hormonal contraception users. These results are largely consistent with previous studies. This study did not report on stage of disease at diagnosis, and it is not clear to what extent the apparent increased risk may be due to a small advance in the timing of diagnosis. This study did not report on the risk associated with the use of a 20-mcg ethinyl estradiol pill. They did find an increasing risk in current users of longer duration and an increased risk with use of the levonorgestrel intrauterine system-both of these potentially important findings have not been consistently found in previous studies and require further investigation. The breast cancer effects described now in multiple studies wane with time, and in the long term, hormonal contraception use has been found not to be associated with any increased total cancer risk.
Topics: Breast Neoplasms; Cohort Studies; Contraception; Ethinyl Estradiol; Humans; Levonorgestrel
PubMed: 30193687
DOI: 10.1016/j.contraception.2018.05.002 -
Journal of Assisted Reproduction and... Jan 2020Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were... (Review)
Review
Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were conducted to evaluate return to fertility after removal of IUDs, majority of them were focused on multiparous women using copper IUDs. Current trends indicate increased use of levonorgestrel (LNG) IUDs in nulliparous women for very long periods of time, with both nulliparity and long duration of LNG-IUD use being potentially associated with trends towards longer time to conception post removal. Understanding the effects that LNG-IUDs may have on endometrial morphology and gene expression has important implications to further understanding their mechanism of action. Studies examining endometrial gene expression show persistent changes in receptivity markers up to 1 year after removal of an inert IUD, and no similar studies have been performed after removal of LNG-IUDs. Given the current gap in the literature and trends in LNG-IUD use in nulliparous young women, studies are needed that specifically look at the interaction of nulliparity, long-term use of LNG-IUD, and return to normal fertility. Herein, we review the available literature on the mechanism of action of IUDs with a specific focus on the effect on endometrial gene expression profile changes associated with IUDs.
Topics: Contraceptive Agents, Hormonal; Female; Fertilization; Humans; Infertility, Female; Intrauterine Devices; Levonorgestrel; Pregnancy
PubMed: 31709489
DOI: 10.1007/s10815-019-01624-5 -
Drugs Nov 2023Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on... (Review)
Review
Adenomyosis, characterized by the growth of endometrial tissue within the uterine wall, poses significant challenges in treatment. The literature primarily focuses on managing abnormal uterine bleeding (AUB) and dysmenorrhea, the main symptoms of adenomyosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) and tranexamic acid provide limited support for mild symptoms or symptom re-exacerbation during hormone therapy. The levonorgestrel-releasing intrauterine system (LNG-IUS) is commonly employed in adenomyosis management, showing promise in symptom improvement and reducing uterine size, despite the lack of standardized guidelines. Dienogest (DNG) also exhibits potential benefits, but limited evidence hinders treatment recommendations. Danazol, while effective, is limited by androgenic side effects. Combined oral contraceptives (COCs) may be less effective than progestins but can be considered for contraception in young patients. Gonadotropin-releasing hormone (GnRH) agonists effectively manage symptoms but induce menopausal symptoms with prolonged use. GnRH antagonists are a recent option requiring further investigation. Aromatase inhibitors (AIs) show promise in alleviating AUB and pelvic pain, but their safety necessitates exploration and limited use within trials for refractory patients. This review highlights the complexity of diagnosing adenomyosis, its coexistence with endometriosis and uterine leiomyomas, and its impact on fertility and quality of life, complicating treatment decisions. It emphasizes the need for research on guidelines for medical management, fertility outcomes, long-term effects of therapies, and exploration of new investigational targets. Future research should optimize therapeutic strategies, expand our understanding of adenomyosis and its management, and establish evidence-based guidelines to improve patient outcomes and quality of life.
Topics: Female; Humans; Adenomyosis; Quality of Life; Uterus; Progestins; Gonadotropin-Releasing Hormone; Levonorgestrel
PubMed: 37837497
DOI: 10.1007/s40265-023-01957-7 -
American Journal of Obstetrics and... Dec 2022The 52-mg levonorgestrel-releasing intrauterine system is an established, long-acting contraceptive option with approved use for up to 7 years.
BACKGROUND
The 52-mg levonorgestrel-releasing intrauterine system is an established, long-acting contraceptive option with approved use for up to 7 years.
OBJECTIVE
The Mirena Extension Trial evaluated the efficacy and safety of the 52-mg levonorgestrel-releasing intrauterine system during extended use beyond 5 and up to 8 years.
STUDY DESIGN
This was a multicenter, single-arm study in the United States, enrolling existing users of the 52-mg levonorgestrel-releasing intrauterine system, aged 18 to 35 years, who have had the system for 4.5 to 5 years. We assessed the contraceptive efficacy (Pearl Index) and cumulative failure rate (using the Kaplan-Meier method) of the 52-mg levonorgestrel-releasing intrauterine system during extended use. We also evaluated bleeding outcomes and adverse events.
RESULTS
Of the 362 participants starting year 6, 243 entered and 223 completed 8 years of 52-mg levonorgestrel-releasing intrauterine system use. Just more than half the participants were parous. The mean (standard deviation) age was 29.2 (±2.9) years, and all participants were aged ≤36 years at the end of year 8. Two pregnancies occurred, both with the device in situ. The year 6 pregnancy was of undetermined location and resolved spontaneously. The pregnancy in year 7 was ectopic and resolved with methotrexate treatment. In both cases, the 52-mg levonorgestrel-releasing intrauterine system was removed and the participants left the trial. For years 6 to 8, the 3-year Pearl Index (95% confidence interval) was 0.28 (0.03-1.00) with a 3-year cumulative failure rate of 0.68% (0.17-2.71). Pearl Indexes for years 6, 7, and 8 were 0.34 (0.01-1.88), 0.40 (0.01-2.25), and 0.00 (0.00-1.90), respectively. The 3-year (years 6-8) ectopic pregnancy Pearl Index was 0.14 (0.00-0.77). We found treatment-emergent adverse events in 249 of 362 participants (68.8%), with 65 (18.0%) events considered to be related to the 52-mg levonorgestrel-releasing intrauterine system. The discontinuation rate was 38.4% (139/362), most commonly because of desire for pregnancy (12.2%, 44/362). During extended use beyond 5 years and up to 8 years, participants reported a decrease in the mean number of bleeding or spotting days with approximately half of the women experiencing amenorrhea or infrequent bleeding. We did not enroll a sufficient number of women using the 52-mg levonorgestrel-releasing intrauterine system for contraception and heavy menstrual bleeding to assess extended use for that indication. At the end of year 8, most (98.7%, 220/223) of the participants who completed the study remained satisfied with the continued use of the 52-mg levonorgestrel-releasing intrauterine system. Of the 31 women who discontinued early because of desire for pregnancy with evaluable data for return-to-fertility analysis, 24 reported a posttreatment pregnancy within 1 year, giving a 12-month return-to-fertility rate of 77.4%.
CONCLUSION
The 52-mg levonorgestrel-releasing intrauterine system, initially approved for 5 years, maintains high contraceptive efficacy, user satisfaction, and a favorable safety profile through 8 years of use. Participants reported 26 posttreatment pregnancies in total, of which 24 occurred in women who had discontinued the 52-mg levonorgestrel-releasing intrauterine system because of a desire for pregnancy. Of note, among women who elected to continue use through 8 years, bleeding patterns remained highly favorable. These findings support continued 52-mg levonorgestrel-releasing intrauterine system use for up to 8 years in women who wish to continue treatment.
Topics: Pregnancy; Female; Humans; Levonorgestrel; Intrauterine Devices, Medicated; Contraceptive Agents, Female; Menorrhagia; Metrorrhagia
PubMed: 36096186
DOI: 10.1016/j.ajog.2022.09.007 -
Fertility and Sterility Nov 2018To assess the efficacy of an etonogestrel (ENG)-releasing contraceptive implant or the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) in the control of... (Randomized Controlled Trial)
Randomized Controlled Trial
Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial.
OBJECTIVE
To assess the efficacy of an etonogestrel (ENG)-releasing contraceptive implant or the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) in the control of endometriosis-associated pelvic pain.
DESIGN
Noninferiority randomized clinical trial in which women with endometriosis were assigned to use an ENG implant (experimental treatment) or an LNG-IUS (active comparator). Monthly follow-up visits were conducted up to 6 months.
SETTING
University teaching hospital.
PATIENT(S)
One hundred three women, with endometriosis-associated chronic pelvic pain, dysmenorrhea, or both for more than 6 months. In cases of deep endometriosis, vaginal ultrasonography and magnetic resonance imaging were used as additional diagnostic tools.
INTERVENTION(S)
The ENG implant or the LNG-IUS were inserted within the first 5 days of the menstrual cycle.
MAIN OUTCOME MEASURE(S)
Daily scores of noncyclic pelvic pain and dysmenorrhea were evaluated using a daily visual analogue scale. Health-related quality of life was evaluated using the Endometriosis Health Profile-30 questionnaire at baseline and up to 6 months. Bleeding patterns were assessed daily from a menstrual calendar.
RESULT(S)
Both contraceptives improved significantly the mean visual analogue scale endometriosis-associated pelvic pain and dysmenorrhea, without significant differences between treatment group profiles. Health-related quality of life improved significantly in all domains of the core and modular segments of the Endometriosis Health Profile-30 questionnaire, with no difference between both treatment groups. The most common bleeding patterns at 180 days of follow-up were amenorrhea and infrequent bleeding and infrequent bleeding and spotting among ENG implant and LNG-IUS users, respectively.
CONCLUSION(S)
In this noninferiority study both contraceptives improved significantly pelvic pain, dysmenorrhea, and health-related quality of life in endometriosis.
CLINICAL TRIAL REGISTRATION NUMBER
Clinicaltrials.gov under number NCT02480647.
Topics: Adult; Contraceptive Agents, Female; Desogestrel; Drug Implants; Drug Liberation; Endometriosis; Female; Follow-Up Studies; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Pain Management; Pelvic Pain
PubMed: 30396557
DOI: 10.1016/j.fertnstert.2018.07.003 -
CMAJ : Canadian Medical Association... Dec 2016
Topics: Body Mass Index; Contraception, Postcoital; Contraceptives, Postcoital; Female; Humans; Intrauterine Devices, Copper; Levonorgestrel; Norpregnadienes; Treatment Outcome
PubMed: 27821461
DOI: 10.1503/cmaj.160720 -
Fertility and Sterility Jul 2018
Topics: Female; Humans; Intrauterine Devices; Levonorgestrel; Ovulation Induction
PubMed: 29980263
DOI: 10.1016/j.fertnstert.2018.04.020 -
Acta Obstetricia Et Gynecologica... Aug 2020Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS).
MATERIAL AND METHODS
We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed).
RESULTS
We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I = 0%, P = .84).
CONCLUSIONS
Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.
Topics: Breast Neoplasms; Contraceptive Agents, Female; Female; Humans; Intrauterine Devices, Medicated; Levonorgestrel; Risk Factors
PubMed: 31990981
DOI: 10.1111/aogs.13817