Long-acting reversible contraception (LARC)—intrauterine devices and the contraceptive implant—are safe and appropriate contraceptive methods for most women and adolescents. The LARC methods are ...top-tier contraceptives based on effectiveness, with pregnancy rates of less than 1% per year for perfect use and typical use. These contraceptives have the highest rates of satisfaction and continuation of all reversible contraceptives. Adolescents are at high risk of unintended pregnancy and may benefit from increased access to LARC methods.
Interventions for emergency contraception Shen, Jie; Che, Yan; Showell, Emily ...
Cochrane database of systematic reviews,
01/2019, Letnik:
2019, Številka:
1
Journal Article
Recenzirano
Odprti dostop
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 doses
It 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 mifepristone
There 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 effects
Nausea 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.
Background
Heavy menstrual bleeding (HMB) is an important cause of ill health in women and it accounts for 12% of all gynaecology referrals in the UK. Heavy menstrual bleeding is clinically defined ...as greater than or equal to 80 mL of blood loss per menstrual cycle. However, women may complain of excessive bleeding when their blood loss is less than 80 mL. Hysterectomy is often used to treat women with this complaint but medical therapy may be a successful alternative.
The intrauterine device was originally developed as a contraceptive but the addition of progestogens to these devices resulted in a large reduction in menstrual blood loss. Case studies of two types of progesterone or progestogen‐releasing systems, Progestasert and Mirena, reported reductions of up to 90% and improvements in dysmenorrhoea (pain or cramps during menstruation). Insertion, however, may be regarded as invasive by some women, which affects its acceptability as a treatment. Frequent intermenstrual bleeding and spotting is also likely during the first few months after commencing treatment.
Objectives
To determine the effectiveness, acceptability and safety of progesterone or progestogen‐releasing intrauterine devices in achieving a reduction in heavy menstrual bleeding.
Search methods
All randomised controlled trials of progesterone or progestogen‐releasing intrauterine devices for the treatment of heavy menstrual bleeding were obtained by electronic searches of The Cochrane Library, the specialised register of MDSG, MEDLINE (1966 to January 2015), EMBASE (1980 to January 2015), CINAHL (inception to December 2014) and PsycINFO (inception to January 2015). Additional searches were undertaken for grey literature and for unpublished trials in trial registers. Companies producing progestogen‐releasing intrauterine devices and experts in the field were contacted for information on published and unpublished trials.
Selection criteria
Randomised controlled trials in women of reproductive age treated with progesterone or progestogen‐releasing intrauterine devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding within primary care, family planning or specialist clinic settings were eligible for inclusion. Women with postmenopausal bleeding, intermenstrual or irregular bleeding, or pathological causes of heavy menstrual bleeding were excluded.
Data collection and analysis
Potential trials were independently assessed by at least two review authors. The review authors extracted the data independently and data were pooled where appropriate. Risk ratios (RRs) were estimated from the data for dichotomous outcomes and mean differences (MD) for continuous outcomes. The primary outcomes were reduction in menstrual blood loss and satisfaction; in addition, rate of adverse effects, changes in quality of life, failure of treatment and withdrawal from treatment were also assessed.
Main results
We included 21 RCTs (2082 women). The included trials mostly assessed the levonorgestrel‐releasing intrauterine device (LNG IUS) (no conclusions could be reached from one small study assessing Progestasert which was discontinued in 2001) and so conclusions are based only on LNG IUS. Comparisons were made with placebo, oral medical treatment, endometrial destruction techniques and hysterectomy. Ratings for the overall quality of the evidence for each comparison ranged from very low to high. Limitations in the evidence included inadequate reporting of study methods and inconsistency.
Seven studies compared the LNG IUS with oral medical therapy: either norethisterone acetate (NET) administered over most of the menstrual cycle, medroxyprogesterone acetate (MPA) (administered for 10 days), the oral contraceptive pill, mefenamic acid or usual medical treatment where participants could choose the oral treatment that was most suitable. The LNG IUS was more effective at reducing HMB as measured by the alkaline haematin method (MD 66.91 mL, 95% CI 42.61 to 91.20; two studies, 170 women; I2 = 81%, low quality evidence) or by Pictorial Bleeding Assessment Chart (PBAC) scores (MD 55.05, 95% CI 27.83 to 82.28; three studies, 335 women; I2 = 79%, low quality evidence), improving quality of life and a greater number of women continued with their treatment at two years when compared with oral treatment. Although substantial heterogeneity was identified for the bleeding outcomes, the direction of effect consistently favoured the LNG IUS. There was insufficient evidence to reach conclusions on satisfaction. Minor adverse effects (such as pelvic pain, breast tenderness and ovarian cysts) were more common with the LNG IUS.
Ten studies compared the LNG IUS with endometrial destruction techniques: three with transcervical resection, one with rollerball ablation and six with thermal balloon ablation. Evidence was inconsistent and very low quality with respect to reduction in bleeding outcomes and satisfaction was comparable between treatments (low and moderate quality evidence). Improvements in quality of life were experienced with both types of treatment. Minor adverse events were more common with the LNG IUS overall, but it appeared more cost effective compared to thermal ablation within a two‐year time frame in one study.
Three studies compared the LNG IUS with hysterectomy. The LNG IUS was not as successful at reducing HMB as hysterectomy (high quality evidence). The women in these studies reported improved quality of life, regardless of treatment. In spite of the high rate of surgical treatment in those having LNG IUS within 10 years, the LNG IUS was more cost effective than hysterectomy.
Authors' conclusions
The levonorgestrel‐releasing intrauterine device (LNG IUS) is more effective than oral medication as a treatment for heavy menstrual bleeding (HMB). It is associated with a greater reduction in HMB, improved quality of life and appears to be more acceptable long term but is associated with more minor adverse effects than oral therapy.
When compared to endometrial ablation, it is not clear whether the LNG IUS offers any benefits with regard to reduced HMB and satisfaction rates and quality of life measures were similar. Some minor adverse effects were more common with the LNG IUS but it appeared to be more cost effective than endometrial ablation techniques.
The LNG IUS was less effective than hysterectomy in reducing HMB. Both treatments improved quality of life but the LNG IUS appeared more cost effective than hysterectomy for up to 10 years after treatment.
OBJECTIVE:To measure discontinuation within 6 months among users of the levonorgestrel intrauterine system, copper intrauterine device (IUD), and etonogestrel implant and identify baseline ...characteristics associated with early discontinuation.
METHODS:This was an analysis of the Contraceptive CHOICE Project, a cohort study of 9,256 participants provided with no-cost contraception and followed with telephone interviews at 3 and 6 months. We used logistic regression to investigate characteristics associated with early discontinuation of the two IUDs and implant and described reasons for discontinuation.
RESULTS:A total of 6,167 participants were eligible for this analysis. Follow-up data were available for 5,928 participants; 5,495 (93%) were using their method at 6 months and 433 (7%) had discontinued. Discontinuation rates were 7.3%, 8.0%, and 6.9% for the levonorgestrel intrauterine system, copper IUD, and implant, respectively. After adjusting for age, race, marital status, low socioeconomic status, and history of sexually transmitted infection, we found that unmarried women were slightly more likely to discontinue compared with married women (adjusted odds ratio OR 1.26, 95% confidence interval CI 1.01–1.59 and adjusted OR 1.62, 95% CI 1.11–2.37, respectively). No other baseline characteristics, including younger age (14–19 years), were associated with early discontinuation. The most common reason given for discontinuation was cramping among IUD users and irregular or frequent bleeding among implant users.
CONCLUSION:Rates of discontinuation of long-acting reversible contraception at 6 months is low and not increased in adolescents and young women. Intrauterine devices and the implant should be considered as first-line contraceptive options among all women to reduce unintended pregnancy.
LEVEL OF EVIDENCE:II
Abstract Objective To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use. Study design In this Phase III study, ...2885 nulliparous and parous women aged 18–35 years were randomized to LNG‐IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction. Results From August 2007 through May 2008, of 2885 women who were enrolled, 1,453 were randomized to LNG-IUS 12. Placement was attempted in 1,452/1,453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months. Conclusion In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG‐IUS 12 offers women a low-dose contraceptive option for up to 5 years.
In this nationwide prospective cohort study from Denmark, women who currently or recently used contemporary hormonal contraception had a significantly higher risk of breast cancer than women with no ...previous use, although absolute increases in risk were small.
Uterine leiomyomas (fibroids) are the most common solid and symptomatic neoplasm in women. They are the leading indication for hysterectomy (1, 2), which is a definitive and effective surgical ...treatment for leiomyoma. However, many patients benefit from and seek out management options other than hysterectomy because they desire future childbearing or wish to retain their uterus. The purpose of this Practice Bulletin is to provide updated evidence-based recommendations for the medical, procedural, and surgical management of symptomatic leiomyomas. Discussion of the use of morcellation in the surgical management of leiomyomas is beyond the scope of this document and is addressed in a separate American College of Obstetricians and Gynecologists (ACOG) publication (3).
Background
Heavy menstrual bleeding and pain are common reasons women discontinue intrauterine device (IUD) use. Copper IUD (Cu IUD) users tend to experience increased menstrual bleeding, whereas ...levonorgestrel IUD (LNG IUD) users tend to have irregular menstruation. Medical therapies used to reduce heavy menstrual bleeding or pain associated with Cu and LNG IUD use include non‐steroidal anti‐inflammatory drugs (NSAIDs), anti‐fibrinolytics and paracetamol. We analysed treatment and prevention interventions separately because the expected outcomes for treatment and prevention interventions differ. We did not combine different drug classes in the analysis as they have different mechanisms of action. This is an update of a review originally on NSAIDs. The review scope has been widened to include all interventions for treatment or prevention of heavy menstrual bleeding or pain associated with IUD use.
Objectives
To evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies.
Search methods
We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021.
Selection criteria
We included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention.
Data collection and analysis
Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random‐effects model in all meta‐analyses. Review authors assessed the certainty of evidence using GRADE.
Main results
This review includes 21 trials involving 3689 participants from middle‐ and high‐income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding.
Treatment of heavy menstrual bleeding
Cu IUD
Vitamin B1 resulted in fewer pads used per day (mean difference (MD) −7.00, 95% confidence interval (CI) −8.50 to −5.50) and fewer bleeding days (MD −2.00, 95% CI –2.38 to −1.62; 1 trial; 110 women; low‐certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low‐certainty evidence).
Treatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD −64.26, 95% CI −105.65 to −22.87; 1 trial, 94 women; low‐certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI −0.27 to 0.42, 2 trials, 152 women; low‐certainty evidence).
LNG IUD
The use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD −9.30 days, 95% CI −26.76 to 8.16; 1 trial, 24 women; low‐certainty evidence).
Unknown IUD type
Mefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD −2.40, 95% CI −13.77 to 8.97; 1 trial; 84 women; low‐certainty evidence).
Treatment of pain
Cu IUD
Treatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low‐certainty evidence).
Unknown IUD type
Naproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low‐certainty evidence).
Prevention of heavy menstrual bleeding
Cu IUD
We found very low‐certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD −14.11, 95% CI −36.04 to 7.82) and duration of bleeding (MD −0.2 days, 95% CI −1.40 to 1.0; 1 trial, 28 women, low‐certainty evidence).
Aspirin may not prevent heavy bleeding in comparison to paracetamol (MD −0.30, 95% CI −26.16 to 25.56; 1 trial, 20 women; very low‐certainty evidence).
LNG IUD
Ulipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low‐certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B.
There were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol.
Prevention of pain
Cu IUD
There was low‐certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low‐certainty evidence).
Authors' conclusions
Findings from this review should be interpreted with caution due to low‐ and very low‐certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.
OBJECTIVE:To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer.
METHODS:This retrospective ...case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined.
RESULTS:Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57–89) at 6 months; 80% (95% CI 52–96) in complex atypical hyperplasia, 67% (95% CI 30–93) in grade 1 endometrial cancer, and 75% (CI 35–97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04).
CONCLUSION:Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.
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