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BMJ (Clinical Research Ed.) Feb 2022To compare the efficacy of bed rest, cervical cerclage (McDonald, Shirodkar, or unspecified type of cerclage), cervical pessary, fish oils or omega fatty acids,... (Comparative Study)
Comparative Study
OBJECTIVES
To compare the efficacy of bed rest, cervical cerclage (McDonald, Shirodkar, or unspecified type of cerclage), cervical pessary, fish oils or omega fatty acids, nutritional supplements (zinc), progesterone (intramuscular, oral, or vaginal), prophylactic antibiotics, prophylactic tocolytics, combinations of interventions, placebo or no treatment (control) to prevent spontaneous preterm birth in women with a singleton pregnancy and a history of spontaneous preterm birth or short cervical length.
DESIGN
Systematic review with bayesian network meta-analysis.
DATA SOURCES
The Cochrane Pregnancy and Childbirth Group's Database of Trials, the Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials of pregnant women who are at high risk of spontaneous preterm birth because of a history of spontaneous preterm birth or short cervical length. No language or date restrictions were applied.
OUTCOMES
Seven maternal outcomes and 11 fetal outcomes were analysed in line with published core outcomes for preterm birth research. Relative treatment effects (odds ratios and 95% credible intervals) and certainty of evidence are presented for outcomes of preterm birth <34 weeks and perinatal death.
RESULTS
Sixty one trials (17 273 pregnant women) contributed data for the analysis of at least one outcome. For preterm birth <34 weeks (40 trials, 13 310 pregnant women) and with placebo or no treatment as the comparator, vaginal progesterone was associated with fewer women with preterm birth <34 weeks (odds ratio 0.50, 95% credible interval 0.34 to 0.70, high certainty of evidence). Shirodkar cerclage showed the largest effect size (0.06, 0.00 to 0.84), but the certainty of evidence was low. 17OHPC (17α-hydroxyprogesterone caproate; 0.68, 0.43 to 1.02, moderate certainty), vaginal pessary (0.65, 0.39 to 1.08, moderate certainty), and fish oil or omega 3 (0.30, 0.06 to 1.23, moderate certainty) might also reduce preterm birth <34 weeks compared with placebo or no treatment. For the fetal outcome of perinatal death (30 trials, 12 119 pregnant women) and with placebo or no treatment as the comparator, vaginal progesterone was the only treatment that showed clear evidence of benefit for this outcome (0.66, 0.44 to 0.97, moderate certainty). 17OHPC (0.78, 0.50 to 1.21, moderate certainty), McDonald cerclage (0.59, 0.33 to 1.03, moderate certainty), and unspecified cerclage (0.77, 0.53 to 1.11, moderate certainty) might reduce perinatal death rates, but credible intervals could not exclude the possibility of harm. Only progesterone treatments are associated with reduction in neonatal respiratory distress syndrome, neonatal sepsis, necrotising enterocolitis, and admission to neonatal intensive care unit compared with controls.
CONCLUSION
Vaginal progesterone should be considered the preventative treatment of choice for women with singleton pregnancy identified to be at risk of spontaneous preterm birth because of a history of spontaneous preterm birth or short cervical length. Future randomised controlled trials should use vaginal progesterone as a comparator to identify better treatments or combination treatments.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020169006.
Topics: Administration, Intravaginal; Bayes Theorem; Female; Humans; Network Meta-Analysis; Pregnancy; Premature Birth; Progesterone; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35168930
DOI: 10.1136/bmj-2021-064547 -
The Cochrane Database of Systematic... Jul 2015Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Progesterone prepares the endometrium for pregnancy by stimulating proliferation in response to human chorionic gonadotropin(hCG) produced by the corpus luteum. This occurs in the luteal phase of the menstrual cycle. In assisted reproduction techniques(ART), progesterone and/or hCG levels are low, so the luteal phase is supported with progesterone, hCG or gonadotropin-releasing hormone (GnRH) agonists to improve implantation and pregnancy rates.
OBJECTIVES
To determine the relative effectiveness and safety of methods of luteal phase support provided to subfertile women undergoing assisted reproduction.
SEARCH METHODS
We searched databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and trial registers. We conducted searches in November 2014, and further searches on 4 August 2015.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of luteal phase support using progesterone, hCG or GnRH agonist supplementation in ART cycles.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected trials, extracted data and assessed risk of bias. We calculated odds ratios (ORs) and 95%confidence intervals (CIs) for each comparison and combined data when appropriate using a fixed-effect model. Our primary out come was live birth or ongoing pregnancy. The overall quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
Ninety-four women RCTs (26,198 women) were included. Most studies had unclear or high risk of bias in most domains. The main limitations in the evidence were poor reporting of study methods and imprecision due to small sample sizes.1. hCG vs placebo/no treatment (five RCTs, 746 women)There was no evidence of differences between groups in live birth or ongoing pregnancy (OR 1.67, 95% CI 0.90 to 3.12, three RCTs,527 women, I2 = 24%, very low-quality evidence, but I2 of 61% was found for the subgroup of ongoing pregnancy) with a random effects model. hCG increased the risk of ovarian hyperstimulation syndrome (OHSS) (1 RCT, OR 4.28, 95% CI 1.91 to 9.6, low quality evidence).2. Progesterone vs placebo/no treatment (eight RCTs, 875 women)Evidence suggests a higher rate of live birth or ongoing pregnancy in the progesterone group (OR 1.77, 95% CI 1.09 to 2.86, five RCTs, 642 women, I2 = 35%, very low-quality evidence). OHSS was not reported.3. Progesterone vs hCG regimens (16 RCTs, 2162 women)hCG regimens included comparisons of progesterone versus hCG and progesterone versus progesterone + hCG. No evidence showed differences between groups in live birth or ongoing pregnancy (OR 0.95, 95% CI 0.65 to 1.38, five RCTs, 833 women, I2 = 0%, low quality evidence) or in the risk of OHSS (four RCTs, 615 women, progesterone vs hCG OR 0.54, 95% CI 0.22 to 1.34; four RCTs,678 women; progesterone vs progesterone plus hCG, OR 0.34, 95% CI 0.09 to 1.26, low-quality evidence).4. Progesterone vs progesterone with oestrogen (16 RCTs, 2577 women)No evidence was found of differences between groups in live birth or ongoing pregnancy (OR 1.12, 95% CI 0.91 to 1.38, nine RCTs,1651 women, I2 = 0%, low-quality evidence) or OHSS (OR 0.56, 95% CI 0.2 to 1.63, two RCTs, 461 women, I2 = 0%, low-quality evidence).5. Progesterone vs progesterone + GnRH agonist (seven RCTs, 1708 women)Live birth or ongoing pregnancy rates were lower in the progesterone-only group and increased in women who received progester one and one or more GnRH agonist doses (OR 0.62, 95% CI 0.48 to 0.81, nine RCTs, 2861 women, I2 = 55%, random effects, low quality evidence). Statistical heterogeneity for this comparison was high because of unexplained variation in the effect size, but the direction of effect was consistent across studies. OHSS was reported in one study only (OR 1.00, 95% CI 0.33 to 3.01, 1 RCT, 300 women, very low quality evidence).6. Progesterone regimens (45 RCTs, 13,814 women)The included studies reported nine different comparisons between progesterone regimens. Findings for live birth or ongoing pregnancy were as follows: intramuscular (IM) versus oral: OR 0.71, 95% CI 0.14 to 3.66 (one RCT, 40 women, very low-quality evidence);IM versus vaginal/rectal: OR 1.24, 95% CI 1.03 to 1.5 (seven RCTs, 2309 women, I2 = 71%, very low-quality evidence); vaginal/rectal versus oral: OR 1.19, 95% CI 0.83 to 1.69 (four RCTs, 857 women, I2 = 32%, low-quality evidence); low-dose versus high-dose vaginal: OR 0.97, 95% CI 0.84 to 1.11 (five RCTs, 3720 women, I2 = 0%, moderate-quality evidence); short versus long protocol:OR 1.04, 95% CI 0.79 to 1.36 (five RCTs, 1205 women, I2 = 0%, low-quality evidence); micronised versus synthetic: OR 0.9, 95%CI 0.53 to 1.55 (two RCTs, 470 women, I2 = 0%, low-quality evidence); vaginal ring versus gel: OR 1.09, 95% CI 0.88 to 1.36 (oneRCT, 1271 women, low-quality evidence); subcutaneous versus vaginal gel: OR 0.92, 95% CI 0.74 to 1.14 (two RCTs, 1465 women,I2 = 0%, low-quality evidence); and vaginal versus rectal: OR 1.28, 95% CI 0.64 to 2.54 (one RCT, 147 women, very low-quality evidence). OHSS rates were reported for only two of these comparisons: IM versus oral, and low versus high-dose vaginal. No evidence showed a difference between groups.7. Progesterone and oestrogen regimens (two RCTs, 1195 women)The included studies compared two different oestrogen protocols. No evidence was found to suggest differences in live birth or ongoing pregnancy rates between a short and a long protocol (OR 1.08, 95% CI 0.81 to 1.43, one RCT, 910 women, low-quality evidence) or between a low dose and a high dose of oestrogen (OR 0.65, 95% CI 0.37 to 1.13, one RCT, 285 women, very low-quality evidence).Neither study reported OHSS.
AUTHORS' CONCLUSIONS
Both progesterone and hCG during the luteal phase are associated with higher rates of live birth or ongoing pregnancy than placebo.The addition of GnRHa to progesterone is associated with an improvement in pregnancy outcomes. OHSS rates are increased with hCG compared to placebo (only study only). The addition of oestrogen does not seem to improve outcomes. The route of progester one administration is not associated with an improvement in outcomes.
Topics: Chorionic Gonadotropin; Drug Therapy, Combination; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Live Birth; Luteal Phase; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Maintenance; Progesterone; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted
PubMed: 26148507
DOI: 10.1002/14651858.CD009154.pub3 -
Human Reproduction Update Jan 2021Although surgery for endometriosis can improve pain and fertility, the risk of disease recurrence is high. There is little consensus regarding the benefit of medical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although surgery for endometriosis can improve pain and fertility, the risk of disease recurrence is high. There is little consensus regarding the benefit of medical therapy in preventing recurrence of endometriosis following surgery.
OBJECTIVE AND RATIONALE
We performed a review of prospective observational studies and randomised controlled trials (RCTs) to evaluate the risk of endometriosis recurrence in patients undergoing post-operative hormonal suppression, compared to placebo/expectant management.
SEARCH METHODS
The following databases were searched from inception to March 2020 for RCTs and prospective observational cohort studies: MEDLINE, Embase, Cochrane CENTRAL and Web of Science. We included English language full-text articles of pre-menopausal women undergoing conservative surgery (conserving at least one ovary) and initiating hormonal suppression within 6 weeks post-operatively with either combined hormonal contraceptives (CHC), progestins, androgens, levonorgesterel-releasing intra-uterine system (LNG-IUS) or GnRH agonist or antagonist. We excluded from the final analysis studies with <12 months of follow-up, interventions of diagnostic laparoscopy, experimental/non-hormonal treatments or combined hormonal therapy. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies.
OUTCOMES
We included 17 studies (13 RCTs and 4 cohort studies), with 2137 patients (1189 receiving post-operative suppression and 948 controls), which evaluated various agents: CHC (6 studies, n = 869), progestin (3 studies, n = 183), LNG-IUS (2 studies, n = 94) and GnRH agonist (9 studies, n = 1237). The primary outcome was post-operative endometriosis recurrence, determined by imaging or recurrence of symptoms, at least 12 months post-operatively. The secondary outcome was change in endometriosis-related pain. Mean follow up of included studies ranged from 12 to 36 months, and outcomes were assessed at a median of 18 months. There was a significantly decreased risk of endometriosis recurrence in patients receiving post-operative hormonal suppression compared to expectant management/placebo (relative risk (RR) 0.41, 95% CI: 0.26 to 0.65), 14 studies, 1766 patients, I2 = 68%, random effects model). Subgroup analysis on patients treated with CHC and LNG-IUS as well as sensitivity analyses limited to RCTs and high-quality studies showed a consistent decreased risk of endometriosis recurrence. Additionally, the patients receiving post-operative hormonal suppression had significantly lower pain scores compared to controls (SMD -0.49, 95% CI: -0.91 to -0.07, 7 studies, 652 patients, I2 = 68%).
WIDER IMPLICATIONS
Hormonal suppression should be considered for patients not seeking pregnancy immediately after endometriosis surgery in order to reduce disease recurrence and pain. Various hormonal agents have been shown to be effective, and the exact treatment choice should be individualised according to each woman's needs.
Topics: Endometriosis; Female; Humans; Observational Studies as Topic; Pregnancy; Progestins; Recurrence
PubMed: 33020832
DOI: 10.1093/humupd/dmaa033 -
Contraception Jan 2017The objective was to determine the association between use of intrauterine devices (IUDs) by young women and risk of adverse outcomes. (Review)
Review
OBJECTIVE
The objective was to determine the association between use of intrauterine devices (IUDs) by young women and risk of adverse outcomes.
METHODS
We searched Pubmed, CINAHL, Embase, Popline and the Cochrane Library for articles from inception of database through December 2015. For outcomes specific to IUD use (IUD expulsion and perforation), we examined effect measures for IUD users generally aged 25 years or younger compared with older IUD users. For outcomes of pregnancy, infection, pelvic inflammatory disease (PID), and heavy bleeding or anemia, we examined young IUD users compared with young users of other contraceptive methods or no method.
RESULTS
We identified 3169 articles of which 16 articles from 14 studies met our inclusion criteria. Six studies (Level II-2, good to poor) reported increased risk of expulsion among younger age groups compared with older age groups using copper-bearing (Cu-) IUDs. Two studies (Level II-2, fair) examined risks of expulsion among younger compared with older women using levonorgestrel-releasing (LNG-) IUDs; one reported no difference in expulsion, while the other reported increased odds for younger women. Four studies (Level II-2, good to poor) examined risk of expulsion among Cu- and LNG-IUD users combined and reported no significant differences between younger and older women. For perforation, four studies (Level II-2, fair to poor) found very low perforation rates (range, 0%-0.1%), with no significant differences between younger and older women. Pregnancies were generally rare among young IUD users in nine studies (Level I to II-2, fair to poor), and no differences were reported for young IUD users compared with young combined oral contraceptive (COC) or etonogestrel (ENG) implant users. PID was rare among young IUD users; one study reported no cases among COC or IUD users, and one reported no difference in PID among LNG-IUD users compared with ENG implant users from nationwide insurance claims data (Level I to II-2, fair). One study reported decreased odds of bleeding with LNG-IUD compared with COC use among young women, while one study of young women reported decreased odds of removal for bleeding with LNG-IUD compared with ENG implant (Level I to II-2, fair).
CONCLUSION
Overall evidence suggests that the risk of adverse outcomes related to pregnancy, perforation, infection, heavy bleeding or removals for bleeding among young IUD users is low and may not be clinically meaningful. However, the risk of expulsion, especially for Cu-IUDs, is higher for younger women compared with older women. If IUD expulsion occurs, a young woman is exposed to an increased risk of unintended pregnancy if replacement contraception is not initiated. IUDs are safe for young women and provide highly effective reversible contraception.
Topics: Adolescent; Contraception; Contraceptive Agents, Female; Contraceptives, Oral, Combined; Desogestrel; Female; Humans; Intrauterine Device Expulsion; Intrauterine Devices, Copper; Levonorgestrel; Pregnancy; Pregnancy, Unplanned; Randomized Controlled Trials as Topic; Risk Assessment; Young Adult
PubMed: 27771475
DOI: 10.1016/j.contraception.2016.10.006 -
Breast Cancer Research and Treatment Jan 2016This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual... (Meta-Analysis)
Meta-Analysis Review
This systematic review summarizes research on the use of progestin and breast cancer risk. Although mainly used for contraception, progestin can help treat menstrual disorders, and benign breast, uterine, and ovarian diseases. Breast cancer is the leading site of new, non-skin, cancers in females in the United States, and possible factors that may modulate breast cancer risk need to be identified. ProQuest (Ann Arbor, MI) and PubMed-Medline (US National Library of Medicine, Bethesda MD, USA) databases were used to search for epidemiologic studies from 2000 to 2015 that examined the association between progestin and breast cancer. Search terms included epidemiologic studies + progesterone or progestin or progestogen or contraceptive or contraceptive agents + breast cancer or breast neoplasms. A total of six studies were included in the review. Five of the six studies reported no association between progestin-only formulations (including norethindrone oral contraceptives, depot medroxyprogesterone acetate, injectable, levonorgestrel system users, implantable and intrauterine devices) and breast cancer risk. Duration of use was examined in a few studies with heterogeneous results. Unlike studies of other oral contraceptives, studies indicate that progestin-only formulations do not increase the risk of breast cancer, although the literature is hampered by small sample sizes. Future research is needed to corroborate these findings, as further understanding of synthetic progesterone may initiate new prescription practices or guidelines for women's health.
Topics: Breast Neoplasms; Contraceptive Agents, Female; Female; Humans; Levonorgestrel; Odds Ratio; Progestins; Risk
PubMed: 26700034
DOI: 10.1007/s10549-015-3663-1 -
Lancet (London, England) Mar 2021Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.
METHODS
We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.
FINDINGS
Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture <34 weeks RR 1·59, 95% CI 1·15-2·22), but we found no consistent evidence of benefit or harm for other outcomes with either vaginal progesterone or 17-OHPC.
INTERPRETATION
Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.
FUNDING
Patient-Centered Outcomes Research Institute.
Topics: 17-alpha-Hydroxyprogesterone; Administration, Intravaginal; Decision Making, Shared; Female; Humans; Infant, Newborn; Injections, Intramuscular; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Premature Birth; Progesterone; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 33773630
DOI: 10.1016/S0140-6736(21)00217-8 -
The Cochrane Database of Systematic... May 2022Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a very common condition in women of reproductive age, affecting 2 to 5 of every 10 women. Diverse treatments, either medical (hormonal or non-hormonal) or surgical, are currently available for HMB, with different effectiveness, acceptability, costs and side effects. The best treatment will depend on the woman's age, her intention to become pregnant, the presence of other symptoms, and her personal views and preferences.
OBJECTIVES
To identify, systematically assess and summarise all evidence from studies included in Cochrane Reviews on treatment for heavy menstrual bleeding (HMB), using reviews with comparable participants and outcomes; and to present a ranking of the first- and second-line treatments for HMB.
METHODS
We searched for published Cochrane Reviews of HMB interventions in the Cochrane Database of Systematic Reviews. The primary outcomes were menstrual bleeding and satisfaction. Secondary outcomes included quality of life, adverse events and the requirement of further treatment. Two review authors independently selected the systematic reviews, extracted data and assessed quality, resolving disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool and evaluated the certainty of the evidence for each outcome using GRADE methods. We grouped the interventions into first- and second-line treatments, considering participant characteristics (desire for future pregnancy, failure of previous treatment, candidacy for surgery). First-line treatments included medical interventions, and second-line treatments included both the levonorgestrel-releasing intrauterine system (LNG-IUS) and surgical treatments; thus the LNG-IUS is included in both groups. We developed different networks for first- and second-line treatments. We performed network meta-analyses of all outcomes, except for quality of life, where we performed pairwise meta-analyses. We reported the mean rank, the network estimates for mean difference (MD) or odds ratio (OR), with 95% confidence intervals (CIs), and the certainty of evidence (moderate, low or very low certainty). We also analysed different endometrial ablation and resection techniques separately from the main network: transcervical endometrial resection (TCRE) with or without rollerball, other resectoscopic endometrial ablation (REA), microwave non-resectoscopic endometrial ablation (NREA), hydrothermal ablation NREA, bipolar NREA, balloon NREA and other NREA.
MAIN RESULTS
We included nine systematic reviews published in the Cochrane Library up to July 2021. We updated the reviews that were over two years old. In July 2020, we started the overview with no new reviews about the topic. The included medical interventions were: non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics (tranexamic acid), combined oral contraceptives (COC), combined vaginal ring (CVR), long-cycle and luteal oral progestogens, LNG-IUS, ethamsylate and danazol (included to provide indirect evidence), which were compared to placebo. Surgical interventions were: open (abdominal), minimally invasive (vaginal or laparoscopic) and unspecified (or surgeon's choice of route of) hysterectomy, REA, NREA, unspecified endometrial ablation (EA) and LNG-IUS. We grouped the interventions as follows. First-line treatments Evidence from 26 studies with 1770 participants suggests that LNG-IUS results in a large reduction of menstrual blood loss (MBL; mean rank 2.4, MD -105.71 mL/cycle, 95% CI -201.10 to -10.33; low certainty evidence); antifibrinolytics probably reduce MBL (mean rank 3.7, MD -80.32 mL/cycle, 95% CI -127.67 to -32.98; moderate certainty evidence); long-cycle progestogen reduces MBL (mean rank 4.1, MD -76.93 mL/cycle, 95% CI -153.82 to -0.05; low certainty evidence), and NSAIDs slightly reduce MBL (mean rank 6.4, MD -40.67 mL/cycle, -84.61 to 3.27; low certainty evidence; reference comparator mean rank 8.9). We are uncertain of the true effect of the remaining interventions and the sensitivity analysis for reduction of MBL, as the evidence was rated as very low certainty. We are uncertain of the true effect of any intervention (very low certainty evidence) on the perception of improvement and satisfaction. Second-line treatments Bleeding reduction is related to the type of hysterectomy (total or supracervical/subtotal), not the route, so we combined all routes of hysterectomy for bleeding outcomes. We assessed the reduction of MBL without imputed data (11 trials, 1790 participants) and with imputed data (15 trials, 2241 participants). Evidence without imputed data suggests that hysterectomy (mean rank 1.2, OR 25.71, 95% CI 1.50 to 439.96; low certainty evidence) and REA (mean rank 2.8, OR 2.70, 95% CI 1.29 to 5.66; low certainty evidence) result in a large reduction of MBL, and NREA probably results in a large reduction of MBL (mean rank 2.0, OR 3.32, 95% CI 1.53 to 7.23; moderate certainty evidence). Evidence with imputed data suggests hysterectomy results in a large reduction of MBL (mean rank 1.0, OR 14.31, 95% CI 2.99 to 68.56; low certainty evidence), and NREA probably results in a large reduction of MBL (mean rank 2.2, OR 2.87, 95% CI 1.29 to 6.05; moderate certainty evidence). We are uncertain of the true effect for REA (very low certainty evidence). We are uncertain of the effect on amenorrhoea (very low certainty evidence). Evidence from 27 trials with 4284 participants suggests that minimally invasive hysterectomy results in a large increase in satisfaction (mean rank 1.3, OR 7.96, 95% CI 3.33 to 19.03; low certainty evidence), and NREA also increases satisfaction (mean rank 3.6, OR 1.59, 95% CI 1.09 to 2.33; low certainty evidence), but we are uncertain of the true effect of the remaining interventions (very low certainty evidence).
AUTHORS' CONCLUSIONS
Evidence suggests LNG-IUS is the best first-line treatment for reducing menstrual blood loss (MBL); antifibrinolytics are probably the second best, and long-cycle progestogens are likely the third best. We cannot make conclusions about the effect of first-line treatments on perception of improvement and satisfaction, as evidence was rated as very low certainty. For second-line treatments, evidence suggests hysterectomy is the best treatment for reducing bleeding, followed by REA and NREA. We are uncertain of the effect on amenorrhoea, as evidence was rated as very low certainty. Minimally invasive hysterectomy may result in a large increase in satisfaction, and NREA also increases satisfaction, but we are uncertain of the true effect of the remaining second-line interventions, as evidence was rated as very low certainty.
Topics: Amenorrhea; Antifibrinolytic Agents; Child, Preschool; Female; Humans; Menorrhagia; Network Meta-Analysis; Progestins; Quality of Life; Systematic Reviews as Topic
PubMed: 35638592
DOI: 10.1002/14651858.CD013180.pub2 -
Contraception Mar 2022Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the...
OBJECTIVE
Studies on the effect of long-term use of combined oral contraceptives (COCs) on cervical dysplasia and/or cancer risk have been inconsistent. Less is known about the effects of other forms of hormonal contraception (HC). We examine whether HC use increases the risk of incident cervical intraepithelial neoplasia (CIN) 2, 3 and/or cancer after accounting for preexisting human papillomavirus (HPV) infection.
STUDY DESIGN
Systematic review of prospective studies on HC use as risk factor for cervical dysplasia with HPV infection documented prior to outcome assessment including PubMed and EMBASE records between January 2000 and February 2020 (Prospero #CRD42019130725).
RESULTS
Among nine eligible studies, seven described recency and type of HC use and therefore comprise the primary analysis; two studies limit comparisons to ever versus never use and are summarized separately. All seven studies explored the relationship between oral contraceptive (OC) use and cervical dysplasia/cancer incidence: two found increased risk (adjusted odds ratio, aOR = 1.5-2.7), one found no association but decreased risk when restricted to women with persistent HPV (adjusted hazard ratio = 0.5), and four found no association. None of the seven studies differentiated between COC and progestin-only pills (POPs) by use recency or duration. The only study that included injectable progestin-only contraception (DMPA) found increased CIN3 incidence among current versus never users (aOR = 1.6). The one study that included Norplant found no association. Two studies included intrauterine device (IUD) use, but did not differentiate between hormonal and copper IUDs, and found no association.
CONCLUSION
We found no consistent evidence that OC use is associated with increased risk for cervical dysplasia/cancer after controlling for HPV infection. There were too few studies of progestin-only injectables, implants or IUDs to assess their effect on cervical dysplasia/cancer risk.
IMPLICATIONS
Use of single self-reported HC measures and insufficient distinction by hormonal constituent cloud our understanding of whether some HCs increase risk for cervical cancer. Methodologically rigorous studies with distinct HCs measured as time-varying exposures are needed to inform cervical cancer prevention efforts and improve our understanding of cervical cancer etiology.
Topics: Contraceptives, Oral, Hormonal; Female; Hormonal Contraception; Humans; Papillomavirus Infections; Progestins; Prospective Studies; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 34752778
DOI: 10.1016/j.contraception.2021.10.018 -
BMJ Clinical Evidence Feb 2011Dysmenorrhoea may begin soon after the menarche, after which it often improves with age, or it may originate later in life after the onset of an underlying causative... (Review)
Review
INTRODUCTION
Dysmenorrhoea may begin soon after the menarche, after which it often improves with age, or it may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for primary dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure, acupuncture, aspirin, behavioural interventions, contraceptives (combined oral), fish oil, herbal remedies, magnets, non-steroidal anti-inflammatory drugs, paracetamol, progestogens (intrauterine), spinal manipulation, surgical interruption of pelvic nerve pathways, thiamine, toki-shakuyaku-san, topical heat, transcutaneous electrical nerve stimulation (TENS), vitamin B12, and vitamin E.
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Chronic Disease; Denervation; Dysmenorrhea; Humans; Progestins; Thiamine
PubMed: 21718556
DOI: No ID Found -
BMJ Clinical Evidence Jan 2012Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may... (Review)
Review
INTRODUCTION
Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curettage, endometrial destruction, and hysterectomy.
Topics: Administration, Oral; Danazol; Dilatation and Curettage; Endometrial Ablation Techniques; Female; Humans; Intrauterine Devices, Medicated; Menorrhagia; Progestins
PubMed: 22305976
DOI: No ID Found