-
The Cochrane Database of Systematic... Aug 2019Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their...
BACKGROUND
Heavy menstrual bleeding (HMB) is a menstrual blood loss perceived by women as excessive that affects the health of women of reproductive age, interfering with their physical, emotional, social and material quality of life. Whilst abnormal menstrual bleeding may be associated with underlying pathology, in the present context, HMB is defined as excessive menstrual bleeding in the absence of other systemic or gynaecological disease. The first-line therapy is usually medical, avoiding possibly unnecessary surgery. Of the wide variety of medications used to reduce HMB, oral progestogens were originally the most commonly prescribed agents. This review assesses the effectiveness of two different types and regimens of oral progestogens in reducing ovulatory HMB.This is the update of a Cochrane review last updated in 2007, and originally named "Effectiveness of cyclical progestagen therapy in reducing heavy menstrual bleeding" (1998).
OBJECTIVES
To determine the effectiveness, safety and tolerability of oral progestogen therapy taken either during the luteal phase (short cycle) or for a longer course of 21 days per cycle (long cycle), in achieving a reduction in menstrual blood loss in women of reproductive age with HMB.
SEARCH METHODS
In January 2019 we searched Cochrane Gynaecology and Fertility's specialized register, CENTRAL, MEDLINE, Embase, CINAHL and PsycInfo. We also searched trials registers, other sources of unpublished or grey literature and reference lists of retrieved trials. We also checked citation lists of review articles to identify trials.
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing different treatments for HMB that included cyclical oral progestogens were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed trials for risk of bias and extracted data. We contacted trial authors for clarification of methods or additional data when necessary. We only assessed adverse events if they were separately measured in the included trials. We compared cyclical oral progestogen in different regimens and placebo or other treatments. Our primary outcomes were menstrual blood loss and satisfaction with treatment; the secondary outcomes were number of days of bleeding, quality of life, compliance and acceptability of treatment, adverse events and costs.
MAIN RESULTS
This review identified 15 randomized controlled trials (RCTs) with 1071 women in total. Most of the women knew which treatment they were receiving, which may have influenced their judgements about menstrual blood loss and satisfaction. Other aspects of trial quality varied among trials.We did not identify any RCTs comparing progestogen treatment with placebo. We assessed comparisons between oral progestogens and other medical therapies separately according to different regimens.Short-cycle progestogen therapy during the luteal phase (medroxyprogesterone acetate or norethisterone for 7 to 10 days, from day 15 to 19) was inferior to other medical therapy, including tranexamic acid, danazol and the progestogen-releasing intrauterine system (Pg-IUS (off of the market since 2001)), releasing 60 mcg of progesterone daily, with respect to reduction of menstrual blood loss (mean difference (MD) 37.29, 95% confidence interval (CI) 17.67 to 56.91; I = 50%; 6 trials, 145 women). The rate of satisfaction and the quality of life with treatment was similar in both groups. The number of bleeding days was greater on the short cycle progestogen group compared to other medical treatments. Adverse events (such as gastrointestinal symptoms and weight gain) were more likely with danazol when compared with progestogen treatment. We note that danazol is no longer in general use for treating HMB.Long-cycle progestogen therapy (medroxyprogesterone acetate or norethisterone), from day 5 to day 26 of the menstrual cycle, is also inferior to the levonorgestrel-releasing intrauterine system (LNG-IUS), releasing tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss (MD 16.88, 95% CI 10.93 to 22.84; I = 87%; 4 trials, 355 women). A higher proportion of women taking norethisterone found their treatment unacceptable compared to women having Pg-IUS (Peto odds ratio (OR) 0.12, 95% CI 0.03 to 0.40; 1 trial, 40 women). However, the adverse effects of breast tenderness and intermenstrual bleeding were more likely in women with the LNG-IUS. No trials reported on days of bleeding or quality of life for this comparison.The evidence supporting these findings was limited by low or very low gradings of quality; thus, we are uncertain about the findings and there is a potential that they may change if we identify other trials.
AUTHORS' CONCLUSIONS
Low- or very low-quality evidence suggests that short-course progestogen was inferior to other medical therapy, including tranexamic acid, danazol and the Pg-IUS with respect to reduction of menstrual blood loss. Long cycle progestogen therapy (medroxyprogesterone acetate or norethisterone) was also inferior to the LNG-IUS, tranexamic acid and ormeloxifene, but may be similar to the combined vaginal ring with respect to reduction of menstrual blood loss.
Topics: Danazol; Female; Humans; Intrauterine Devices, Medicated; Medroxyprogesterone Acetate; Menorrhagia; Progesterone; Progestins; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid
PubMed: 31425626
DOI: 10.1002/14651858.CD001016.pub3 -
The Cochrane Database of Systematic... Feb 2015Sexual offending is a serious social problem, a public health issue, and a major challenge for social policy. Victim surveys indicate high incidence and prevalence... (Review)
Review
BACKGROUND
Sexual offending is a serious social problem, a public health issue, and a major challenge for social policy. Victim surveys indicate high incidence and prevalence levels and it is accepted that there is a high proportion of hidden sexual victimisation. Surveys report high levels of psychiatric morbidity in survivors of sexual offences.Biological treatments of sex offenders include antilibidinal medication, comprising hormonal drugs that have a testosterone-suppressing effect, and non-hormonal drugs that affect libido through other mechanisms. The three main classes of testosterone-suppressing drugs in current use are progestogens, antiandrogens, and gonadotropin-releasing hormone (GnRH) analogues. Medications that affect libido through other means include antipsychotics and serotonergic antidepressants (SSRIs).
OBJECTIVES
To evaluate the effects of pharmacological interventions on target sexual behaviour for people who have been convicted or are at risk of sexual offending.
SEARCH METHODS
We searched CENTRAL (2014, Issue 7), Ovid MEDLINE, EMBASE, and 15 other databases in July 2014. We also searched two trials registers and requested details of unidentified, unpublished, or ongoing studies from investigators and other experts.
SELECTION CRITERIA
Prospective controlled trials of antilibidinal medications taken by individuals for the purpose of preventing sexual offences, where the comparator group received a placebo, no treatment, or 'standard care', including psychological treatment.
DATA COLLECTION AND ANALYSIS
Pairs of authors, working independently, selected studies, extracted data, and assessed the risk of bias of included studies. We contacted study authors for additional information, including details of methods and outcome data.
MAIN RESULTS
We included seven studies with a total of 138 participants, with data available for 123. Sample sizes ranged from 9 to 37. Judgements for categories of risk of bias varied: concerns were greatest regarding allocation concealment, blinding of outcome assessors, and incomplete outcome data (dropout rates in the five community-based studies ranged from 3% to 54% and results were usually analysed on a per protocol basis).Participant characteristics in the seven studies were heterogeneous, but the vast majority had convictions for sexual offences, ranging from exhibitionism to rape and child molestation.Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA); a seventh evaluated two antipsychotics (benperidol and chlorpromazine). Five studies were placebo-controlled; in two, MPA was administered as an adjunctive treatment to a psychological therapy (assertiveness training or imaginal desensitisation). Meta-analysis was not possible due to heterogeneity of interventions, comparators, study designs, and other issues. The quality of the evidence overall was poor. In addition to methodological issues, much evidence was indirect.
PRIMARY OUTCOME
recividism. Two studies reported recidivism rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reports of recividism at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of recidivism amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm of this study (n = 5) dropped out immediately, despite treatment being court mandated.Two studies did not report recidivism rates as they both took place in one secure psychiatric facility from which no participant was discharged during the study, whilst another three studies did not appear directly to measure recividism but rather abnormal sexual activity alone.
SECONDARY OUTCOMES
The included studies report a variety of secondary outcomes. Results suggest that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself (three studies). Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and with anxiety (two studies). One study measured anxiety formally; one study measured anger or aggression. Adverse events: Six studies provided information on adverse events. No study tested the effects of testosterone-suppressing drugs beyond six to eight months and the cross-over design of some studies may obscure matters (given the 'rebound effect' of some hormonal treatments). Considerable weight gain was reported in two trials of oral MPA and CPA. Side effects of intramuscular MPA led to discontinuation in some participants after three to five injections (the nature of these side effects was not described). Notable increases in depression and excess salivation were reported in one trial of oral MPA. The most severe side effects (extra-pyramidal movement disorders and drowsiness) were reported in a trial of antipsychotic medication for the 12 participants in the study. No deaths or suicide attempts were reported in any study. The latter is important given the association between antilibidinal hormonal medication and mood changes.
AUTHORS' CONCLUSIONS
We found only seven small trials (all published more than 20 years ago) that examined the effects of a limited number of drugs. Investigators reported issues around acceptance and adherence to treatment. We found no studies of the newer drugs currently in use, particularly SSRIs or GnRH analogues. Although there were some encouraging findings in this review, their limitations do not allow firm conclusions to be drawn regarding pharmacological intervention as an effective intervention for reducing sexual offending.The tolerability, even of the testosterone-suppressing drugs, was uncertain given that all studies were small (and therefore underpowered to assess adverse effects) and of limited duration, which is not consistent with current routine clinical practice. Further research is required before it is demonstrated that their administration reduces sexual recidivism and that tolerability is maintained.It is a concern that, despite treatment being mandated in many jurisdictions, evidence for the effectiveness of pharmacological interventions is so sparse and that no RCTs appear to have been published in two decades. New studies are therefore needed and should include trials with larger sample sizes, of longer duration, evaluating newer medications, and with results stratified according to category of sexual offenders. It is important that data are collected on the characteristics of those who refuse and those who drop out, as well as those who complete treatment.
Topics: Adolescent; Adult; Aged; Androgen Antagonists; Antipsychotic Agents; Child; Child Abuse, Sexual; Desensitization, Psychologic; Exhibitionism; Humans; Libido; Male; Middle Aged; Randomized Controlled Trials as Topic; Rape; Recurrence; Sex Offenses; Sexual Behavior
PubMed: 25692326
DOI: 10.1002/14651858.CD007989.pub2 -
Fertility and Sterility Feb 2017To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained... (Meta-Analysis)
Meta-Analysis Review
Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials.
OBJECTIVE
To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained recurrent miscarriage.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Women with a history of unexplained recurrent miscarriage.
INTERVENTION(S)
Randomized, controlled trials were identified by searching electronic databases. We included randomized, controlled trials comparing supplementation with progestogens (i.e., intervention group) in the first trimester of pregnancy with control (either placebo or no treatment) in women with a history of recurrent miscarriage. All types of progestogens, including natural P and synthetic progestins, were analyzed.
MAIN OUTCOME MEASURE(S)
The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI).
RESULT(S)
Ten trials including 1,586 women with recurrent miscarriage were analyzed. Eight studies used placebo as control and were double-blind. Regarding the intervention, two RCTs used natural P, whereas the other eight studies used progestins: medroxyprogesterone, cyclopentylenol ether of progesterone, dydrogesterone, or 17-hydroxyprogesterone caproate. Pooled data from the 10 trials showed that women with a history of unexplained recurrent miscarriage who were randomized to the progestogens group in the first trimester and before 16 weeks had a lower risk of recurrent miscarriage (RR 0.72, 95% CI 0.53-0.97) and higher live birth rate (RR 1.07, 95% CI 1.02-1.15) compared with those who did not. No statistically significant differences were found in the other secondary outcomes, including preterm birth (RR 1.09, 95% CI 0.71-1.66), neonatal mortality (RR 1.80, 95% CI 0.44-7.34), and fetal genital abnormalities (RR 1.68, 95% CI 0.22-12.62).
CONCLUSION(S)
Our findings provide evidence that supplementation with progestogens may reduce the incidence of recurrent miscarriages and seem to be safe for the fetuses. Synthetic progestogens, including weekly IM 17-hydroxyprogesterone caproate, but not natural P, were associated with a lower risk of recurrent miscarriage. Given the limitations of the studies included in our meta-analysis, it is difficult to recommend route and dose of progestogen therapy. Further head-to-head trials of P types, dosing, and route of administration are required.
Topics: Abortion, Habitual; Chi-Square Distribution; Drug Administration Schedule; Female; Humans; Odds Ratio; Pregnancy; Pregnancy Trimester, First; Progestins; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27887710
DOI: 10.1016/j.fertnstert.2016.10.031 -
The Cochrane Database of Systematic... Mar 2015Postpartum contraception improves the health of mothers and children by lengthening birth intervals. For lactating women, contraception choices are limited by concerns... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum contraception improves the health of mothers and children by lengthening birth intervals. For lactating women, contraception choices are limited by concerns about hormonal effects on milk quality and quantity and passage of hormones to the infant. Ideally, the contraceptive chosen should not interfere with lactation or infant growth. Timing of contraception initiation is also important. Immediately postpartum, most women have contact with a health professional, but many do not return for follow-up contraceptive counseling. However, immediate initiation of hormonal methods may disrupt the onset of milk production.
OBJECTIVES
To determine the effects of hormonal contraceptives on lactation and infant growth
SEARCH METHODS
We searched for eligible trials until 2 March 2015. Sources included the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, POPLINE, Web of Science, LILACS, ClinicalTrials.gov, and ICTRP. We also examined review articles and contacted investigators.
SELECTION CRITERIA
We sought randomized controlled trials in any language that compared hormonal contraception versus another form of hormonal contraception, nonhormonal contraception, or placebo during lactation. Hormonal contraception includes combined or progestin-only oral contraceptives, injectable contraceptives, implants, and intrauterine devices.Trials had to have one of our primary outcomes: breast milk quantity or biochemical composition; lactation initiation, maintenance, or duration; infant growth; or timing of contraception initiation and effect on lactation. Secondary outcomes included contraceptive efficacy while breastfeeding and birth interval.
DATA COLLECTION AND ANALYSIS
For continuous variables, we calculated the mean difference (MD) with 95% confidence interval (CI). For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% CI. Due to differing interventions and outcome measures, we did not aggregate the data in a meta-analysis.
MAIN RESULTS
In 2014, we added seven trials for a new total of 11. Five reports were published before 1985 and six from 2005 to 2014. They included 1482 women. Four trials examined combined oral contraceptives (COCs), and three studied a levonorgestrel-releasing intrauterine system (LNG-IUS). We found two trials of progestin-only pills (POPs) and two of the etonogestrel-releasing implant. Older studies often lacked quantified results. Most trials did not report significant differences between the study arms in breastfeeding duration, breast milk composition, or infant growth. Exceptions were seen mainly in older studies with limited information.For breastfeeding duration, two of eight trials indicated a negative effect on lactation. A COC study reported a negative effect on lactation duration compared to placebo but did not quantify results. Another trial showed a lower percentage of the LNG-IUS group breastfeeding at 75 days versus the nonhormonal IUD group (reported P < 0.05) but no significant difference at one year.For breast milk volume, two older studies indicated lower volume for the COC group versus the placebo group. One trial did not quantify results. The other showed lower means (mL) for the COC group, e.g. at 16 weeks (MD -24.00, 95% CI -34.53 to -13.47) and at 24 weeks (MD -24.90, 95% CI -36.01 to -13.79). Another four trials did not report any significant difference between the study groups in milk volume or composition with two POPs, a COC, or the etonogestrel implant.Seven trials studied infant growth; one showed greater weight gain (grams) for the etonogestrel implant versus no method for six weeks (MD 426.00, 95% CI 58.94 to 793.06) but less compared with depot medroxyprogesterone acetate (DMPA) from 6 to 12 weeks (MD -271.00, 95% CI -355.10 to -186.90). The others studied POPs, COCs versus POPs, or an LNG-IUS.
AUTHORS' CONCLUSIONS
Results were not consistent across the 11 trials. The evidence was limited for any particular hormonal method. The quality of evidence was moderate overall and low for three of four placebo-controlled trials of COCs or POPs. The sensitivity analysis included six trials with moderate quality evidence and sufficient outcome data. Five trials indicated no significant difference between groups in breastfeeding duration (etonogestrel implant insertion times, COC versus POP, and LNG-IUS). For breast milk volume or composition, a COC study showed a negative effect, while an implant trial showed no significant difference. Of four trials that assessed infant growth, three indicated no significant difference between groups. One showed greater weight gain in the etonogestrel implant group versus no method but less versus DMPA.
Topics: Breast Feeding; Child Development; Contraception; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Desogestrel; Female; Humans; Infant; Lactation; Levonorgestrel; Milk, Human; Progestins; Randomized Controlled Trials as Topic
PubMed: 25793657
DOI: 10.1002/14651858.CD003988.pub2 -
BMJ Global Health 2019Depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) may facilitate self-administration and expand contraceptive access. To inform WHO...
INTRODUCTION
Depot medroxyprogesterone acetate subcutaneous injectable contraception (DMPA-SC) may facilitate self-administration and expand contraceptive access. To inform WHO guidelines on self-care interventions, we conducted a systematic review and meta-analysis comparing self-administration versus provider administration of injectable contraception on outcomes of pregnancy, side effects/adverse events, contraceptive uptake, contraceptive continuation, self-efficacy/empowerment and social harms.
METHODS
We searched PubMed, Cumulative Index to Nursing and Allied Health Literature, LILACS and EMBASE in September 2018 for peer-reviewed studies comparing women who received injectable contraception with the option of self-administration with women who received provider-administered injectable contraception on at least one outcome of interest. Risk of bias was assessed using the Cochrane tool for randomised controlled trials (RCTs) and the Evidence Project tool for non-randomised studies. Meta-analysis was conducted using random-effects models to generate pooled estimates of relative risk (RR).
RESULTS
Six studies with 3851 total participants met the inclusion criteria: three RCTs and three controlled cohort studies. All studies examined self-injection of DMPA-SC; comparison groups were either provider-administered DMPA-SC or provider-administered intramuscular DMPA. All studies followed women through 12 months of contraceptive coverage and measured (dis)continuation of injectable contraception. Meta-analysis found higher rates of continuation with self-administration compared with provider administration in three RCTs (RR: 1.27, 95% CI 1.16 to 1.39) and three controlled cohort studies (RR: 1.18, 95% CI 1.10 to 1.26). Four studies reported pregnancies; all showed no difference across study arms. Four studies reported side effects/adverse events; while two controlled cohort studies showed increased injection site reactions with self-administration, no other side effects increased with self-administration. One study found no difference in social harms. No studies reported measuring uptake or self-efficacy/empowerment.
CONCLUSION
A growing evidence base suggests that self-administration of DMPA-SC can equal or improve contraceptive continuation rates compared with provider administration. This benefit comes without notable increases in pregnancy or safety concerns. Self-injection of DMPA-SC is a promising approach to increasing contraceptive use.
PubMed: 31179026
DOI: 10.1136/bmjgh-2018-001350 -
The Cochrane Database of Systematic... Aug 2016Obesity has reached epidemic proportions around the world. Effectiveness of hormonal contraceptives may be related to metabolic changes in obesity or to greater body... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obesity has reached epidemic proportions around the world. Effectiveness of hormonal contraceptives may be related to metabolic changes in obesity or to greater body mass or body fat. Hormonal contraceptives include oral contraceptives (OCs), injectables, implants, hormonal intrauterine contraception (IUC), the transdermal patch, and the vaginal ring. Given the prevalence of overweight and obesity, the public health impact of any effect on contraceptive efficacy could be substantial.
OBJECTIVES
To examine the effectiveness of hormonal contraceptives in preventing pregnancy among women who are overweight or obese versus women with a lower body mass index (BMI) or weight.
SEARCH METHODS
Until 4 August 2016, we searched for studies in PubMed (MEDLINE), CENTRAL, POPLINE, Web of Science, ClinicalTrials.gov, and ICTRP. We examined reference lists of pertinent articles to identify other studies. For the initial review, we wrote to investigators to find additional published or unpublished studies.
SELECTION CRITERIA
All study designs were eligible. The study could have examined any type of hormonal contraceptive. Reports had to contain information on the specific contraceptive methods used. The primary outcome was pregnancy. Overweight or obese women must have been identified by an analysis cutoff for weight or BMI (kg/m(2)).
DATA COLLECTION AND ANALYSIS
Two authors independently extracted the data. One entered the data into RevMan and a second verified accuracy. The main comparisons were between overweight or obese women and women of lower weight or BMI. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale. Where available, we included life-table rates. We also used unadjusted pregnancy rates, relative risk (RR), or rate ratio when those were the only results provided. For dichotomous variables, we computed an odds ratio with 95% confidence interval (CI).
MAIN RESULTS
With 8 studies added in this update, 17 met our inclusion criteria and had a total of 63,813 women. We focus here on 12 studies that provided high, moderate, or low quality evidence. Most did not show a higher pregnancy risk among overweight or obese women. Of five COC studies, two found BMI to be associated with pregnancy but in different directions. With an OC containing norethindrone acetate and ethinyl estradiol (EE), pregnancy risk was higher for overweight women, i.e. with BMI ≥ 25 versus those with BMI < 25 (reported relative risk 2.49, 95% CI 1.01 to 6.13). In contrast, a trial using an OC with levonorgestrel and EE reported a Pearl Index of 0 for obese women (BMI ≥ 30) versus 5.59 for nonobese women (BMI < 30). The same trial tested a transdermal patch containing levonorgestrel and EE. Within the patch group, obese women in the "treatment-compliant" subgroup had a higher reported Pearl Index than nonobese women (4.63 versus 2.15). Of five implant studies, two that examined the six-capsule levonorgestrel implant showed differences in pregnancy by weight. One study showed higher weight was associated with higher pregnancy rate in years 6 and 7 combined (reported P < 0.05). In the other, pregnancy rates differed in year 5 among the lower weight groups only (reported P < 0.01) and did not involve women weighing 70 kg or more.Analysis of data from other contraceptive methods indicated no association of pregnancy with overweight or obesity. These included depot medroxyprogesterone acetate (subcutaneous), levonorgestrel IUC, the two-rod levonorgestrel implant, and the etonogestrel implant.
AUTHORS' CONCLUSIONS
The evidence generally did not indicate an association between higher BMI or weight and effectiveness of hormonal contraceptives. However, we found few studies for most contraceptive methods. Studies using BMI, rather than weight alone, can provide information about whether body composition is related to contraceptive effectiveness. The contraceptive methods examined here are among the most effective when used according to the recommended regimen.We considered the overall quality of evidence to be low for the objectives of this review. More recent reports provided evidence of varying quality, while the quality was generally low for older studies. For many trials the quality would be higher for their original purpose rather than the non-randomized comparisons here. Investigators should consider adjusting for potential confounding related to BMI or contraceptive effectiveness. Newer studies included a greater proportion of overweight or obese women, which helps in examining effectiveness and side effects of hormonal contraceptives within those groups.
Topics: Body Mass Index; Body Weight; Contraception; Contraceptive Agents, Female; Female; Humans; Obesity; Overweight; Pregnancy; Pregnancy Rate; Pregnancy, Unplanned; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 27537097
DOI: 10.1002/14651858.CD008452.pub4 -
Medical Science Monitor : International... Sep 2014The aim of this study was to compare the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) with conventional medical treatment in reducing heavy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of this study was to compare the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) with conventional medical treatment in reducing heavy menstrual bleeding.
MATERIAL AND METHODS
Relevant studies were identified by a search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and clinical trials registries (from inception to April 2014). Randomized controlled trials comparing the LNG-IUS with conventional medical treatment (mefenamic acid, tranexamic acid, norethindrone, medroxyprogesterone acetate injection, or combined oral contraceptive pills) in patients with menorrhagia were included.
RESULTS
Eight randomized controlled trials that included 1170 women (LNG-IUS, n=562; conventional medical treatment, n=608) met inclusion criteria. The LNG-IUS was superior to conventional medical treatment in reducing menstrual blood loss (as measured by the alkaline hematin method or estimated by pictorial bleeding assessment chart scores). More women were satisfied with the LNG-IUS than with the use of conventional medical treatment (odds ratio [OR] 5.19, 95% confidence interval [CI] 2.73-9.86). Compared with conventional medical treatment, the LNG-IUS was associated with a lower rate of discontinuation (14.6% vs. 28.9%, OR 0.39, 95% CI 0.20-0.74) and fewer treatment failures (9.2% vs. 31.0%, OR 0.18, 95% CI 0.10-0.34). Furthermore, quality of life assessment favored LNG-IUS over conventional medical treatment, although use of various measurements limited our ability to pool the data for more powerful evidence. Serious adverse events were statistically comparable between treatments.
CONCLUSIONS
The LNG-IUS was the more effective first choice for management of menorrhagia compared with conventional medical treatment. Long-term, randomized trials are required to further investigate patient-based outcomes and evaluate the cost-effectiveness of the LNG-IUS and other medical treatments.
Topics: Contraceptive Agents, Female; Drug Administration Routes; Female; Humans; Levonorgestrel; Menorrhagia; Uterus
PubMed: 25245843
DOI: 10.12659/MSM.892126 -
The Cochrane Database of Systematic... Mar 2015Uterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms such as bleeding and pain. Medical treatment of this condition is limited and gonadotropin-releasing hormone (GnRH) analogues are the most effective agents. Long-term treatment with such agents, however, is restricted due to their adverse effects. The addition of other medications during treatment with GnRH analogues, a strategy known as add-back therapy, may limit these side effects. There is concern, however, that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects.
OBJECTIVES
To assess the short-term (within 12 months) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding, pelvic pain, or urinary symptoms.
SEARCH METHODS
We searched electronic databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, LILACS, CINAHL, PsycINFO; and electronic registries of ongoing trials including ClinicalTrials.gov, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform. All searches were from database inception to 16 June 2014.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that included women with uterine fibroids experiencing irregular or intense uterine bleeding, cyclic or non-cyclic pelvic pain, or urinary symptoms, and that compared treatment with a GnRH analogue plus add-back therapy versus a GnRH analogue alone or combined with placebo were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed the identified titles and abstracts for potentially eligible records. Two review authors reviewed eligible studies and independently extracted data. Two authors independently assessed the studies' risk of bias. They assessed the quality of the evidence using GRADE criteria.
MAIN RESULTS
Fourteen RCTs were included in the review. Data were extracted from 12 studies (622 women). The primary outcome was quality of life (QoL).Add-back therapy with medroxyprogesterone (MPA): no studies reported QoL or uterine bleeding. There was no evidence of effect in relation to bone mass (standardized mean difference (SMD) 0.38, 95% confidence interval (CI) -0.62 to 1.38, 1 study, 16 women, P = 0.45, low quality evidence) and MPA was associated with a larger uterine volume (mean difference (MD) 342.19 cm(3), 95% CI 77.58 to 606.80, 2 studies, 32 women, I(2) = 0%, low quality evidence).Tibolone: this was associated with a higher QoL but the estimate was imprecise and the effect could be clinically insignificant, small or large (SMD 0.47, 95% CI 0.09 to 0.85, 1 study, 110 women, P = 0.02, low quality evidence). It was also associated with a decreased loss of bone mass, which could be insignificant, small or moderate (SMD 0.36, 95% CI 0.03 to 0.7, 3 studies, 160 women, I(2) = 7%, moderate quality evidence). Tibolone may, however, have been associated with larger uterine volumes (MD 23.89 cm(3), 95% CI= 8.13 to 39.66, 6 studies, 365 women, I(2) = 0%, moderate quality evidence) and more uterine bleeding (results were not combined but three studies demonstrated greater bleeding with tibolone while two other studies demonstrated no bleeding in either group). Four studies (268 women; not pooled owing to extreme heterogeneity) reported a large benefit on vasomotor symptoms in the tibolone group.Raloxifene: there was no evidence of an effect on QoL (SMD 0.11, 95% CI -0.57 to 0.34, 1 study, 74 women, P = 0.62, low quality evidence), while there was a beneficial impact on bone mass (SMD 1.01, 95% CI 0.57 to 1.45, 1 study, 91 women, P < 0.00001, low quality evidence). There was no clear evidence of effect on uterine volume (MD 27.1 cm(3), 95% CI -17.94 to 72.14, 1 study, 91 women, P = 0.24, low quality evidence), uterine bleeding or severity of vasomotor symptoms (MD 0.2 hot flushes/day, 95% CI -0.34 to 0.74, 1 study, 91 women, P = 0.46, low quality evidence).Estriol: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. Add-back with estriol may have led to decreased loss of bone mass, from results of a single study (SMD 3.93, 95% CI 1.7 to 6.16, 1 study, 12 women, P = 0.0005, low quality evidence).Ipriflavone: no studies reported QoL, uterine size or uterine bleeding. Iproflavone was associated with decreased loss of bone mass in a single study (SMD 2.71, 95% CI 2.14 to 3.27, 1 study, 95 women, P < 0.00001, low quality evidence); there was no evidence of an effect on the rate of vasomotor symptoms (RR 0.67, 95% Cl 0.44 to 1.02, 1 study, 95 women, P = 0.06, low quality evidence).Conjugated estrogens: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. One study suggested that adding conjugated estrogens to GnRH analogues resulted in a larger decrease in uterine volume in the placebo group (MD 105.2 cm(3), 95% CI 27.65 to 182.75, 1 study, 27 women, P = 0.008, very low quality evidence).Nine of 12 studies were at high risk of bias in at least one domain, most commonly lack of blinding. All studies followed participants for a maximum of six months. This short-term follow-up is usually insufficient to observe any significant effect of the treatment on bone health (such as the occurrence of fractures), limiting the findings.
AUTHORS' CONCLUSIONS
There was low or moderate quality evidence that tibolone, raloxifene, estriol and ipriflavone help to preserve bone density and that MPA and tibolone may reduce vasomotor symptoms. Larger uterine volume was an adverse effect associated with some add-back therapies (MPA, tibolone and conjugated estrogens). For other comparisons, outcomes of interest were not reported or study findings were inconclusive.
Topics: Antineoplastic Agents, Hormonal; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Estriol; Female; Gonadotropin-Releasing Hormone; Humans; Isoflavones; Leiomyoma; Medroxyprogesterone; Norpregnenes; Quality of Life; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Uterine Hemorrhage; Uterine Neoplasms
PubMed: 25793972
DOI: 10.1002/14651858.CD010854.pub2 -
BMJ Sexual & Reproductive Health Jan 2020To update a 2016 systematic review on hormonal contraception use and HIV acquisition.
OBJECTIVE
To update a 2016 systematic review on hormonal contraception use and HIV acquisition.
METHODS
We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses.
RESULTS
In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk.
CONCLUSIONS
High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.
Topics: Adolescent; Adult; Female; HIV Infections; Hormonal Contraception; Humans
PubMed: 31919239
DOI: 10.1136/bmjsrh-2019-200509 -
The Cochrane Database of Systematic... Jun 2020Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heavy menstrual bleeding (HMB) impacts the quality of life of otherwise healthy women. The perception of HMB is subjective and management depends upon, among other factors, the severity of the symptoms, a woman's age, her wish to get pregnant, and the presence of other pathologies. Heavy menstrual bleeding was classically defined as greater than or equal to 80 mL of blood loss per menstrual cycle. Currently the definition is based on the woman's perception of excessive bleeding which is affecting her quality of life. 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: users of the levonorgestrel-releasing intrauterine system (LNG-IUS) reported reductions of up to 90%. Insertion may, however, be regarded as invasive by some women, which affects its acceptability.
OBJECTIVES
To determine the effectiveness, acceptability and safety of progestogen-releasing intrauterine devices in reducing heavy menstrual bleeding.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL (from inception to June 2019); and we searched grey literature and for unpublished trials in trial registers.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in women of reproductive age treated with LNG-IUS devices versus no treatment, placebo, or other medical or surgical therapy for heavy menstrual bleeding.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data, assessed risk of bias and conducted GRADE assessments of the certainty of evidence.
MAIN RESULTS
We included 25 RCTs (2511 women). Limitations in the evidence included risk of attrition bias and low numbers of participants. The studies compared the following interventions. LNG-IUS versus other medical therapy The other medical therapies were norethisterone acetate, medroxyprogesterone acetate, oral contraceptive pill, mefenamic acid, tranexamic acid or usual medical treatment (where participants could choose the oral treatment that was most suitable). The LNG-IUS may improve HMB, lowering menstrual blood loss according to the alkaline haematin method (mean difference (MD) 66.91 mL, 95% confidence interval (CI) 42.61 to 91.20; 2 studies, 170 women; low-certainty evidence); and the Pictorial Bleeding Assessment Chart (MD 55.05, 95% CI 27.83 to 82.28; 3 studies, 335 women; low-certainty evidence). We are uncertain whether the LNG-IUS may have any effect on women's satisfaction up to one year (RR 1.28, 95% CI 1.01 to 1.63; 3 studies, 141 women; I² = 0%, very low-certainty evidence). The LNG-IUS probably leads to slightly higher quality of life measured with the SF-36 compared with other medical therapy if (MD 2.90, 95% CI 0.06 to 5.74; 1 study: 571 women; moderate-certainty evidence) or with the Menorrhagia Multi-Attribute Scale (MD 13.40, 95% CI 9.89 to 16.91; 1 trial, 571 women; moderate-certainty evidence). The LNG-IUS and other medical therapies probably give rise to similar numbers of women with serious adverse events (RR 0.91, 95% CI 0.63 to 1.30; 1 study, 571 women; moderate-certainty evidence). Women using other medical therapy are probably more likely to withdraw from treatment for any reason (RR 0.49, 95% CI 0.39 to 0.60; 1 study, 571 women, moderate-certainty evidence) and to experience treatment failure than women with LNG-IUS (RR 0.34, 95% CI 0.26 to 0.44; 6 studies, 535 women; moderate-certainty evidence). LNG-IUS versus endometrial resection or ablation (EA) Bleeding outcome results are inconsistent. We are uncertain of the effect of the LNG-IUS compared to EA on rates of amenorrhoea (RR 1.21, 95% CI 0.85 to 1.72; 8 studies, 431 women; I² = 21%; low-certainty evidence) and hypomenorrhoea (RR 0.98, 95% CI 0.73 to 1.33; 4 studies, 200 women; low-certainty evidence) and eumenorrhoea (RR 0.55, 95% CI 0.30 to 1.00; 3 studies, 160 women; very low-certainty evidence). We are uncertain whether both treatments may have similar rates of satisfaction with treatment at 12 months (RR 0.95, 95% CI 0.85 to 1.07; 5 studies, 317 women; low-certainty evidence). We are uncertain if the LNG-IUS compared to EA has any effect on quality of life, measured with SF-36 (MD -14.40, 95% CI -22.63 to -6.17; 1 study, 33 women; very low-certainty evidence). Women with the LNG-IUS compared with EA are probably more likely to have any adverse event (RR 2.06, 95% CI 1.44 to 2.94; 3 studies, 201 women; moderate-certainty evidence). Women with the LNG-IUS may experience more treatment failure compared to EA at one year follow up (persistent HMB or requirement of additional treatment) (RR 1.78, 95% CI 1.09 to 2.90; 5 studies, 320 women; low-certainty evidence); or requirement of hysterectomy may be higher at one year follow up (RR 2.56, 95% CI 1.48 to 4.42; 3 studies, 400 women; low-certainty evidence). LNG-IUS versus hysterectomy We are uncertain whether the LNG-IUS has any effect on HMB compared with hysterectomy (RR for amenorrhoea 0.52, 95% CI 0.39 to 0.70; 1 study, 75 women; very low-certainty evidence). We are uncertain whether there is difference between LNG-IUS and hysterectomy in satisfaction at five years (RR 1.01, 95% CI 0.94 to 1.08; 1 study, 232 women; low-certainty evidence) and quality of life (SF-36 MD 2.20, 95% CI -2.93 to 7.33; 1 study, 221 women; low-certainty evidence). Women in the LNG-IUS group may be more likely to have treatment failure requiring hysterectomy for HMB at 1-year follow-up compared to the hysterectomy group (RR 48.18, 95% CI 2.96 to 783.22; 1 study, 236 women; low-certainty evidence). None of the studies reported cost data suitable for meta-analysis.
AUTHORS' CONCLUSIONS
The LNG-IUS may improve HMB and quality of life compared to other medical therapy; the LNG-IUS is probably similar for HMB compared to endometrial destruction techniques; and we are uncertain if it is better or worse than hysterectomy. The LNG-IUS probably has similar serious adverse events to other medical therapy and it is more likely to have any adverse events than EA.
Topics: Antifibrinolytic Agents; Contraceptives, Oral; Endometrium; Female; Humans; Hysterectomy; Intrauterine Devices, Medicated; Levonorgestrel; Mefenamic Acid; Menorrhagia; Norethindrone; Progesterone; Quality of Life; Randomized Controlled Trials as Topic; Tranexamic Acid; Treatment Outcome
PubMed: 32529637
DOI: 10.1002/14651858.CD002126.pub4