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The Cochrane Database of Systematic... Jul 2007Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an oestrogen dependent condition. This... (Review)
Review
BACKGROUND
Endometriosis is the finding of endometrial glands or stroma in sites other than the uterine cavity. Endometriosis appears to be an oestrogen dependent condition. This hormonal dependency has prompted the therapeutic use of ovulation suppression agents, in an effort to improve subsequent fertility.
OBJECTIVES
To assess the effectiveness of ovulation suppression agents, including danazol, progestins and oral contraceptives, in the treatment of endometriosis-associated subfertility in improving pregnancy outcomes including live birth.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders and Sub-fertility Group's specialised register of trials (searched October 5th, 2007) the Cochrane Register of Controlled Trials (The Cochrane Library, Issue 3, 2007), MEDLINE (1966-October 2007), EMBASE (1980 - October 2007) and reference lists of articles.
SELECTION CRITERIA
Randomised trials comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception in women with endometriosis. A total of twenty three RCTs comparing an ovulation suppression agent with placebo or no treatment, or a suppressive agent with danazol or a GnRH with oral contraception were identified.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed quality. We contacted study authors for additional information. Quality was assessed by of method of randomization,allocation concealment, blinding, completeness of follow-up, presence or absence of crossover and co-intervention. 2 x 2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using the I(2) test of heterogeneity. Subgroup analysis was conducted on those couples clearly identifiable as infertile or wanting to conceive.
MAIN RESULTS
Twenty four trials were included. The odds ratio for pregnancy following ovulation suppression versus placebo or no treatment for all women randomised was 0.79 (95% CI 0.54 to 1.14), P = 0.21 and 0.80 (95% CI 0.51 to 1.24), P = 0.32 respectively for subfertile couples only despite the use of a variety of suppression agents. There was no evidence of benefit from the treatment. The common odds ratio for pregnancy following all agents versus danazol for all women randomised was 1.38 (95% CI 1.05 to 1.82), P = 0.02 and OR 1.37 (95% CI 0.94 to 1.99), P = 0.10 for subfertile couples only. When GnRHa and danazol were directly compared, OR was 1.45 (95% CI 1.08 to 1.95) P = 0.01 for all women randomised and OR 1.63( 95% CI 1.12 to 2.37), P = 0.01 for subfertile couples only in favour of GnRH. No effect was observed for GnRH compared with oral contraception; OR 0.99 (95% CI 0.52 to 1.89), P = 0.98 for all women randomised and OR 0.79 ( 95% CI 0.37 to 1.69), P = 0.55. In all analyses the data were statistically homogeneous (I(2)=0%).
AUTHORS' CONCLUSIONS
There is no evidence of benefit in the use of ovulation suppression in subfertile women with endometriosis who wish to conceive.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Fertility Agents, Female; Humans; Infertility, Female; Ovulation; Randomized Controlled Trials as Topic
PubMed: 17636607
DOI: 10.1002/14651858.CD000155.pub2 -
The Cochrane Database of Systematic... Jul 2007Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an attractive treatment option, but there is considerable variation in practice and uncertainty about the most effective therapy. Danazol is a synthetic steroid with anti-oestrogenic and anti progestogenic activity, and weak androgenic properties. Danazol suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss and to amenorrhoea in some women.
OBJECTIVES
To determine the effectiveness and tolerability of Danazol when used for heavy menstrual bleeding in women of reproductive years.
SEARCH STRATEGY
We searched the Menstrual Disorders and Subfertility Group's Specialised Register (April 2007). We also searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2007), MEDLINE (1966 to April 2007), EMBASE (1980 to April 2007, CINAHL (1982 to April 2007). Attempts were also made to identify trials from citation lists of included trials and relevant review articles.
SELECTION CRITERIA
Randomised controlled trials of Danazol versus placebo, any other medical (non-surgical) therapy or Danazol in different dosages for heavy menstrual bleeding in women of reproductive age with regular HMB measured either subjectively or objectively. Trials that included women with post menopausal bleeding, intermenstrual bleeding and pathological causes of heavy menstrual bleeding were excluded.
DATA COLLECTION AND ANALYSIS
Nine RCTs, with 353 women, were identified that fulfilled the inclusion criteria. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were menstrual blood loss, the number of women experiencing adverse effects, weight gain, withdrawals due to adverse effects and dysmenorrhoea. If data could not be extracted in a form suitable for meta-analysis, they were presented in a descriptive format.
MAIN RESULTS
Most data were not in a form suitable for meta analysis, and the results are based on a small number of trials, all of which are under-powered. Danazol appears to be more effective than placebo, progestogens, NSAIDs and the OCP at reducing MBL, but confidence intervals were wide. Treatment with Danazol caused more adverse events than NSAIDs (OR 7.0; 95% CI 1.7 to 28.2) and progestogens (OR 4.05, 95% CI 1.6 to10.2). Danazol was shown to significantly lower the duration of menses when compared with NSAIDs (WMD -1.0; 95% CI -1.8 to -0.3) and a progesterone releasing IUD (WMD -6.0; 95% CI -7.3 to -4.8). There were no randomised trials comparing Danazol with tranexamic acid or the levonorgestrel-releasing intrauterine system.
AUTHORS' CONCLUSIONS
Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments. The use of Danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. The small number of trials, and the small sample sizes of the included trials limit the recommendations for clinical care. Further studies are unlikely in the future and this review will not be updated unless further studies are identified.
Topics: Danazol; Estrogen Antagonists; Female; Humans; Menorrhagia; Randomized Controlled Trials as Topic
PubMed: 17636649
DOI: 10.1002/14651858.CD001017.pub2 -
The Cochrane Database of Systematic... Jul 2017Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.
OBJECTIVES
To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis.
SEARCH METHODS
We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.
MAIN RESULTS
We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis.
AUTHORS' CONCLUSIONS
Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.
Topics: Danazol; Dysmenorrhea; Dyspareunia; Endometriosis; Estrenes; Female; Gestrinone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Mifepristone; Norpregnadienes; Oximes; Prevalence; Randomized Controlled Trials as Topic; Receptors, Progesterone
PubMed: 28742263
DOI: 10.1002/14651858.CD009881.pub2 -
The Indian Journal of Surgery Jun 2014Breast pain or mastalgia is the common symptom in the breast. The two most common concerns of patients presenting with mastalgia are: the fear that breast pain is a...
Breast pain or mastalgia is the common symptom in the breast. The two most common concerns of patients presenting with mastalgia are: the fear that breast pain is a symptom of breast cancer and the presence of severe pain that affects a woman's quality of life. Breast pain requires thorough assessment and should be investigated in the same manner as any other breast symptom. We conducted a systematic review of treatment for breast pain. We searched various reviews, randomized controlled trial, and observational studies over Pubmed and Medline via internet. Searches were carried out on MEDLINE (1950-present), EMBASE (1980-present), and CINAHL (1981-present) using the NHS Evidence Healthcare Databases Advanced Search interface. A further search was also carried out on Cochrane Database of Systematic Reviews (issue 12 of 12, Dec 2011) and Central Register of Controlled Trials (issue 4 of 4, Oct 2011). If no abnormality is found in the breast on assessment, then a combination of reassurance, breast support brassiere, and topical NSAID gel massage are usually effective. Antiestrogen (centchroman/tamoxifen) therapy for 3 to 6 months is the second-line treatment of choice. Danazol may be used in resistant cases. Gamma-linolenic acid or evening primrose oil though commonly prescribed is not effective.
PubMed: 25177120
DOI: 10.1007/s12262-013-0813-8 -
The Cochrane Database of Systematic... 2002Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an... (Review)
Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in pre menopausal women. Medical therapy, with the avoidance of possibly unnecessary surgery is an attractive treatment option, but there is considerable variation in practice and uncertainty about the most effective therapy. Danazol is a synthetic steroid with anti-oestrogenic and anti progestogenic activity, and weak androgenic properties. Danazol suppresses oestrogen and progesterone receptors in the endometrium, leading to endometrial atrophy (thinning of the lining of the uterus) and reduced menstrual loss and to amenorrhoea in some women.
OBJECTIVES
To determine the effectiveness and tolerability of danazol when used for heavy menstrual bleeding in women of reproductive years.
SEARCH STRATEGY
All studies which might describe randomised controlled trials of danazol for the treatment of heavy menstrual bleeding were obtained by electronic searches of MEDLINE, EMBASE, Current Contents, CINAHL, National Research Register and the Menstrual Disorders and Subfertility Group's Specialist Register of controlled trials (on 6 November 2001). Attempts were also made to identify trials from citation lists of included trials and relevant review articles. In most cases the first author of each included trial was contacted for unpublished additional information.
SELECTION CRITERIA
Randomised controlled trials of danazol versus placebo, any other medical (non-surgical) therapy or danazol in different dosages for heavy menstrual bleeding in women of reproductive age with regular HMB measured either subjectively or objectively. Trials that included women with post menopausal bleeding, intermenstrual bleeding and pathological causes of heavy menstrual bleeding were excluded.
DATA COLLECTION AND ANALYSIS
Nine RCTs, with 353 women, were identified that fulfilled the inclusion criteria for this review. Quality assessment and data extraction were performed independently by two reviewers. The main outcomes were menstrual blood loss, the number of women experiencing adverse effects, weight gain, withdrawals due to adverse effects and dysmenorrhoea. If data could not be extracted in a form suitable for meta-analysis, they were presented in a descriptive format.
MAIN RESULTS
Most data were not in a form suitable for meta analysis, and the results are based on a small number of trials, all of which are under-powered. Danazol appears to be more effective than placebo, progestogens, NSAIDs and the OCP at reducing MBL, but confidence intervals were wide. Treatment with danazol caused more adverse events than NSAIDs (OR 7.0; 95% CI 1.7, 28.2) and progestogens (OR 4.05, 95% CI 1.6, 10.2), but this did not appear to affect adherence to treatment. Danazol was shown to significantly lower the duration of menses when compared with NSAIDs (WMD -1.0; 95% CI -1.8, -0.3) and a progesterone releasing IUD (WMD -6.0; 95% CI -7.3, -4.8). There were no randomised trials comparing danazol with tranexamic acid or the levonorgestrel-releasing intrauterine system.
REVIEWER'S CONCLUSIONS
Danazol appears to be an effective treatment for heavy menstrual bleeding compared to other medical treatments, though it is uncertain whether it is acceptable to women. The use of danazol may be limited by its side effect profile, its acceptability to women and the need for continuing treatment. Overall no strong recommendations can be made due to the small number of trials, and the small sample sizes of the included trials.
Topics: Danazol; Estrogen Antagonists; Female; Humans; Menorrhagia; Randomized Controlled Trials as Topic
PubMed: 12076401
DOI: 10.1002/14651858.CD001017 -
The Cochrane Database of Systematic... May 2012Endometriosis is characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in locations outside the uterus. Surgical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometriosis is characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in locations outside the uterus. Surgical and hormonal treatment of endometriosis have unpleasant side effects and high rates of relapse. In China, treatment of endometriosis using Chinese herbal medicine (CHM) is routine and considerable research into the role of CHM in alleviating pain, promoting fertility, and preventing relapse has taken place.This review is an update of a previous review published in the Cochrane Database of Systematic Reviews 2009, issue No 3.
OBJECTIVES
To review the effectiveness and safety of CHM in alleviating endometriosis-related pain and infertility.
SEARCH METHODS
We searched the Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) and the following English language electronic databases (from their inception to 31/10/2011): MEDLINE, EMBASE, AMED, CINAHL, and NLH.We also searched Chinese language electronic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Sci & Tech Journals (VIP), Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and Chinese Medical Current Contents (CMCC).
SELECTION CRITERIA
Randomised controlled trials (RCTs) involving CHM versus placebo, biomedical treatment, another CHM intervention; or CHM plus biomedical treatment versus biomedical treatment were selected. Only trials with confirmed randomisation procedures and laparoscopic diagnosis of endometriosis were included.
DATA COLLECTION AND ANALYSIS
Risk of bias assessment, and data extraction and analysis were performed independently by three review authors. Data were combined for meta-analysis using relative risk (RR) for dichotomous data. A fixed-effect statistical model was used, where appropriate. Data not suitable for meta-analysis were presented as descriptive data.
MAIN RESULTS
Two Chinese RCTs involving 158 women were included in this review. Both these trials described adequate methodology. Neither trial compared CHM with placebo treatment.There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (95.65% versus 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). The intention-to-treat analysis also showed no significant difference between the groups (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT).CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). Overall, 100% of women in all the groups showed some improvement in their symptoms.Oral plus enema administration of CHM showed a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25; P < 0.01). Combined oral and enema administration of CHM also showed a greater improvement measured as the disappearance or shrinkage of adnexal masses than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference between CHM and danazol.
AUTHORS' CONCLUSIONS
Post-surgical administration of CHM may have comparable benefits to gestrinone but with fewer side effects. Oral CHM may have a better overall treatment effect than danazol; it may be more effective in relieving dysmenorrhoea and shrinking adnexal masses when used in conjunction with a CHM enema. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis.
Topics: Danazol; Drugs, Chinese Herbal; Dysmenorrhea; Endometriosis; Enema; Estrogen Antagonists; Female; Gestrinone; Humans; Pelvic Pain; Progestins; Randomized Controlled Trials as Topic
PubMed: 22592712
DOI: 10.1002/14651858.CD006568.pub3 -
The Cochrane Database of Systematic... 2000Although the etiology of endometriosis is unknown, several theories exist, the most popular of which is retrograde menstruation. As endometriosis can only be diagnosed... (Review)
Review
BACKGROUND
Although the etiology of endometriosis is unknown, several theories exist, the most popular of which is retrograde menstruation. As endometriosis can only be diagnosed by laparoscopy, neither the incidence (annual occurrence) nor the prevalence (proportion of the population affected) of endometriosis is known. The association between endometriosis and infertility isn't clear in Stage I (minimal) and Stage II (mild) endometriosis. Endometriosis appears to be an estrogen dependent condition. At the time of menopause, most endometriosis becomes quiescent. This hormonal dependency prompted researchers to seek agents which would suppress ovarian activity.
OBJECTIVES
To determine effectiveness of a) ovulation suppression with danazol, medroxy progesterone acetate, gestrinone, combined oral contraceptive pills and GnRH analogues versus placebo or no treatment and b) any of the above agents versus danazol, for the treatment of endometriosis explained infertility in terms of clinical pregnancy rate.
SEARCH STRATEGY
The Cochrane Subfertility Review Group specialised register of controlled trials was searched.
SELECTION CRITERIA
Four RCTs with five treatment arms compared an ovulation suppression agent with placebo or no treatment. Eight trials were identified comparing a suppressive agent with danazol.
DATA EXTRACTION
A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention.
DATA SYNTHESIS
2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2.
MAIN RESULTS
The common odds ratio for pregnancy following ovulation suppression versus placebo or no treatment was 0.83 (95% CI 0.5-1.39). These data were statistically homogeneous although clinical heterogeneity was present. Their consistency in showing no treatment benefit suggests that this group of interventions is ineffective. Common odds ratio for pregnancy following all agents versus danazol was 1.20 (95% CI 0. 85-1.68). Again these data were homogeneous and suggest no significant treatment benefit in terms of pregnancy rate.
REVIEWER'S CONCLUSIONS
Given the significant period of amenorrhea associated with ovulation suppression, the lack of treatment benefit demonstrated and the adverse effects commonly associated with these treatments, ovulation suppression cannot be recommended as a standard therapy for endometriosis-associated infertility.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Fertility Agents, Female; Humans; Infertility, Female; Ovulation
PubMed: 10796697
DOI: 10.1002/14651858.CD000155 -
The Cochrane Database of Systematic... 2004In emergency contraception a drug or IUD is used to prevent pregnancy shortly after unprotected intercourse. Except for some Western-European countries and China,... (Review)
Review
BACKGROUND
In emergency contraception a drug or IUD is used to prevent pregnancy shortly after unprotected intercourse. Except for some Western-European countries and China, emergency contraception is largely under-utilised worldwide. In many developing countries lack of access to emergency contraception may subject women to unsafe abortions, which contribute significantly to maternal mortality and morbidity. Currently, several interventions (IUD, the Yuzpe regimen, levonorgestrel, mifepristone, danazol and some combination regimens) are available for emergency contraception. Information on the comparative efficacy, safety and convenience of these methods is crucial for reproductive health care providers and the women they serve.
OBJECTIVES
To determine which emergency contraceptive method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.
SEARCH STRATEGY
The search included the Cochrane Controlled Trials Register, Popline, MEDLINE, Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (July 2003). Content experts and pharmaceutical companies were contacted.
SELECTION CRITERIA
Randomised controlled trials and controlled clinical trials including women attending services for emergency contraception following a single act of unprotected intercourse were eligible.
DATA COLLECTION AND ANALYSIS
Data on outcomes and trial characteristics were extracted in duplicate and independently by two reviewers. Quality assessment was also done by two reviewers independently. Meta-analysis results are expressed as relative risk (RR) using a fixed-effects model with 95% confidence interval (CI). In the presence of significant heterogeneity a random-effect model was applied.
MAIN RESULTS
Forty-eight trials with 33110 women were included. Most trials were conducted in China (37/48). Levonorgestrel is more effective than the Yuzpe regimen in preventing pregnancy (2 trials, RR: 0.51; 95% CI: 0.31 to 0.83). Single dose (1.5 mg) administration seems to have similar effectiveness as the standard 12 hours apart split-dose (0.75 mg twice) of levonorgestrel (2 trials, RR: 0.77, 95% CI: 0.45 to 1.30). Levonorgestrel has similar effectiveness to mid-dose (8 trials, RR: 1.64; 95% CI: 0.82 to 3.25) or low-dose (7 trials, RR: 1.38; 95% CI: 0.93 to 2.05) mifepristone. Low-dose (=< 10 mg) mifepristone is similarly effective as mid doses (25-50 mg) when only high quality trials are considered. Delay in the onset of subsequent menses is the main unwanted effect of mifepristone and seems to be dose-related. The Yuzpe regimen can be used when levonorgestrel and mifepristone are not available. Half-dose Yuzpe with single administration is associated with fewer side-effects but it is not clear whether it is as effective as the standard Yuzpe regimen (RR: 1.41; 95% CI: 0.76 to 2.61).
REVIEWERS' CONCLUSIONS
Levonorgestrel 1.5 mg (two split doses or a single dose) and low and mid-doses (25-50 mg) of mifepristone offer high efficacy with an acceptable side-effect profile. Single dose simplifies the use of levonorgestrel for emergency contraception without an increase in side-effects. However, mifepristone might delay the following menstruation, which could increase anxiety, particularly in higher doses. The Yuzpe regimen could be used if levonorgestrel or mifepristone are not available. The intrauterine device (IUD) is another effective emergency contraceptive, and can be kept for ongoing contraception.
Topics: Contraception, Postcoital; Contraceptives, Oral, Combined; Contraceptives, Postcoital; Female; Humans; Levonorgestrel; Mifepristone; Randomized Controlled Trials as Topic
PubMed: 15266446
DOI: 10.1002/14651858.CD001324.pub2 -
The Cochrane Database of Systematic... Dec 2010See https://pubmed.ncbi.nlm.nih.gov/37341141/ for a more recent review that covers this topic and has superseded this review. (Meta-Analysis)
Meta-Analysis Review
EDITORIAL NOTE
See https://pubmed.ncbi.nlm.nih.gov/37341141/ for a more recent review that covers this topic and has superseded this review.
BACKGROUND
Endometriosis is a common gynaecological condition, characterised by the presence of endometrial tissue in sites other than the uterine cavity (excluding adenomyosis) that frequently presents with pain. The gonadotrophin-releasing hormone analogues (GnRHas) comprise one intervention that has been offered for pain relief in pre-menopausal women. GnRHas can be administered intranasally, by subcutaneous, or intramuscular injection. They are thought to result in down regulation of the pituitary and induce a hypogonadotrophic hypogonadal state.
OBJECTIVES
To determine the effectiveness and safety of GnRHas in the treatment of the painful symptoms associated with endometriosis.
SEARCH STRATEGY
Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialist register, CENTRAL, MEDLINE, EMBASE, PSYCInfo and CINAHL were conducted in April 2010 to identify relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of GnRHas as treatment for pain associated with endometriosis versus no treatment, placebo, danazol, intra-uterine progestagens, or other GnRHas were included. Trials using add-back therapy, oral contraceptives, surgical intervention, GnRH antagonists or complementary therapies were excluded.
DATA COLLECTION AND ANALYSIS
Quality assessment and data extraction were performed independently by two reviewers. The primary outcome was pain relief. Relative risk was used as the measure of effect for dichotomous data. For continuous data, mean differences or standardised mean differences were used.
MAIN RESULTS
Forty one trials (n=4935 women) were included. The evidence suggested that GnRHas were more effective at symptom relief than no treatment/placebo. There was no statistically significant difference between GnRHas and danazol for dysmenorrhoea RR 0.98 (95%CI 0.92 to 1.04; P = 0.53). This equates to 3 fewer women per 1000 (95%CI 12 to 6) with symptomatic pain relief in the GnRHa group. More adverse events were reported in the GnRHa group. There was a benefit in overall resolution for GnRHas RR1.10 (95%CI 1.01 to 1.21, P=0.03) compared with danazol. There was no statistically significant difference in overall pain between GnRHas and levonorgestrel SMD -0.25 (95%CI -0.60 to 0.10, P=0.46). Evidence was limited on optimal dosage or duration of treatment for GnRHas. No route of administration appeared superior to another.
AUTHORS' CONCLUSIONS
GnRHas appear to be more effective at relieving pain associated with endometriosis than no treatment/placebo. There was no evidence of a difference in pain relief between GnRHas and danazol although more adverse events reported in the GnRHa groups. There was no evidence of a difference in pain relief between GnRHas and levonorgestrel and no studies compared GnRHas with analgesics.
Topics: Danazol; Drug Administration Routes; Dysmenorrhea; Dyspareunia; Endometriosis; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Humans; Levonorgestrel; Pain; Pelvic Pain; Randomized Controlled Trials as Topic
PubMed: 21154398
DOI: 10.1002/14651858.CD008475.pub2 -
The Cochrane Database of Systematic... Mar 2012Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endometriosis is a chronic inflammatory condition defined by the presence of glands and stroma outside the uterine cavity. It occurs in 7% to 10% of all women of reproductive age and may present as pain or infertility. The pelvic pain may be in the form of dysmenorrhoea, dyspareunia or pelvic pain. Initially a combination of estrogens and progestagens was used to create a pseudopregnancy and alleviate the symptoms associated with endometriosis. Progestagens alone or anti-progestagens have been considered as alternatives because they are inexpensive and may have a better side effect profile than other choices.
OBJECTIVES
To determine the effectiveness of both the progestagens and anti-progestagens in the treatment of painful symptoms ascribed to the diagnosis of endometriosis.
SEARCH METHODS
We used the search strategy of the Menstrual Disorders and Subfertility Group to identify all publications which described or might have described randomised controlled trials (RCTs) of any progestagen or any anti-progestagen in the treatment of symptomatic endometriosis. We updated the review in 2011.
SELECTION CRITERIA
We considered only RCTs which compared the use of progestagens and anti-progestagens with other interventions, placebo or no treatment for the alleviation of symptomatic endometriosis.
DATA COLLECTION AND ANALYSIS
We have added six new studies, bringing the total of included studies to 13 in the update of this review. The six newly included studies evaluated progestagens (comparisons with placebo, danazol, oral or subdermal contraceptive, oral contraceptive pill and danazol, gonadotrophin-releasing hormone (GnRH) analogue and other drugs). The remaining studies compared the anti-progestagen gestrinone with danazol, GnRH analogues or itself.
MAIN RESULTS
The progestagen medroxyprogesterone acetate (100 mg daily) appeared to be more effective at reducing all symptoms up to 12 months of follow-up (MD -0.70, 95% CI -8.61 to -5.39; P < 0.00001) compared with placebo. There was evidence of significantly more cases of acne (six versus one) and oedema (11 versus one) in the medroxyprogesterone acetate group compared with placebo. There was no evidence of a difference in objective efficacy between dydrogesterone and placebo.There was no evidence of a benefit with depot administration of progestagens versus other treatments (low dose oral contraceptive or leuprolide acetate) for reduced symptoms. The depot progestagen group experienced significantly more adverse effects.There was no overall evidence of a benefit of oral progestagens over other medical treatment at six months of follow-up for self-reported efficacy. Amenorrhoea and bleeding were more frequently reported in the progestagen group compared with other treatment groups.There was no evidence of a benefit of anti-progestagens (gestrinone) compared with danazol. GnRH analogue (leuprorelin) was found to significantly improve dysmenorrhoea compared with gestrinone (MD 0.82, 95% CI 0.15 to 1.49; P = 0.02) although it was also associated with increased hot flushes (OR 0.20, 95% CI 0.06 to -0.63; P = 0.006).
AUTHORS' CONCLUSIONS
There is only limited evidence to support the use of progestagens and anti-progestagens for pain associated with endometriosis.
Topics: Danazol; Dydrogesterone; Endometriosis; Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Medroxyprogesterone Acetate; Pelvic Pain; Progesterone Congeners; Progestins
PubMed: 22419284
DOI: 10.1002/14651858.CD002122.pub2