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IDrugs : the Investigational Drugs... May 2004Endometriosis is an important clinical problem in routine practice. Besides the problems of dysmenorrhea, dyspareunia and chronic abdominal pain, women with... (Review)
Review
Endometriosis is an important clinical problem in routine practice. Besides the problems of dysmenorrhea, dyspareunia and chronic abdominal pain, women with endometriosis are often infertile. We performed a systematic literature review on two issues: firstly, we clarified which medical treatment options have been investigated in prospective, randomized studies. Secondly, potential future treatments, still being preclinically investigated, were examined. A meta-analysis was not possible as the studies varied too much in their protocols and inclusion and exclusion criteria, as well as in the drugs and doses administered. Gonadotropin-releasing hormone (GnRH) agonists, progestins and oral contraceptives all appear to offer certain advantages for endometriosis patients. GnRH agonists appear to be the most effective but they are expensive and long-term treatment is not possible because of loss of bone mineral density. Estrogen add-back may offer some benefit for the clinical complaints of patients, but it may reduce the efficacy of GnRH agonists. Progestins have the best clinical profile and a good cost-effectiveness balance; however, most studies found that they were not as effective as GnRH agonists. Oral contraceptives are only effective during treatment and have a high relapse rate after therapy is completed. Future options may include the use of GnRH agonists, selective estrogen receptor modulators (SERMs) and anti-estrogens, as well as immunomodulators.
Topics: Danazol; Endometriosis; Estrogen Antagonists; Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Progesterone Congeners; Progestins; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 15154107
DOI: No ID Found -
The Cochrane Database of Systematic... 2000Heavy menstrual bleeding is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also... (Review)
Review
BACKGROUND
Heavy menstrual bleeding is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Nonsteroidal anti-inflammatory drugs or prostaglandin synthetase inhibitors reduce prostaglandin levels which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
The primary objective of this review was to investigate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB).
SEARCH STRATEGY
Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were approached for unpublished data. In most cases, the first author of each included trial was contacted for additional information.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs with either each other, placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment induced) causes for their heavy menstrual blood loss.
DATA COLLECTION AND ANALYSIS
Sixteen RCTs were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The remaining seven trials were of crossover design with data unsuitable for pooling and their individual results were described in text form.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing heavy menstrual bleeding but less effective than either tranexamic acid or danazol. Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There was a non significant trend towards greater efficacy of NSAIDs compared to oral progestogen (luteal phase) and ethamsylate but no differences were demonstrated between NSAIDs and the progesterone releasing intra-uterine system (IUS) and the oral contraceptive pill, although these results were based on very small studies. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB.
REVIEWER'S CONCLUSIONS
NSAIDs reduce heavy menstrual bleeding when compared with placebo but are less effective than either tranexamic acid or danazol. However, adverse events are more severe with danazol therapy. In the limited number of small scale studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral progestogen given in the luteal phase, ethamsylate, oral contraceptive pill and the progesterone releasing IUS.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Menorrhagia
PubMed: 10796714
DOI: 10.1002/14651858.CD000400 -
Annals of Allergy, Asthma & Immunology... Apr 2015To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE). (Review)
Review
OBJECTIVE
To provide an objective basis for evaluating the risk-benefit ratio of long-term androgen use in patients with hereditary angioedema (HAE).
DATA SOURCES
PubMed was searched with no time limitations using the keywords hereditary angioedema or angio-oedema combined with danazol, stanozolol, and androgen.
STUDY SELECTION
Qualifying articles were English-language reports of androgen use in patients with HAE, with relevant safety and/or efficacy information. Reports were categorized according to level of evidence (LOE).
RESULTS
The search process identified 153 citations, 63 of which contained relevant information; 2 additional publications were identified while other citations were being reviewed. Fifteen LOE 2 studies and multiple LOE 4 reports provided efficacy data, confirming a high level of prophylactic efficacy for androgen therapy in HAE, with occasional reports of poor prophylactic response. Common adverse events include weight gain, menstrual irregularities, virilization, headaches, myalgias or cramps, mood changes, and elevations in creatine phosphokinase level, liver function test results, and serum lipid level. The risk of adverse events is often correlated with dose and/or treatment duration. Rare cases of hepatic adenomas and hepatocellular carcinoma associated with long-term androgen use often had no preceding changes in liver function test results.
CONCLUSION
Androgen therapy may be effective for most patients with HAE; however, potential risks and adverse effects must be carefully considered and discussed with patients when considering options for long-term HAE prophylaxis.
Topics: Androgens; Angioedemas, Hereditary; Animals; Danazol; Drug Dosage Calculations; Female; Humans; Lipid Metabolism; Menstruation Disturbances; Obesity; Risk Assessment; Stanozolol; Time Factors; Virilism
PubMed: 25707325
DOI: 10.1016/j.anai.2015.01.003 -
The Cochrane Database of Systematic... 2002Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies... (Review)
Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Nonsteroidal anti-inflammatory drugs reduce prostaglandin levels which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
The primary objective of this review was to investigate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in achieving a reduction in menstrual blood loss in women of reproductive years HMB.
SEARCH STRATEGY
Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, MEDLINE, EMBASE, Current Contents, the Cochrane Library and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were approached for unpublished data. In most cases, the first author of each included trial was contacted for additional information. An updated search was performed in September and October 2001 but no new eligible trials were identified.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs with either each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment induced) causes for their heavy menstrual blood loss.
DATA COLLECTION AND ANALYSIS
Sixteen RCTs were identified that fulfilled the inclusion criteria for this review and data were extracted independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The results of the remaining seven crossover trials with data unsuitable for pooling were described in the Other Data section.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing heavy menstrual bleeding but less effective than either tranexamic acid or danazol. Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There were no statistically significant differences between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, progesterone releasing intra-uterine system (IUS), oral contraceptive pill (OCC)) but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB.
REVIEWER'S CONCLUSIONS
NSAIDs reduce HMB when compared with placebo but are less effective than either tranexamic acid or danazol. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or IUS.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Menorrhagia; Randomized Controlled Trials as Topic
PubMed: 11869575
DOI: 10.1002/14651858.CD000400 -
The Cochrane Database of Systematic... 2000Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is... (Review)
Review
BACKGROUND
Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary).
OBJECTIVES
To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions.
SEARCH STRATEGY
The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis.
SELECTION CRITERIA
Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis.
DATA COLLECTION AND ANALYSIS
Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are 5 studies comparing GnRHas with GnRHas plus add-back therapy, 3 comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo. Data was extracted independently by two reviewers. The authors of 11 studies have been contacted to clarify missing or unclear data. Only 4 have replied to date. Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected.
MAIN RESULTS
No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms.
REVIEWER'S CONCLUSIONS
There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.
Topics: Danazol; Endometriosis; Female; Fertility Agents, Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Pain
PubMed: 10796530
DOI: 10.1002/14651858.CD000346 -
The Cochrane Database of Systematic... Jul 2007Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is... (Review)
Review
BACKGROUND
Endometriosis is a common gynaecological condition that frequently presents with the symptom of pain. The precise pathogenesis (mode of development) of endometriosis is unclear but it is evident that endometriosis arises by the dissemination of endometrium to ectopic sites and the subsequent establishment of deposits of ectopic endometrium. The observation that endometriosis is rarely seen in the hypo-oestrogenic (low levels of oestrogen) post-menopausal woman led to the concept of medical treatment by induction of a pseudo-menopause using Gonadotrophin Releasing Hormone Analogues (GnRHas). When administered in a non-pulsatile manner (the pituitary is normally stimulated by pulses of natural GnRH and all analogues act on the pituitary at a constant level) their use results in down regulation (switching off) of the pituitary and a hypogonadotrophic hypogonadal state (low levels of female hormones due to non stimulation of the ovary).
OBJECTIVES
To determine the effectiveness of Gonadotrophin Releasing Hormone analogues (GnRHas) in the treatment of the painful symptoms of endometriosis by comparing them with no treatment, placebo, other recognised medical treatments, and surgical interventions.
SEARCH STRATEGY
The search strategy of the Menstrual Disorders and Subfertility review group (please see Review Group details) was used to identify all randomised trials of the use of GnRHas for the treatment of the painful symptoms of endometriosis.
SELECTION CRITERIA
Trials were included if they were randomised, and considered the effectiveness of GnRHas in the treatment of the painful symptoms of endometriosis.
DATA COLLECTION AND ANALYSIS
Twenty-six studies had data appropriate for inclusion in the review. The largest group (15 studies) compared GnRHas with danazol. There are five studies comparing GnRHas with GnRHas plus add-back therapy, three comparing GnRHa with GnRHa in a different form or dose, one compares them with gestrinone, one with the combined oral contraceptive pill, and one with placebo. Data was extracted independently by two reviewers. The authors of eleven studies have been contacted to clarify missing or unclear data. Only four have replied to date. Data on relief of pain, change in revised American Fertility Society (rAFS) scores, and side effects was collected.
MAIN RESULTS
No difference was found between GnRHas and any of the other active comparators with respect to pain relief or reduction in endometriotic deposits. The side effect profiles of the different treatments were different, with danazol and gestrinone having more androgenic side effects, while GnRHas tend to produce more hypo-oestrogenic symptoms.
AUTHORS' CONCLUSIONS
There is little or no difference in the effectiveness of GnRHas in comparison with other medical treatments for endometriosis. GnRHas do appear to be an effective treatment. Differences that do exist relate to side effect profiles. Side effects of GnRHas can be ameliorated by the addition of addback therapy.
Topics: Danazol; Endometriosis; Female; Fertility Agents, Female; Gestrinone; Gonadotropin-Releasing Hormone; Humans; Pain
PubMed: 17636631
DOI: 10.1002/14651858.CD000346.pub2 -
The Cochrane Database of Systematic... 2000Excessively heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Eighty per cent of women treated for HMB have no anatomical... (Review)
Review
BACKGROUND
Excessively heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Eighty per cent of women treated for HMB have no anatomical pathology and so medical therapy, with the avoidance of possibly unnecessary surgery, is an attractive alternative. Of the wide variety of medications used to reduce heavy menstrual bleeding, oral progestogens are the most commonly prescribed in many western countries, although there is little objective evidence to support their use, especially in women with ovulatory menstruation. This review assesses the effectiveness of 2 different regimens of oral progestogens in reducing ovulatory HMB.
OBJECTIVES
The primary objective of this review is to investigate the effectiveness of oral progestogen therapy taken either during the luteal phase or for a longer course of 21 days in achieving a reduction in menstrual blood loss in women of reproductive years with heavy menstrual bleeding (HMB).
SEARCH STRATEGY
Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsychLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles. In most cases, the first author of each included trial was contacted.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of oral progestogen therapy versus placebo or other medical treatments in women of reproductive years with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic causes for their heavy menstrual blood loss.
DATA COLLECTION AND ANALYSIS
Seven randomised controlled trials (RCTs) were identified that fulfilled the inclusion criteria for this review. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data.
MAIN RESULTS
No RCTs comparing progestogen treatment with placebo were identified. Comparisons between oral progestogens and other medical therapies were assessed separately according to dosage regimen, progestogens given during the luteal phase of the menstrual cycle and progestogens given for 21 days between day 5 and 26. Progestogen therapy during the luteal phase was significantly less effective at reducing menstrual blood loss when compared with tranexamic acid, danazol and the progesterone releasing intrauterine system (IUS) and there was also a strong non-significant trend in favour of nonsteroidal anti-inflammatory drugs (NSAIDs). Duration of menstruation was significantly longer with the progesterone IUS when compared with oral progestogen therapy but significantly shorter under danazol treatment. Compliance and acceptability of treatment where measured did not differ between treatments. Adverse events were significantly more likely under danazol when compared with progestogen treatment. Change in quality of life was not significantly different with progestogen and tranexamic acid therapy but there was a non-significant trend in favour of tranexamic acid for all three categories. Progestogen therapy administered from day 5 to 26 of the menstrual cycle was significantly less effective at reducing menstrual blood loss than the progestogen releasing intrauterine system (LNG IUS) although the reduction from baseline was significant for both groups. The odds of the menstrual period becoming "normal" (ie <80mls/cycle) were also less likely in patients treated with norethisterone (NET) (days 5 to 26) compared to patients treated with LNG IUS. A significantly higher proportion of NET patients found their treatment unacceptable compared to LNG IUS patients. However, the adverse events breast tenderness and intermenstrual bleeding were more likely in the patients with the IUS. (ABSTRACT TRUNCATED)
Topics: Administration, Oral; Female; Humans; Menorrhagia; Progestins
PubMed: 10796587
DOI: 10.1002/14651858.CD001016 -
The Cochrane Database of Systematic... Oct 2007Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Nonsteroidal anti-inflammatory drugs reduce prostaglandin levels which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
The primary objective of this review was to investigate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in achieving a reduction in menstrual blood loss in women of reproductive years HMB.
SEARCH STRATEGY
We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched April 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2007), MEDLINE (1966 to April 2007), EMBASE (1985 to April 2007), CINAHL (1982 to April 2007), Current Contents (1993 to April 2007) and reference lists of articles. We also contacted manufacturers and researchers in the field.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs with either each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment induced) causes for their heavy menstrual blood loss.
DATA COLLECTION AND ANALYSIS
Seventeen RCTs were identified that fulfilled the inclusion criteria for this review and data were extracted independently. Odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data of nine trials. The results of the remaining seven crossover trials with data unsuitable for pooling and one trial with skewed data were described in the Other Data section.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing heavy menstrual bleeding but less effective than either tranexamic acid, danazol or the levonorgestrel releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs but this did not appear to affect the acceptability of treatment. There were no statistically significant differences between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone releasing intra-uterine system (Progestasert), oral contraceptive pill (OCC)) but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB.
AUTHORS' CONCLUSIONS
NSAIDs reduce HMB when compared with placebo but are less effective than either tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, no significant difference in efficacy was demonstrated between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCC or another type of IUS, Progestasert.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dysmenorrhea; Female; Humans; Menorrhagia; Randomized Controlled Trials as Topic
PubMed: 17943741
DOI: 10.1002/14651858.CD000400.pub2 -
The Cochrane Database of Systematic... 2002Menorrhagia is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Although medical therapy is generally the first approach, many... (Review)
Review
BACKGROUND
Menorrhagia is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Although medical therapy is generally the first approach, many women will eventually require or request a hysterectomy. Hysterectomy is associated with a significant in-patient hospital stay and a period of convalescence that makes it an unattractive and unnecessarily invasive option for many women. Hysteroscopic endometrial ablation or resection, and more recently "second generation" devices such as balloon or microwave ablation offer a day-case surgical alternative to hysterectomy for these women. They are also cheaper procedures than hysterectomy. Complete endometrial removal or destruction is one of the most important determinants of treatment success. Therefore surgery will be most effective if undertaken when endometrial thickness is less than four mm, in the immediate post-menstrual phase, however there are often difficulties in reliably arranging surgery for this time. The other option is the use of hormonal agents which induce endometrial thinning or atrophy prior to surgery. The most commonly evaluated agents have been goserelin (a GnRH analogue) and danazol. Progestogens and other GnRH analogues have also been studied although less data are available. It has been suggested that the use of these agents, particularly GnRH analogues, will reduce operating time, improve the intra-uterine operating environment, and reduce distension medium absorption (this is the fluid used to distend the uterine cavity during surgery). They may also result in a greater improvement in long term outcomes such as menstrual loss and dysmenorrhoea.
OBJECTIVES
To investigate the effectiveness of gonadotrophin-releasing hormone (GnRH) analogues, danazol, and progestogens, when used for endometrial thinning prior to endometrial destruction for menorrhagia, in improving the intra-uterine operating environment and treatment outcome after surgery.
SEARCH STRATEGY
The Menstrual Disorders and Subfertility Group search strategy (see Review Group details) was used to identify randomised trials that had compared the use of these drugs with either each other, or placebo, or no pre-operative treatment. An updated search was performed in 2001-2002 to identify new trials.
SELECTION CRITERIA
Trials were included if they compared the effects of these agents with each other, or with placebo or no treatment on relevant intra-operative and post-operative treatment outcomes. Only randomised studies were included in this review.
DATA COLLECTION AND ANALYSIS
Twelve studies met the inclusion criteria for this review. Five studies compared goserelin (a GnRH analogue) with no treatment or placebo and one study compared decapeptyl (a GnRH analogue) with no treatment. Three studies compared goserelin with danazol. Two studies compared progestogens, danazol and triptorelin or nasal spray nafarelin (both GnRH analogues) with no treatment. Only one study comparing triptorelin with no treatment assessed outcomes after balloon ablation and no studies assessing endometrial thinning agents prior to other second generation ablation techniques were identified. One study assessed the effects of progestogens compared to no treatment. Data were extracted independently by two reviewers. A third reviewer checked data extraction for accuracy and wrote to authors where relevant data was missing or unclear. Intra-operative parameters included endometrial thickness, duration of surgery, ease of surgery, distension medium absorption and complication rate. Post-operative outcomes included the proportion of women with amenorrhoea, post-operative menstrual loss and dysmenorrhoea, and the need for further surgery. Data on side-effects were also recorded.
MAIN RESULTS
When compared with no treatment, GnRH analogues are associated with a shorter duration of surgery, greater ease of surgery and a higher rate of post-operative amenorrhoea at 12 months with hysteroscopic resection or ablation. Post-operative dysmenorrhoea also appears to be reduced. The use of GnRH analogues has no effect on intra-operative complication rates and patient satisfaction with this surgery is high irrespective of the use of any pre-operative endometrial thinning agent. GnRH analogues produce more consistent endometrial atrophy than danazol. For other intra-operative and post-operative outcomes, any differences are minimal and there were no benefits of GnRHa pre-treatment in the one small study where women had balloon (second generation ablation). Both GnRH analogues and danazol produce side-effects in a significant proportion of women, though few studies have reported these in detail. Few randomised data are available to assess the effectiveness of progestogens as endometrial thinning agents. The effect of any thinning agent on longer-term results is less certain but where reported the effect of endometrial thinning agents on benefits such as post-operative amenorrhoea appears to reduce with time.
REVIEWER'S CONCLUSIONS
Endometrial thinning prior to hysteroscopic surgery in the early proliferative phase of the menstrual cycle for menorrhagia improves both the operating conditions for the surgeon and short term post-operative outcome. Gonadotrophin-releasing hormone analogues produce slightly more consistent endometrial thinning than danazol, though both agents produce satisfactory results. The effect of these agents on longer term post-operative outcomes such as amenorrhoea and the need for further surgical intervention reduces with time.
Topics: Danazol; Endometrium; Estrogen Antagonists; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hysteroscopy; Menorrhagia; Progestins
PubMed: 12137619
DOI: 10.1002/14651858.CD001124 -
The Cochrane Database of Systematic... Sep 2019Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies...
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
To determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB.
SEARCH METHODS
We searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB.
DATA COLLECTION AND ANALYSIS
We identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision.
AUTHORS' CONCLUSIONS
NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Contraceptives, Oral, Combined; Dysmenorrhea; Female; Humans; Menorrhagia; Naproxen; Progesterone; Randomized Controlled Trials as Topic
PubMed: 31535715
DOI: 10.1002/14651858.CD000400.pub4