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Biomedical subjects

A Lethaby

Publications and source records attributed to A Lethaby.

32 records · Page 2Linked to original sources
PubMed2002

Endometrial destruction techniques for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is a significant health problem in premenopausal women that can reduce quality of life and cause anaemia. First line therapy has traditionally been medical therapy but this is not always completely effective. Hysterectomy, often used after the failure of medical therapy, is 100% effective but is risky, costly and can cause complications. Endometrial ablation is less invasive, less costly and preserves the uterus. A large number of techniques have been developed to "ablate" (remove) the lining of the endometrium. The gold standard techniques (laser, transcervical resection of the endometrium and rollerball) require visualisation of the uterus with a hysteroscope and, although safe, require skilled surgeons. A number of newer techniques have recently been developed, most of which can be performed blind and are less time consuming. Many of these techniques are still under development, refinement and investigation. OBJECTIVES: To compare the efficacy, safety and acceptability of methods used to destroy the endometrium to reduce HMB in premenopausal women. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (issue 4, 2001), Medline (1966 to September 2001), EmBase (1980 to August 2001), Current Contents (1993 to week 38, 2001), Biological Abstracts (1980 to June 2001), Psyclit (1967 to August 2001) and Cinahl (1982 to July 2001). We also searched the specialised register of the Cochrane Menstrual Disorders and Subfertility Group (August 2001). We also searched reference lists of articles and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing endometrial ablation techniques in women with a complaint of heavy menstrual bleeding without uterine pathology. The outcomes included reduction of heavy menstrual bleeding, improvement in quality of life, operative outcomes, satisfaction with outcome, complications and need for further surgery. DATA COLLECTION AND ANALYSIS: The two reviewers independently selected trials for inclusion, assessed trials for quality and extracted data. Attempts were made to contact authors for clarification of data in some trials. Adverse events were only assessed if they were separately measured in the included trials. MAIN RESULTS: In comparing hysteroscopic techniques, the vaporising electrode procedure was less difficult to perform (OR=0.25, 95%CI 0.1, 0.7) and had less fluid deficit (WMD=-258mls, 95% CI -342.1, -174.0) than TCRE. The odds of fluid overload and equipment failure were higher ((OR=5.2, 95% CI 1.5, 18.4) and (OR=6.0, 95% CI 1.7, 20.9) respectively) for those women having laser as compared to TCRE (transcervical resection of the endometriuim). In comparing traditional hysteroscopic endometrial ablation with the newer 2nd generation techniques overall, the newer techniques took less time to perform (WMD=-11mins, 95% CI -18.6, -2.6) and were more likely to be performed under local anaesthesia (OR=7.6, 95% CI 1.1, 52.7) but had a greater chance of equipment failure (OR=4.1, 95% CI 1.1, 15.0). The reduction in heavy bleeding did not differ significantly between any of the groups. REVIEWER'S CONCLUSIONS: Endometrial ablation techniques continue to play an important role in the management of HMB. The rapid development of a number of new methods of endometrial destruction has made systematic comparisons between methods and with the "gold standard" of TCRE difficult. Most of the newer techniques are performed blind and are technically easier than hysteroscopy-based methods. Overall, the existing evidence suggests success rates and complication profile of newer techniques of ablation compares favourably with TCRE, although technical difficulties with new equipment need to be ironed out.

Adult↗
PubMed2002

Endometrial destruction techniques for heavy menstrual bleeding: a Cochrane review.

UNLABELLED: This paper is based on a Cochrane review published in The Cochrane Library, issue 3, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration and Update Software. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. BACKGROUND: The objective of this review was to compare the efficacy, safety and acceptability of methods used to destroy the endometrium to reduce heavy menstrual bleeding (HMB) in premenopausal women. METHODS: We searched the Cochrane Controlled Trials Register, Medline, Embase, Current Contents, Biological Abstracts, Psyclit and CINAHL. We also searched the specialized register of the Cochrane Menstrual Disorders and Subfertility Group and reference lists of articles, and contacted pharmaceutical companies and experts in the field. Randomized controlled trials comparing endometrial ablation techniques in women with a complaint of HMB without uterine pathology were selected. The outcomes included reduction of HMB, improvement in quality of life, operative outcomes, satisfaction with outcome, complications and need for further surgery. The two reviewers independently selected trials for inclusion, assessed trials for quality and extracted data. Attempts were made to contact authors for clarification of data in some trials. Adverse events were only assessed if they were separately measured in the included trials. RESULTS: In comparing hysteroscopic techniques, the vaporizing electrode procedure was less difficult to perform [odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.1, 0.7] and had less fluid deficit [weighted mean difference (WMD) = -258 ml; 95% CI: -342.1, -174.0] than transcervical resection of the endometrium (TCRE). The odds of fluid overload and equipment failure were higher (OR = 5.2; 95% CI: 1.5, 18.4 and OR = 6.0; 95% CI: 1.7, 20.9 respectively) for those women having laser treatment as compared with TCRE. In comparing traditional hysteroscopic endometrial ablation with the newer second generation techniques overall, the newer techniques took less time to perform (WMD = -11 min; 95% CI: -18.6, -2.6) and were more likely to be performed under local anaesthesia (OR = 7.6; 95% CI: 1.1, 52.7) but had a greater chance of equipment failure (OR = 4.1; 95% CI: 1.1, 15.0). The reduction in HMB did not differ significantly between any of the groups. CONCLUSIONS: The rapid development of a number of new methods of endometrial destruction has made systematic comparisons between methods and with the 'gold standard' of TCRE difficult. Most of the newer techniques are performed blind and are technically easier than hysteroscopy-based methods. Overall, the existing evidence suggests that success rates and complication profile of newer techniques of ablation compare favourably with TCRE, although technical difficulties with new equipment need to be ironed out.

Endometrium↗
PubMed2000

Antifibrinolytics for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is an important cause of ill health in women. Medical therapy, with the avoidance of possibly unnecessary surgery, is an attractive treatment option. A wide variety of medications are available to reduce heavy menstrual bleeding but there is considerable variation in practice and uncertainty about the most appropriate therapy. Plasminogen activators are a group of enzymes that cause fibrinolysis (the dissolution of clots). An increase in the levels of plasminogen activators has been found in the endometrium of women with heavy menstrual bleeding compared to those with normal menstrual loss. Plasminogen activator inhibitors (antifibrinolytic agents) have therefore been promoted as a treatment for heavy menstrual bleeding. There has been a reluctance to prescribe tranexamic acid due to possible side effects of the drugs such as an increased risk of thrombogenic disease (deep venous thrombosis). Long term studies in Sweden, however, have shown that the rate of incidence of thrombosis in women treated with tranexamic acid is comparable with the spontaneous frequency of thrombosis in women. OBJECTIVES: To determine the effectiveness of antifibrinolytics in achieving a reduction in heavy menstrual bleeding. SEARCH STRATEGY: All studies which might describe randomised controlled trials of antifibrinolytic therapy for the treatment of heavy menstrual bleeding were obtained by electronic searches of the MEDLINE 1966-1997, EMBASE 1980-1997 and the Cochrane Library. Companies producing antifibrinolytics and experts within the field were contacted for reference lists and information on unpublished trials. SELECTION CRITERIA: Randomised controlled trials in women of reproductive age treated with antifibrinolytic agents versus placebo, no treatment or any other medical (non-surgical) therapy for regular heavy menstrual bleeding within either the primary, family planning or specialist clinic settings. Women with post menopausal bleeding, intermenstrual bleeding, iatrogenic or pathological causes of heavy menstrual bleeding were excluded. DATA COLLECTION AND ANALYSIS: Fifteen eligible trials were assessed by three reviewers and eight of these did not meet with the inclusion criteria. Of the seven remaining trials, four of these could be included within the meta-analysis. The remaining three trials had a crossover design and despite contacting the authors and appropriate companies, we were unable to extract the results in a format suitable to include these within the meta-analysis. However the results are included within the text of the review for discussion. MAIN RESULTS: Antifibrinolytic therapy compared to placebo showed a significant reduction in mean blood loss (WMD -94.0 [-151.4, -36.5]) and significant change in mean reduction of blood loss (WMD -110.2 [-146. 5, -73.8]). This objective improvement was not mirrored by a patient perceived improvement in monthly menstrual blood loss (RR 2.5 [0.9, 7.3]) in the one study which recorded this outcome ( approximately approximately Edlund 1995 approximately approximately ). Antifibrinolytic agents were compared to only three other medical (non-surgical) therapies: mefenamic acid, norethisterone administered in the luteal phase and ethamsylate. In all instances, there was a significant reduction in mean blood loss (WMD -73.0 [-123.4, -22.6], WMD -111.0 [-178.5, -43.5] and (WMD -100 [-143.9, -56.1] respectively) and a strong, although non-significant trend in favour of tranexamic acid in the participants' perception of an improvement in menstrual blood loss. There were no significant differences in the frequency of reported gastrointestinal side effects with tranexamic acid when compared to either NSAIDs (RR 0.9 [0.4, 2.1], oral luteal phase progestagens (RR 0.4 [0.1, 1.2]) or ethamsylate (RR 0.88 [0.3, 2.9]) when these treatments were used for heavy menstrual bleeding. (ABSTRACT TRUNCATED)

Antifibrinolytic Agents↗
PubMed2000

Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) or menorrhagia is an important cause of ill health in women. Surgical treatment of HMB often follows failed or ineffective medical therapy and the definitive treatment is hysterectomy but this is a major surgical procedure with significant physical and emotional complications and social and economic costs. A number of less invasive surgical techniques (e.g. endometrial resection and laser ablation) have been developed with the purpose of removing the entire thickness of the endometrium. The benefits claimed for these therapies are reduced trauma and post-operative complications to the woman, reduced need for a general anaesthetic, direct cost savings to the health service due largely to a shift from inpatient to day case treatment and indirect cost savings to society as women return more quickly to their usual activities. However, endometrial hysteroscopic techniques are not always completely successful and additional surgical treatment is required in a proportion of cases. Although initially the resource and patient costs of these techniques are much cheaper than the cost of hysterectomy, the need for re treatment at a later stage may reduce the cost differential. Thus, the effectiveness of these techniques to improve a woman's perception of her own wellbeing long term has yet to be confirmed. OBJECTIVES: The objective of this review is to compare endometrial destruction techniques with hysterectomy by any means for the treatment of heavy menstrual bleeding (HMB). SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Sub fertility 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 hand searching. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of endometrial destruction techniques with hysterectomy by any means for the treatment of heavy menstrual bleeding in premenopausal women. DATA COLLECTION AND ANALYSIS: Five RCTs were identified that fulfilled the inclusion criteria for this review. For two trials, a number of publications were identified which assessed different outcomes and different follow up time points for the same patients. The reviewers extracted the data independently and odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes were estimated from the data. Outcomes analysed included improvement in menstrual blood loss, satisfaction, change in quality of life, duration of surgery and hospital stay, time to return to work, adverse events and requirement for repeat surgery because of failure of the initial surgical treatment. MAIN RESULTS: There was a significant advantage in favour of hysterectomy in the improvement in HMB and satisfaction rates (up to 4 years post surgery) compared with endometrial destruction techniques. Although many quality of life scales reported no differences between surgery groups, there was some evidence of a greater improvement in general health for hysterectomy patients. Duration of surgery, hospital stay and recovery time were all shorter following endometrial destruction. Most adverse events, both major and minor, were significantly more likely after hysterectomy and before discharge from hospital. After discharge from hospital, the only difference that was reported for this group was a higher rate of infection. Repeat surgery because of failure of the initial treatment, either endometrial ablation or hysterectomy, was more likely after endometrial destruction than hysterectomy. (ABSTRACT TRUNCATED)

Endometrium↗
PubMed2000

Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding.

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.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding.

BACKGROUND: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. OBJECTIVES: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. 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 contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. DATA COLLECTION AND ANALYSIS: Twenty three RCTs were identified and five were excluded. The reviewers assessed the eighteen included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from 5.4 (1. 4-20.9) for 6 months of treatment to 16.0 (9.3-27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens with greater effects with higher dose therapy. There was no evidence of increased hyperplasia rates, however, with low dose oestrogen. The addition of progestogens, either in continuous combined or sequential regimens, helped to prevent the development of endometrial hyperplasia and improved adherence to therapy (odds ratios of 3.7 for sequential therapy and 6.0 for continuous therapy). Irregular bleeding, however, was more likely under a continuous than a sequential oestrogen-progestogen regimen (OR = 2.3, 95% CI 2.1-2.5) but at longer duration of treatment, continuous therapy was more protective than sequential therapy in preventing endometrial hyperplasia (OR = 0.3, 95% CI 0.1-0.97). There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every 3 months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of the treatment groups during the limited duration (maximum of 3 years) of these trials. (ABSTRACT TRUNCATED)

Endometrial Hyperplasia↗
PubMed2000

Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fibroids.

BACKGROUND: Uterine fibroids, smooth muscle tumours of the uterus, are found in at least 25 to 35% of women over the age of 35 years. Although some of these tumours are asymptomatic, up to 50% cause symptoms severe enough to warrant therapy and surgery is the standard treatment. Fibroid growth is stimulated by oestrogen and gonadotropin releasing hormone agonists (GnRHa) which induce a state of hypoestrogenism have been investigated as a potential treatment. GnRHa treatment causes fibroids to shrink but cannot be used long term because of unacceptable symptoms and bone loss. Therefore, GnRHa may be useful pre-operatively both to reduce fibroid and uterine volume and control bleeding. OBJECTIVES: The objective of this review is to evaluate the role of pre-treatment with gonadotropin releasing hormone (GnRH) analogues prior to a major surgical procedure, either hysterectomy or myomectomy, for uterine fibroids. 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 for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of GnRH analogue treatment versus placebo, no treatment, or other medical therapy prior to surgery, either myomectomy or hysterectomy, for uterine fibroids. DATA COLLECTION AND ANALYSIS: Nineteen 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 twelve trials where GnRH analogue treatment was compared with no pre-treatment and five trials where GnRH analogue treatment was compared with placebo (two trials are awaiting assessment). No RCTs of GnRH analogue treatment versus other medical therapy were identified. Results from pre-operative outcomes were combined for both types of surgery but results from intra- and post-operative outcomes were reported separately for myomectomy and hysterectomy. Subgroup analysis was performed according to type of control group, no pre-treatment or placebo, and for some outcomes there were additional subgroup analyses according to size of the uterus in gestational weeks. MAIN RESULTS: Pre- and post-operative haemoglobin (Hb) and haematocrit (HCT) were significantly improved by GnRH analogue therapy prior to surgery, and uterine volume, uterine gestational size and fibroid volume were all reduced. Pelvic symptoms were also reduced but some adverse events were more likely during GnRH analogue therapy. Hysterectomy appeared to be easier after pre-treatment with GnRH analogue therapy; there was reduced operating time and a greater proportion of hysterectomy patients were able to have a vaginal rather than an abdominal procedure. Duration of hospital stay was also reduced. Blood loss and rate of vertical incisions were reduced for both myomectomy and hysterectomy. Evidence of increased risk of fibroid recurrence after GnRH analogue pre-treatment in myomectomy patients was equivocal and no data were available to assess change in post-operative fertility. The increased costs associated with GnRH analogue therapy were not assessed. REVIEWER'S CONCLUSIONS: The use of GnRH analogues for 3 to 4 months prior to fibroid surgery reduce both uterine volume and fibroid size. They are beneficial in the correction of pre-operative iron deficiency anaemia, if present, and reduce intra-operative blood loss. If uterine size is such that a mid-line incision is planned, this can be avoided in many women with the use of GnRH analogues. For patients undergoing hysterectomy, a vaginal procedure is more like

Antineoplastic Agents, Hormonal↗
PubMed2000

Cyclical progestogens for heavy menstrual bleeding.

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)

Administration, Oral↗
PubMed2000

Pre-operative endometrial thinning agents before hysteroscopic surgery for heavy menstrual bleeding.

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 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 offers a day-case surgical alternative to hysterectomy for these women. It is also a cheaper procedure 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 4mm, 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). OBJECTIVES: To investigate the effectiveness of gonadotrophin-releasing hormone (GnRH) analogues, danazol, and progestogens, when used for endometrial thinning prior to hysteroscopic surgery 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. 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: Eight studies met the inclusion criteria for this review. Four studies compared goserelin (a GnRH analogue) with no treatment or placebo. Three studies compared goserelin with danazol. One study compared progestogens, danazol and triptorelin (a GnRH analogue) with no treatment. Data was 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 compared were 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. 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. Both GnRH analogues and danazol produce side-effects in a significant proportion of women, though few studies have reported these in detail. Little randomised data is available to assess the effectiveness of progestogens as endometrial thinning agents and the effect of any thinning agent

Danazol↗
PubMed1999

An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding.

OBJECTIVE: We sought to determine the clinical risk factors for endometrial hyperplasia in premenopausal women with abnormal bleeding. STUDY DESIGN: A laboratory database was searched to identify all endometrial samples taken in 1033 premenopausal women over a 30-month period from January 1995 to July 1997. Clinical data were extracted from the patients' clinical records retrospectively, and univariate and multivariate analyses were performed. The setting was the gynecologic service of a large teaching hospital. RESULTS: There were 46 cases of endometrial hyperplasia and 5 cases of endometrial cancer diagnosed. The following factors were independently associated with increased risk of endometrial hyperplasia or the presence of carcinoma: age >/=45 years (odds ratio, 3.1; 95% confidence interval, 1.5-6.1), weight >/=90 kg (odds ratio, 5.5; 95% confidence interval, 2.9-10.6), history of infertility (odds ratio, 3.6; 95% confidence interval, 1.3-9.9), family history of colonic carcinoma (odds ratio, 5.0; 95% confidence interval, 1.3-19.1), and nulliparity (odds ratio, 2.8; 95% confidence interval, 1.1-7.2). There was no increased association of endometrial hyperplasia on the basis of irregularity of menstrual cycle or duration of menstrual bleeding. CONCLUSIONS: The following are risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding: body weight >/=90 kg, age >/=45 years, infertility, family history of colonic carcinoma, and nulliparity. Current guidelines may need to be reconsidered.

Adolescent↗
PubMed1997

Seasonal variation in the secretion of mammotrophic hormones in normal women and women with previous breast cancer.

Hormones such as melatonin whose serum concentrations vary seasonally have been previously implicated in the growth of breast cancer. The present study was undertaken to identify possible seasonal variation in a range of mammotrophic hormones which could exert a chronobiologic influence in women with breast tumours. Fifteen premenopausal women with a history of previous breast cancer (BC subjects) and 10 control women underwent 2-hourly serum sampling for 24 h at both summer and winter solstice for measurement of melatonin, growth hormone (GH), insulin-like growth factor-I (IGF-I), cortisol, prolactin and thyrotrophin (TSH). Hormone secretion at the different seasons was compared by measuring the area under the 24 h serum hormone concentration x time curves and by time series analysis of summer-to-winter differences in hormone concentration. Control women had significantly higher GH and IGF-I levels in summer compared to winter and significantly higher cortisol secretion in winter than summer. In contrast, BC women had no significant seasonal difference in IGF-I concentrations and had a reversal of the normal seasonal pattern of melatonin secretion, although seasonal changes in GH production were similar to controls. Prolactin and TSH showed no significant summer/winter variation in either group. Thus, seasonal variations in hormone secretion seen in normal women were, with exception of GH, absent or reversed in women with a previous history of breast cancer. As a result these individuals may be exposed to an asynchronous hormonal stimulus which could influence tumour growth. These changes could reflect a constitutional abnormality in BC women or may have been induced by the previous breast tumour.

Breast Neoplasms↗