Biomedical subjects

A Lethaby

Publications and source records attributed to A Lethaby.

At least 19 recordsLinked to original sources

PubMed2006

Local oestrogen for vaginal atrophy in postmenopausal women.

BACKGROUND: Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the oestradiol-releasing ring). OBJECTIVES: The objective of this review was to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Register of trials (searched January 2006), The Cochrane Library (2006,Issue 2), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), Current Contents (1993 to January 2006, Biological Abstracts (1969 to 2006), Social Sciences Index (1980 to January 2006), PsycINFO (1972 to February 2006), CINAHL (1982 to January 2006) and reference list of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis. DATA COLLECTION AND ANALYSIS: Thirty-seven trials were identified: of these 18 were excluded. Included trials were assessed for quality and two reviewer authors extracted data independently. The ratios for dichotomous outcomes and means for continuous outcomes were calculated. The outcomes analysed were categorised under the headings of: efficacy, safety and acceptability. MAIN RESULTS: Nineteen trials with 4162 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy, with various outcome measures. When comparing the efficacy of different oestrogenic preparations (in the form of creams, pessaries, tablets and the oestradiol-releasing vaginal ring) in relieving the symptoms of vaginal atrophy, results indicated significant findings favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and seven looked at adverse effects. One trial showed significant adverse effects of the cream (conjugated equine oestrogen) when compared to tablets (oestradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by a progestagen challenge test with the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to the cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (oestradiol). Eleven studies compared acceptability to the participants by comparing: comfort of product use, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the oestradiol-releasing vaginal ring. AUTHORS' CONCLUSIONS: Creams, pessaries, tablets and the oestradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following use of the cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the oestradiol-releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

Administration, Intravaginal↗

PubMed2006

Progesterone for Premenstrual Syndrome.

BACKGROUND: Premenstrual Syndrome (PMS) is the term for severe symptoms experienced by about 5% of menstruating women up to two weeks before their menstrual periods, but not at other times. Treatment with progesterone may restore a deficiency, or balance the level of progesterone with other menstrual hormones. Progesterone therapy may reduce the effects of falling progesterone levels on the brain or on electrolytes in the blood. OBJECTIVES: The objectives were to determine if progesterone has been found to be an effective treatment for all or some premenstrual symptoms, and if adverse events associated with this treatment have been reported. SEARCH STRATEGY: We last searched the Cochrane Menstrual Disorders and Subfertility Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2005), MEDLINE (1966 to 2005) and EMBASE (1980 to 2005) in March 2005, and PsycINFO (1806 to 2006) in April 2006. We contacted pharmaceutical companies for information about unpublished trials. SELECTION CRITERIA: We included randomised double-blind, placebo-controlled trials of progesterone on women with PMS diagnosed by at least two prospective cycles, without current psychiatric disorder. DATA COLLECTION AND ANALYSIS: Two reviewers (BM and OF) extracted data independently, and decided on the trials to be included. OF wrote to the trial investigators to ask for missing data. MAIN RESULTS: We considered 17 studies. We included two trials totaling 280 participants aged from 18 to 45 years. Of these 115 yielded analysable results. Both studies measured outcomes using subjective scales of symptom severity but made calculations as if they were interval data. The two studies differed in design, participants, dose of progesterone, how and when the dose was administered and in outcome measures. It was impossible to combine data in a meta-analysis. Adverse events which may or may not have been the side effects of the treatment, were generally described as mild. Both trials intended to exclude women whose symptoms continued after their periods; unfortunately the larger multicentre study had some ineligible participants. Overall, participants benefited more from progesterone than placebo. This was statistically significant in per protocol analysis but not in the intention-to-treat analysis, except for the first cycle. The smaller, crossover study found no statistically significant difference between oral progesterone, vaginally absorbed progesterone and placebo. AUTHORS' CONCLUSIONS: We could not say that progesterone helped women with PMS, nor that it was ineffective. Neither trial distinguished a subgroup of women who benefited.

Female↗

PubMed2006

Surgical approach to hysterectomy for benign gynaecological disease.

BACKGROUND: There are three approaches to hysterectomy for benign disease - abdominal hysterectomy (AH), vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH). Laparoscopic hysterectomy has three further subdivisions - laparoscopic assisted vaginal hysterectomy (LAVH) where a vaginal hysterectomy is assisted by laparoscopic procedures that do not include uterine artery ligation, laparoscopic hysterectomy (which we will abbreviate to LH(a)) where the laparoscopic procedures include uterine artery ligation, and total laparoscopic hysterectomy (TLH) where there is no vaginal component and the vaginal vault is sutured laparoscopically. OBJECTIVES: To assess the most appropriate surgical approach to hysterectomy. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group's Specialised Register of controlled trials (searched 23 March 2004), CENTRAL (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to Mar 2004), EMBASE (1985 to Mar 2004), Biological Abstracts (1968 to Mar 2004), the National Research Register and relevant citation lists. SELECTION CRITERIA: Only randomised trials comparing one surgical approach to hysterectomy with another were included. DATA COLLECTION AND ANALYSIS: Twenty-seven trials that included 3643 participants were included. Independent selection of trials and data extraction were employed following Cochrane guidelines. MAIN RESULTS: The benefits of VH versus AH were shorter duration of hospital stay (WMD 1.0 day, 95%CI 0.7 to 1.2 days), speedier return to normal activities (WMD 9.5 days, 95%CI 6.4 to 12.6 days), fewer unspecified infections or febrile episodes (OR 0.42, 95%CI 0.21 to 0.83). The benefits of LH versus AH were lower intraoperative bloodloss (WMD 45.3 mls, 95%CI 17.9 to 72.7 mls) and a smaller drop in haemoglobin level (WMD 0.55g/L, 95%CI 0.28 to 0.82g/L), shorter duration of hospital stay (WMD 2.0 days, 95%CI 1.9 to 2.2 days), speedier return to normal activities (WMD 13.6 days, 95%CI 11.8 to 15.4 days), fewer wound or abdominal wall infections (OR 0.32, 95%CI 0.12 to 0.85), fewer unspecified infections or febrile episodes (OR 0.65, 95%CI 0.49 to 0.87), at the cost of longer operating time (WMD 10.6 minutes, 95%CI 7.4 to 13.8 minutes) and more urinary tract (bladder or ureter) injuries (OR 2.61, 95%CI 1.22 to 5.60). There was no evidence of benefits of LH versus VH and the operating time was increased (WMD 41.5 minutes, 95%CI 33.7 to 49.4 minutes). There was no evidence of benefits of LH(a) versus LAVH and the operating time was increased for LH(a) (WMD 25.3 minutes, 95%CI 10.0 to 40.6 minutes). There was statistical heterogeneity in many of the outcome measures when randomised trials were pooled for meta-analysis. No other statistically significant differences were found. However, for some important outcomes, the analyses were underpowered to detect important differences, or they were simply not reported in trials. Data were notably absent for many important long-term outcome measures. AUTHORS' CONCLUSIONS: Significantly improved outcomes suggest VH should be performed in preference to AH where possible. Where VH is not possible, LH may avoid the need for AH, however the length of the surgery increases as the extent of the surgery performed laparoscopically increases, particularly when the uterine arteries are divided laparoscopically and laparoscopic approaches require greater surgical expertise. The surgical approach to hysterectomy should be decided by a woman in discussion with her surgeon in light of the relative benefits and hazards. Further research is required with full reporting of all relevant outcomes, particularly important long-term outcomes, in large RCTs, to minimise the possibility of reporting bias. Further research is also required to define the role of the newer approaches to hysterectomy such as TLH.

Female↗

PubMed2006

Surgery versus medical therapy for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) significantly impairs the quality of life of many otherwise healthy women. Perception of HMB is subjective and management usually depends upon what symptoms are acceptable to the individual. Medical treatment options include oral medication and a hormone-releasing intrauterine system (LNG-IUS). Surgical options include conservative surgery (uterine resection or ablation) and hysterectomy. OBJECTIVES: To compare the effectiveness, safety and acceptability of surgery versus medical therapy for HMB. SEARCH STRATEGY: In September 2005 we searched the Cochrane Menstrual Disorders and Subfertility Group trials register Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2005), MEDLINE EMBASE, Current Contents, Biological Abstracts, PsycINFO, and CINAHL. We also searched reference lists of articles retrieved and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Controlled randomised trials comparing conservative surgery or hysterectomy versus medical therapy (oral or intrauterine) for HMB DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data . MAIN RESULTS: The eight included trials randomised 821 women. In comparisons of oral medication versus surgery, 58% of women randomised to medical treatment had received surgery by two years. Compared to oral medication, endometrial resection was significantly more effective in controlling bleeding (at four months: OR 10.62, 95% CI 5.30 to 21.27) and significantly less likely to cause side effects (at four months: OR 0.15, 95% CI 0.07 to 0.31) and hysterectomy resulted in significantly greater improvements in mental health (at six months p = 0.04). In comparisons of LNG-IUS versus conservative surgery or hysterectomy, at one year there was no statistically significant difference in satisfaction rates or quality of life, though adverse effects were significantly less likely with conservative surgery (OR 0.24, 95% CI 0.11 to 0.49). Two trials found conservative surgery significantly more effective than LNG-IUS in controlling bleeding at one year (OR 3.99, 95% CI 1.53 to 10.38). Two other small trials with longer follow-up found no difference or favoured LNG-IUS - however in both these studies the data were skewed and fewer than two thirds of participants were analysed. Hysterectomy stopped all bleeding but caused serious complications for some women. AUTHORS' CONCLUSIONS: Surgery, especially hysterectomy, reduces menstrual bleeding at one year more than medical treatments but LNG-IUS appears equally effective in improving quality of life. The evidence for longer term comparisons is weak and inconsistent. Oral medication suits a minority of women long term.

Adult↗

PubMed2006

Total versus subtotal hysterectomy for benign gynaecological conditions.

BACKGROUND: Hysterectomy using an abdominal approach removes either the uterus alone (subtotal hysterectomy) or both the uterus and the cervix (total hysterectomy). The latter is more common but outcomes have not been systematically compared. OBJECTIVES: To assess and compare outcomes with subtotal hysterectomy versus total abdominal hysterectomy for benign gynaecological conditions. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of controlled trials (December 2005), Central (December 2005), Medline (1966 to December 2005), EmBase (1980 to December 2005), Biological Abstracts (1980 to December 2005), the National Research Register and relevant citation lists. SELECTION CRITERIA: Only randomised controlled trials of women undergoing either total or subtotal hysterectomy for benign gynaecological conditions were included. DATA COLLECTION AND ANALYSIS: Three trials that included 733 participants were included. Independent selection of trials and data extraction were undertaken by 2 reviewers and results compared. MAIN RESULTS: There was no evidence of a difference in the rates of incontinence, constipation or measures of sexual function. In one unblinded trial, a significantly greater proportion of women indicated that they had frequent episodes of urinary incontinence after subtotal hysterectomy when compared with total hysterectomy (OR=2.1, 1.02 to 4.3), but these results were not confirmed by the other two trials that measured both stress and urge incontinence and urinary frequency. . Length of surgery and amount of blood lost during surgery were significantly reduced during subtotal hysterectomy when compared with total hysterectomy, but there was no evidence of a difference in the odds of transfusion. Febrile morbidity was less likely (OR=0.43, 0.25 to 0.75) and ongoing cyclical vaginal bleeding one year after surgery was more likely (OR=11.3, 4.1 to 31.2) after subtotal when compared with total hysterectomy. There was no evidence of a difference in the rates of other complications, recovery from surgery or readmission rates. AUTHORS' CONCLUSIONS: This review has not confirmed the perception that subtotal hysterectomy offers improved outcomes for sexual, urinary or bowel function when compared with total abdominal hysterectomy. Surgery is shorter and intraoperative blood loss and fever are reduced but women are more likely to experience ongoing cyclical bleeding up to a year after surgery with subtotal hysterectomy compared to total hysterectomy.

Blood Loss, Surgical↗

PubMed2006

A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding.

OBJECTIVE: To compare the levonorgestrel intrauterine system (LNG-IUS) (Mirena); Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoice; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding. DESIGN: An open, pragmatic, prospective randomised trial. SETTING: A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand. POPULATION: Seventy-nine women with heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women). METHODS: Women were randomised to treatment with the LNG-IUS or thermal balloon ablation and followed up by a postal and telephone questionnaire. MAIN OUTCOME MEASURES: Menstrual loss measured by a pictorial bleeding assessment chart (PBAC) at 3, 6, 12 and 24 months. Patient satisfaction, quality of life and menstrual symptoms were assessed by questionnaire administered at 3, 6, 12 and 24 months. Treatment side effects and treatment failures were also recorded. RESULTS: Both the treatments resulted in a significant reduction in PBAC scores. At 12 and 24 months, median PBAC scores were significantly lower in women treated with the LNG-IUS compared with women treated by thermal balloon ablation (11.5 versus 60.0 at 12 months [P= 0.002]; 12.0 versus 56.5 [P= 0.002] at 24 months). At 24 months, nine (35%) women still using the LNG-IUS had amenorrhoea compared with one (5%) woman successfully treated by thermal balloon ablation (P = 0.025). There were no significant differences in patient satisfaction between two treatments during follow up. Treatment failed in 11 (28%) women using the LNG-IUS and in 10 (26%) women treated with thermal balloon ablation. Overall, women in both groups showed an increased quality of life as a result of the treatment, with Short Form-36 scores increasing from 63.7 at randomisation to 76.1 at 24 months. CONCLUSIONS: At 12 and 24 months of follow up, women with heavy menstrual bleeding treated with the LNG-IUS have significantly lower PBAC scores than women treated with thermal balloon ablation. Both the treatments resulted in a significant increase in overall quality of life, but there were no significant differences between either treatment in quality of life, patient satisfaction or the number of women requesting an alternative treatment during 24 months of follow up.

Adult↗

PubMed2006

Cost-effectiveness analysis of levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding.

OBJECTIVE: To compare the cost-effectiveness of levonorgestrel intrauterine system (LNG-IUS) (Mirena; Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoicetrade mark; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding. DESIGN: An open, pragmatic, prospective randomised trial. SETTING: A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand. POPULATION: Seventy-nine women with self-defined heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women). METHODS: Decision tree modelling using primary source data was used to identify the incremental cost-effectiveness of the two treatments. MAIN OUTCOME MEASURES: Direct and indirect costs of medical treatment, including treatment costs, subsequent medical procedures, lost income and medical treatment for failed procedures. The change in quality of life as assessed by the Short Form-36 (SF-36) measured between time of treatment and 24 months was the primary outcome measure. Economic modelling examined the expected cost and outcome for a woman entering each treatment. Sensitivity analysis explored the robustness of the results. RESULTS: The expected cost of treatment was $NZ1241 ($US869) for the LNG-IUS and $NZ2418 ($US1693) for the thermal balloon ablation. The LNG-IUS was associated with an increase of 15 points on the SF-36 scale, compared with 12 points for the thermal balloon ablation. Sensitivity analysis indicates that the results are robust to a 25% decrease in the price of the primary cost drivers and to variations in the rates of failed treatment between the conditions. CONCLUSION: The LNG-IUS would appear to be cost-effective when compared with the thermal balloon ablation for treatment of heavy menstrual bleeding.

Catheterization↗

PubMed2005

Endometrial destruction techniques for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding (HMB) is a significant health problem in premenopausal women; it can reduce their quality of life and cause anaemia. First-line therapy has traditionally been medical therapy but this is frequently ineffective. On the other hand, hysterectomy is obviously 100% effective in stopping bleeding but is more costly and can cause severe complications. Endometrial ablation is less invasive and preserves the uterus, although long-term studies have found that the costs of ablative surgery approach the cost of hysterectomy due to the requirement for repeat procedures. 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 are less time consuming. However, hysteroscopy may still be required as part of the ablative techniques and some of them must be considered to be still under development, requiring 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 Menstrual Disorders and Subfertility Group Specialised Register of controlled trials (April 2004). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to July 2004), EMBASE (1980 to July 2004), Current Contents (1993 to week 38, 2001), Biological Abstracts (1980 to June 2001), PsycLIT (1967 to August 2001), CINAHL (1982 to July 2004) and the metaregister of controlled trials and ISRCTN register (December 2004). We also searched reference lists of articles and contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing different 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 the outcome, complications and need for further surgery or hysterectomy. DATA COLLECTION AND ANALYSIS: The two review authors 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 the comparison of the newer non-hysteroscopic techniques (second generation) with the gold standard hysteroscopic ablative techniques (first generation) overall, surgery was an average of 15 minutes shorter (weighted mean difference (WMD) 14.9, 95% CI 10.1 to 19.7), local anaesthesia was more likely to be employed (odds ratio (OR) 8.3, 95% CI 3.9 to 17.5) and equipment failure was more likely (OR 4.2, 95% CI 1.3 to 13.8) with second-generation ablation. Women undergoing newer ablative procedures were less likely to have fluid overload, uterine perforation, cervical lacerations and hematometra than women undergoing the more traditional type of ablation and resection techniques (OR 0.13, 95% CI 0.04 to 0.5; OR 0.21, 95% CI 0.07 to 0.7; OR 0.12, 95% CI 0.05 to 0.3 and OR 0.25, 95% CI 0.09 to 0.7, respectively). However, women were more likely to have nausea and vomiting and uterine cramping (OR 2.3, 95% CI 1.5 to 3.4 and OR 1.8, 95% CI 1.1 to 2.9, respectively). Some differences were also found in amenorrhoea rates and satisfaction rates, but there did not appear to be a trend over time so these results may be due to chance. AUTHORS' 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 transcervical resection of the endometrium (TCRE) difficult. Most of the newer techniques are technically easier than hysteroscopy-based methods to perform. However, uterine perforation, which is the major complication of endometrial ablation, cannot be excluded without hysteroscopy. Overall, the existing evidence suggests that success rates and complication profiles of newer techniques of ablation compare favourably with TCRE, although technical difficulties with new equipment need to be ironed out.

Adult↗

PubMed2005

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

BACKGROUND: Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the patient is both donor and recipient) has been considered a promising technique because it allows much higher doses of chemotherapy to be used. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. Outcomes were survival rates, toxicity and quality of life. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group specialised register, The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), PsycINFO (1984 to November 2004), Cinahl (1982 to November 2004), web sites of co-operative research groups and ASCO (American Society of Clinical Oncologists) and reference lists of articles found. SELECTION CRITERIA: Randomised controlled trials comparing high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. DATA COLLECTION AND ANALYSIS: Fifteen trials were considered. Thirteen were included and two were excluded. Three independent reviewers extracted data. MAIN RESULTS: Analysis included 2535 women randomised to receive high dose chemotherapy with autograft and 2529 randomised to receive conventional chemotherapy. There were 65 treatment-related deaths on the high dose arm and four on the conventional dose arm (RR 8.58 (95% CI 4.13, 17.80). Many studies have not completed follow-up and have reported only preliminary results. There was a statistically significant benefit in event-free survival for women in the high dose group at three years (RR 1.12 (95% CI 1.06, 1.19)) and at four years (RR 1.30 (95% CI 1.16, 1.45)). At five and six years there was no statistically significant difference between the groups in event-free survival. With respect to overall survival, there was no statistically significant difference between the groups at any stage of follow up. Morbidity was more common and more severe in the high dose group. However there was no statistically significant difference between the groups with respect to the incidence of second cancers at five to seven years' follow up. Women in the high dose group reported significantly worse quality of life scores immediately after treatment, but few statistically significant differences were found between the groups by one year. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of high dose chemotherapy with autograft for women with early poor prognosis breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer.

BACKGROUND: There is a hypothesis that high dose chemotherapy with autologous bone marrow or peripheral stem cell transplantation (autograft) may improve survival for women with metastatic breast cancer. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autologous bone marrow or stem cell transplantation with conventional chemotherapy for women with metastatic breast cancer. SEARCH STRATEGY: We used the Cochrane Breast Cancer Group search strategy, adding these terms: bone marrow transplantation, stem cell transplantation, autologous stem cell support. The following databases were searched: MEDLINE (until November 2004), EMBASE (until November 2004), ASCO (American Society of Clinical Oncology) (1995-2004) and the COCHRANE LIBRARY (Issue 4 2004). We searched the Cochrane Breast Cancer Group database and cooperative research groups' websites for unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft with conventional chemotherapy for women with metastatic breast cancer. Studies included one or more of the following outcomes: treatment related mortality, overall or progression-free survival at 1, 2, 3, 5 or 7 years, morbidity, quality of life measures, time to tumour progression, overall survival time. DATA COLLECTION AND ANALYSIS: Six randomised controlled trials met the inclusion criteria. Two independent reviewers extracted data. MAIN RESULTS: In total 438 eligible women were randomised to receive high dose chemotherapy with autograft and 412 were randomised to receive conventional treatment. There were fifteen treatment-related deaths among the high dose group and two in the control (conventional dose) group (RR 4.07 (95% CI 1.39, 11.88)). There was no statistically significant difference in overall survival between the high dose and control groups at one year, three years or five years. At one and five years of follow up, there was a statistically significant difference in event-free survival, favouring the high dose group (one year: RR 1.76 (95% CI 1.40, 2.21); five years: RR 2.84 (95% CI 1.07, 7.50). Toxicity was more severe in the high dose group. Only one of the trials has followed up all women for five years and further data are awaited. AUTHORS' CONCLUSIONS: Although there is statistically significant evidence that high dose chemotherapy and autograft improves event free survival compared to conventional chemotherapy, there is no statistically significant evidence of benefit in overall survival for women with metastatic breast cancer. High dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Long term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women but the evidence supporting its use for these indications is largely observational. OBJECTIVES: To assess the effect of long-term HT on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, gallbladder disease, cognitive function, dementia, fractures and quality of life. SEARCH STRATEGY: We searched the following databases up to November 2004: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biological Abstracts. Relevant non-indexed journals and conference abstracts were also searched. SELECTION CRITERIA: Randomised double-blind trials of HT (oestrogens with or without progestogens) versus placebo, taken for at least one year by perimenopausal or postmenopausal women. DATA COLLECTION AND ANALYSIS: Fifteen RCTs were included. Trials were assessed for quality and two review authors extracted data independently. They calculated risk ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Clinical heterogeneity precluded meta-analysis for most outcomes. MAIN RESULTS: All the statistically significant results were derived from the two biggest trials. In relatively healthy women, combined continuous HT significantly increased the risk of venous thromboembolism or coronary event (after one year's use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long-term oestrogen-only HT also significantly increased the risk of stroke and gallbladder disease. Overall, the only statistically significant benefits of HT were a decreased incidence of fractures and colon cancer with long-term use. Among relatively healthy women over 65 years taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thromboembolism. No trials focussed specifically on younger women. However, one trial analysed subgroups of 2839 relatively healthy 50 to 59 year-old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT; their absolute risk remained very low. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.

Aged↗

PubMed2005

Surgical approach to hysterectomy for benign gynaecological disease.

Female↗

PubMed2004

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: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to January 2003), EMBASE (1980 to January 2003), Current Contents (1993 to January 2003), Biological Abstracts (1969 to 2002), Social Sciences Index (1980 to January 2003), PsycINFO (1972 to February 2003) and CINAHL (1982 to January 2003). The search strategy was developed by the Cochrane Menstrual Disorder and Subfertility Group. 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: Sixty RCTs were identified. Of these 23 were excluded and seven remain awaiting assessment. The reviewers assessed the thirty 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 when compared to placebo 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 (1 RCT; OR 5.4, 95% CI 1.4 to 20.9) for 6 months of treatment to (4 RCTs; OR 9.6, 95% CI 5.9 to 15.5) for 24 months treatment and (1 RCT; OR 15.0, 95% CI 9.3 to 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 that increased bleeding with higher dose therapy. Although not statistically significant, there was a 3% incidence (2 RCTs) of hyperplasia in women who took low dose oestrogen compared to no incidence of hyperplasia in the placebo group. The addition of progestogens, either in continuous combined or sequential regimens, helped to reduce the risk of endometrial hyperplasia and improved adherence to therapy. At longer duration of treatment, continuous therapy was more effective than sequential therapy in reducing the risk of endometrial hyperplasia. There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every three months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of t in any of the treatment groups during the duration (maximum of six years) of these trials. During the first year of therapy irregular bleeding and spotting was more likely in continuous combined therapy than sequential therapy. However, during the second year of therapy bleeding and spotting was more likely under sequential regimens. REVIEWERS' CONCLUSIONS: There is strong and consistent evidence in this review that unopposed oestrogen therapy, at moderate and high doses, is associated with increased rates of endometrial hyperplasia, irregular bleeding and consequent non adherence to therapy. The addition of oral progestogens administered either sequentially or continuously is associated with reduced rates of hyperplasia and improved adherence to therapy. Irregular bleeding is less likely under sequential than continuous therapy during the first year of therapy but there is a suggestion that continuous therapy over long duration is more protective than sequential therapy in the prevention of endometrial hyperplasia. Hyperplasia is more likely when progestogen is given every three months in a sequential regimen compared to a monthly progestogen sequential regimen.

Endometrial Hyperplasia↗

PubMed2003

Local oestrogen for vaginal atrophy in postmenopausal women.

BACKGROUND: Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the estradiol releasing ring). OBJECTIVES: The objective of this review is to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group register of trials (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966-January 2003), EMBASE (1980-January 2003), Current Contents (1993-January 2003), Biological Abstracts (1969-2002), Social Sciences Index (1980-January 2003), PsycINFO (1972-February 2003), CINAHL (1982-January 2003) and reference list of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis. DATA COLLECTION AND ANALYSIS: Twenty nine trials were identified, of these 13 were excluded. Trials were assessed for quality and two reviewers extracted data independently. Ratios for dichotomous and means for continuous outcomes were estimated. Outcomes analysed were included under the headings of efficacy, safety and acceptability. MAIN RESULTS: Sixteen trials with 2129 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy with various outcome measures. When comparing efficacy of oestrogenic preparations (in the form of creams, pessaries, tablets and the estradiol releasing vaginal ring) with each other in relieving the symptoms of vaginal atrophy, results indicated significant differences favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and six looked at adverse effects. One trial showed significant adverse effects of cream (conjugated equine oestrogen) when compared to tablets (estradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by progestagen challenge test in the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (estradiol). Nine studies compared acceptability to the participants by comparing comfort of product, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the estradiol releasing vaginal ring. REVIEWER'S CONCLUSIONS: Creams, pessaries, tablets and the estradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects noted following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the estradiol releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

Administration, Intravaginal↗

PubMed2003

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

BACKGROUND: Overall survival rates are disappointing for women with early poor prognosis breast cancer. There is a hypothesis that high dose chemotherapy with autologous bone marrow or stem cell transplant (autograft) may improve survival rates by permitting higher doses of adjuvant chemotherapy to be given. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group specialised register, The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002), MEDLINE (1966 to Aug. 2002), EMBASE (1980 to Aug. 2002), PsycINFO (1984 to Aug. 2002), Cinahl (1982 to July 2002), the websites of co-operative research groups and ASCO (American Society of Clinical Oncologists) and reference lists of articles found. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. DATA COLLECTION AND ANALYSIS: We identified nine trials that met the inclusion criteria. Three independent reviewers extracted data. MAIN RESULTS: In total 1758 women were randomised to receive high dose chemotherapy with autograft and 1767 women were randomised to receive conventional chemotherapy. There were 48 non cancer-related deaths on the high dose arm and four on the conventional dose arm (RR 7.74, 95% CI (3.43, 17.50). Since many studies have not completed follow-up, overall survival rates were in most cases based on results to date. There was no statistically significant difference in overall survival between women who received high dose chemotherapy with autograft and women who received conventional chemotherapy, either at three years (RR 1.02, 95% CI (0.98, 1.06)), or at five years (RR 0.98, 95% CI (0.93, 1.05)). There was a statistically significant benefit in event-free survival at three years for the group who received high dose chemotherapy (RR 1.11, 95% CI (1.05, 1.18)). However at five years there was no statistically significant difference between the groups (RR 1.00, 95% CI (0.92, 1.08)). Side-effects were more common and more severe in the high dose group though most were reversible. Women in the high dose group reported significantly worse quality of life scores immediately after treatment but at one year there was no statistically significant difference between the groups in quality of life scores. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the routine use of high dose chemotherapy with autograft for women with early poor prognosis breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer.

BACKGROUND: There is a hypothesis that high dose chemotherapy with autologous bone marrow or stem cell transplantation (autograft) may improve survival for women with metastatic breast cancer. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autologous bone marrow or stem cell transplantation with conventional chemotherapy for women with metastatic breast cancer. SEARCH STRATEGY: We used the Cochrane Breast Cancer Group search strategy, adding these terms: bone marrow transplantation, stem cell transplantation, autologous stem cell support. The following databases were searched: MEDLINE (until August 2002), EMBASE (until July 2002), ASCO (American Society of Clinical Oncology) (1995-2002) and the COCHRANE LIBRARY (Issue 3 2002). We searched the Cochrane Breast Cancer Group database and cooperative research groups' websites for unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft with conventional chemotherapy for women with metastatic breast cancer. Studies included one or more of the following outcomes: treatment related mortality, overall or progression-free survival at 1, 2, 3, 5 or 7 years, morbidity, quality of life measures, time to tumour progression, overall survival time. DATA COLLECTION AND ANALYSIS: Five randomised controlled trials met the inclusion criteria. Two independent reviewers extracted data. MAIN RESULTS: In total 382 women were randomised to receive high dose chemotherapy with autograft and 358 were randomised to receive conventional treatment. There were ten treatment related deaths among the high dose group and none reported in the control (conventional dose) group (RR 5.70, 95%CI (1.30, 25)). There was no statistically significant difference in overall survival between the high dose and control groups (at one year: RR 0.99, 95% CI (0.91, 1.08); three years: RR 1.16 95% CI (0.90, 1.51); five years: RR 1.28, 95% CI (0.72, 2.27)). At one and two years of follow up, a statistically significant difference in progression free survival was reported, favouring the high dose group (one year: RR 1.81, 95% CI (1.39,2.34); two years: RR 1.96, 95% CI (1.32, 2.90 ). However this difference was not evident at three or five years (three years: RR 1.44, 95% CI (0.85, 2.44); five years: RR 1.21, 95% CI (0.40, 3.69). Toxicity was more severe in the high dose group. None of the trials has completed follow up and further data are awaited. REVIEWER'S CONCLUSIONS: Although there is evidence that high dose chemotherapy and autograft improves progression free survival at one and two years' follow up compared to conventional chemotherapy, there is no evidence of benefit in overall survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Surgery versus medical therapy for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding significantly impairs the quality of life of many otherwise healthy women. Perception of heavy bleeding is highly subjective and management of the condition usually depends upon the degree of bleeding and discomfort found acceptable by the individual woman. Medical treatment options include oral medications and a hormone-releasing intrauterine system (LNG-IUS). Surgical options include conservative surgery (uterine resection or ablation) and hysterectomy. OBJECTIVES: To compare the effectiveness, safety and acceptability of surgery versus medical therapy for heavy menstrual bleeding. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (October 2002), Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (1966 to October 2002), EMBASE (1980 to October 2002), Current Contents (1993 to week 45, 2002), Biological Abstracts (1969 to September 2002), PsycINFO (1985 to October 2002), CINAHL (1982 to October 2002), and reference lists of articles. We also contacted pharmaceutical companies and experts in the field. SELECTION CRITERIA: Controlled randomised trials comparing surgery (conservative surgery and hysterectomy) versus medical therapy (both oral and intrauterine) for heavy menstrual bleeding DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. MAIN RESULTS: Five trials met the inclusion criteria. They randomised 625 women, 311 to receive surgery and 314 to receive medical treatment. One trial compared endometrial resection with oral medication: surgery proved significantly more effective in controlling bleeding (OR 10.62, 95% CI 5.30 to 21.27) and significantly less likely to cause side effects (OR 0.15, 95% CI 0.07 to 0.31). In the other four trials the medical arms received LNG-IUS and the surgical arms received conservative surgery or hysterectomy. At one year no statistically significant difference was shown between LNG-IUS and any surgical treatment in satisfaction rates or quality of life, though conservative surgery was significantly less likely to cause adverse effects (OR 0.24, 95% CI 0.11 to 0.49). Although conservative surgery was significantly more effective than LNG-IUS in controlling bleeding at one year (OR 3.99, 95% CI 1.53 to 10.38), a small trial showed no significant difference between the treatments at two and three years. Hysterectomy stopped all bleeding but caused serious complications for some women. REVIEWER'S CONCLUSIONS: Surgery reduces menstrual bleeding at one year more than medical treatments, but LNG-IUS appears equally beneficial in improving quality of life and may control bleeding as effectively as conservative surgery over the long term. Oral medication suits a minority of women long term.

Antifibrinolytic Agents↗

PubMed2002

Danazol for heavy menstrual bleeding.

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.

Danazol↗