Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/10643
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dc.contributor.authorLethaby, Anneen_UK
dc.contributor.authorFarquhar, Cynthiaen_UK
dc.contributor.authorSarkis, Alvaroen_UK
dc.contributor.authorRoberts, Helenen_UK
dc.contributor.authorJepson, Ruthen_UK
dc.contributor.authorBarlow, Daviden_UK
dc.date.accessioned2018-05-05T01:40:42Z-
dc.date.available2018-05-05T01:40:42Z-
dc.date.issued2004en_UK
dc.identifier.otherCD000402en_UK
dc.identifier.urihttp://hdl.handle.net/1893/10643-
dc.description.abstractBackground: 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, PsycLIT, 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Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data.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 three 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 three years) of these trials. 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 cyclically or continuously is associated with reduced rates of hyperplasia and improved adherence to therapy. Irregular bleeding is less likely under sequential than continuous 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.en_UK
dc.language.isoenen_UK
dc.publisherWiley-Blackwell for the Cochrane Collaborationen_UK
dc.relationLethaby A, Farquhar C, Sarkis A, Roberts H, Jepson R & Barlow D (2004) Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding (Review). Cochrane Database of Systematic Reviews, (2), Art. No.: CD000402. https://doi.org/10.1002/14651858.CD000402en_UK
dc.rightsThis review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2004, Issue 2. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review. This is the reference to the original version of this review: Lethaby A, Farquhar C, Sarkis A, Roberts H, Jepson R, Barlow D. Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. The Cochrane Database of Systematic Reviews 1999, Issue 2. Art. No.: CD000402. DOI: 10.1002/14651858.CD000402.en_UK
dc.titleHormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleedingen_UK
dc.typeJournal Articleen_UK
dc.identifier.doi10.1002/14651858.CD000402en_UK
dc.identifier.pmid15266429en_UK
dc.citation.jtitleCochrane Database of Systematic Reviewsen_UK
dc.citation.issn1469-493Xen_UK
dc.citation.issue2en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.author.emailruth.jepson@stir.ac.uken_UK
dc.description.notesOutput Type: Reviewen_UK
dc.contributor.affiliationUniversity of Aucklanden_UK
dc.contributor.affiliationUniversity of Aucklanden_UK
dc.contributor.affiliationUniversity of Aucklanden_UK
dc.contributor.affiliationUniversity of Aucklanden_UK
dc.contributor.affiliationHealth Sciences Stirlingen_UK
dc.contributor.affiliationUniversity of Aucklanden_UK
dc.identifier.wtid889247en_UK
dc.contributor.orcid0000-0002-9446-445Xen_UK
dcterms.dateAccepted2004-12-31en_UK
dc.date.filedepositdate2013-01-21en_UK
rioxxterms.typeJournal Article/Reviewen_UK
rioxxterms.versionVoRen_UK
local.rioxx.authorLethaby, Anne|en_UK
local.rioxx.authorFarquhar, Cynthia|en_UK
local.rioxx.authorSarkis, Alvaro|en_UK
local.rioxx.authorRoberts, Helen|en_UK
local.rioxx.authorJepson, Ruth|0000-0002-9446-445Xen_UK
local.rioxx.authorBarlow, David|en_UK
local.rioxx.projectInternal Project|University of Stirling|https://isni.org/isni/0000000122484331en_UK
local.rioxx.freetoreaddate2013-01-21en_UK
local.rioxx.licencehttp://www.rioxx.net/licenses/all-rights-reserved|2013-01-21|en_UK
local.rioxx.filenameJepson et al_Cochrane_2004.pdfen_UK
local.rioxx.filecount1en_UK
Appears in Collections:Faculty of Health Sciences and Sport Systematic Reviews

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