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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Increased ovarian cancer risk associated with menopausal estrogen therapy is reduced by adding a progestin

CL Pearce, K Chung, MC Pike, and AH Wu.

Review published: 2009.

CRD summary

The authors concluded that oestrogen therapy use increased ovarian cancer in a duration-dependent manner; adding progestins appeared to reduce this effect to some extent. The conclusions appeared to be supported by the evidence but the limited search, lack of reporting of review methods and study quality, and reliance upon predominantly observational studies mean that findings should be interpreted with caution.

Authors' objectives

To examine the relationship between oestrogen-only and oestrogen plus progestin menopausal hormone therapy and the risk of ovarian cancer.

Searching

PubMed was searched through to December 2007 for studies published in English. Search terms were reported. Reference lists were screened and addition studies were traced through the ‘related articles’ link.

Study selection

Randomised controlled trials (RCTs), cohort studies and population-based case control studies of oestrogen-only and oestrogen plus progestin hormone therapy were eligible for inclusion, if they restricted analysis to invasive epithelial ovarian cancers or combined invasive and borderline epithelial ovarian cancers. Studies had to report data separately for oestrogen-only and oestrogen plus progestin hormone therapy and to report the duration of hormone use. Three studies conducted in the early 1980’s when sequential oestrogen plus progestin hormone use was just starting that did not report data separately were included and data assumed to apply to oestrogen-only therapy. Studies that used hospital controls were excluded.

Most studies were conducted in North America; others were set in Europe and Australia. Controls were obtained from national survey populations, population or electoral registries and random digit dialling. Cancer ascertainments were mostly obtained from cancer registries or death certificates. Where reported, studies included patients with invasive and low malignant potential ovarian cancer. Data were obtained using in-person interviews or self-administered questionnaires. The duration of hormone use ranged from one to over 20 years.

The authors did not state how papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

For each study, adjusted relative risks with 95% confidence intervals were extracted in relation to duration of oestrogen-only and oestrogen plus progestin hormone therapy use. Risk estimates of ovarian cancer per year of hormone use were extracted or estimated (methods were reported). In the review, data for duration of use of less than one year were combined with never used data.

The authors did not state how many reviewers performed the data extraction.

Methods of synthesis

Pooled relative risks per five years of hormone use and 95% confidence intervals were calculated using fixed-effect and random-effects models. Differences between oestrogen-only and oestrogen plus progestin menopausal hormone therapy use in ovarian cancer risk were compared within the ten studies that provided data for both types of hormone therapy; pooled weighted differences in RR5 were calculated. Heterogeneity was apparently assessed but methods were not reported. The influence of menopause type was discussed. Publication bias was assessed using funnel plots.

Results of the review

Fourteen studies were included (n was unclear but more than 1,419,833 participants). These included one RCT (n=16,608), five cohort studies (n=1,384,941) and eight population-based case control studies (n at least 13,345).

The authors stated that all studies adjusted for appropriate potential confounders in their analysis. Results were similar for fixed-effect and random-effects models. Results from only fixed-effect models were presented.

Oestrogen-only and oestrogen plus progestin hormone therapy: The risk of ovarian cancer was significantly increased among oestrogen-only users (relative risk per five years of hormone use 1.22, 95% confidence interval (CI): 1.18 to 1.27; 13 studies) and oestrogen plus progestin hormone therapy users (relative risk per five years of hormone use 1.10, 95% CI: 1.04 to 1.16; 11 studies). There was no evidence of heterogeneity or publication bias for either analysis.

Oestrogen-only versus oestrogen plus progestin hormone therapy: The risk of ovarian cancer was significantly higher among oestrogen-only compared to oestrogen plus progestin users (p=0.004; 10 studies). Results were similar for the five studies in which duration of use was similar for both types of hormone oestrogen plus progestin therapy (p=0.011).

Authors' conclusions

Oestrogen use increased the risk of ovarian cancer in a duration-dependent manner and it appeared that adding progestins reduced this effect to some extent.

CRD commentary

The review question was stated and appropriate inclusion criteria were defined. Limiting the search to English language published studies identified in one database plus references and linked articles may have resulted in the omission of other relevant studies and raised the potential for publication and language bias. However, no evidence of publication bias was found. Methods used to select studies and extract data were not described, so it is not known whether efforts were made to reduce reviewer errors and bias. Study validity was not assessed, so results from these studies and any synthesis may not be reliable.

Other than duration of oestrogen-only therapy/oestrogen plus progestin therapy use, no information was provided about participants. No information was provided about which potential confounders were adjusted for in individual studies. Data were pooled using meta-analysis and heterogeneity was assessed. Studies were predominantly observational and adjustments were made for potential confounders. The authors’ conclusions appeared to be supported by the evidence, but the limited search, lack of reporting of review methods and study quality, and reliance upon predominantly observational studies mean that findings should be interpreted with caution.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further research is required to determine the association between hormone therapy use and histological subtypes of ovarian cancer and stage of disease and the effects of past and current hormone therapy use.

Funding

Flora L. Thornton Chair in Preventative Medicine; National Cancer Institute, grant number 5P01 CA 017054-28.

Bibliographic details

Pearce C L, Chung K, Pike M C, Wu A H. Increased ovarian cancer risk associated with menopausal estrogen therapy is reduced by adding a progestin. Cancer 2009; 115(3): 531-539. [PMC free article: PMC4203480] [PubMed: 19127543]

Indexing Status

Subject indexing assigned by NLM

MeSH

Estrogen Replacement Therapy /adverse effects; Estrogens /administration & dosage; Female; Humans; Menopause; Ovarian Neoplasms /epidemiology; Progestins /administration & dosage; Risk Assessment

AccessionNumber

12009104538

Database entry date

30/09/2009

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 19127543

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