Effects of the levonorgestrel-releasing intrauterine system plus estrogen therapy in perimenopausal and postmenopausal women: systematic review and meta-analysis

Objective: The objective of this study was to compare the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) with those of systemic progestogen in perimenopausal and postmenopausal women taking systemic estrogen therapy (ET). Methods: We searched Medline (August 8, 2009), Embase (August 8, 2009), the Cochrane Central Register of Controlled Trials on the Cochrane Library Issue 3 (2009), the MetaRegister of Controlled Trials, and the reference lists of articles for relevant trials. Randomized controlled studies of LNG-IUS versus systemic progestogen in perimenopausal and postmenopausal women taking ET were included in the review. Two reviewers abstracted the trials independently. Any disagreement was resolved through discussion with the third reviewer. For dichotomous outcomes, a Peto odds ratio was calculated. For continuous outcomes, nonskewed data from valid scales were synthesized using a weighted mean difference or a standardized mean difference. Results: Six trials with a total of 518 participants were included. The methodological limitation was an attrition bias. In perimenopausal and postmenopausal women taking ET, the incidence of a proliferative endometrium was comparable between the use of systemic progestogen and LNG-IUS, except for sequential medroxyprogesterone acetate, which had a higher incidence of proliferative endometrium. Descriptive data synthesis showed that ET combined with either LNG-IUS or systemic progestogen effectively relieved climacteric symptoms. Vaginal bleeding and spotting were common in the LNG-IUS group for the first 3 to 6 months of use. The discontinuation rate was not different. There was insufficient evidence to draw any conclusions about the other outcomes. Conclusions: The LNG-IUS was more effective than sequential medroxyprogesterone acetate but was comparable with other systemic progestogen regimens for endometrial protection in perimenopausal and postmenopausal women taking ET.