The efficacy of levonorgestrel intrauterine systems for endometrial protection: a systematic review

Oral progestogens are commonly used for endometrial protection in women at higher risk of developing endometrial abnormality. Long-term intrauterine progestogens may offer an attractive alternative to oral therapy.

To review the evidence regarding the efficacy of intrauterine levonorgestrel-releasing systems (LNG-IUS) in preventing endometrial pathology in high-risk women.

Searches were made of the Cochrane Central Register of Controlled Trials, UK National Research Register (NRR) Archive, Current Controlled Trials, MEDLINE, EMBASE and CINAHL. The selection criteria were randomized, controlled trials (RCTs) comparing LNG-IUS with no treatment, placebo or other hormonal therapy in adult females. Where no RCTs were available, prospective cohort studies were analyzed. Data was extracted using a standardized data collection form. Meta-analysis was performed using RevMan software.

There were six RCTs that investigated LNG-IUS in women using estrogen replacement therapy (ERT). LNG-IUS was at least as effective as other routes of progestogen administration. Only two studies investigated LNG-IUS as treatment for endometrial hyperplasia. Hyperplasia without atypia regressed in all women treated with LNG-IUS. In three studies of LNG-IUS in tamoxifen users, LNG-IUS was associated with reduced risk of endometrial polyps (Peto odds ratio (OR) 0.28; 95% confidence interval (CI) 0.15-0.55) and hyperplasia (Peto OR 0.14; 95% CI 0.02-0.80).

LNG-IUS counters endometrial proliferation and causes regression of and prevents endometrial hyperplasia in selected groups of women. There is, however, insufficient evidence to recommend LNG-IUS as the treatment of choice for hyperplasia and no evidence to adequately support its use as chemoprevention in women with hereditary non-polyposis colorectal cancer syndrome or obesity.