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In women with non-atypical endometrial hyperplasia, progestin given through the uterus produces a treatment response more than oral progestin

Abu Hashim H, Ghayaty E, El Rakhawy M. Levonorgestrel-releasing intrauterine system vs oral progestins for non-atypical endometrial hyperplasia: a systematic review and metaanalysis of randomized trials. Am J Obstet Gynecol. 2015;213:469-78.

Review question

In women with non-atypical endometrial hyperplasia, does intra-uterine progestin improve treatment response more than oral progestin?


Endometrial hyperplasia is an excessive thickening of the lining of the uterus. In non-atypical endometrial hyperplasia, the cells are normal, but there are too many of them. Endometrial hyperplasia can result in heavier than usual bleeding during menstruation or bleeding after menopause.

Endometrial hyperplasia is more common after menopause when the hormone progesterone is no longer made.

A common treatment for endometrial hyperplasia is progestin, which is man-made progesterone. Progestin is often taken orally (by mouth). Progestin can also be given through the uterus (intra-uterine) with a small plastic device that a physician inserts into a woman’s uterus. This device, called the levonorgestrel-releasing intra-uterine system (LNG-IUS), releases progestin into a woman’s uterus for up to 5 years.

How the review was done

The researchers did a systematic review based on studies available up to August 2014.

They found 7 randomized controlled trials with 766 women (average age ranged from 38 to 45 years across groups).

Key features of the trials were:

  • women had non-atypical endometrial hyperplasia;
  • treatment was intra-uterine progestin (LNG-IUS);
  • intra-uterine progestin was compared with oral progestins, including norethisterone acetate, medroxyprogesterone acetate, and dydrogesterone; and
  • outcomes were measured after 3, 6, 12, or 24 months of treatment.

What the researchers found

The quality of evidence was low to moderate. Only evidence of moderate quality is reported here.

Compared with oral progestin, intra-uterine progestin:

  • increased the likelihood that the lining of the uterus responded after 3, 6, 12, and 24 months of treatment and
  • reduced the risk of hysterectomy.


In women with non-atypical endometrial hyperplasia, intra-uterine progestin increases the likelihood of a treatment response and reduces the need for hysterectomy compared with oral progestin.

Intra-uterine vs oral progestin for treatment response* in women with non-atypical endometrial hyperplasia

Time of assessment

Number of trials (women)

Rate of response with intra-uterine progestin

Rate of response with oral progestin

Absolute effect of intra-uterine progestin

After 3 months of treatment

5 trials (376 women)



About 14 more women out of 100 had a response

After 6 months of treatment

4 trials (397 women)



About 19 more women out of 100 had a response

After 12 months of treatment

2 trials (224 women)



About 26 more women out of 100 had a response

After 24 months of treatment

1 trial (104 women)



About 34 more women out of 100 had a response

*Treatment response = lining of the uterus responded to the treatment.



Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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