Risk of relapse of endometrial hyperplasia is high and long-term treatment and follow up are recommended.

Abstract

Endometrial hyperplasia can progress to endometrial cancer if left untreated. Hormonal therapies such as the levonorgestrel-releasing intrauterine system (LNG-IUS) and oral progestogens have a role in preventing disease progression. However, once regression of endometrial hyperplasia is achieved the risk of relapse remains. Relapse of endometrial hyperplasia is common and is higher in obese women or those that have been treated with short courses of oral progestogens (Gallos et al. Obstet Gynecol 2013;121:1165–71; Gallos et al. Hum Reprod 2013;28:1231–6). A case–control study with long-term follow up has confirmed that women diagnosed with non-atypical or atypical endometrial hyperplasia are at higher risk of progression to endometrial cancer than women never diagnosed with endometrial hyperplasia (Lacey et al. J Clin Oncol 2010;28:788–92). Moreover, up to 10% of women that relapse will be diagnosed with endometrial cancer at the final hysterectomy specimen (Gallos et al. Hum Reprod 2013;28:1231–6). So can the risk of relapse of endometrial hyperplasia be mitigated? Obesity is the main modifiable risk factor; the risk of relapse is threefold higher for obese women (body mass index > 35 kg/m2) compared with women below this threshold and long-term follow up has been advised for these women (Gallos et al. Obstet Gynecol 2013;121:1165–71). The relapse risk also depends on the type of hormonal therapy used to treat the endometrial hyperplasia. Local intrauterine progestogen should be preferred over other administrative routes to treat endometrial hyperplasia because it is more effective in inducing disease remission (Orbo et al. BJOG 2014;121:477–86). In addition, the risk of relapse is almost three times greater for oral progestogen treatment compared with the LNG-IUS (Gallos et al. Hum Reprod 2013;28:1231–6). However, the LNG-IUS was used for the duration of its licensed use, i.e. 5 years, whereas oral progestogens were restricted in general to courses of up to 6 months. The current randomised study by Orbo et al. (BJOG 2016;123:1512–9.) has demonstrated that the relapse rate is similar in women treated with oral progestogens or the LNG-IUS when both hormonal therapies are limited to 6-month duration. Hence it appears that the increased relapse rate in this current randomised study compared with published observational data is related to the shorter duration of LNG-IUS treatment. From the current trial published in BJOG and the available background observational literature we can infer that the LNG-IUS is preferred for treatment of non-atypical endometrial hyperplasia because it is most effective in reversing the hyperplastic endometrial process and it does reduce the risk of relapse compared with oral progestogen therapy, if used for the full 5-year duration of its licensed use. Obese women should be instructed to normalise their weight to reduce the risk of relapse further. The optimal follow up regimen for women with endometrial hyperplasia not managed by hysterectomy remains to be elucidated. However, women at high risk of relapse or disease progression such as the obese, those refractory to hormonal therapy, those unwilling to receive hormonal or surgical treatment, and those with cytological atypia, should undergo long-term endometrial surveillance. Full disclosure of interests available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.