We previously reported on the successful management of nonatypical and atypical endometrial hyperplasia with an LNG-IUS [6
]. Endometrial cancer is a very common disorder. Over 40,000 cases are diagnosed in the United States annually with almost 75% of cases presenting with FIGO stage I disease (Cancer fact & figures, 2004). The underlying mechanism for the development of some types of endometrial cancer is exogenous or endogenous hormone stimulation [8
]. Therefore, progesterone or progestin treatment, by counteracting the effect of estrogen, may reverse the neoplastic process. Levonorgestrel, delivered locally with a drug delivery system, is probably the best choice as the tissue concentrations are many times higher than when the hormone is administered orally. “Progestasert,” a progesterone-releasing IUS (Alza Corp., Palo Alto, CA), has been used with good results. However, a levonorgestrel-releasing IUS should be preferred as it is much more potent [9
]. Histological regression of early endometrial cancer has also been obtained with orally administered progestins but the results cannot be expected to be as good as local treatment [10
]. In addition, with an IUS there is less risk of systemic side effects, often leading to poor compliance. Intrauterine delivery of levonorgestrel causes a more uniform response throughout the whole thickness of the endometrium, including the basal layer, compared to intrauterine progesterone delivery or orally administered progestins [12
]. The Femilis, currently still an experimental IUS, releases the same amount of LNG as Mirena (BayerSchering Inc., Berlin, Germany) but the initial release is approximately three times higher than the release of LNG of Mirena during the first weeks. This could be advantageous as it increases the impact on the neoplastic endometrial cells. It is possible that the fast remission in this patient is due to the strong suppression of the endometrium immediately after insertion of the LNG-IUS. Several cases of endometrial carcinoma treated with an LNG-IUS (Mirena) have been published [11
]. The LNG-IUS should be high up in the fundus to guarantee proper release of the hormone in the fundal area of the uterus. We question if the LNG-IUS was properly located in the uterine cavity in some of these unsuccessful cases. A frameless LNG-IUS should be preferred in case of displacement, partial or total expulsion of a framed LNG-IUS. This LNG-IUS is anchored to the uterine fundus and is unlikely to become displaced or expelled [15
]. We would also recommend to remain cautious in women presenting with irregular bleeding after 6 to 12 months following the insertion of an LNG-IUS and to evaluate the endometrium thoroughly.
Evidently, the best candidates for local treatment with the LNG-IUS are those with no or only minimal endometrial invasion. In these cases, the LNG-IUS could be the treatment of choice especially in women with contraindications for surgery, or even for older women. We agree with Bahamondes et al. that the intrauterine route should be preferred over the oral route. Perhaps, the LNG-IUS, releasing 20μ
g of LNG/d, or a higher dose, may be curative in a larger proportion of women with early endometrial carcinoma. Clearly further studies are needed to elucidate this possibility.
In the meantime, we can conclude that selected women could benefit from treatment with LNG-IUS but we should keep in mind that continued observation is necessary as the endometrial cells may preserve their neoplastic capacity. Women who respond positively should remain protected for years with a long-acting hormone-releasing intrauterine system.