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Endometrial hyperplasia (EH) is a condition in which the uterine lining is thicker than normal. It may have many causes, but the most important association is with endometrial malignancy. For this reason, it is mandatory to distinguish between different types of EH, namely, those which are benign and those which are precancerous.
The most useful systems of classification based on microscopic appearances categorize EH as:
The first category is a response to abnormal estrogen stimulation of the endometrium, and regresses once the exposure ceases and adequate progesterone exposure is initiated. The cells are normal in appearance and there are no mutations associated with malignancy
On the other hand, the second type of lesion is premalignant, with genetic changes linked to malignant transformation, and is associated strongly with coexistent endometrioid cancer (in 36%), or a high risk of developing it within a few years.
The management of EH depends on the etiology and direction of the lesion, thus factors which determine the choice of treatment include:
In most cases, benign EH is treated conservatively. Attention is given to identifying and removing sources of estrogen, whether exogenous or endogenous. Modifiable risk factors of this condition include:
In most cases, benign EH may be treated with progesterone, in various 14-day regimens, using formulations such as:
Each 14-day cycle is followed by cyclic bleeding and the endometrium is reassessed by a biopsy after 3 or 4 months of this treatment.
Progestins inhibit cell division in the endometrium within 11 days of initiation of treatment. This is important in reversing the proliferative changes of EH. The typical features of a progesterone-stimulated endometrium include atrophy of the glandular epithelium, increased eosinophilic staining of the cytoplasm and changes in the stromal fluid retention. The response to progestins is determined mostly by the progestin receptor status of the abnormal endometrium.
After 3 months the endometrium is reassessed by biopsy.
In premenopausal patients, EIN is treated with high doses of progestational agents:
Postmenopausal women with EIN should undergo total hysterectomy because of the high risk of endometrial cancer, and because 80% will not respond to progestins.
In 25-90% of premenopausal women with EIN, it is reversed to a secretory type of endometrium. The outcome using an LNG-IUS is generally better with EH, up to 100%, compared to 67-88% in EIN. Once this reversal is seen, a biopsy should be repeated every 6 months until the endometrium is completely normal on several visits, which cover several years. Following the appearance of secretory changes in response to progesterone, the induction of ovulation is recommended to prevent unopposed estrogenic action from recurring in the endometrium.
However, the fact remains that a hysterectomy specimen remains the only definitive mode of confirmation of the presence or absence of an invasive lesion. In such a case, a cancer could well have been undertreated by progestin therapy.
In the percentage of patients with benign EH who do not respond to progestins by cessation of abnormal bleeding, a total hysterectomy is recommended with or without removal of the fallopian tubes and ovaries.
Some patients with EIN are not suitable for surgical management or have not completed their family. In such a case, studies have shown that a trial of progestin therapy could be offered for 6 months followed by repeat endometrial biopsy. If this showed persistent atypia and abnormal gland architecture, total hysterectomy is the only option.
Several newer techniques have been described in the management of benign EH. These include:
It could be said that some patients are not suitable for conservative techniques. Risk factors which help screen out these patients include:
This decision may in future become easier with the use of new diagnostic criteria such as the histomorphometric 4-class rule, which aims to predict the presence of frankly invasive cancer at the time of hysterectomy. It usES characteristics such as epithelial cell number, epithelial thickness, and nuclear pleomorphism as observed on endometrial biopsies. While early studies indicate that it can predict or rule out a myoinvasive outcome in patients with EH, it needs to be adapted to widespread use before its usefulness can be properly gauged.