Premalignant disease of the uterus
Endometrial cancer is the commonest gynaecological malignancy in the Western world, and the incidence increased in the United Kingdom by 43% between 1993-1995 and 2007-2009 (52).
Endometrial hyperplasia is a precursor for endometrial cancer (53). The increasing obesity epidemic is the main factor behind the rising incidence of this disease, as obesity, diabetes, and hypertension are important risk factors. In younger women, polycystic ovarian syndrome (PCOS) is an additional recognized risk factor, due to prolonged unopposed oestrogen exposure of the endometrium. Women with PCOS are three times more likely to develop endometrial cancer than women without PCOS (54). While unopposed endogenous oestrogen is the main risk factor, other factors including infection, immunosuppression, insulin resistance, glutathione-S-transferase and progesterone resistance can be instrumental (55-57).Endometrial hyperplasia should be suspected in premenopausal women with risk factors who present with abnormal vaginal bleeding. United Kingdom guidelines published in 2014 concluded that endometrial hyperplasia is unlikely where the endometrial thickness measures less than 7 mm on transvaginal ultrasound scan. Endometrial biopsy and usually hysteroscopy are indicated in women with persistent symptoms, and women with complex endometrial hyperplasia with atypia should be counselled regarding the possibility of occult malignant disease (58).
Young women with endometrial hyperplasia who wish to preserve fertility are managed with progesterone, and require monitoring with endometrial biopsy to assess response to treatment. The levonorgestrel-releasing intrauterine system (Mirena®) or continuous oral progesterone should be used for a minimum of 6 months for the management of hyperplasia without atypia, with longer treatment planned for women with atypical hyperplasia. While on progesterone treatment, women treated for atypical hyperplasia should undergo endometrial biopsy every 3 months to exclude progression to invasive cancer (59).
Disease regression should be demonstrated on at least one endometrial sample before women attempt to conceive, and it is advised that women with endometrial hyperplasia who wish to conceive are referred to a fertility specialist to discuss the options for attempting conception. Assisted reproduction may be considered as it is associated with a higher live birth rate and it may also prevent relapse of hyperplasia, compared with women who attempt natural conception. Regression of endometrial hyperplasia prior to attempting conception is associated with higher implantation and clinical pregnancy rates (60).Due to high circulating endogenous progesterone levels in pregnancy, endometrial hyperplasia is unlikely to progress during pregnancy. Endometrial biopsy during pregnancy is clearly contraindicated, but repeat biopsy is recommended after the puer- perium. Once fertility is no longer required, hysterectomy should be offered in view of the high risk of disease relapse. Following pregnancy, evidence of histological disease regression should be confirmed by a minimum of two consecutive negative endometrial biopsies, and long-term follow-up with an endometrial biopsy every 6-12 months is recommended until a hysterectomy is performed (61).