Endometrial Hyperplasia

During the first half of the menstrual cycle, rising levels of follicle stimulating hormone (FSH) stimulate follicular development in the ovary - the follicular phase. The ovarian follicles secrete oestrogen which causes duct proliferation in the breast and glandular changes in the endometrium - the proliferative phase. The rising oestrogen causes a surge of luteinising hormone (LH) by positive feedback, precipitating ovulation. The corpus luteum then secretes progesterone - the luteal phase, which leads to secretory changes in the breast ducts and endometrium - secretory phase.

• Exogenous oestrogen use
• Oestrogen-secreting ovarian tumour
• Tamoxifen use; it has an anti-oestrogen effect on the breast, but a pro-oestrogen effect on the uterus and bones
• Polycystic ovarian syndrome
• Hereditary non-polyposis colorectal carcinoma
• Obesity combined with diabetes

There are four types of endometrial hyperplasia:

• Simple
• Complex
• Simple atypical
• Complex atypical

90% of cases of simple and complex hyperplasia regress spontaneously. In one study progression to carcinoma occurred in:¹

• 1% of patients with simple hyperplasia
• 3% of patients with complex hyperplasia
• 8% of the patients with simple atypical hyperplasia
• 29% of the patients with complex atypical hyperplasia

There is a high prevalence of underlying endometrial adenocarcinoma among women undergoing hysterectomy for any of atypical endometrial proliferation.²

• Endometrial hyperplasia usually presents clinically as abnormal vaginal bleeding; intermenstrual, polymenorrhoea or postmenopausal. The risk of endometrial hyperplasia in a polyp that also involves nonpolypoid endometrium is significant.³
• Vaginal discharge
• Glandular abnormalities on a cervical smear

Transvaginal Ultrasound

Where sufficient local skills and resources exist, transvaginal ultrasound is an appropriate first-line procedure to identify which women with post-menopausal bleeding are at higher risk of endometrial cancer.
The mean endometrial thickness in post-menopausal women is much thinner than in pre-menopausal women. Thickening of the endometrium may indicate the presence of pathology. In general, the thicker the endometrium, the higher the likelihood of important pathology i.e. endometrial cancer being present. The threshold in the UK is 5mm; a thickness of >5mm gives 7.3% likelihood of endometrial cancer.⁴ A thickness of <5mm has a negative predictive value of 98%.⁵ A recent meta-analysis found that a TVUS result of 5 mm or less reduced the risk of disease by 84%.⁶ Some pathology may be missed and it is recommended that hysteroscopy and biopsy should be performed if clinical suspicion is high.^7,8 The accuracy of assessing endometrial thickness in women with diabetes and obesity has been questioned,⁹ but models have been developed to take personal characteristics into account when predicting the risk of cancer.¹⁰

Endometrial Biopsy

A definitive diagnosis in post-menopausal bleeding is made by histology. Historically, endometrial samples have been obtained by dilatation and curettage. Nowadays it is more usual to obtain a sample by endometrial biopsy, which can be undertaken using samplers. Endometrial biopsy can be performed as either an outpatient procedure, or under GA. All methods of sampling the endometrium will miss some cancers.

Hysteroscopy

Hysteroscopy and biopsy (curettage) is the preferred diagnostic technique to detect polyps and other benign lesions. Hysteroscopy may be performed as an outpatient procedure, although some women will require general anesthetic.
A significant development has been direct referral to 'one stop' specialist clinics.^11,12 At such clinics several investigations are available to complement clinical evaluation, including ultrasound, endometrial sampling techniques and hysteroscopy. Following such assessment reassurance can be given or further investigations or treatment can be discussed and arranged.

MRI

Can also demonstrate endometrial hyperplasia, and though not often used may be helpful in cases where TVUS is not possible, or when superimposed invasive endometrial carcinoma is suspected.

Medical

Simple endometrial hyperplasia without atypia responds to high dose progestogens, with repeat histology after three months.
This can be effectively delivered by the levonorgestrel intra-uterine system.^13,14,15 It is also given orally, if desired.

Surgical

• Endometrial ablation or trans cervical resection of the endometrium (TCRE)¹⁶
• Hysterectomy; usually advised for atypical endometrial hyperplasia

The author is grateful to Dr C Tidy for his original work on this record.