Nonatypical Endometrial Hyperplasia

Nonatypical endometrial hyperplasia is an overgrowth of endometrial glands with a higher gland to stroma ratio than normal but without cytological atypia. It results from prolonged oestrogen without progesterone.

• Causes include anovulation (polycystic ovary syndrome, perimenopause), obesity, unopposed oestrogen therapy, tamoxifen and oestrogen-secreting tumours.
• The risk of progressing to cancer is below 5 percent over 20 years, but atypical foci may be missed.
• Progestogen treatment reverses most cases.

Heavy or irregular menstrual bleeding, intermenstrual bleeding, postmenopausal bleeding, or no symptoms.

• Examination is often normal; many women are obese.
• Differential diagnosis: endometrial polyp, atypical hyperplasia, endometrial cancer, submucosal fibroid, endometritis, atrophic bleeding.
• Complications: anaemia, progression to atypical hyperplasia or cancer, recurrence.

Diagnosis is by endometrial sampling, supported by ultrasound.

• Transvaginal ultrasound for endometrial thickness.
• Endometrial sampling with a Pipelle, or hysteroscopy with biopsy, with histology.
• Pregnancy test, full blood count, thyroid function, fasting glucose, and testosterone and androgens when polycystic ovary syndrome is possible.
• Review of drugs: tamoxifen, unopposed oestrogen.

Give progestogen therapy with weight loss, and repeat biopsy to confirm regression.

• Supportive: weight reduction by 5 to 10 percent of body weight; stop unopposed oestrogen; control diabetes; counsel on repeat biopsy.
• Pharmacological: first line is levonorgestrel 52 mg intrauterine system for at least 6 months. Oral alternative: medroxyprogesterone acetate 10 mg oral daily (continuous) for 6 months. For heavy bleeding add tranexamic acid 1 g oral 8-hourly for up to 4 days (maximum 4 g in 24 hours). Anaemia: ferrous sulphate 200 mg oral 8-hourly, continued for 3 months after haemoglobin normalises. Ovulation induction if pregnancy is wanted: letrozole 2.5 mg oral daily on days 3 to 7, increased to 7.5 mg (maximum).
• Procedures: hysteroscopy and removal of focal lesions; hysterectomy if hyperplasia persists after 12 months of treatment, or if bleeding continues, or if the woman does not accept follow-up.
• Special groups: in women with a history of venous thromboembolism prefer the levonorgestrel intrauterine system over oral progestogen. In women on tamoxifen use the intrauterine system, with specialist advice.
• Red flags: atypia on biopsy, rapid bleeding, endometrial thickness above 10 mm, persistence after treatment.
• Follow-up: endometrial biopsy at 3 to 6 months; continue until two negative biopsies at least 6 months apart; yearly review thereafter if the risk factors remain.