Endometrial hyperplasia

Question 1

What is endometrial hyperplasia?

Answer 1

Endometrial hyperplasia is excessive growth of the inner lining of the uterus caused by prolonged stimulation of the endometrium with unopposed oestrogen. If left untreated, it can progress to type 1 endometrial cancer!

Question 2

What are the causes of endometrial hyperplasia?

Answer 2

Causes:

Caused by excess unopposed oestrogen

• Obesity
  
  • The extra adipose tissue converts androgens to oestrogen
• Oestrogen-secreting ovarian tumour e.g. granulosa cell tumours
• Polycystic ovarian syndrome (PCOS)
  
  • The cystic follicles on the ovary can all secrete oestrogen –> high oestrogen level
  • The follicles don’t ovulate –> no corpus luteum formed –> no progesterone secreted –> low progesterone level
  • Unopposed oestrogen –> increases the risk of endometrial hyperplasia
• Drugs (exogenous oestrogens)
  
  • Oestrogen-only hormone replacement therapy
    
    • Usually taken to relieve menopausal symptoms e.g. hot flushes and vaginal dryness
  • Tamoxifen (selective estrogen receptor modulator, SERM)
    
    • Used to treat breast cancer that are ‘oestrogen receptor +’
      
      • It blocks the oestrogen receptors on the breast BUT at the same time, it stimulates those on the endometrium

A person could have normal oestrogen production throughout their life, but the number of years the endometrium is exposed to oestrogen is also a factor for developing endometrial hyperplasia. Oestrogen exposure is increased in people who have:

• Early menarche
• Late menopause
• Nulliparity

(These patients have experienced a greater number of menstrual cycles, where more follicles have grown, and more oestrogen was secreted by these follicles)

Pregnancy is a protective factor because follicular growth and the effect of oestrogen is inhibited by progesterone during pregnancy. Thus, people who have been pregnant will have fewer menstrual cycles in their lifetime compared to someone who hasn’t!

Causes independent of hormone levels

• Mutations of a tumour suppressor gene, called PTEN, which normally acts like a brake on the cell cycle. When this gene becomes defective, cells in the endometrium will grow and proliferate out of control, leading to hyperplasia

Question 3

What are the clinical features of endometrial hyperplasia?

Answer 3

Presentations:

• Menorrhagia (heavy/ prolonged bleeding)
• Intermenstrual bleeding
• In some cases, there could also be amenorrhoea (missed periods)
• Any vaginal bleeding in a postmenopausal female could be a sign of endometrial hyperplasia

Question 4

Which cancer can endometrial hyperplasia cause?

Answer 4

Endometrial cancer - the most common cancer in female reproductive system

Question 5

The risk of endometrial cancer depends on the histological features of cells in endometrial hyperplasia.

What are different types of endometrial hyperplasia?

Answer 5

Different types:

Simple - there is a lot of dilated glands and stroma, but there is a normal stroma: gland ratio

Complex - there are way more glands and less stroma, so there is a decreased stroma: gland ratio

Simple atypical - ‘simple’ type + presence of nuclear atypia (large, hyperchromatic nuclei found inside the glandular cells)

Complex atypical - ‘complex’ type + presence of nuclear atypia

(Nuclear atypia is the most important factor in terms of progression to endometrial cancer. Simple hyperplasia alone has a risk of 1% to progress to endometrial cancer, but it goes up to 10% if it’s associated with atypia. Similarly, complex hyperplasia alone has a risk of 5% but if it’s associated with atypia, it increases up to 30%)

Question 6

What are the investigations for endometrial hyperplasia?

Answer 6

Ix:

Diagnosis of endometrial hyperplasia requires histological examination of the endometrial tissue:

• Endometrial sampling by outpatient endometrial biopsy
• Diagnostic hysteroscopy should be considered to facilitate or obtain an endometrial sample, especially where outpatient sampling fails or is nondiagnostic
• Transvaginal ultrasound may have a role in diagnosing endometrial hyperplasia in pre- and postmenopausal women

Question 7

How do you manage endometrial hyperplasia?

Answer 7

Mx:

• Treat the underlying cause of excess oestrogen e.g. weight loss, stopping unopposed oestrogen therapy, correcting the problem of anovulation in cases of PCOS
• Simple endometrial hyperplasia without atypia –> high-dose progesterone therapy with repeat sampling in 3-4 months
• Endometrial hyperplasia with atypia –> hysterectomy + bilateral salpingo-oophorectomy (BSO)