Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Endometrial hyperplasia is an abnormal proliferation of the endometrium (ie greater than the normal proliferation that occurs during the menstrual cycle). It is a risk factor for the development of endometrial carcinoma.
There are four types of endometrial hyperplasia:
- Simple atypical
- Complex atypical
For simple and complex hyperplasia, the risk of progression to carcinoma is less than 5%. The risk in atypical hyperplasia is around 30%.Statistics vary, which may be due to the poor diagnostic reproducibility.
- Exogenous oestrogen use (without cyclical progesterone).
- 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.
NB: use of combined oral contraceptive decreases risk.
- Endometrial hyperplasia usually presents clinically as abnormal vaginal bleeding - intermenstrual, polymenorrhoea or postmenopausal. The risk of endometrial hyperplasia in a polyp that also involves non-polypoid endometrium is significant.
- Vaginal discharge.
- Glandular abnormalities on a cervical smear
Transvaginal ultrasound (TVUS)
TVUS is an appropriate first-line procedure to identify which women with postmenopausal bleeding are at higher risk of endometrial cancer.
The mean endometrial thickness in postmenopausal women is much thinner than in premenopausal women. Thickening of the endometrium may indicate the presence of pathology. In general, the thicker the endometrium, the higher the likelihood of important pathology, ie endometrial cancer, being present. The threshold in the UK is 5 mm; a thickness of >5 mm gives 7.3% likelihood of endometrial cancer.In a woman with postmenopausal bleeding, if endometrial thickness is less than 5 mm uniformly, the probability of carcinoma is less than 1%.Some pathology may be missed and it is recommended that hysteroscopy and biopsy should be performed if clinical suspicion is high.Models have been developed to take personal characteristics into account when predicting the risk of cancer to improve predictive accuracy.
A definitive diagnosis in postmenopausal 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 outpatient endometrial sampling, most commonly a pipelle biopsy. Occasionally this has to be performed under general anaesthetic (GA). All methods of sampling the endometrium will miss some cancers.
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 GA.
Where they are available, direct referral to 'one-stop' specialised clinics is ideal.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. National Institute for Health and Care Excellence (NICE) guidelines advise postmenopausal women not on HRT and presenting with postmenopausal bleeding should be referred urgently.
This 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. It is more helpful in the staging of established carcinoma.
Simple endometrial hyperplasia without atypia responds to high-dose progestogens, with repeat histology after three months.
This can be effectively delivered by the levonorgestrel intrauterine system (IUS).[10, 11]It is also given orally, if desired. Studies suggest the IUS is more effective, with higher regression rates and reduced need for hysterectomy, even for atypical hyperplasia.However, a Cochrane review in 2013 concluded there is not yet the evidence of safety and efficacy to be convincing in patients with atypical hyperplasia.
Relapse occurs relatively frequently (approximately 14% with the IUS and 30% with oral treatment) after regression, especially in complex hyperplasia, so long-term follow-up is advised.
- Transcervical resection of the endometrium (TCRE).
- Hysterectomy - usually advised for atypical endometrial hyperplasia.
Recurrence after treatment may occur. Endometrial hyperplasia may develop into endometrial carcinoma. Women who don't have atypical changes have a very small risk of developing a cancer. As many as 30-40% of women diagnosed with atypical hyperplasia are found to have a concurrent carcinoma.The rest with atypical changes are at significant risk as above. Risk increases after menopause.
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Further reading & references
- Management of Endometrial Hyperplasia; RCOG/BSGE Joint Guideline (2016)
- Lacey JV Jr, Sherman ME, Rush BB, et al; Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia. J Clin Oncol. 2010 Feb 10 28(5):788-92. doi: 10.1200/JCO.2009.24.1315. Epub 2010 Jan 11.
- Lacey JV Jr, Chia VM; Endometrial hyperplasia and the risk of progression to carcinoma. Maturitas. 2009 May 20 63(1):39-44. doi: 10.1016/j.maturitas.2009.02.005. Epub 2009 Mar 13.
- Kelly P, Dobbs SP, McCluggage WG; Endometrial hyperplasia involving endometrial polyps: report of a series and discussion of the significance in an endometrial biopsy specimen. BJOG. 2007 Aug 114(8):944-50. Epub 2007 Jun 12.
- Smith-Bindman R, Weiss E, Feldstein V; How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol. 2004 Oct 24(5):558-65.
- Sahdev A; Imaging the endometrium in postmenopausal bleeding. BMJ. 2007 Mar 24 334(7594):635-6.
- Litta P, Merlin F, Saccardi C, et al; Role of hysteroscopy with endometrial biopsy to rule out endometrial cancer in postmenopausal women with abnormal uterine bleeding. Maturitas. 2005 Feb 14 50(2):117-23.
- Opmeer BC, van Doorn HC, Heintz AP, et al; Improving the existing diagnostic strategy by accounting for characteristics of the women in the diagnostic work up for postmenopausal bleeding. BJOG. 2007 Jan 114(1):51-8.
- Lotfallah H, Farag K, Hassan I, et al; One-stop hysteroscopy clinic for postmenopausal bleeding. J Reprod Med. 2005 Feb 50(2):101-7.
- Referral for suspected cancer; NICE Clinical Guideline (2005)
- Kriplani A, Singh BM, Lal S, et al; Efficacy, acceptability and side effects of the levonorgestrel intrauterine system for menorrhagia. Int J Gynaecol Obstet. 2007 Jun 97(3):190-4. Epub 2007 Mar 26.
- Wildemeersch D, Janssens D, Pylyser K, et al; Management of patients with non-atypical and atypical endometrial hyperplasia with a levonorgestrel-releasing intrauterine system: long-term follow-up. Maturitas. 2007 Jun 20 57(2):210-3. Epub 2007 Jan 31.
- Gallos ID, Krishan P, Shehmar M, et al; LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long-term comparative cohort study. Hum Reprod. 2013 Nov 28(11):2966-71. doi: 10.1093/humrep/det320. Epub 2013 Aug 23.
- Luo L, Luo B, Zheng Y, et al; Levonorgestrel-releasing intrauterine system for atypical endometrial hyperplasia. Cochrane Database Syst Rev. 2013 Jun 5 6:CD009458. doi: 10.1002/14651858.CD009458.pub2.
- Gallos ID, Krishan P, Shehmar M, et al; Relapse of endometrial hyperplasia after conservative treatment: a cohort study with long-term follow-up. Hum Reprod. 2013 May 28(5):1231-6. doi: 10.1093/humrep/det049. Epub 2013 Mar 6.
- Saso S, Chatterjee J, Georgiou E, et al; Endometrial cancer. BMJ. 2011 Jul 6 343:d3954. doi: 10.1136/bmj.d3954.
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