Women diagnosed with a precancerous condition known as endometrial hyperplasia need better care to avoid future cancer development, new research has found.
Research published in PLOS Medicine and conducted by the UK Audit and Research Collaborative in Obstetrics and Gynaecology (UK ARCOG) aimed to find out whether or not national guidance published in 2016 was being followed. The team, including academics from the University of Birmingham compared the recommendations with the actual care received by 3,307 women who were diagnosed with endometrial hyperplasia between 2012 and 2020. 1,655 of the 3,307 women had non-atypical endometrial hyperplasia and 1,652 had atypical endometrial hyperplasia.
The study found that initial treatment of women without atypia changed following the introduction of national guidance. In 2012-15, 9% without atypia received no initial treatment, 31% received an initial intra-uterine hormone and 15% had an initial hysterectomy. In 2016-19, only 3% received no initial treatment, 48% received an initial intra-uterine hormone, and 12% had an initial hysterectomy.
However, between 2016-19, 37% of the women who were diagnosed with atypical endometrial hyperplasia on a biopsy and who had an initial hysterectomy were found to have endometrial cancer on histological analysis of their womb after surgery, reinforcing the need for high quality counselling when deciding on treatment.
while the new national guidance in 2016 [which Gupta was a senior co-author on] has evidently led to more women receiving appropriate care, more needs to be done to help avoid the development of cancer of the womb
Professor Janesh Gupta
Other findings include:
- At two years from the initial diagnosis, the proportion of women without atypia who had successful treatment without requiring a hysterectomy increased from 38% to 52%;
- The initial treatment of women with atypia did not change, with 68% having an initial hysterectomy in 2012-15 and 67% in 2016-19;
- In 2020, coinciding with the COVID-19 pandemic, only 52% of women with atypia had an initial hysterectomy; and
- For women who did not have a hysterectomy, only 27% without atypia and only 19% with atypia received the recommended schedule of follow up biopsies after the introduction of the guidance.
Dr Ian Henderson, Clinical Research Fellow at Oxford Population Health and a lead author of the study, said:
“The results of our study demonstrate that, while the care of women diagnosed with endometrial hyperplasia has improved with the introduction of national guidance, care of women with endometrial hyperplasia who are not treated with a hysterectomy in particular must be improved given the risk of developing cancer.”
More than quarter of a century of endometrial hyperplasia research
Professor Janesh Gupta at the University of Birmingham is a world authority on endometrial hyperplasia and senior author of the current paper. He was the original instigator behind the research on the subject, and between 1998 and 2007 made a prospective database of endometrial biopsies (small pieces of tissue taken from the womb lining) from 250 women with endometrial hyperplasia (EH) attending the gynaecology department at the Birmingham Women’s Hospital, UK and treated with progestogens to evaluate the efficacy of managing EH with either:
- Progestogen delivered directly into the womb using a hormonal coil known as a Levonorgestrel Intrauterine System (LNG-IUS) delivering a continuous low dose progestogen over a 5 years period.
- Short course of oral progestogens (OP) (average 6-months, range 3-12 months).
The women were monitored with regular follow-up biopsies and the longest follow-up now exceeds 15 years and represents the largest and longest prospective study of patients with EH in the world. The research found that:
- Regression of EH occurs within 1 year of starting progestogen therapy for most women and is higher with LNG-IUS compared to oral progestogens (94.8% vs 84%). This is true for both non-atypical (96.5% vs 90.1%) and atypical EH (76.2% vs 46.2%).
- Risk of relapse after initial regression is lower with LNG-IUS compared to oral progestogens (12.7% vs 28.3%).
- Obesity (Body Mass Index ≥35) is strongly associated with both failure of hyperplasia to regress and with relapse following LNG-IUS treatment.
Gupta and colleagues also conducted several systematic reviews between 2009 and 2012 to assess the overall evidence to support LNG-IUS as the first-line therapy for EH and oral progestogen as an option for women with atypical EH or early clinical stage EC who wish to preserve their fertility or who are not suitable for surgery. These reviews showed that Progestogen therapy can induce regression and/or delay progression of disease in women with atypical EH or EC enabling women to have a child before needing surgery.
Professor Janesh Gupta, Honorary Clinical Professor in the Institute of Metabolism and Systems Research at the University of Birmingham, Clinical Consultant at Birmingham Women’s and Children’s NHS Foundation Trust and senior co-author of the study said:
“We have been working with women with endometrial hyperplasia for more than a quarter of a century and while the new national guidance in 2016 [which Gupta was a senior co-author on] has evidently led to more women receiving appropriate care, more needs to be done to help avoid the development of cancer of the womb.
"Our findings that more than one in three women with atypical EH already had cancer demonstrates the seriousness of the problem.”
Most common gynaecological cancer in Western World
Endometrial carcinoma (EC) (cancer of the womb) is the most common gynaecological cancer in the western world. Globally, 199,000 new cases of EC are diagnosed each year, including 9,300 in the UK. Endometrial hyperplasia (EH), which is increased abnormal cell division in the womb lining, can lead to EC if not treated.
Before 2000, all types of endometrial hyperplasia (EH) were treated by hysterectomy (surgical removal of the womb). The risk of developing EC is up to 40% for atypical EH (grossly abnormal cells on microscopy) but most women present with non-atypical EH (early abnormal changes to cells on microscopy) which has only a 5% risk of EC.
Hysterectomy remains the recommended treatment for atypical EH as the risk of progression to EC is high but clinicians debated whether the low (5%) incidence of EC in non-atypical EH warranted the risks of hysterectomy (pain, scarring, loss of fertility and increased susceptibility to osteoporosis, in addition to, the resource burden on the NHS (each operation costing approximately £5000).
