The links between diet, obesity and endometrial (womb) cancer – diagnosis and treatment

Contents

• Introduction
• What is endometrial cancer?
• How common is endometrial cancer?
• Obesity rates in England
• Why does obesity increase the risk of endometrial cancer?
• What are the other risk factors for endometrial cancer?
• Does anything reduce the risk of endometrial cancer?
• What are the symptoms of endometrial cancer?
• What happens when you are referred to a specialist for post-menopausal bleeding?
• Treatment for endometrial cancer
• Will I need any treatment after the hysterectomy?
• What happens after treatment?
• Survival after endometrial cancer
• Summary points

Introduction

Endometrial cancer is cancer of the lining of the womb and it is the most common gynaecological cancer in the UK. It is mainly a disease of post-menopausal women and occurs most commonly in women aged 50 to 60 years, although women should be aware that this cancer can occur in younger women also and that 7% of cases are seen in pre-menopausal women.

Endometrial cancer is much more common among women who live in the developing world, particularly Europe and North America compared with women who live in less developed countries. This is likely to be because endometrial cancer is linked to obesity, with obese women three times as likely to get this disease as women who have a body weight in the healthy range. A healthy balanced diet and an active lifestyle can help to reduce the risk of this cancer.

Often the first symptom of this cancer is post-menopausal bleeding – bleeding from the vagina after the periods have ceased. This is an early warning sign and it means that this type of cancer is diagnosed early in the vast majority of women, before it has had a chance to spread outside the womb. As a result, the cancer is potentially curable.

Treatment is by a total hysterectomy, which is the removal of the womb and cervix and, in addition, the ovaries and fallopian tubes are also removed. The keyhole (laparoscopic) technique has the advantage that women recover much more quickly, with less scarring. Some women will need additional treatment after the hysterectomy and this may be radiotherapy, chemotherapy or a combination of the two.

Almost eight out of ten women will be cured after treatment for endometrial cancer.

What is endometrial cancer?

The endometrium is the lining of the womb. The womb is the chamber in which pregnancies develop. It is a pear-shaped organ that sits in the pelvis, attached to the upper vagina. The womb is divided into two parts; the body is the upper part in which the baby grows during pregnancy and the lower part, cervix, which is also known as the neck of the womb, and which is the area that expands (dilates) to enable the baby to pass through during child birth. The scientific name for the womb is the uterus.

The womb is made of muscle and the lining of the inside of the body of the womb is called the endometrium. During the reproductive years, (the years in which a woman is capable of having children) the endometrium is under the influence of hormones produced by the ovaries. It thickens after ovulation (the shedding of the egg for fertilisation) to prepare for a pregnancy. If pregnancy does not occur, it sheds in the form of a monthly period. After the menopause, the ovaries effectively stop producing hormones and the lining of the womb becomes very thin. Any bleeding from the womb after the menopause is abnormal.

Cancer occurs when cells (the building blocks of the body) start to multiply out of control, forming a growth which can then spread to other tissues. A cancer that develops in the lining of the womb is known as endometrial cancer.

How common is endometrial cancer?

Endometrial cancer is now the most common gynaecological cancer (cancer of the female reproductive tract) in the UK. It is the fourth most common cancer in women in the UK with 7,536 cases diagnosed in 2007.

The rates of endometrial cancer in Great Britain remained stable between 1975 and 1993, and then increased by more than 40% between 1993 and 2007.

Endometrial cancer is a disease of post-menopausal women. The vast majority (93%) of endometrial cancer cases are diagnosed in women aged over 50 years with very few women diagnosed under the age of 35. Endometrial cancer incidence rates decline after the age of 75.

Endometrial cancer is mainly a cancer of the developed world with incidence rates double those of the less developed countries. In North America, Australasia and many European countries, it is now the most commonly diagnosed gynaecological cancer. Endometrial cancer incidence rates are highest in Northern America; up to eight times higher than in parts of Africa. In contrast, cervical cancer, cancer of the neck of the womb is far more common in developing countries where three out of every four cases occur.

These differences in world-wide rates of endometrial cancer may be related to the fact that women who are obese or over-weight are more likely to develop this cancer and the rates of obesity are rising in the developing world.

According to the American Cancer Society (2009), an overweight woman's risk of endometrial cancer is double the risk for women of healthy weight. This risk increases for obese women, who are three times more likely to develop this cancer.

You are three times as likely to develop endometrial cancer if you are obese.

Obesity rates in England

Scientists say that, after avoiding smoking, maintaining a healthy weight is the most important thing you can do to reduce your risk of developing cancer. Obesity is a word used to describe people who have an abnormally high and unhealthy proportion of body fat.

One of the easiest ways to find out if you are a healthy weight for your height is by measuring your Body Mass Index (BMI). BMI is calculated as height in metres divided by the square of your weight in metres.

Guidelines established by the National Institutes of Health place adults aged 20 and older into one of four categories based on their BMI.

In England, the proportion of overweight or obese adults increased between 1993 and 2007 from 34 to 41 per cent in men and from 42 to 49 per cent among women. There has been a big increase in the proportion of the population who are obese. This figure rose from 13 to 24 per cent in men and from 16 to 24 per cent in women between 1993 and 2007. This means that approximately one of every two adult women carries an unhealthy amount of body fat and one in every four women is clinically obese.

You can check your BMI here:

It is estimated that rates of obesity will rise even further by 2025. As well as increasing the risk of cancer, obesity is associated with poor quality of life and poor sexual outcomes. In a study, thirty per cent of obese women were less likely to report a sexual partner in the last twelve months.

In England, one in two adult women is overweight or obese.

Why does obesity increase the risk of endometrial cancer?

The reasons for why obesity increases the risk of endometrial cancer are not fully understood. One theory is that levels of oestrogen, a female reproductive hormone, are linked to this cancer. Most of the oestrogen in the body is made by the ovaries. Oestrogen has a direct effect on the lining of the womb, causing it to thicken in preparation for ovulation. This thickening is prevented from getting out of control by a second hormone, progesterone which is also produced by the ovaries in response to ovulation (release of the egg by the ovary; if the egg is fertilised by a sperm cell, pregnancy occurs). If pregnancy does not occur, the lining of the womb is shed in form of a monthly period.

Oestrogen is also made in the body fat and the more fat a women has, the more oestrogen is produced. The ovaries stop producing oestrogen and progesterone after the menopause but the body fat continues to produce oestrogen. Under these circumstances, oestrogen acts on the endometrium without the regulating effect of progesterone. High oestrogen levels with little or no progesterone to balance the effects is known as ‘unopposed’ oestrogen production and this is linked to an increased risk of endometrial cancer.

Clearly not all overweight or obese women will develop this cancer and some women with a healthy body mass index will develop endometrial cancer so obesity is not the only factor that determines the likelihood of endometrial cancer.

What are the other risk factors for endometrial cancer?

Diet and alcohol

If you eat a high fat diet you may have a higher risk of developing endometrial cancer. It is not clear whether this is directly to do with the fat in your diet, or whether it is because eating more fat leads to obesity.

There is some evidence that fibre in the diet and higher intake of vegetables reduces endometrial cancer risk but this has not been confirmed in other studies and more research is required.

However, even if the evidence is not as clear or as conclusive as we would like it to be, what we do know is that if we eat a diet which is plentiful in fruits and vegetables, ideally hitting a good five or so portions every day, this will help us to reduce our risk of all sorts of cancers and other diseases such as heart disease and diabetes. The five-a-day message has been around for a long time, yet whilst we may be getting better at eating fruit, be this as a banana with our cereal in the morning, or a glass of smoothie instead of a fizzy drink, we still have some way to go with vegetables. Vegetables can be steamed and drizzled with a little olive oil, a salad can be quickly made with all the exotic and colourful bagged salad leaves, some ripe avocado, deep red tomatoes (ideally kept out of the fridge for the best flavour), and can be dressed in a simple vinaigrette, and still count towards our five a day. So too can a soup made with vegetables and beans- who could say that a bowl of Tuscan bean soup is anything but delicious? If you manage to include something based around vegetables with your lunch and evening meal, and include something fruity with your breakfast, be this some stewed apple topped with a dollop of Greek-style natural yoghurt and some toasted nuts, it’s highly likely that you’ll be well ahead of the five a day mantra.

Menstrual history

Some factors linked with periods (menstruation) can increase your risk of endometrial cancer because they cause higher levels of ‘unopposed’ oestrogen. Examples are

• Starting your periods early (before the age of 11)
• Having longer than average periods
• Infertility due to a failure to ovulate (release an egg every month)
• Not having periods, or not having them often
• A late menopause (after the age of 52)

All of these factors can contribute to your risk of endometrial cancer.

Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) is a condition that causes a hormone imbalance in women. The name of the condition derives from the fact that the ovaries form multiple small cysts around the edges. These cysts are said to look like a string of pearls when looked at with an ultrasound scanner. The cysts themselves are not a problem and do not require surgical removal. It is important to recognise the syndrome though, as it can cause a number of problems. PCOS is typically characterised by

• Being obese or overweight
• Abnormal hair growth – on the chin, chest or stomach – this is known as hirsuitism
• Infrequent or absent periods due to a failure to ovulate regularly
• Infertility

Women with PCOS have an increased risk of endometrial cancer compared to women who do not. The risk is probably linked to high levels of unopposed oestrogen because, as well as failing to ovulate, women with PCOS are also likely to be obese. Thus it is important to recognise and treat the condition.

Family history and personal history of other cancers

A history of certain previous cancers can increase your risk of endometrial cancer. Thus, if you have had cancer of the colon, rectum or breast in the past, you are at a slightly increased risk of getting endometrial cancer. Similarly, once you have had endometrial cancer, you have a slightly increased risk of developing certain other cancers.

Research has shown that women with mothers who have had endometrial cancer have twice the risk of women in the general population.

Most cancers however are 'sporadic', which means they are not caused by an inherited gene. Some people are at a higher risk of developing cancers because of faulty genes, sometimes known as cancer genes or onco-genes that do run in families. If you have several close relatives on the same side of the family who have suffered from bowel or endometrial cancer, this suggests that there may be a faulty gene in the family and that you may be at an increased risk of also suffering from these cancers. Not every family member will be affected by these cancers as not everyone will inherit the faulty gene. Therefore, even if there is a faulty gene in your family, you may not have inherited it.

Hereditary nonpolyposis colon cancer (HNPCC) is a faulty gene which, if inherited, increases the risk of a variety of cancers, especially bowel cancer. This condition is also sometimes called Lynch syndrome. Other than bowel cancer, endometrial cancer is the most common cancer linked with this syndrome. Out of every 100 women who carry the HNPCC gene fault, 60 will develop endometrial cancer at some point in their lives. In this group of women, endometrial cancer tends to occur at a younger age than in the general population. About one in six endometrial cancers in women with the HNPCC gene fault are diagnosed before age 40. It is important to remember that endometrial cancers in these women are often picked up at an early stage when there is a good chance of cure. If you have a strong family history of bowel and endometrial cancer, you can ask your GP to refer you for genetic testing to see if you carry the HNPCC gene.

If you are known to carry the HNPCC gene, you may be offered frequent monitoring by ultrasound scanning so that any abnormality in the lining of the womb is picked up early and treated.

Tamoxifen

Women who have been treated for breast cancer are often prescribed a drug called tamoxifen to reduce the risk of the cancer returning. Tamoxifen has a similar effect on the lining of the womb as oestrogen and scientists think that this is why it increases the risk of endometrial cancer. The key indication that there may be a problem is abnormal bleeding from the vagina. It is important to tell your doctor if you develop any unexpected vaginal bleeding while you are taking tamoxifen, particularly if your periods have stopped.

If you have had breast cancer, the benefits of taking tamoxifen to prevent your breast cancer from coming back are far more important than the small risk of getting endometrial cancer. Never stop taking tamoxifen without seeking medical advice.

Hormone replacement therapy

Hormone replacement therapy (HRT) is used by many women to control the symptoms of the menopause. There are different types of HRT but most contain both oestrogen and progesterone. HRT that contains only oestrogen increases the risk of endometrial cancer and is normally only prescribed to women who have had their womb removed (hysterectomy). Some studies suggest that even women taking HRT containing a combination of oestrogen and progesterone are at increased risk of endometrial cancer, particularly if they take it for many years.

You should discuss the risks and benefits of HRT for you as an individual before starting this medication and review these with your GP every year that you remain on HRT. Or, take expert advice from a gynaecologist who specialises in hormone therapy.

Diabetes and high blood pressure

Women with diabetes are four times more likely to get endometrial cancer. Diabetes and high blood pressure are both linked to being overweight and so may be linked to endometrial cancer for that reason. However, several studies show a higher risk of endometrial cancer in women with diabetes, even after taking bodyweight into account.

Does anything reduce the risk of endometrial cancer?

Contraceptive pills

Most types of birth control pills used today normally decrease the risk of endometrial cancer. These contain either a combination of oestrogen and progesterone (combination pills), or progesterone only (mini-pills).

Having children

Having had a baby lowers your risk of endometrial cancer. Studies seem to show that having one child lowers your risk by about a third. Different studies give different figures but if you have 3 or more children your risk could be lowered by up to two thirds. If you have never been pregnant you are more likely to develop endometrial cancer than if you have had children.

Oestrogen levels are low and progesterone levels are high in pregnancy and this may have a protective effect on the endometrium.

Physical activity

Some studies show a reduced risk of endometrial cancer for women who are more physically active. However there are other studies that do not show a reduced risk. So any link may just be because physically active women have a lower bodyweight.

Maintaining a healthy weight

If excess weight increases the risk of endometrial cancer, we assume that weight loss should logically protect against the disease.

Medical experts already know that losing just 10 percent of excess weight yields many health benefits, including a lower risk of Type 2 diabetes. Since diabetes quadruples a woman's risk of cancer of the endometrium, lowering the risk of diabetes should also lower that of endometrial cancer.

Doctors suggest physical activity as a preventive measure for endometrial cancer. Combined with a healthy diet and regular exercise, however, weight loss may improve quality of life.

It appears that we are all aware of the need to lose weight. The WebWatch 2010 report from the health information portal Private Healthcare UK reveals that searches related to body mass index, dieting, weight loss and fitness dominate internet health searches. Three of the top twenty most visited UK web sites in the Health and Medical sector relate to obesity, weight loss and dieting. Furthermore, the British Medical Journal (BMJ), a clinical research journal, claims a ten-fold rise in gastric bands and other weight-loss operations in the last decade.

People can become desperate and at times wish that obesity could simply be cured by having an operation such as the insertion of a gastric band or removal of part of the stomach. Whilst weight loss surgery can be successful for some people it is a serious decision to take and unless it is coupled with behavioural and nutritional support it will often be unsuccessful in the long term. Studies continue to show that changing eating habits and adopting a healthy eating lifestyle is ultimately what will win the battle against obesity.

Three of the top twenty most visited internet health sites relate to obesity, weight loss and dieting.

What are the symptoms of endometrial cancer?

Approximately three out of every four women (75%) with endometrial cancer are post-menopausal and nine out of ten (90%) of these will suffer vaginal bleeding. Vaginal bleeding after the menopause is known as post-menopausal bleeding and should never be ignored.

Although post-menopausal bleeding is the most common symptom of endometrial cancer, only one in ten women with post-menopausal bleeding will turn out to have endometrial cancer. The majority will have benign (non-cancerous) causes.

As post-menopausal bleeding is such an obvious symptom, most women seek help immediately and are referred by their General Practitioner (GP) to a specialist without delay. As a result of this, the majority of women have early stage endometrial cancer (confined to the womb and potentially curable) at diagnosis.

90% of women with endometrial cancer present with post-menopausal bleeding.

Other symptoms of endometrial cancer include an abnormal vaginal discharge, pelvic pain or, in pre-menopausal women, heavy prolonged periods or bleeding between periods, known as inter-menstrual bleeding.

What happens when you are referred to a specialist for post-menopausal bleeding?

Only one in ten women with post-menopausal bleeding will be diagnosed with endometrial cancer. It is very important however that you report any bleeding after the menopause to your GP and that your GP refers you urgently to a specialist. The purpose of the referral is so that the specialist can exclude or detect endometrial cancer and offer appropriate treatment.

The specialist, a gynaecologist; may ask you questions about your personal and family history. He/she will ask you to have an ultrasound scan to look at the thickness of the lining of the womb. This is a helpful test as the lining of the womb becomes very thin after the menopause. If it is thickened on ultrasound measurement to 5mm or more this raises the suspicion of endometrial cancer. In this case you may be asked to have a biopsy (sampling) of the endometrium which can be done in the outpatient clinic. It is similar to having a cervical smear. If obtaining a biopsy in the clinic proves difficult you may be asked to have it done under anaesthesia. The biopsy will determine conclusively if you have cancer or not. If you do have cancer, you will be referred to a gynaecological oncologist (gynaecological cancer specialist) for more tests and treatment.

Tests to diagnose endometrial cancer include:

• Ultrasound scan to measure the thickness of the lining of the womb
• Biopsy of the lining of the womb

Treatment for endometrial cancer

Treatment for endometrial cancer is carried out by a team of specialists, known as a multi-disciplinary team (MDT). Members of the MDT include a gynaecological oncologist (gynaecological cancer specialist surgeon), a clinical or medical oncologist (specialist in radiotherapy or chemotherapy) a clinical nurse specialist (sometimes known as Macmillan Nurse), a clinical psychologist, a specialist radiologist and a specialist pathologist. This ensures that your case is looked at in detail and that you receive the best possible treatment, improving your chances of surviving the cancer.

75% of women with endometrial cancer present when the cancer is still confined to the womb and can be treated with a hysterectomy. Women recover more quickly after a keyhole hysterectomy. Ask your surgeon if the keyhole approach is suitable for you.

Usually, your initial referral will be to the gynaecological oncologist.

As most women with endometrial cancer experience bleeding after the menopause and are promptly diagnosed, three out of four women will have the disease detected when it is still confined to the womb and treatable. Treatment in the majority of cases involves a hysterectomy.

Before proceeding to a hysterectomy the gynaecological oncologist may arrange some more specialised scans. A magnetic resonance imaging (MRI) scan provides more detail about the womb and the surrounding tissue and can give an indication about whether the cancer is confined to the lining of the womb or if it has spread to the muscle of the womb. It may also indicate if the regional lymph glands are enlarged and likely to be involved. A CT (computerised tomography) scan may show evidence of more distant spread.

If the scans confirm that the disease does not appear to have spread beyond the womb, then you will be advised to have the womb, cervix, ovaries and fallopian tubes removed. This is known as a total hysterectomy with bilateral salpingo-oophorectomy (THBSO). In some cases, the specialist may advice removing the regional lymph nodes as well. Lymph nodes are tiny glands that lie alongside blood vessels. They act as filters and trap any cancer cells or germs that get into the blood. The important lymph nodes for endometrial cancer lie alongside the blood vessels on either side of the pelvis and the back of the abdomen. (See figure I). The traditional approach in the UK is to do an abdominal hysterectomy (known as open surgery) but there is growing evidence that the keyhole (laparoscopic) approach may lead to an improved outcome.

Figure I: Lymph Glands that may be affected in Endometrial Cancer

With laparoscopic surgery, you do not have a big cut made in your abdomen (tummy). Instead the surgeon puts a telescope in through a 1cm cut in the belly button and introduces the instruments through three or four ½ to 1 cm cuts in the abdomen. The womb, ovaries and fallopian tubes and where appropriate, the lymph glands, are removed and the womb is delivered through the vagina. The keyhole technique usually means you recover much more quickly and can be discharged home within a day or two of surgery.

Laparoscopic surgery has particular benefits in obese women as studies have shown that they are less likely to get wound infections and other surgical complications when compared with open surgery. Despite this it is important to remember that risks of surgery are increased if you are significantly overweight or obese. This is because obese and overweight women can be more difficult to anaesthetise (put to sleep for the operation) and are more likely to suffer from chest and wound infections and blood clots.

Figure II: Laparoscopic (Keyhole) Surgery for Gynaecological Cancer

Will you need any other treatment after the hysterectomy?

When your hysterectomy is performed, the womb, ovaries and lymph nodes if they were removed, are sent to the pathology laboratory for analysis. The pathologist will issue a report stating the extent of the cancer.

The MDT will look at your case, taking into consideration your general health and fitness, the extent and features of the disease and decide if additional treatment is required.

If the cancer is confined to the womb and there are no features to suggest that it might behave aggressively, then no further treatment is required.

If your cancer is considered to be ‘high risk’ (see table 2) you may be offered radiotherapy treatment to the pelvis. In some cases, you may also be offered chemotherapy. Sometimes you may be asked to participate in a research study that will determine what additional treatment you have.

What happens after treatment?

When your treatment is completed, you will be followed up (monitored) by your doctors, usually for five years. The aim of follow up is usually three-fold:

1. To detect and, where possible, treat recurrence of the cancer
2. To monitor you for side-effects of treatment
3. To reassure you and offer you psychological support. 

At the follow up visit, the doctor will ask you questions about your health and any symptoms you may be experiencing. He/she will then examine you. If appropriate, you may be referred for a scan.

If you develop any abnormal symptoms in between visits, you must notify the specialist immediately. Table 3 lists some of the symptoms but if you develop anything new, even if it is not on the list, do let your specialist know.

The follow up visits become less frequent as more time passes since your treatment. If all is well at five years, you will usually be discharged from the cancer clinic.

Survival after endometrial cancer

In the majority of cases endometrial cancer is potentially curable as it is often detected early, before the cancer has had a chance to spread to other tissues. Survival from cancer is often defined as the percentage (number out of one hundred) of women alive and free of disease after five years. Survival from endometrial cancer in the UK has improved in the last 30 years or so. In 1971 to 1975, survival was 61% which means 6 in every 10 woman was alive and free of disease five years after treatment. This figure rose to 77% in 2000 to 2001.This means approximately 8 out of 10 women treated for endometrial cancer is likely to be alive and free of the cancer five years after treatment. Doctors and scientists continue to research ways of improving survival from this cancer.

As survival improves, attention is turning to quality of life after treatment for cancer. This includes making sure that the side effects of treatment are kept to a minimum. In addition, we know that if women pay closer attention to a healthy diet and lifestyle, their overall quality of life is improved. You are less likely to go on to develop other serious diseases such as heart disease and stroke if you maintain a healthy weight and remain active.

Eight out of ten women will be alive and free of endometrial cancer five years after treatment.

Summary points

• Obese or overweight women are significantly more likely to develop endometrial cancer
• The majority of endometrial cancers occur after the menopause
• The commonest symptom of endometrial cancer is bleeding from the vagina after the menopause
• In most women, endometrial cancer is detected early and can be successfully treated
• Treatment is usually by hysterectomy and there is growing evidence that the laparoscopic (keyhole) approach is better, particularly for obese women.
• A small proportion of women will require additional treatment which may be radiotherapy or chemotherapy
• Eight out of ten women will survive five years after treatment for endometrial cancer.
• A healthy diet and active lifestyle help to reduce the risk of endometrial cancer and contribute to quality of life after treatment for endometrial cancer.

Useful Links

• www.uclhwomenscancer.com
• www.hcacancercare.co.uk
• www.eveappeal.org.uk
• www.cancerresearchuk.org
• www.macmillan.org.uk

For further information on the author of this article, Consultant Gynaecologist, Dr Adeola Olaitan, please click here.