Scientists map risk of premature menopause after cancer treatment
Women treated for the cancer Hodgkin lymphoma will be able to better understand their risks of future infertility after researchers estimated their risk of premature menopause with different treatments.
The findings, set out in the Journal of the National Cancer Institute, are based on the experience of more than 2,000 young women in England and Wales treated for the cancer over a period of more than 40 years.
Previous research has suggested that women with Hodgkin lymphoma who receive certain types of chemotherapy or radiotherapy are at increased risk of going through the menopause early – but there was insufficient information to provide patients with detailed advice.
But the new study, led by scientists at The Institute of Cancer Research, London, provides precise estimates of risk for women depending on which treatment types and doses they received and at what age - allowing doctors to give them detailed advice about their risks of future infertility.
The research was largely funded by Breakthrough Breast Cancer and involved researchers from across the UK at more than 50 universities and hospitals.
The research team followed-up 2,127 women who had been treated for Hodgkin lymphoma in England and Wales between 1960 and 2004, and who had been aged under 36 at the time. All had received treatment with chest radiotherapy, sometimes alongside other treatments.
Some 605 of the women in the study underwent non-surgical menopause before the age of 40. This was a large enough number for the researchers to estimate accurate risks of menopause at different ages, depending on the mixture and doses of treatments they received and the age they received them.
Menopause does not cause cancer, but the risk of developing cancer increases as a woman ages. Therefore, women who have been through natural menopause are more likely to develop cancer because they are older.
Menopause occurs when a woman’s ovaries stop releasing eggs. During natural menopause, a woman’s body makes less of the hormones estrogen and progesterone, causing irregular menstrual periods that eventually stop. It generally begins during a woman’s mid-40s or early- to mid-50s. However, it may begin earlier if cancer treatment - such as surgery, chemotherapy, or hormone therapy - stops the ovaries from working; this is called premature menopause. Learn more about long-term side effects of cancer treatment.
The symptoms of menopause include hot flashes, night sweats, vaginal dryness, painful sexual intercourse, decreased sex drive, osteoporosis (thinning of the bones), bladder control difficulties, mood swings, and insomnia. Find out how to manage menopausal symptoms.
Menopause and cancer risk
A woman who experiences menopause after age 55 has an increased risk of ovarian, breast, and uterine cancers. The risk is greater if a woman also began menstruating before age 12. This is because a woman who menstruates longer than normal during her lifetime is exposed to more estrogen and has more ovulations. A longer exposure to estrogen increases a woman’s risk of uterine and breast cancers, and having more ovulations than normal increases a woman’s risk of ovarian cancer.
The researchers produced a risk table which could help improve the advice that clinicians are able to give to women who have undergone treatment for the disease. Several of the treatments caused a sharp increase in premature menopause risk.
For example, a woman who had received six or more cycles of a standard chemotherapy regimen in her late 20s, but without receiving radiotherapy to the pelvic area, had a chance of around 18 per cent of undergoing menopause by the age of 30, or 58 per cent by age 40.
Overall, risk of premature menopause was more than 20-fold raised after ovarian radiotherapy, and also after some specific chemotherapy regimens. Risk of menopause by age 40 was 81 per cent after receiving ovarian radiotherapy at an overall dose of 5 or more Grays, and up to 75 per cent after chemotherapy, depending on the type, although only one per cent after receiving a chemotherapy regimen called ABVD.
Study leader Professor Anthony Swerdlow, Professor of Epidemiology at The Institute of Cancer Research, London, said:
“Hodgkin lymphoma often affects younger women, and although fortunately most survive the disease, treatments including certain types of chemotherapy and pelvic radiotherapy can lead to premature menopause.
Many young women are at increased risk for premature menopause following adjuvant treatment for breast cancer. These women must deal with consequences of menopause, including loss of fertility and physiologic symptoms such as night sweats, hot flashes, vaginal dryness, and weight gain. These symptoms can be particularly distressing for young women and can adversely affect both health-related and psychosocial quality of life (QOL). While there are a wide range of pharmacologic and non-pharmacologic interventions available to help with these symptoms and in turn, improve QOL, there is little data available about the use and efficacy of these interventions in younger women who become menopausal as a result of their breast cancer treatment. Future studies should focus on this vulnerable population, with the goal of identifying effective strategies to relieve symptoms and improve quality of life in young breast cancer survivors.
It is well established that the diagnosis and treatment of breast cancer can have a profound impact on a patient’s short and long term quality of life (QOL). Young women with breast cancer have unique health and psychosocial concerns and are also more likely to experience poorer QOL outcomes following diagnosis compared to older women. In particular, fertility concerns and outcomes as well as associated menopausal issues may greatly impact on a young women’s survivorship.
Amenorrhea is a common consequence of systemic breast cancer therapy among young women, the vast majority of whom are premenopausal at diagnosis. In many cases, it is temporary, with menses resuming in the months following the end of treatment. For some women, amenorrhea is permanent, and heralds the onset of early menopause. Even if menses do resume, many breast cancer survivors are at an increased risk of premature ovarian failure (POF). Most women who remain amenorrheic for at least a year will not resume menstruation and will be considered to have POF.
POF resulting from chemotherapy is largely dependent on both age and treatment type. For example, in women under 40, a regimen consisting of cyclophosphomide, methotrexate, and 5-fluorouracil (CMF) for 6 months is associated with a risk of premature menopause approximated to be between 30-40%; in women aged 40 and older this risk is greater than 80% and has been reported to be as high as 96%. Treatment with doxorubicin and cyclophosphomide (AC) is associated with a lower risk of menopause: 13% for women younger than 40 and 57-63% in women aged 40 and older. Adjuvant tamoxifen therapy has also been identified as a risk factor for premature menopause in young breast cancer survivors. Additionally, choices like bilateral prophylactic oophorectomy as a means of ovarian suppression or as a risk reduction strategy in women at high risk for ovarian cancer (i.e., BRCA 1 or 2 mutation carriers) may also cause early menopause among young women with breast cancer. Regardless of the reason, these women face the physiological changes that frequently accompany menopause, as well as the emotional reality of becoming prematurely potentially infertile. While these experiences might be “normal” for women who are in their 50s, for women in their 20s, 30s and early 40s, these changes can be extremely distressing and have the potential to negatively affect QOL.
“We hope our study will help women to understand better, in consultation with their doctors, their risks of future infertility following treatment for this malignancy. By looking in a much larger group of women than previous studies of this type, we were able to produce age and treatment specific risk estimates that we hope will be of practical use to individual women. I’m extremely grateful to the patients and doctors who made it possible for us to produce this information.”
Notes to editors
The Institute of Cancer Research, London, is one of the world’s most influential cancer research institutes.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR’s mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk
Breakthrough Breast Cancer is the UK’s leading breast cancer charity dedicated to saving lives through improving early diagnosis, developing new treatments and preventing all types of the disease.
The need for Breakthrough Breast Cancer’s work has never been greater. Breast cancer is the most common of all cancers in the UK, with 50,000 women diagnosed every year and 1,000 women dying every month.
Breast cancer is not yesterday’s problem; it’s a disease that affects more women every year. Breakthrough Breast Cancer is working harder than ever before to stop women getting, and dying from, the disease.
The charity funds 25% of the breast cancer research in the UK, campaigns to ensure survival rates are among the best in the world and educates women to recognise the signs and symptoms of the disease.
Over the next six years Breakthrough will take its ground-breaking work to the next level by investing at least ?100 million in research that has the power to stop breast cancer for good.
Institute of Cancer Research