Wednesday July 20 2011
Obesity had the strongest association with hormone levels
“Obesity is the biggest driving force behind the most common form of breast cancer,” BBC News has reported. Alcohol and then cigarettes are the next largest culprits, it added.
The news is based on research that analysed how closely a number of lifestyle factors are linked to hormone levels in postmenopausal women – higher hormone levels after the menopause are known to be associated with an increased risk of breast cancer. The researchers gathered data on more than 6,000 women who did not have breast cancer to look at how their hormone levels related to factors such as their age, intake of alcohol and cigarettes, and weight.
They found that hormone levels, particularly oestrogen hormones, were higher in obese women than in lean ones. They also found that women who drank 2.5 or more units of alcohol (20g+) daily, or who smoked 15 or more cigarettes, had higher hormone levels.
The authors say that the relationship between higher BMI and higher levels of oestrogen is not new, and it explains why obese, postmenopausal women are at an increased risk of breast cancer. However, though this research suggests how these lifestyle risk factors may be associated with breast cancer risk, the design of this study means that it cannot prove this link.
For example, we cannot tell if obesity definitely raises hormone levels or if hormone levels contribute to a women’s obesity. Also, this study only examined women who did not develop breast cancer during study follow-up: for comparison, it would be helpful to look at whether women who had gone on to develop breast cancer had had higher hormone levels and other associated risk factors prior to their diagnosis.
Despite these limitations, this study is consistent with current advice that maintaining a healthy weight, limiting alcohol intake and abstaining from smoking can all reduce the risk of cancer, particularly breast cancer.
Where did the story come from?
The study was carried out by researchers from the University of Oxford and was funded by Cancer Research UK. The study was published in the peer-reviewed British Journal of Cancer.
Generally, the media reported the story accurately, although headlines implying that obesity is the “leading driver” or “biggest avoidable cause” perhaps overstated the findings – the study did not in itself analyse data on women who developed cancer. Instead, it looked at whether obesity and other lifestyle factors were related to hormone levels, which can in turn affect cancer risk.
What kind of research was this?
This study examined the relationship between risk factors for breast cancer and levels of circulating sex hormones, drawing on data on 6,000 women gathered from 13 previously published studies.
Some, though not all, breast cancers are hormone-dependent – i.e. they are fuelled by sex hormones, particularly oestrogen. The study authors say that although the breast cancer risk for postmenopausal women is known to be associated with levels of sex hormones such as oestrogens, the factors that determine the levels of these hormones are not well understood. While obesity is thought to increase the risk of cancer through its association with high levels of oestrogen, it is unclear how other risk factors affect sex hormone levels.
The studies gathered for this analysis were prospective cohort studies that had assessed women at the start of the study and then followed them to see if they later developed breast cancer. The authors of this new paper, however, were looking at cross-sectional data from these studies, i.e. they were looking at data collected at the time of the women’s first assessment. This data covered various aspects of health and factors potentially related to breast cancer risk, e.g. blood tests to check the women’s hormone levels, measurements of height and weight, and lifestyle factors (smoking, alcohol, etc). This new analysis only looked at those women in the cohort studies who had not gone on to develop breast cancer during the follow-up period.
What did the research involve?
The researchers say they aimed to gather cohort studies which had included data on hormone levels and breast cancer risk in postmenopausal women. Studies were identified by computer-aided literature searches, from relevant review articles and from discussions with colleagues. Studies were eligible for inclusion if they featured published data on hormone levels and breast cancer risk, using prospectively collected blood samples from postmenopausal women. In these previous studies the women were then followed-up to identify who developed breast cancer. The analysis in the current paper used data only from those women who had not developed breast cancer during each study’s follow-up.
The description of inclusion criteria for eligible studies, and the researchers’ stated use of ‘computer-aided literature searches’ suggests that this could have been a systematic review. However, as the methods are not explicitly stated and a list of searched medical databases is not given, it is not clear whether or how the researchers ensured their search was comprehensive and that all relevant studies were identified.
The researchers looked at the gathered data on levels of all hormones thought to have an effect on breast cancer risk, including oestrogens, androstenedione, DHEAS (dehydroepiandrosterone sulphate) and testosterone. They also looked at a hormone called sex hormone-binding globulin (SHBG), which binds to sex hormones - as only ‘free’, unbound hormone molecules are biologically active, levels of this hormone will determine the activity of the sex hormones. They also identified information on reproductive factors and other risk factors in postmenopausal women, including age at puberty, type of menopause, (whether natural or caused by surgery), smoking status, alcohol intake and body mass index (BMI, the measurement which indicates normal weight, underweight, overweight or obesity).
Using statistical methods, they explored any association between hormone levels and breast cancer risk factors.
What were the basic results?
The researchers say that 13 international studies contributed data on more than 6,000 women. Briefly, the main findings were:
- The strongest correlation was between sex hormone levels and women’s BMI scores (higher sex hormone levels were found in people with higher BMI).
- All hormones were higher in obese than lean women. The largest difference was in levels of unbound (free) oestradiol (SHBG was lower in obese women, meaning that more oestrogen was freely circulating and biologically available).
- Women who smoked 15 or more cigarettes a day had higher levels of all hormones than non-smokers. The largest difference was in levels of testosterone (higher testosterone in smokers).
- Women who drank 20g or more of alcohol a day (about 2.5 units) had higher levels of all hormones (but lower SHBG) than non-drinkers. The largest difference was in levels of DHEAS, which was higher in drinkers DHEAS is a steroid hormone produced by the adrenal gland positioned above the kidney; it is a ‘prohormone’, which acts as a building block in the production of both oestrogen and testosterone.
Researchers also found that:
- all hormone levels (apart from SHBG) were lower in older women than in younger women
- male hormones (androgens – the most well known of which is testosterone) were lower in women who had undergone a ‘surgical menopause’ (women who have had their ovaries surgically removed) than those who had natural menopause; the largest difference was in testosterone levels
- hormone levels were not strongly related to other known risk factors for breast cancer, such as age at menopause, number of children, age at first pregnancy or family history
How did the researchers interpret the results?
The researchers say that levels of sex hormones, known to increase breast cancer risk, are associated with several known or suspected risk factors, such as BMI, smoking and alcohol. They say their study helps to understand why these are risk factors and how they might influence hormone levels.
This large study has combined cross-sectional data from 13 international studies which had previously collected information on postmenopausal women’s sex hormone levels, while also assessing other risk factors for breast cancer, such as their weight, smoking and alcohol intake. The researchers looked at how hormone levels correlated with these risk factors. They found that weight was the risk factor mostly strongly associated with breast cancer hormones, followed by alcohol and smoking (i.e. there was positive correlation between them - higher weight, alcohol intake and smoking each related to higher hormone levels).
However, although the researchers’ findings may suggest that hormone levels could potentially be the mechanism through which these lifestyle factors increase breast cancer risk, this cannot be concluded for definite. In particular, the fact that this was a cross-sectional study means it cannot tell us how these risk factors are associated with hormone levels. Cross-sectional research looks at a series of factors at only a single point of time and therefore cannot tell us how factors are related to each other or how they progress over time. Given this limitation, we cannot establish important facts, such as whether changes in a woman’s weight cause corresponding changes in her hormone level, or whether higher levels of hormones have caused the women to gain greater amounts of weight.
Also, as the authors point out, other factors that are potentially important to risk, such as diet and physical exercise, were not included in the analyses. In addition, most of the women in the studies were of white European ethnic origin, so we do not know if the findings would be applicable to other ethnic groups. Nor do we know what patterns between hormone levels and lifestyle risk factors for breast cancer would be seen in premenopausal women. In premenopausal women there is a natural variation in levels of sex hormones during the woman’s menstrual cycle, and sex hormone levels have not been demonstrated to influence breast cancer risk in premenopausal in the same way as for postmenopausal women.
The researchers also restricted their sample to women who were not known to have gone on to develop breast cancer. It would have been beneficial, for comparison, to look at the hormone levels and prevalence of risk factors in women who were known to have developed breast cancer to see if there were similar patterns.
Though this study cannot conclusively prove how lifestyle factors may be linked to breast cancer risk, it is consistent with current advice that keeping to a healthy weight, limiting alcohol intake and abstaining from smoking can all reduce the risk of cancer, particularly breast cancer.