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Hormone use confuses menopausal status and obesity cancer link
- Ellen C G Grant (23 November 2007)
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The Influence of Physical Activity on Endogenous Oestrogen Levels and Breast Cancer
- Saurabh Upadhyay (31 December 2007)
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Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames. KT2 7JU, UK
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Gillian Reeves and colleagues found a significant increased relative risk (RR) of endometrial cancer with increasing BMI in the Million Women Study (MWS) for both postmenopausal (RR 3.98 for 1149 cases) and premenopausal (RR 1.77 for 164 cases) women.1 The MWS authors referred to speculation published in 1988 that, “whereas the effect of obesity on postmenopausal endometrial cancer is thought to be due to increased concentrations of unopposed oestrogens, any effect in premenopausal women may be due to progesterone deficiency rather than an excess of oestrogen”. There is no physiological evidence to back this suggestion. Endometrial hyperplasia and endometrial cancer result from higher levels of oestrogen than is usual in the follicular phase of a normal ovulatory cycle, at time when progesterone levels are low. Furthermore, menopausal status was difficult or impossible to define at baseline for some women and more would have become postmenopausal during the follow-up years whentheir cancers were registered. Between 1996 and 2001 the MWS recruited 1 084 110 women aged 50-64. At baseline 54% of the women had previously taken oral contraceptives and 50% were users or past users of HRT. 83% were postmenopausal, including women whose periods had ceased either naturally or as the result of a bilateral oophorectomy and women aged 53 and over who had either had a hysterectomy without oophorectomy or had begun use of HRT before their natural menopause. 7.1% were listed as perimenopausal. 10% women (all aged 50-52) were listed as of unknown menopausal status because of hysterectomy and/or HRT use before the menopause. Although only 5.8% of women were premenopausal at baseline, 12.8% of endometrial cancers, 9.3% of ovarian cancers and 17% of breast cancers occurred in premenopausal women. Menopausal status is being emphasized, rather than age, perhaps because more young women have had hysterectomies and oophorectomies in the decades since the contraceptive pill became to be used at some time by a majority of younger women. By 1981, in England and Wales, 34,500 women under age 45 had hysterectomies and had 6,500 oophorectomies. In the same year, 119 women developed endometrial cancer and 411 developed ovarian cancer. Such large-scale preventative surgery in young women must have contributed to the conflicting findings of epidemiological studies on the risks of endometrial and ovarian cancer with use of progestogens and oestrogens whether given for contraception (decreased) or for HRT (increased). Follow-up studies have underestimated the total carcinogenicity of exogenous progesterones and oestrogens by muddling up hormone use in different age groups. HRT users have been listed as never users in hormonal contraceptive studies and hormone contraceptive users as never users in HRT studies. Also there are many metabolic and immunological reasons why exogenous progesterone and oestrogen use can cause obesity. This increases the storage of lipophilic environmental contaminants with hormonal activity in body fat. Rapid weight gain is a common reason for discontinuing hormone use. 1 Reeves GK, Pirie J, Beral V, Green J, Spencer E, Bull E. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study BMJ, Nov 2007; doi:10.1136/bmj.39367.495995.AE Competing interests: None declared |
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Saurabh Upadhyay, Foundation Doctor Oncology Department, Ninewells Hospital and Medical School, Dundee DD2 9SY
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The complete influence of physical activity on good health remains a mystery. Some of the benefits and risks (like injuries) are unquestionable. Moreover, the optimum ( moderate or extreme) amount of regular exercise/physical activity and the exact pathophysiology of the benefits and risks is unknown and needs further research. One of the areas of debate remains the role of exercise in breast cancer. It is presumed that physical activity may have a link in the causation and influence outcome (prognosis)in breast cancer. Breast cancer has been linked to amount and duration of oestrogen exposure and there is a strong possibility that regular exercise affects the level of circulating natural oestrogen, though not to the same extent as the day of the menstrual cycle. Race(low in asians) and pregnancy are known to affect oestradiol and prolactin levels. Therefore, exercise may be one of the other factors which might affect the hormonal levels and hence influence breast cancer by altering the ovarian function. It is believed that insulin metabolism and weight loss have some influence on breast cancer across different age groups. Similarly, other mechanisms such as growth factor, immune function and stress would modify with physical activity and hence have some influence on health. Physical activity and energy balance are complex processes and hopefully future research will answer many of the unanswered questions. The incidence of breast cancer and survival time from it have been improving over the last decade in the western world. However, the recent spurt in the obese population, increasing BMI and lack of exercise risks offsetting the current trend. Therefore, the public has to be educated about the benefits of regular excercise. Competing interests: None declared |
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