Abstract
Large analysis of the Million Women Sstudy has suggested that cancer risk may be increased by 16% for every 10 cm in height.
A large study of more than a million women has revealed that height may be directly linked to an increased risk of total and location-specific cancers, an effect that was still seen following adjustment for confounding personal and socioeconomic variables. The results of the analysis, published by authors from Oxford University (UK) online in Lancet Oncology, add to epidemiological evidence suggesting that height may be linked to cancer growth mechanisms and the authors hope that it will lead to increased understanding of risk factors in cancer development.
Although there have been studies examining the association between overall height and cancer risk in the past, doubts existed about the validity of the effect. Speaking to Women's Health, the lead author of the study Jane Green (Oxford University), explained why the authors chose to analyze the effect of height in cancer: “Most individual studies were too small and/or lacking in detail on other risk factors (e.g., smoking) for a clear picture to emerge as to whether the link was specific to some cancers, or seen for all; and this was so particularly for cancer incidence, rather than mortality.”
The large analysis used data from the Million Women Study, a national UK-based cohort of more than a million women over 50 years of age, which aims to help elucidate how certain factors affect the incidence of disease in this age group. The recently published study analyzed 1,297,124 women for a median of 9 years per women, during which time, over 97,000 cancer cases were identified.
When performing regression analysis, the relative risk for total cancer incidence was found to the 16% higher for each 10 cm increase in height. This was true for most major sites and was significant for many common cancer locations including the rectum, breast, ovary, endometrium and the brain. Interestingly, the relative risk did not vary significantly when considering socioeconomic status or other personal characteristics, although the effect was less pronounced in smoking-related cancers. Talking to Women's Health, Green theorized that this may be caused by the influence of height being “swamped by the larger effect of smoking”, which may explain some inconsistencies in previous studies of this type.
“The link between height and cancer risk seems to be common to many different types of cancer and in different people; suggesting that there may be a basic common mechanism, perhaps acting early in peoples' lives, when they are growing.”
In an accompanying meta-analysis of similar studies, the authors found little variation across geographically diverse populations, strengthening the thought that the association may not simply be an environmental one.
“We showed that the link between greater height and increased total cancer risk is similar across many different populations from Asia, Australasia, Europe and North America,” explained Green. “The link between height and cancer risk seems to be common to many different types of cancer and in different people; suggesting that there may be a basic common mechanism, perhaps acting early in peoples' lives, when they are growing.”
Suggested mechanisms for this effect include diet and infection history, as well as hormonal and genetic factors. However, Green was very keen to point out that this study “is important not for individual or public health, but because it may help us to understand better how cancer develops.” She later went on to reassure that “of course people cannot change their height. Being taller has been linked to a lower risk of other conditions, such as heart disease.”
Sources: Green J, Cairns BJ, Casabonne D, Wright FL, Reeves G, Beral V; for the Million Women Study collaborators. Height and cancer incidence in the Million Women Study: prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol. 12(8), 785–794 (2011); Direct quotes from Jane Green, Oxford University, UK.
Temporary ovarian suppression could reduce chemotherapy-induced premature menopause in young breast cancer patients
Administration of a gonadotropin-releasing hormone analog before and during chemotherapy may help to reduce the number of young women who experience premature ovarian failure during breast cancer treatment.
A large European study has suggested that temporarily suppressing ovarian function using triptorelin, a gonadotropin-releasing hormone analog, may help to reduce the incidence of premature ovarian failure in young women undergoing adjuvant and neoadjuvant chemotherapy for breast cancer. The trial, led by researchers from Genova, Italy, and published in the JAMA, indicated that combining chemotherapy with triptorelin in women may reduce the 1-year incidence of early menopause by nearly a fifth.
It is estimated that 6% of breast cancer patients are under the age of 40, with most considered suitable for chemotherapy. Chemotherapy-induced premature ovarian failure is one of the main concerns of women of child bearing age who undergo treatment and standard strategies for its prevention have yet to be enacted.
The results of the Phase III, parallel, randomized trial – the so called Prevention of Menopause Induced by Chemotherapy: A Study in Early Breast Cancer Patients – Gruppo Italiano Mammella 6 (PROMISE–GIM6) study – selected patients with stage I–III breast cancer who were about to undergo adjuvant or neoadjuvant chemotherapy. Triptorelin was administrated before and during chemotherapy, with the main outcome of the study the levels of early menopause (defined as no resumption of menstrual activity and levels of follicle-stimulating hormone and estradiol) 1 year after the last cycle of chemotherapy.
“Chemotherapy-induced premature ovarian failure is one of the main concerns of women of child bearing age who undergo treatment and standard strategies for its prevention have yet to be enacted.”
Clinical and tumor characteristics were similar, but the absolute difference of 17% between chemotherapy alone (25% rate of early menopause) and triptorelin plus chemotherapy (17% rate of early menopause) was seen to be very significant. The resumption of menses rate was higher in triptorelin-treated patients (63.3% resumed), compared with the chemotherapy alone group (49.6% resumed). The significant effect on the number of people developing early menopause was also not dependent on age of the patient or type of chemotherapy.
Gonadotropin-releasing hormone agonists are synthetic hormones designed to elicit the release of follicle-stimulating hormone and luteinizing hormone and can be used to suppress ovarian activity. Preclinical and clinical results have suggested that the agonists may help protect ovarian function from the cytotoxic effect of chemotherapy; however, this is the largest clinical trial so far to suggest its efficacy.
Sources: Del Mastro L, Boni L, Michelotti A et al. Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA 306(3), 269–276 (2011); JAMA Press release: http://pubs.ama-assn.org/media/2011j/0719.dtl#3
About the Bulletin Board
The Bulletin Board highlights some of the most important events and research in the field of women's health. If you have newsworthy information, please contact:
Louise Rishton, Commissioning Editor, Women's Health, Future Medicine Ltd, Unitec House, London, N3 1QB, UK,
Polycystic ovary syndrome could be prevented or delayed by diabetes drug
A recent study has demonstrated that early, prolonged treatment with the diabetes drug metformin may prevent or delay the development of polycystic ovary syndrome (PCOS) in adolescence. It is hoped that the clinical results supporting an early regime of treatment to prevent PCOS may reduce the numbers affected by the hormonal syndrome in later life.
Polycystic ovary syndrome is the most common cause of infertility in women and it is currently estimated that between 5 and 6 million women in the USA alone are affected. Infertile women with PCOS are treated using several methods including diet monitoring, lifestyle modifications and clomiphene, which may delay infertility. The current control methods are fairly effective, but can only treat the symptoms, not cure the syndrome.
The purpose of the recent study published in the Journal of Clinical Endocrinology and Metabolisms was to compare the efficacy of early versus late metformin treatment in preventing adolescent PCOS. The study was composed of girls with a history of low birth weight and precocious pubarche, a population known to be at risk for developing PCOS.
“Polycystic ovary syndrome often presents in adolescence, with irregular menstrual cycles, acne, or too much body hair,” commented the senior author of the study, Lourdes Ibáñez from the University of Barcelona, Spain. “But we believe the critical years for PCOS development may be during childhood and puberty when excessive amounts of fat are stored. That excessive weight gain overexposes the ovaries to insulin, causing them to stop ovulating and start releasing male hormones, resulting in PCOS.”
The study was a randomized, open-label study carried out over 7 years, involving 38 girls. It was reported that 19 of the girls were treated with daily doses of metformin over a period of 4 years from the age of 8 years. The other 19 girls received no treatment between the ages of 8 and 13 years, before receiving the same treatment at the age of 13 years for 1 year only. The researchers found that the early metformin treatment regime prevented or delayed the development of hirsutism, androgen excess and PCOS in a more effective manner than late metformin treatment.
Further research will be required in order to prove how effective metformin is when used as a drug to prevent or delay the development of PCOS, and to ascertain whether it should be used by all girls in their early puberty who are viewed to be at risk of developing the syndrome.
Ibáñez concluded that “In the years ahead, the focus of attention should shift from late treatment of PCOS and its complications, toward the early and large-scale prevention of PCOS, with measures such as diet, exercise and metformin in young girls.”
Sources: Ibáñez L, López-Bermejo A, Díaz M, Marcos MV, de Zegher F. Early metformin therapy (age 8–12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence. J. Clin. Endocrinol. Metab. 96(8), E1262–E1267 (2011); The Endocrine Society Press release: www.endo-society.org/media/press/2011/News-Briefs-from-The-Endocrine-Society.cfm?RenderForPrint=1
Ovulatory status may affect frequency of seizures in epileptic women
A study has revealed that the different serum levels of estradiol and progesterone during the different phases of an epileptic womens ovulatory cycle increase the frequency of secondary generalized tonic-clonic seizures.
The study, published recently in Epilepsia, aimed to look at the effects of progesterone therapy in the onset of seizures, and involved a total of 281 women who completed the 3 month period of study. Of the 281 women included in the study, 92 had both anovulatory and ovulatory cycles, and their average daily seizure frequency (ADSF) was compared between these cycles by studying the proportional differences in ADSF and the ratio of estradiol:progesterone in serum. The researchers observed the effects on three kinds of seizures; secondary generalized tonic–clonic seizures (2GTCS), complex partial seizures and simple partial seizures.
They found that the ADSF was 29.5% greater for 2GTCS during anovulatory than during ovulatory cycles, but the ADSF did not differ significantly for complex partial seizures or simple partial seizures or for all seizures combined. Among the 281 women, the three seizure types did not differ in terms of ovulatory rates, but estradiol:progesterone ratios were found to be greater for cycles with 2GTCS than partial seizures only.
The authors concluded that “these findings support a possible role for reproductive steroids in 2GTCS occurrence.”
Source: Herzog AG, Fowler KM, Sperling MR et al. Variation of seizure frequency with ovulatory status of menstrual cycles. Epilepsia doi: 10.1111/j.1528-1167.2011.03194.x (2011) (Epub ahead of print).
Initiation of menopause not found to be associated with increased diabetes risk
A study conducted by the Diabetes Prevention Program Research Group has revealed that the diabetes risk in postmenopausal women does not differ between those who have experienced natural menopause and those who have had their ovaries removed.
It had previously been hypothesized that the increase in testosterone levels associated with menopause would increase the risk of progression to diabetes; however, this recent study published in Menopause provides evidence against this theory.
The randomized placebo-controlled trial of glucose-intolerant adults involved 708 premenopausal women, 328 women in natural menopause and 201 women with bilateral oophorectomy (surgical removal of ovaries). Statistical models were used to evaluate associations between menopause and diabetes risk, and the effect of lifestyle intervention (e.g., diet and exercise, and hormone replacement therapy) on diabetes risk.
The researchers found that among women with a high risk for diabetes, natural menopause was not associated with an increased diabetes risk and did not affect response to diabetes prevention interventions. In the lifestyle intervention section of the study, bilateral oophorectomy was found to be associated with a decreased diabetes risk.
“Among women with glucose intolerance, the menopausal transition does not seem to increase risk, despite the relative increase in androgens: estrogen associated with menopause … lifestyle changes seemed more effective at diabetes prevention than among women in natural menopause or women in premenopause.”
Catherine Kim, Assistant Professor in the Department of Medicine at the University of Michigan (MI, USA) and co-author of the study commented on the findings to Future Science Group; “Among women with glucose intolerance, the menopausal transition does not seem to increase risk, despite the relative increase in androgens: estrogen associated with menopause.” Kim continues; “Among women who were in menopause and who had their ovaries removed, lifestyle changes seemed more effective at diabetes prevention than among women in natural menopause or women in premenopause.”
The team at the University of Michigan are currently researching how androgens and estrogen change with intervention and whether they predict decrease in glucose.
Sources: Kim C, Edelstein SL, Crandall JP et al. Menopause and risk of diabetes in the Diabetes Prevention Program. Menopause 18(8), 857–868 (2011); University of Michigan Health System: www.uofmhealth.org/news/menopause-diabetes-2011; Direct quotes from Catherine Kim (
In brief…
Researchers from Harvard Medical School (MA, USA) and Brigham and Women's Hospital, Boston (MA, USA) have found that women with a high mammographic breast density may be more likely to have more aggressive forms of breast cancer The study published online in the Journal of the National Cancer Institute, analyzed 1042 postmenopausal women with breast cancer and 1794 matched controls, comparing reports of breast density with tumor characteristic subtypes including invasiveness, size, grade, histology, receptor status and involvement of lymph nodes. As expected, women with a higher density were more than three-times more likely to be diagnosed with breast cancer Furthermore, an association between breast density and aggressive characteristics was found when analyzing for tumor size, and the percentage that were high grade and estrogen-negative status. The association between density and breast cancer risk was also found to be stronger with in situ tumors. The authors recommended that breast density should be included in risk prediction models for breast cancer.
An observational trial published in the Journal of Clinical Cancer Research has found that treatment of CNS metastases in HER2-positive breast cancer patients can significantly extend overall survival time. In the observational analysis of the registHER study 1023 recently diagnosed breast cancer patients who were HER2-positive, 37.3% were found to have CNS metastases. These patients were found to be younger overall, with a higher disease burden and a high proportion of hormone receptor-negative status. Treatment with trastuzumab, chemotherapy or surgery all significantly increased overall survival, with a nonsignificant effect of radiotherapy on prolonging the overall survival. Multivariable proportional hazards proved the effect of trastuzumab and chemotherapy to be independent. Lead author Adam Brufsky, University of Pittsburgh Cancer Center (PA, USA) commented “It is surprising that chemotherapy/trastuzumab adds to these women's survival. We thought that the brain metastases would be dominant in this regard no matter what therapy.”