Multivitamins and breast cancer risk

An observational study of more than 35,000 postmenopausal women which found an association between multivitamin intake and a small increased risk of breast cancer has received wide media coverage. The study can be found here.

The following commentary was written for the Australasian Menopause Society by AMS council member Professor Martha Hickey MBChB MD FRANZCOG.

Multivitamin supplements are widely used by men and women in the developed world. About 40% of US women reported using multivitamins in 1999–2000 (1). The reasons why people choose to take multivitamins are not well defined, but are likely to relate to perceived benefits for general health and for reduction of specific common conditions such as cardiovascular disease and cancer.

Breast cancer affects up to one in eight Australian women. Any intervention which potentially increases the risk of breast cancer is of significant public health concern since even small increases in risk can translate into large numbers of women affected.

The relationship between multivitamin use and breast cancer is not well understood and previous studies have reported conflicting results. Of concern is a relationship between multivitamin use and increased breast density (2). Increased breast density is important for two main reasons: Firstly, it may be a risk factor for breast cancer; and, secondly, increased density may decrease the ability of mammography to detect a breast abnormality.

A new publication using a prospective cohort of over 35,000 postmenopausal Swedish women without breast cancer attending for mammography (3) reports that multivitamin use was associated with an increased risk of developing breast cancer over a nine-year follow-up period. Twenty-five per cent of women in this study were taking multivitamins. The increased risk was small (relative risk increase of 19%) but was statistically significant (so was not thought to be due to chance). The study was large enough to also account for many other factors known to contribute to breast cancer risk. Taking calcium did not appear to increase breast cancer risk in this study. A Canadian study has recently reported that vitamin D supplements are associated with a reduction in breast cancer risk of 24% (4).

The key message from this study is that multivitamin use may be associated with a small increased risk of breast cancer in postmenopausal women. The increased risk equates to about five extra cases of breast cancer per 1000 women over ten years (5). Since multivitamins have not been shown to benefit women taking a varied and healthy diet, and are a significant expense, the AMS recommends obtaining required vitamins from dietary sources rather than supplements. Advice on health and diet can be obtained from the NHMRC at http://www.nhmrc.gov.au/publications/synopses/dietsyn.htm

 1. Radimer K., Bindewald B., Hughes J., Ervin B., Swanson C., Picciano M.F. Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Am J Epidemiol 2004; 160: 339–49.

 2. Berube S., Diorio C., Brisson J. Multivitamin-multimineral supplement use and mammographic breast density. Am J Clin Nutr 2008; 87:1400–04.

 3. Susanna C. Larsson, Agneta Åkesson, Leif Bergkvist, and Alicja Wolk. Multivitamin use and breast cancer incidence in a prospective cohort of Swedish women. Am J Clin Nutr 2010 91:1268-1272. First published online March 24; doi:10.3945/ajcn.2009.28837.

4. Anderson L.N., Cotterchio M., Vieth R., Knight J.A. Vitamin D and calcium intakes and breast cancer risk in pre- and postmenopausal women. Am J Clin Nutr. 2010, April 14. doi:10.3945/ajcn.2009.28869 [E-published ahead of print].

 5. Jean Hailes Foundation for Women’s Health (2010, April 23). Breast cancer and multivitamins: Jean Hailes experts weigh in. Published online www.jeanhailes.org.au

Content updated 27 April 2010

Only infrequent incontinence symptoms appear attributable to the menopause, according to researchers who conducted a longitudinal study. Modifiable factors including anxiety, weight gain and diabetes were associated with more frequent incontinence, they found.

A single dose and once-yearly dose of zoledronic acid protects against bone loss in postmenopausal women with low bone mass over two years, a randomised, placebo-controlled study shows.

Postmenopausal women with decreased bone mineral density may have higher risk of subclinical coronary atherosclerosis, researchers say.

Apart from vasomotor symptoms, common midlife complaints include stiff or painful joints and difficulty sleeping, data from the Australian Longitudinal Study on Women's Health shows.

The study found only a slightly increased risk of urinary incontinence associated with the perimenopause but a positive association with ageing.  Headaches and migraine were negatively associated with ageing.

Symptoms reported by women in midlife: menopausal transition or aging?

Vaginal suppositories containing combination oestriol and progesterone may be useful in women with atrophic vaginitis, a study shows.   The intravaginal therapy may be a safe and effective alternative to systemic therapy, researchers said.

Efficacy and safety of vaginal estriol and progesterone in postmenopausal women with atrophic vaginitis

DHEA applied intravaginally for 12 weeks improves desire, arousal and orgasm in postmenopausal women with vaginal atrophy, a study shows.  The randomised, controlled study of DHEA (Prasterone) shows a dose-dependent reduction in pain at sexual activity and in measures of sexual dysfunction.

Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women.

 

Post-hoc analysis of the WHI trial report that in post-menopausal women conjugated equine estrogen plus medroxyprogesterone acetate did not increase the incidence of lung cancer but increased mortality from lung cancer.

Flavonoids in berries may benefit cardiovascular health, a review shows.

Adding berries to the diet may also prevent some cancers and animal studies suggest a potential benefit for cognition, researchers found.

However they said evidence was limited and it was not possible to define which berries were most beneficial.

 Effects of botanicals and combined hormone therapy on cognition in postmenopausal women.

Red clover and black cohosh have no impact on cognitive function in midlife women with vasomotor symptoms, a small study suggests.

Comparison of the botanicals with combined hormone therapy or placebo showed no changes in verbal memory among those taking the herbs.

HT worsened some aspects of verbal memory but was the only intervention reducing hot flushes in this study.

In a nationwide prospective cohort study of Danish women who turned 50 years old between 1995 and 2002 [1], 909,946 women were eventually included in the analysis; 575,883 were never-users of HRT and 334,063 were ever-users. During an average follow-up of 8 years, there were 3068 ovarian cancers of which 2681 were epithelial tumors.

Ever-use of HRT was associated with an increased risk of ovarian cancer of 1.38 (95% confidence interval (CI) 1.26-1.51). The risk declined with years since last use and had disappeared after 2 years. The risk of epithelial ovarian cancer was 1.44 (95% CI 1.30-1.58). There was no significant difference between risk for users of estrogen-only therapy compared with combined estrogen plus progestin therapy and there was no significant difference in risk between those taking continuous or cyclic progestin. There was a non-significant trend to a lesser risk for women using transdermal estrogen compared to oral estrogen; however, the trend was reversed for transdermal compared to oral estrogen plus progestin therapy. There was no effect of dose or duration of therapy and no effect of age. The estimated absolute increase in risk of ovarian cancer for users of hormone replacement therapy (HRT) was 0.52 per 1000 woman-years compared to 0.40 per 1000 woman-years for non-users. This equates to one extra case per approximately every 8300 women taking HRT.

HRT may prevent diabetes in postmenopausal women, a commentator concludes following findings from a large cohort study.

HRT and the new incidence of diabetes mellitus

The Kuopio Osteoporosis Risk Factor and Prevention Study is a prospective population-based cohort study. In a new publication [1], the effect of hormone replacement therapy (HRT) on the new incidence of diabetes mellitus was examined.

Almost 8500 women in the early postmenopause were followed over a 5-year period. Almost one-third of the women were current users of HRT whilst around one-quarter had previously used HRT.

The diagnosis of new diabetes was ascertained from the registry of specially refunded drugs which gives the right to full reimbursement for drugs used in chronic illnesses following a physician's diagnosis.

The incidence of diabetes was slightly reduced in past users of HRT (hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.57-1.16), further reduced in HRT users for <2½ years' duration (HR 0.53; 95% CI 0.24-1.15), and significantly reduced in HRT users for >2½ years' duration (HR 0.31; 95% CI 0.16-0.60).

There were some baseline differences between HRT users and non-users. The HRT users were slightly younger, had lower body mass index, lower parity, lower prevalence of hypertension and greater prevalence of hysterectomy. However, the analyses were adjusted for these factors.

The type and dose of HRT were not recorded, although the population is thought to reflect the use of oral 17ß-estradiol, with or without a progestogen.

 

Women who taper HT report significantly lower menopausal symptom scores after discontinuation compared to women who go ‘cold turkey', a survey shows. However tapering HT was also associated with resumption of therapy at a later date, researchers found. 

Discontinuing postmenopausal hormone therapy: an observational study of tapering versus quitting cold turkey: is there a difference in recurrence of postmenopausal symptoms?

Haskell, Sally G et al

Menopause 2009;16(3)494-99

Related editorial:

Tapering versus cold turkey: symptoms versus successful discontinuation of menopausal hormone therapy

Suffoletto, J.; Hess, R.

Menopause 2009; 16 (3): 436-37

 

Content updated 1 June 2009

Combined vaginal and oral low-dose oestrogen plus progestogen therapy improves dyspareunia, sexual experience, and quality of life in postmenopausal women, a small randomised, placebo-controlled trial finds.

Postmenopausal women aged 45 to 65 years received daily oral conjugated oestrogens (0.45 mg medroxyprogesterone (1.5 mg) tablet for six 28 day cycles along with 1 g conjugated oestrogen vaginal cream (0.625 mg) intravaginally or placebo.

The treated women had a significant decrease in frequency of dyspareunia. In addition, treatment was associated with improvement in level of sexual interest, and the frequency and pleasure of orgasm.

A randomised study of low-dose conjugated oestrogens on sexual function and quality of life in postmenopausal women.

Gast, MJ et al Menopause 2009; 16(2):247-256

 

Content Updated April 24 2009

Many studies have found a significantly lower frequency of reported hot flushes in Japanese and Japanese American women, leading to speculation about dietary, genetic or cultural differences with Western women.

In a study comparing reported hot flush frequency with objective measurement, researchers found that while Japanese Americans were less likely to report hot flushes and other symptoms, they did not have significantly fewer hot flushes as measured by skin conductance monitoring compared with European American women.

The common finding of fewer hot flushes in Japanese women may be a consequence of reporting bias, probably due to cultural factors, the researchers concluded.

 

Do Japanese American women really have fewer hot flashes than European Americans? The Hilo Women's Health Study.

Brown, DE et al

Menopause 2009; online 8 April
 

http://www.ncbi.nlm.nih.gov/pubmed/19367185?dopt=Abstract

Content updated April 24 2009

The age of menopause varies across Europe, shifting toward higher ages, a study shows. The trend appears paradoxical because determinants of early menopause, such as overweight, smoking, sedentarity and nulliparity are rising, the researchers say.

Median age of natural menopause was 54 years.

The heterogeneity of the secular trend suggests country -specific factors not included in the study such as improved childhood nutrition and health.

The determinant for later menopause was multiparity, with oral contraceptive use yielding heterogenous effects on timing of menopause.

 

Is age at menopause increasing across Europe? Results on age at menopause and determinants from two population-based studies.

Dratva, J et al

Menopause 2009;16 (2):385-394

http://www.menopausejournal.com/pt/re/menopause/abstract.00042192-200916020-00025.htm;jsessionid=JxGWQ4fbpT514W9BZDMkpMFx102GbJhwhJYsBcxCTJJn1D2Q8Q0h!928310026!181195629!8091!-1

 

Content Updated April 24 2009

HT use continues to slide, with 11.8% of women over age 50 using TGA-registered conventional therapy and a further 4.0% using unregistered hormonal products in 2008.

These findings from the latest South Australian Health Omnibus Survey show a medically concerning increase in use of alternative therapies which are poorly controlled by Australia's regulators, according to Professor Alastair MacLennan and colleagues.

In 2008, use of registered HT was 19.8% and use of unregistered hormones was rare.

Continuing decline in hormone therapy use: population trends over 17 years

AH MacLennan, TK Gill, JL Broadbent, and AW Taylor

Climacteric 2009;12:122-130

http://www.ncbi.nlm.nih.gov/pubmed/19259854?orordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

 

Content Updated April 24 2009

The Medical Journal of Australia published an article by Barry G Wren on 16 March 2009; Why HRT should be offered to postmenopausal women MJA 2009; 190 (6): 321-325

http://www.mja.com.au/public/issues/190_06_160309/wre10851_fm.html

The New England Journal of Medicine published an article by Chlebowski and colleagues on Thursday 5th February 2009, entitled Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women (Volume 360:573, February 5, 2009, Number 6). 

The abstract from the paper concluded that the increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.

The AMS web committee suggests that this paper should be read in conjunction with the commentary written by Dr Syd Shapiro and Dr Anne Gompel for IMS.

An international study, led by Monash University's Professor Susan Davis has confirmed steroid patches can significantly increase the sex drive of postmenopausal women not using hormone replacement therapies.
It is the first study in the world to show that when used alone, testosterone administered by a skin patch significantly improved sexual well-being in postmenopausal women.