Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women

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Abstract

Objective

Lifetime cumulative number of menstrual cycles is related to breast cancer risk. The aim of this study is to investigate the relation between this index and serum sex hormone levels in postmenopausal women.

Methods

Cross-sectional study including 860 naturally postmenopausal Dutch participants of the European Prospective Investigation into Cancer and Nutrition. Lifetime cumulative number of menstrual cycles was computed using questionnaire data on ages at menarche and menopause, number of pregnancies, breastfeeding, oral contraceptive use (OC) and regularity pattern. Measurements of hormones included estrone (E1), estradiol (E2), andostrenedione, testosterone, sex-hormone binding globulin (SHBG) and dehydroepiandrostenedione sulfate (DHEAS). The relation between the lifetime cumulative number of menstrual cycles and hormone levels was assessed using analysis of covariance. Relations between reproductive characteristics and hormone levels were also studied. Adjustments for characteristics at blood collection included age, years since menopause, BMI, hormone replacement therapy use, OC use, smoking habits, alcohol intake and physical activity were done.

Results

Lifetime cumulative number of cycles was related with SHBG; participants in the lowest category had higher SHBG levels. For the separate characteristics, DHEAS and androstenedione increased significantly with increasing age at menarche, while androstenedione and testosterone decreased with increasing age at menopause. For the parity characteristics, SHBG levels increased according to the number of live births.

Conclusions

Lifetime cumulative number menstrual cycles was related only to SHBG. Therefore, free levels of estrogens or androgens may be related to this number of menstrual cycles estimate, reflecting lifetime exposure to ovarian hormones.

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Most cited references 41

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A physical activity questionnaire for the elderly.

L. Voorrips, A C J Ravelli, P Dongelmans … (1991)

A validated physical activity questionnaire for young adults was adapted and validated for use in free living, apparently healthy people, aged 63-80 yr. Test-retest reliability of the questionnaire on 29 participants was 0.89 as determined by Spearman's correlation coefficient. Further classification by tertiles of activity resulted in 72% of the participants being correctly classified and 0% grossly misclassified on two separate occasions. In a similar group of 31 subjects, classifications based on questionnaire activity scores were compared with classifications obtained by repeated 24-h activity recalls and pedometer measurements, showing Spearman's correlations of 0.78 and 0.73, for both methods, respectively. Seventy-one and 67% of the subjects, respectively, were classified in the same activity tertile for both methods. It is concluded that the questionnaire provides a reliable and valid method for classifying elderly subjects into categories of high, medium, and low physical activity.

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Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition.

R. Kaaks, S. Rinaldi, T J Key … (2005)

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids - notably androgens and oestrogens - promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Delta4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids -the androgens as well as the oestrogens - elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23-2.33), androstenedione 1.94 (1.40-2.69), testosterone 1.85 (1.33-2.57) and free testosterone 2.50 (1.76-3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42-3.02), oestradiol 2.28 (1.61-3.23) and free oestradiol (odds ratios 2.13 (1.52-2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

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Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC).

Araceli GonzÁlez, Teresa Norat, Heiner Boeing … (2005)

Contrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian androgen excess and progesterone deficiency, estrogen excess, estrogen and progesterone excess, and both an excess or lack of adrenal androgens (dehydroepiandrosterone [DHEA] or its sulfate [DHEAS]) as risk factors. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk. Levels of DHEAS, (Delta4-)androstenedione, testosterone, and sex hormone binding globulin (SHBG) were measured in single prediagnostic serum samples from 370 premenopausal women who subsequently developed breast cancer (case patients) and from 726 matched cancer-free control subjects. Levels of progesterone, estrone, and estradiol were also measured for the 285 case patients and 555 matched control subjects who had provided information about the day of menstrual cycle at blood donation. Conditional logistic regression models were used to estimate relative risks of breast cancer by quartiles of hormone concentrations. All statistical tests were two-sided. Increased risks of breast cancer were associated with elevated serum concentrations of testosterone (odds ratio [OR] for highest versus lowest quartile = 1.73, 95% confidence interval [CI] = 1.16 to 2.57; P(trend) = .01), androstenedione (OR for highest versus lowest quartile = 1.56, 95% CI = 1.05 to 2.32; P(trend) = .01), and DHEAS (OR for highest versus lowest quartile = 1.48, 95% CI = 1.02 to 2.14; P(trend) = .10) but not SHBG. Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk (OR for highest versus lowest quartile = 0.61, 95% CI = 0.38 to 0.98; P(trend) = .06). The absolute risk of breast cancer for women younger than 40 followed up for 10 years was estimated at 2.6% for those in the highest quartile of serum testosterone versus 1.5% for those in the lowest quartile; for the highest and lowest quartiles of progesterone, these estimates were 1.7% and 2.6%, respectively. Breast cancer risk was not statistically significantly associated with serum levels of the other hormones. Our results support the hypothesis that elevated blood concentrations of androgens are associated with an increased risk of breast cancer in premenopausal women.

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Author and article information

Contributors

: mchavezm@im.wustl.edu

Journal

Journal ID (nlm-ta): Breast Cancer Res Treat

Title: Breast Cancer Research and Treatment

Publisher: Springer US (Boston )

ISSN (Print): 0167-6806

ISSN (Electronic): 1573-7217

Publication date (Electronic): 22 May 2007

Publication date (Print): March 2008

Volume: 108

Issue: 1

Pages: 101-112

Affiliations

[1 ]Julius Center for Health Sciences and Primary care, University Medical Center, STR 6.131, PO BOX 85500, 3508 GA Utrecht, The Netherlands

[2 ]Department of Medicine, Washington University School of Medicine, Campus Box 8121, 660 South Euclid, St. Louis, MO 63110 USA

Article

Publisher ID: 9574

DOI: 10.1007/s10549-007-9574-z

PMC ID: 2244694

PubMed ID: 18274909

SO-VID: 25d2eec5-dac7-4ea4-a089-3fd6fc72c640

History

Date received : 13 March 2007

Date accepted : 16 March 2007

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cumulative number of menstrual cycles,sex hormones,risk factors,reproductive characteristics,steroids,breast cancer

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: cumulative number of menstrual cycles, sex hormones, risk factors, reproductive characteristics, steroids, breast cancer

Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women

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Sex hormones and lung development

Most cited references 41

A physical activity questionnaire for the elderly.

Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition.

Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC).

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