• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Cancer. Author manuscript; available in PMC Jun 15, 2010.
Published in final edited form as:
PMCID: PMC2764240
NIHMSID: NIHMS137531

Relationship Between Caffeine Intake and Plasma Sex Hormone Concentrations in Premenopausal and Postmenopausal Women

Abstract

BACKGROUND

Circulating estrogens and androgens are important factors in the development of various female cancers. Caffeine intake may decrease risk of breast and ovarian cancer, although the data are not entirely consistent. Whether or not caffeine affects cancer risk by altering sex hormone levels is currently unknown.

METHODS

We examined the relationship of caffeine, coffee, decaffeinated coffee, and tea with plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone binding globulin (SHBG) in 524 premenopausal and 713 postmenopausal women from the Nurses’ Health Study (NHS) and NHSII.

RESULTS

In premenopausal women, caffeine intake was inversely associated with luteal total and free estradiol, while positively associated with luteal progesterone levels (P-trend=0.02, 0.01, 0.03, respectively). Coffee intake was significantly associated with lower luteal total and free estradiol levels, but not luteal progesterone levels (P-trend=0.007, 0.004, 0.20, respectively). Among the postmenopausal women, there was a positive association between caffeine and coffee intake and SHBG levels (P-trend=0.03 and 0.06). No significant associations were detected with the other hormones.

CONCLUSIONS

Data from this cross-sectional study suggest that caffeine may alter circulating levels of luteal estrogens and SHBG, representing possible mechanisms by which coffee or caffeine may be associated with pre- and postmenopausal malignancies, respectively. Future studies evaluating how caffeine-mediated alterations in sex hormones and binding protein levels affect the risk of female cancers are warranted.

Keywords: caffeine, sex hormones, ovarian cancer, breast cancer, cross-sectional

INTRODUCTION

Coffee is one of the most frequently consumed beverages worldwide. Although drinking habits vary between countries, coffee’s widespread use has led to the evaluation of its consumption with various health outcomes. Coffee is a primary dietary source of caffeine, and also contains many other biologically active ingredients including minerals, polyphenols, and other phytochemicals 1, 2, many of which been associated with chemopreventive and antioxidant properties. To date, the exact mechanism(s) by which coffee or caffeine may influence the development of certain conditions, particularly cancer, have not been elucidated.

Several epidemiological studies have evaluated a role of coffee and other caffeine-containing beverages in the etiology of breast and ovarian cancer, albeit, with conflicting findings3 (reviewed in 4). Interestingly, the Nurses’ Health Study (NHS) recently reported an inverse association between caffeine and risk of breast cancer among postmenopausal women 4. Similarly, in the NHS increasing caffeine intake was associated with a decreased risk of postmenopausal but an increased risk of premenopausal ovarian cancer5. Due to its biochemical complexity, there are various plausible mechanisms by which coffee or caffeine may affect health. Since a substantial body of evidence has implicated sex hormones in the etiology of both breast and ovarian cancer6, 7, an effect associated with coffee consumption may be due to the ability of caffeine to influence hormone metabolism8. Whether caffeine affects cancer risk by altering sex hormone levels is currently unclear, although sex hormones and caffeine are metabolized via similar enzymes.

Our aim was to explore the biological basis for possible associations between coffee consumption and risk of hormone-related cancers. To address this issue, we examined caffeine intake, as well as coffee, decaffeinated coffee, and tea consumption, in relation to plasma concentrations of estrogens, androgens, progesterone, prolactin, and sex hormone binding globulin (SHBG) in a cross-sectional study 524 premenopausal and 713 postmenopausal women from the NHS and NHSII.

MATERIALS AND METHODS

Study Population

The NHS was established in 1976 among 121,700 US female registered nurses, ages 30 to 55 years, and the NHSII was established in 1989 among 116,609 female registered nurses, ages 25 to 42 years. All women completed an initial questionnaire and have been followed biennially by questionnaire to update exposure status and disease diagnoses. Data have been collected on numerous ovarian and breast cancer risk factors including parity, hormone use, tubal ligation, and family history of cancer.

From 1989–1990, 32,826 NHS participants (ages 43–70 years) provided blood samples and completed a short questionnaire9. Briefly, women arranged to have their blood drawn and shipped with an icepack, via overnight courier, to our laboratory, where it was processed.

From 1996–1999, 29,611 NHSII participants (ages 32–54 years) provided blood samples and completed a short questionnaire10. Briefly, premenopausal women (n=18,521) who had not taken hormones, been pregnant, or lactated within 6 months provided blood samples drawn on the 3rd to 5th day of their menstrual cycle (follicular) and 7 to 9 days before the anticipated start of their next cycle (luteal, called timed samples). Other women (n=11,090) provided a single 30 mL untimed blood sample. Since collection, samples have been archived at −130 °C or colder in continuously monitored liquid nitrogen freezers. These studies were approved by the Committee on the Use of Human Subjects in Research at the Brigham and Women’s Hospital (Boston, MA).

We considered a woman to be premenopausal if (1) she gave timed samples, (2) her periods had not ceased, or (3) she had a hysterectomy with at least one ovary remaining and was ≤47 years (nonsmokers) or ≤45 years (smokers). We considered a woman to be postmenopausal if (1) her natural menstrual periods had ceased permanently, (2) she had a bilateral oophorectomy, or (3) she had a hysterectomy with at least one ovary remaining and was ≥56 years (nonsmokers) or ≥54 years (smokers)11. The remaining women, most of whom had a simple hysterectomy and were 48–55 years old, were of unknown menopausal status and therefore excluded.

Participants in this study were controls from nested case-control studies of breast cancer10, 12 who were matched to women diagnosed with breast cancer after blood collection through June 1, 2000 (NHS postmenopausal women not using postmenopausal hormones {PMH}, n=713) or June 2003 (NHSII premenopausal women)(n=411), and a subset of premenopausal women who were included in a reproducibility study (n=113)13.

Laboratory Assays

Premenopausal hormone assay methods for estrogens and testosterone have been described previously14. We measured premenopausal hormone levels on the following samples: estradiol, estrone, and estrone sulfate in follicular and luteal samples; testosterone, androstenedione, prolactin, and SHBG in follicular, luteal, and untimed samples; DHEA and DHEAS in luteal and untimed samples; and progesterone in luteal samples. Follicular and luteal samples from each woman were assayed together; samples were assayed in three batches. Details regarding the methods used to assay postmenopausal hormones have been published previously12, 15. The interassay coefficients of variation (CV) based on blinded replicates were 6–14%, except for progesterone (CV=17%).

Samples were assayed in a random order. When hormone values were less than the detection limit, we set the value to one half the limit (n, estrone=25, testosterone=2, androstenedione=1, DHEA=1, DHEAS=7, estrone sulfate=5). The stability of these hormones in whole blood not processed for 24–48 hours has been shown previously 16.

Dietary Assessment

In both the NHS and NHSII, diet was assessed through a validated, self-administered, semi-quantitative food frequency questionnaire (FFQ)17. Caffeine consumption was calculated using US Department of Agriculture food composition sources1820. Respondents were asked the average frequency of use of caffeine-containing beverages (coffee, tea and soda) and foods (chocolate) with choices ranging from “never or almost never” to “6 or more times per day”. The estimated caffeine content used was 137mg per cup of coffee, 47 mg per cup of tea, 46mg per can or bottle of caffeinated soda, and 7mg per chocolate serving. FFQs in both cohorts asked about non-herbal tea (i.e. caffeinated) only. The frequency of consumption was modeled as cups per day for coffee and tea, and mg per day for caffeine.

We evaluated intake using two approaches. First, we looked at consumption reported on the FFQ closest to the blood collection (1990 for NHS, 1995 for NHSII). Second, we calculated the average intake from the FFQ completed four years prior to blood collection (1986 for NHS, 1991 for NHSII) and that closest to blood collection. Since the results were similar for these approaches, we only report the results of the former.

Statistical Analysis

All analyses were stratified by menopausal status. For each analyte, we excluded women with missing values related to assay difficulties or low plasma volume. We identified and excluded values (n=0–11 for postmenopausal and 0–3 for premenopausal women) that were statistical outliers21. Among premenopausal women, the associations for the estrogens were assessed separately for follicular and luteal measurements. For testosterone, androstenedione, prolactin, and SHBG, we averaged the follicular and luteal values, as levels did not vary substantially by phase10, 22, 23, and included untimed samples for all hormones except estrogens24.

We calculated adjusted geometric means for each log-transformed hormone by exposure category using a generalized linear model. For coffee, decaffeinated coffee and tea intakes, tests for trend were conducted by modeling the continuous variable and for caffeine modeling the quartile median intake and calculating the Wald statistic25. Women with missing FFQ or hormone information were excluded for the specific analyses with missing data.

Among the premenopausal women, multivariate models were adjusted for assay batch (13), age at blood draw (<40, 40-<45, ≥45 years), fasting status (≤10, >10 hours), time of day of the blood draw(s) (1–8 a.m., 9 a.m.-noon, 1 p.m.-midnight), month of blood draw (continuous), difference between luteal draw date and date of the next menstrual period (3–7, 8–21 days, unknown/untimed), duration of past oral contraceptive use (never, <4, ≥4 years, missing), parity (yes, no), BMI at blood draw (continuous), physical activity (<5, 5–18, ≥18 MET-hr/wk), alcohol consumption (0, 0–10, >10 g/d), and smoking (never, past, current). Primary analyses were restricted to premenopausal women with ovulatory cycles at the blood draw (for timed samples); secondary analyses included all women and adjusted for ovulatory status (ovulatory [luteal progesterone ≥400ng/dl], anovulatory, untimed). Since the results were similar, we report results for the former to eliminate confounding by, and added variability due to ovulatory status.

For postmenopausal women, we adjusted for assay batch (16), age at blood draw (55, 55–60, 60–65, >65 years), age at first birth/parity (nulliparous, age at first birth<25 years/1–4 children, age at first birth 25–29 years/1–4 children, age at first birth 30 years/1–4 children, age at first birth<25 years/5 children, age at first birth>25 years/5 children), and time of day of blood draw (1–8 a.m., 9 a.m.-noon, 1 p.m.–4 p.m., 5 p.m.-midnight).

We also assessed whether the associations differed by BMI, a major source of hormone production in postmenopausal women, and cholesterol, a precursor for ovarian hormone production, using multiplicative interaction terms. P-values were two-sided and considered statistically significant if ≤0.05.

RESULTS

There were 524 premenopausal and 713 postmenopausal women available for analysis, with a mean age at blood draw of 43 and 62 years, respectively (Table 1). Women were, on average, overweight in both groups. Among premenopausal women, 83% provided timed samples, 84% had previously used oral contraceptives, and 5% were current smokers. Among postmenopausal women, 32% had previously used oral contraceptives and 12% were current smokers. Mean parity was higher, and physical activity was lower, among the postmenopausal women. Sex hormone levels were in the expected ranges24.

TABLE 1
Characteristics of Premenopausal and Postmenopausal Women in the Nurses’ Health Study and Nurses’ Health Study II, Respectively

Cut-points for each exposure were based on the distribution in the population or on what has previously been associated with cancer risk5. The cut-points were ≤6 cups/week, 1 cups/day, 2–3 cups/day and ≥4 cups/day for coffee; ≤1cups/week, 2–6 cups/week, 1 cup/day and ≥2 cups/day for tea; and ≤1–3cups/month, 1–6 cups/week, 1 cups/day and ≥2 cups/day for decaffeinated coffee. For caffeine intake, the quartiles were based on the distribution in the premenopausal and postmenopausal women separately (see tables 3 and and5,5, respectively).

TABLE 3
Adjusted Geometric Mean Levelsa of Estrogens, Androgens, Progesterone, Prolactin and SHBG by Quartiles of Coffee Intake in Premenopausal Women
TABLE 5
Adjusted Geometric Mean Levelsa of Estrogens, Androgens, Prolactin, and SHBG by Quartiles of Coffee Intake in Postmenopausal Women Not Taking PMH

Among premenopausal women with an ovulatory cycle at blood draw, caffeine intake was inversely associated with luteal total estradiol (mean for the highest (Q4) versus lowest (Q1) quartile=117 versus 134pg/mL; P-trend=0.02) and luteal free estradiol (mean, Q4 versus Q1=1.44 versus 1.70pg/mL; P-trend=0.01), and positively associated with luteal progesterone levels (mean, Q4 versus Q1=1585 versus 1412ng/dL; P-trend=0.03) (Table 2). Similarly, higher coffee intake was associated with lower luteal total estradiol (P-trend=0.007) and luteal free estradiol levels (P-trend=0.004), but not with progesterone levels (P-trend=0.20) (Table 3). There were no significant associations with any other hormones. Results were similar, although somewhat weaker, when including women with anovulatory cycles (data not shown).

TABLE 2
Adjusted Geometric Mean Levelsa of Estrogens, Androgens, Progesterone, Prolactin and SHBG by Quartile of Caffeine Intake in Premenopausal Women

Decaffeinated coffee was associated with significantly lower DHEAS levels (mean, Q4 versus Q1=66.4 versus 79.6μg/dL; P-trend=0.04). We did not observe any other associations between decaffeinated coffee and hormone levels (data not shown). Tea intake was positively associated with follicular estradiol (mean, Q4 versus Q1=54.6 versus 45.8pg/mL; P-trend=0.05) and follicular free estradiol levels (mean, Q4 versus Q1=0.70 versus 0.57pg/mL; P-trend=0.009). There was a suggestive inverse association between tea and DHEAS (P-trend=0.08).

There were no significant interactions with BMI for any exposure (all P-interactions≥0.11); however, the relationship of caffeine intake with DHEA and DHEAS levels differed by cholesterol intake (P-interaction=0.02 and 0.04, respectively). Caffeine intake was positively associated with DHEA and DHEAS levels among women at or above the median for cholesterol intake (P-trend=0.04 and 0.11, respectively) but not among those below the median.

Among postmenopausal women, caffeine intake was associated with higher levels of SHBG (mean, Q4 versus Q1=52 versus 47nmol/l; P-trend=0.03) (Table 4). Similarly, higher coffee intake was modestly positively associated with SHBG levels (P-trend=0.06) (Table 5). There was also a suggestion of an inverse association between caffeine and free testosterone (P-trend=0.09). Caffeine and coffee intakes were not associated with other circulating hormones. Decaffeinated coffee was modestly inversely associated with free estradiol (P-trend=0.06) and estrone sulfate (P-trend=0.07) levels, and was significantly inversely associated with DHEAS levels (mean, Q4 versus Q1=79 versus 75μg/dL; P-trend=0.01). We observed no significant associations between circulating sex hormones and tea intake (P-trend≥0.22). Generally the results showed a stronger dose-response relationship with deciles of intake (data not shown).

TABLE 4
Adjusted Geometric Mean Levelsa of Estrogens, Androgens, Prolactin, and SHBG by Quartiles of Caffeine Intake in Postmenopausal Women Not Taking PMH

DISCUSSION

We examined the relationships between caffeine, coffee, and tea intake with circulating sex hormones, prolactin and SHBG levels in a large cross-sectional study. Among premenopausal women, caffeine and coffee intake were inversely associated with luteal levels of total and free estradiol. Furthermore, caffeine intake was positively associated with luteal progesterone levels. We also observed a positive association between tea intake and follicular and free estradiol levels. There was a positive association of caffeine and coffee intake with SHBG levels among postmenopausal women. Decaffeinated coffee was inversely associated with DHEAS levels in both groups.

The results from three earlier studies of these associations in premenopausal women have been inconsistent8, 26, 27. Lucero et al. reported higher early follicular estradiol levels with increasing daily caffeine and coffee consumption (n=498)8. Conversely, among 50 premenopausal women, green tea, but not coffee or total caffeine intake, was inversely correlated with follicular estradiol27. London et al. reported a significant inverse correlation between caffeine intake and free estradiol among 325 perimenopausal women aged 50–60 years 26. In our study, premenopausal women with the highest versus lowest quartile of caffeine and coffee intake had 12–15% lower luteal total and free estradiol levels, while follicular estradiol and free estradiol levels were 16–19% higher among women in the highest versus lowest quartile of tea intake. Differences between studies may be due to small sample sizes or poor timing of blood collection during the menstrual cycle in prior studies. With our method of blood collection, we were able to accurately calculate the date of the menstrual cycle for women with timed samples.

Because of the similar associations of coffee and caffeine with luteal estrogen levels, it is probable that caffeine is the component influencing estrogen metabolism. Since there was suggestive evidence for higher testosterone levels with higher intakes of caffeine and coffee, caffeine may be inhibiting CYP19, or aromatase, the key enzyme mediating the conversion of androgens to estrogens24, 28. Nevertheless, it is unclear why this would not also influence follicular estrogen levels or sex hormone levels in postmenopausal women where aromatase plays a more critical role in dictating estrogen and testosterone levels. We observed a significant trend for higher circulating progesterone with higher caffeine but not coffee intake. To our knowledge, there are no prior reports of caffeine and progesterone levels in humans; however, one study in male rats showed increased plasma progesterone with intraperitoneal injections of caffeine29.

Since we did not observe any effect of coffee or caffeine on follicular estrogen levels, the positive association with tea could be attributed to another component rather than caffeine. Our results require further exploration and should be interpreted with caution given that there are no prior assessments of this association and the number of women with daily tea consumption was small (24% consumed ≥1 cup/day). Nagata et al. reported an inverse correlation between follicular estradiol levels and green but not black tea among premenopausal women27. Another study reported that tea intake was not associated with estradiol and SHBG levels8. We were not able to evaluate the effect of green tea since our FFQ asked about non-herbal tea intake, which consists primarily of black tea in the United States.

Although androgens and estrogens are well-established risk factors for postmenopausal breast cancer30, the role of these hormones in premenopausal breast cancer is not fully understood. Our findings of lower luteal estrogen levels with higher caffeine intake represents one potential protective mechanism for premenopausal hormonally-dependent cancers. Of the two studies examining estrogens and breast cancer risk in premenopausal women, one reported no association 31, and the other reported an increased risk of premenopausal breast cancer only with follicular, but not luteal, estradiol levels14. The elevated levels of follicular estrogens with tea intake suggests that tea may increase the risk of hormone-related cancers, although to our knowledge no epidemiologic data have reported an association between tea intake and premenopausal breast cancer risk. The higher progesterone levels with caffeine intake requires further exploration particularly given the inconsistency in the data regarding a role for this hormone in breast cancer development14, 31 and the possible inverse relationship with ovarian cancer6. Furthermore, our findings do not explain the increased risk of premenopausal ovarian cancer with caffeine intake we and others have reported5, 32, 33.

Among postmenopausal, but not premenopausal, women, high intakes of caffeine or caffeinated coffee were associated with a 13% higher SHBG levels versus low intakes. Four previous studies have reported a similar positive association with caffeine and/or coffee intake and levels of SHBG8, 26, 27, 34; however, only one study was limited to postmenopausal women34. Since SHBG is the major carrier of estrogen and testosterone, we expected to see a concomitant inverse association with free levels of these two hormones. We did not observe a strong effect; however, there was suggestive evidence for decreasing free testosterone levels with increasing caffeine intake; testosterone preferentially binds SHBG versus estradiol35. Similarly, Ferrini et al. reported an inverse association between caffeine intake and bioavailable testosterone levels, but a positive association with estrone levels34. The lack of an association with estrogen levels may be attributed to the sensitivity our assays and consequently, inability to detect small changes in circulating levels particularly given the low estrogen, and to a lesser extent androgen, production among postmenopausal women.

Higher SHBG levels have been associated with a lower risk of postmenopausal breast cancer among both users and non- users of PMH7, 12, 36. Only one study has evaluated the relationship between SHBG concentrations and ovarian cancer risk, observing an inverse association among women diagnosed before age 5537. In general, the protective effect of caffeine and/or coffee on breast and ovarian cancer appears to be strongest among postmenopausal women4, 5. Hormonal changes in postmenopausal women include a substantial decrease in estradiol and estrone levels, but only a small change in androgen synthesis by the ovaries and adrenal glands24. This suggests that the inverse association between caffeine intake and risk of postmenopausal ovarian and breast cancer may be mediated by its effect on hepatic production of SHBG and subsequent reduction in free testosterone. Indeed, high endogenous testosterone levels have been clearly implicated in the etiology of postmenopausal breast cancer7,12, although a positive association with risk of ovarian cancer is less clear38.

Since adipose tissue is an important source of sex hormones in postmenopausal women, we also evaluated whether BMI modified any of these associations. The inverse association between caffeine and SHBG appeared strongest among overweight/obese women. Although not statistically significant, this possible interaction warrants further evaluation since adiposity has consistently been associated with lower SHBG levels.

We did not observe associations between caffeine, coffee, or tea with levels of androgens, estrogens, or prolactin in the postmenopausal women. The null association with prolactin is of interest given that this hormone has been associated with an increased risk of premenopausal10 and postmenopausal breast cancer15. However, in other studies of postmenopausal women, black tea has been associated with higher plasma levels of estrone and prolactin39, 40.

The inverse association between decaffeinated coffee and DHEAS requires further confirmation given the small percentage of women that regularly consumed decaffeinated coffee in our cohort (≥ 2 cups/day: 12% for premenopausal, 31% for postmenopausal women) and more importantly, the biological effect of decaffeinated coffee on adrenal androgens levels has never been explored.

This is the largest study to examine the relationship between endogenous androgens, estrogens, prolactin and SHBG with caffeine, coffee and tea intake. We were able to obtain timed blood samples from a large number of premenopausal women to accurately assess hormone concentrations during both the luteal and follicular phases and we limited our analysis of postmenopausal women to those not using PMH. The major limitation of this study is the inability to establish a temporal relationship between the exposure (i.e. caffeine) and hormones levels, although it is unlikely that endogenous sex hormones would influence coffee consumption. Also, validation studies have shown a high correlation between self-reported coffee intake on the FFQ compared to that from a 28-day diet record (ρ=0.75) 41.

In summary, our data suggest that caffeine-mediated changes in circulating levels of luteal estrogens and SHBG represent possible mechanisms by which coffee or caffeine may be associated with pre- and postmenopausal hormonally-related malignancies, respectively. Since hormones are clearly implicated in the etiology of many female cancers, further evaluation of how caffeine-mediated alterations in sex hormones and binding protein levels affect the risk of breast or ovarian cancer are warranted.

Acknowledgments

The authors thank Dr. Robert Barbieri for his valuable comments on this manuscript. This research was supported by Research Grants CA105009, CA50385, P50 CA105009, CA49449, and P01 CA87969 from the National Cancer Institute. J.K. is a Research Fellow of the Canadian Cancer Society supported through an award from the National Cancer Institute of Canada.

References

1. Devasagayam TP, Kamat JP, Mohan H, Kesavan PC. Caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive oxygen species. Biochim Biophys Acta. 1996 Jun 13;1282(1):63–70. [PubMed]
2. Mazur W. Phytoestrogen content in foods. Baillieres Clin Endocrinol Metab. 1998 Dec;12(4):729–742. [PubMed]
3. Steevens J, Schouten LJ, Verhage BA, Goldbohm RA, van den Brandt PA. Tea and coffee drinking and ovarian cancer risk: results from the Netherlands Cohort Study and a meta-analysis. Br J Cancer. 2007 Nov 5;97(9):1291–1294. [PMC free article] [PubMed]
4. Ganmaa D, Willett WC, Li TY, et al. Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up. Int J Cancer. 2008 May 1;122(9):2071–2076. [PubMed]
5. Tworoger SS, Gertig DM, Gates MA, Hecht JL, Hankinson SE. Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer. Cancer. 2008 Mar 1;112(5):1169–1177. [PubMed]
6. Lukanova A, Kaaks R. Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):98–107. [PubMed]
7. Key T, Appleby P, Barnes I, Reeves G. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. 2002 Apr 17;94(8):606–616. [PubMed]
8. Lucero J, Harlow BL, Barbieri RL, Sluss P, Cramer DW. Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use. Fertil Steril. 2001 Oct;76(4):723–729. [PubMed]
9. Hankinson SE, Willett WC, Manson JE, et al. Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer Inst. 1995 Sep 6;87(17):1297–1302. [PubMed]
10. Tworoger SS, Sluss P, Hankinson SE. Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women. Cancer Res. 2006 Feb 15;66(4):2476–2482. [PubMed]
11. Hankinson SE, Willett WC, Michaud DS, et al. Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 1999 Apr 7;91(7):629–634. [PubMed]
12. Missmer SA, Eliassen AH, Barbieri RL, Hankinson SE. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst. 2004 Dec 15;96(24):1856–1865. [PubMed]
13. Missmer SA, Spiegelman D, Bertone-Johnson ER, Barbieri RL, Pollak MN, Hankinson SE. Reproducibility of plasma steroid hormones, prolactin, and insulin-like growth factor levels among premenopausal women over a 2- to 3-year period. Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):972–978. [PubMed]
14. Eliassen AH, Missmer SA, Tworoger SS, et al. Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. J Natl Cancer Inst. 2006 Oct 4;98(19):1406–1415. [PubMed]
15. Tworoger SS, Eliassen AH, Rosner B, Sluss P, Hankinson SE. Plasma prolactin concentrations and risk of postmenopausal breast cancer. Cancer Res. 2004 Sep 15;64(18):6814–6819. [PubMed]
16. Hankinson SE, London SJ, Chute CG, et al. Effect of transport conditions on the stability of biochemical markers in blood. Clin Chem. 1989 Dec;35(12):2313–2316. [PubMed]
17. Willett WC, Sampson L, Stampfer MJ, et al. Reproducibility and validity of a semiquantitative food frequency questionnaire. Am J Epidemiol. 1985 Jul;122(1):51–65. [PubMed]
18. U.S. Department of Agriculture A. Agricultural Handbook No. 8 Series. Washington, DC: Department of Agriculture, Government Printing Office; 1993. Composition of foods-raw, processed, and prepared.
19. U.S. Department of Agriculture A. Release 11: Nutrient Data Laboratory Home Page. Washington, DC: Department of Agriculture, Government Printing Office; 1996. USDA Nutrient Database for Standard Reference.
20. U.S. Department of Agriculture A. Release 14: Nutrient Data Laboratory Home Page. Washington, DC: Department of Agriculture, Government Printing Office; 2001. USDA Nutrient Database for Standard Reference.
21. Rosner B. Percentage points for generalized ESD many-outlier procedure. Technometrics. 1983;25:165–172.
22. Eliassen AH, Missmer SA, Tworoger SS, Hankinson SE. Endogenous steroid hormone concentrations and risk of breast cancer: does the association vary by a woman’s predicted breast cancer risk? . J Clin Oncol. 2006 Apr 20;24(12):1823–1830. [PubMed]
23. Tworoger SS, Missmer SA, Eliassen AH, et al. The association of plasma DHEA and DHEA sulfate with breast cancer risk in predominantly premenopausal women. Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):967–971. [PubMed]
24. Strauss JF, Barbieri RL. Yen and Jaffe’s Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. 5. Philadelphia: Elsevier Saunders; 2004.
25. Hosmer D, Lemeshow S. Applied Logistic Regression. New York: John Wiley & Sons; 1989.
26. London S, Willett W, Longcope C, McKinlay S. Alcohol and other dietary factors in relation to serum hormone concentrations in women at climacteric. Am J Clin Nutr. 1991 Jan;53(1):166–171. [PubMed]
27. Nagata C, Kabuto M, Shimizu H. Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women. Nutr Cancer. 1998;30(1):21–24. [PubMed]
28. Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol. 2003 Sep;86(3–5):225–230. [PubMed]
29. Concas A, Porcu P, Sogliano C, Serra M, Purdy RH, Biggio G. Caffeine-induced increases in the brain and plasma concentrations of neuroactive steroids in the rat. Pharmacol Biochem Behav. 2000 May;66(1):39–45. [PubMed]
30. Hankinson SE. Endogenous hormones and risk of breast cancer in postmenopausal women. Breast Dis. 2005;24:3–15. [PubMed]
31. Kaaks R, Berrino F, Key T, et al. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) J Natl Cancer Inst. 2005 May 18;97(10):755–765. [PubMed]
32. Kuper H, Titus-Ernstoff L, Harlow BL, Cramer DW. Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer. Int J Cancer. 2000 Oct 15;88(2):313–318. [PubMed]
33. Jordan SJ, Purdie DM, Green AC, Webb PM. Coffee, tea and caffeine and risk of epithelial ovarian cancer. Cancer Causes Control. 2004 May;15(4):359–365. [PubMed]
34. Ferrini RL, Barrett-Connor E. Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol. 1996 Oct 1;144(7):642–644. [PubMed]
35. Sodergard R, Backstrom T, Shanbhag V, Carstensen H. Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem. 1982 Jun;16(6):801–810. [PubMed]
36. Tworoger SS, Missmer SA, Barbieri RL, Willett WC, Colditz GA, Hankinson SE. Plasma sex hormone concentrations and subsequent risk of breast cancer among women using postmenopausal hormones. J Natl Cancer Inst. 2005 Apr 20;97(8):595–602. [PubMed]
37. Rinaldi S, Dossus L, Lukanova A, et al. Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):23–29. [PubMed]
38. Tworoger SS, Lee IM, Buring JE, Hankinson SE. Plasma androgen concentrations and risk of incident ovarian cancer. Am J Epidemiol. 2008 Jan 15;167(2):211–218. [PubMed]
39. Wu AH, Arakawa K, Stanczyk FZ, Van Den Berg D, Koh WP, Yu MC. Tea and circulating estrogen levels in postmenopausal Chinese women in Singapore. Carcinogenesis. 2005 May;26(5):976–980. [PubMed]
40. Geleijnse JM, Witteman JC, Launer LJ, Lamberts SW, Pols HA. Tea and coronary heart disease: protection through estrogen-like activity? Arch Intern Med. 2000 Nov 27;160(21):3328–3329. [PubMed]
41. Salvini S, Hunter DJ, Sampson L, et al. Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. Int J Epidemiol. 1989 Dec;18(4):858–867. [PubMed]
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...