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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Int J Cancer. Author manuscript; available in PMC 2011 January 1.
Published in final edited form as:
PMCID: PMC2875384

The Association of Plasma Androgen Levels with Breast, Ovarian, and Endometrial Cancer Risk Factors Among Postmenopausal Women


Although androgens may play an etiologic role in breast, ovarian, and endometrial cancers, little is known about factors that influence circulating androgen levels. We conducted a cross-sectional analysis among 646 postmenopausal women in the Nurses' Health Study to examine associations between adult risk factors for cancer, including the Rosner/Colditz breast cancer risk score, and plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS). All analyses were adjusted for age, laboratory batch, and other cancer risk factors. Free testosterone levels were 79% higher among women with a BMI of ≥30 vs. <22 kg/m2 (p-trend<0.01) and 25% higher among women with a waist circumference of >89 vs. ≤ 74 cm (p-trend=0.02). Consuming >30 grams of alcohol a day vs. none was associated with a 31% increase in DHEA and 59% increase in DHEAS levels (p-trend=0.01 and <0.01, respectively). Smokers of ≥25 cigarettes per day had 35% higher androstenedione and 44% higher testosterone levels than never smokers (p-value, F-test=0.03 and 0.01, respectively). No significant associations were observed for height or time since menopause with any androgen. Testosterone and free testosterone levels were approximately 30% lower among women with a hysterectomy vs. without (both p-values<0.01). Overall breast cancer risk was not associated with any of the androgens. Thus, several risk factors, including body size, alcohol intake, smoking, and hysterectomy, were related to androgen levels among postmenopausal women, while others, including height and time since menopause, were not. Future studies are needed to clarify further which lifestyle factors modulate androgen levels.

Keywords: androgens, endogenous hormones, cancer risk factors, epidemiology


Sex steroid hormones play a key role in the development of breast, ovarian, and endometrial cancers.14 As associations with estrogens have been increasingly well-delineated, more attention has focused on androgens. Prospective studies have linked circulating androgen levels to the risk of postmenopausal breast cancer.58 Excessive androgen levels also have been proposed as a causal mechanism in the pathogenesis of ovarian cancer, given the relatively high levels of circulating androgens compared with estrogens, presence of androgen receptors in normal ovarian epithelial cells, and animal data suggesting that testosterone may increase ovarian tumor growth.9 Epidemiologic data have been conflicting but provide some support for an association between androgens and ovarian cancer risk.1013 Similarly, two prospective studies on endometrial cancer have produced discrepant results regarding associations with androgen levels.14, 15 Androgens have been hypothesized to increase endometrial cancer risk, likely through the aromatization of androgens into estrogens,16 but alternatively might decrease risk by decreasing the proliferative effects of estrogens in the endometrium.17, 18

Although androgens may be important in disease etiology, relatively little is known about non-genetic determinants of circulating levels among postmenopausal women. To assess whether factors associated with breast, ovarian, and endometrial cancers might influence cancer risk by altering androgen levels, we examined associations between several adult risk factors for cancer and plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS) in a large cross-sectional study of over 600 participants of the Nurses' Health Study. We further examined associations between circulating androgen levels and overall risk for breast cancer using the Rosner/Colditz risk score for breast cancer.1921


Study Population

The Nurses' Health Study (NHS) began in 1976 when 121,701 female registered nurses age 30 to 55 years completed a self-administered, mailed questionnaire. Follow-up questionnaires have been mailed biennially to collect updated exposure and health information. In 1989 and 1990, a subset of NHS participants (n=32,826) provided a blood sample. The nurses received instructions for taking the blood sample and returned it with an ice-pack via overnight courier; 97% of samples were received within 26 hours of being drawn. The nurses also completed a supplementary questionnaire at the time of blood sample collection that included questions on reason for menopause and use of postmenopausal hormones.

The study population consisted of controls from previous nested case-control studies in the NHS on hormone levels and breast cancer risk.6, 22 Over 600 postmenopausal women who had not used postmenopausal hormones in the 3 months prior to blood draw had data available for each androgen. The study was approved by the Institutional Review Board of Brigham and Women's Hospital, and all study participants provided informed consent.

Laboratory Methods

Details on the collection, storage, and assays of the blood data have been published previously.22 Upon receipt, blood samples were separated into plasma, white blood cells, and red blood cells and stored in liquid nitrogen freezers. A validation study compared hormone levels, including testosterone and androstenedione, in blood processed immediately with those processed after mailing (24 to 48 hour delay). Although testosterone levels slightly increased while androstenedione levels slightly decreased, the between-person variability was three times as great as the within-person variability for both hormones.23

All laboratory assays were performed by the Nichols Institute (San Juan Capistrano, CA). Plasma samples were assayed by radioimmunoassay following extraction and celite column chromatography. No separation step was used before the radioimmunoassay of DHEAS. Masked replicate samples were included to assess within-batch (within-plate) variability, which was greatest for DHEA (13.6%).22 Identical quality control samples were included across sets of samples assayed at different time periods (i.e. meta-batch;1 replicate per 10 samples), and indicated some laboratory drift over time.6, 22 We therefore adjusted for laboratory meta-batch in all analyses. The assay detection limit was 5 ng/dl for androstenedione, 2 ng/dl for testosterone, 10 ng/dl for DHEA, and 5 μg/dl for DHEAS. Values below the detection limit were set to half the limit (androstenedione: n=1; testosterone: n=2; DHEA: n=1, DHEAS: n=5). Free testosterone was calculated using the Sodergard formula.24, 25


We examined associations with four anthropometric measures: body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and height. Waist circumference and height were originally collected in inches but have been converted to centimeters and meters, respectively. Height was collected in 1976. BMI was calculated as kg/m2 using weight from the questionnaire completed at blood collection or, if missing, from the regular 1990 NHS questionnaire (n=11). Waist and hip measurements were obtained from the 1986 NHS questionnaire, which asked women to measure their waist (standing up) and hip (widest) circumference to the nearest quarter of an inch using a tape measure. Women who reported a “0” were set to missing, as was one woman who reported a hip circumference of <51 cm. We also assessed BMI and waist circumference together, comparing women with high BMI and high waist circumference (≥25 kg/m2 and >81 cm, respectively) to women with low BMI and low waist circumference (<25 kg/m2 and ≤81 cm, respectively).

For analyses of alcohol consumption, we used reported alcohol intake in the year prior to the 1990 questionnaire (or, where missing, from the 1986 questionnaire, n=14) Information on cigarette smoking also was collected on the 1990 NHS questionnaire. Family history (mother or sister) of breast cancer was reported in 1976, 1982, 1988, and 1992; family history of ovarian cancer was reported in 1992. Information on hysterectomy and oophorectomy was obtained from the blood collection questionnaire. For women reporting natural menopause or a bilateral oophorectomy, time since menopause was calculated as the age at blood draw minus age at menopause. Tubal ligation was coded as any report of tubal ligation through 1982 or in 1994.

Risk scores for breast cancer using the Rosner/Colditz model were previously developed within the NHS and have been described in detail elsewhere.1921 Briefly, the Rosner/Colditz model incorporates data on BMI, alcohol intake, height, duration of premenopausal and postmenopausal time, type of menopause, postmenopausal hormone use, parity (including details on age at each birth), history of benign breast disease, and family history of breast cancer. Risk deciles were previously created within 5-year age groups in the larger NHS cohort, and those rankings were used for this analysis. Decile 1 represents the lowest risk group and decile 10 represents the highest risk group. Scores were calculated only for women with non-missing and consistent data on a number of the risk factors (e.g., parity and age at births from different questionnaire years) and with known age at menopause (hence women with simple hysterectomy were excluded).21 Thus, the analysis on the breast cancer risk score included 469 women.

Data Analysis

Hormone values were natural log-transformed to improve normality for analyses, and outliers were identified within batch by the extreme studentized deviate many-outlier procedure.26 Using this method, 4 values were dropped for androstenedione, 3 for testosterone, 2 for free testosterone, 1 for DHEA, and 5 for DHEAS.

Linear regression models were used to compute geometric mean hormone levels across exposure categories. All analyses were run in SAS version 9.1.3 and were adjusted for age in years (continuous and centered at 60 years) and laboratory batch. In multivariable analyses, all exposures were mutually adjusted for one another, with the small amount of missing data coded to a missing category as necessary. Because results for analyses adjusting for age and batch only were similar to results from multivariable models, only results from multivariable models are presented. The exposures were defined as follows: BMI (<22, 22 to <25, 25 to <30, ≥ 30 kg/m2), height (≤1.60, >1.60 to 1.63, >1.63 to 1.68, >1.68 m), alcohol intake (none, >0 to 5, >5 to 10, >10 to 15, >15 to 30, >30 grams/day), cigarette smoking (never, past, and current smokers of 1–14,15–24,≥ 25 cigarettes per day), time since natural menopause (≤5, >5 to ≤ 10, >10 to ≤15, >15 years), family history of breast cancer (yes/no), family history of ovarian cancer (yes/no), tubal ligation (yes/no), and hysterectomy (none, uterus only removed, uterus and both ovaries removed). Women who reported hysterectomy with one or unknown ovaries removed were included with the missing category. In addition, WHR (<0.75, 0.75 to <0.80, 0.80 to <0.84, ≥ 0.84) and waist circumference (≤74, >74 to ≤81, >81 to ≤89, >89 cm) were examined in multivariable models (but were not included in all models due to a larger amount of missing data).

Analyses of the Rosner/Colditz breast cancer risk score were adjusted for age and batch, as well as covariates from our multivariable models that were not already included in the risk scores (i.e., we additionally adjusted for smoking, family history of ovarian cancer, and tubal ligation).

When appropriate, continuous values of an exposure were used to calculate tests for trend and partial Spearman correlations. For trend analyses of cigarettes per day, only current smokers were included and were assigned the midpoint of their smoking category (1–14, 15–24, ≥ 25 cigarettes per day). An F-test was used to assess the significance of smoking overall (including never, former, and current smokers).


There were 646 women in our study population: 627 had measures for androstenedione, 631 for testosterone, 613 for free testosterone, 606 for DHEA, and 635 for DHEAS. The average age was 62 years. Among women reporting natural menopause or bilateral oophorectomy, the median age at menopause was 51 years and median time since menopause was 12 years. The median BMI was 25 kg/m2 and median WHR was 0.79 (Table 1). Additional characteristics of the study population are provided in Table 1.

Table 1
Study Population Characteristics Among 646 Postmenopausal Women in the Nurses' Health Study.

Anthropometric Measures (Table 2)

Table 2
Anthropometric Measures and Adjusted* Geometric Mean Levels of Circulating Androgens Among Postmenopausal Women.

The anthropometric measures (BMI, WHR, waist circumference, and height) were not associated with most circulating androgen levels. However, free testosterone levels were 79% higher among women with a BMI of ≥30 kg/m2 vs. <22 kg/m2 (p-trend<0.01) and 25% higher among women with a waist circumference of >89 cm vs. ≤ 74 cm (p-trend=0.02 adjusting for BMI and the other covariates), and a borderline significant association was observed with WHR (p-trend=0.08). The correlation with free testosterone was strongest for BMI (r=0.33). Results were similar when BMI and waist circumference were cross-classified (high BMI / high waist circumference vs. low BMI / low waist circumference). Combining the two measures did not result in larger differences in mean hormone values and remained significant for free testosterone only (p<0.01).

Lifestyle Factors (Table 3)

Table 3
Lifestyle Factors and Adjusted* Geometric Mean Levels of Circulating Androgens Among Postmenopausal Women.

Alcohol intake was significantly associated with increasing levels of DHEA (p=0.01) and DHEAS (p<0.01) but was not associated with the other androgens (p≥0.07). Compared to non-drinkers, women who consumed 30 or more grams of alcohol per day (about 2 drinks) had 31% higher levels of DHEA and 59% higher levels of DHEAS; hormone levels among women with lower alcohol intakes were similar to or just modestly higher than those among non-drinkers. Cigarette smoking was significantly associated with increased levels of androstenedione (p=0.03) and testosterone (p=0.01). Compared to never smokers, current smokers of 25 or more cigarettes daily had 35% increased androstenedione levels and 44% increased testosterone levels. Never and past smokers had nearly identical levels of androstenedione, testosterone, and free testosterone. For DHEA and DHEAS, the associations with smoking were somewhat U-shaped, with androgen levels highest among never smokers and current smokers of 15–24 or 25 or more cigarettes per day. The trend among current smokers across cigarettes per day was not statistically significant for any androgen (p≥0.12).

Non-Lifestyle Factors (Table 4)

Table 4
Non-Lifestyle Factors and Adjusted* Geometric Mean Levels of Circulating Androgens Among Postmenopausal Women.

No associations were observed between androgen levels and time since natural menopause. Analyses of time since menopause that included women with a bilateral oophorectomy were similarly null (data not shown). Hysterectomy was associated with approximately 30% lower levels of testosterone and free testosterone; the decreases were similar regardless of whether a bilateral oophorectomy also was performed. Borderline significant associations were observed between family history of ovarian cancer and DHEAS levels (p=0.05), as well as between tubal ligation and DHEA (p=0.09).

There were no significant associations between the breast cancer risk score and androgen levels. However, there was a weak positive association between overall risk for breast cancer and levels of free testosterone, which increased by 22% over risk groups (p-trend=0.06; r=0.10, p=0.04).


We examined the association between circulating levels of five androgens and anthropometric, lifestyle, and non-lifestyle factors among postmenopausal women. Increasing BMI was associated with increasing levels of free testosterone but not with androstenedione, total testosterone, DHEA, or DHEAS. Two other large studies that examined associations between free testosterone and BMI among postmenopausal women also reported significant positive associations.27, 28 The observed association is likely due to the known inverse association between sex hormone-binding globulin (SHBG) levels and BMI.27, 28 In contrast to our findings, several,2731 but not all,32, 33 studies have observed positive associations with testosterone. Most studies did not find an association between BMI and androstenedione,28, 29, 3134 although significant associations have been reported.27, 30 Consistent with our findings, associations have not been observed between BMI and DHEA29, 30 or DHEAS2731, 35 in previous studies.

Few studies have examined other anthropometric measures. Our WHR results were similar to our BMI results, with a borderline positive association for free testosterone but no associations with the other androgens. We also observed a weak positive correlation between free testosterone and waist circumference. In a prior study, a positive association was observed between free testosterone and waist circumference, as well as between free testosterone and WHR.28 Another study found a positive association between waist circumference and testosterone and androstenedione, but not DHEAS,31 while a small study of postmenopausal women (n=88) did not observe relationships between WHR and androstenedione, testosterone, or free testosterone.33 We did not observe any association between height and androgen levels, consistent with the few existing studies.29, 31, 34, 35 It is possible that height may primarily reflect hormone levels during youth that do not remain important in adulthood.

Significant, positive associations were observed between daily alcohol intake and levels of DHEA and DHEAS; compared to non-drinkers, women consuming about two or more drinks per day had 31% higher DHEA and 59% higher DHEAS levels. In a randomized controlled feeding study, DHEAS, but not DHEA, was significantly increased among postmenopausal women who drank 15–30 grams of alcohol per day.36 Other epidemiologic studies also support an increase in DHEAS levels with alcohol consumption, although the trend became non-significant after adjusting for covariates in one study.35, 37 In animal studies, alcohol stimulates the adrenal gland, suggesting that DHEAS, which is synthesized exclusively in the adrenal gland, might also increase.37 Consistent with our findings, most prior studies did not find associations between alcohol intake and levels of androstenedione and testosterone,32, 34, 3638 although it has been suggested that testosterone levels are lower among alcoholics than non-alcoholics.39 Cumulatively, these data suggest that an increase in DHEAS levels (which have been associated with increases in breast cancer risk5, 6, 8, 40) may be another mechanism through which alcohol influences cancer risk. The association with DHEA is less clear and warrants additional assessments.

Smoking was associated with higher levels of androstenedione and testosterone. Other studies also have observed elevated levels of testosterone among current smokers.41, 42 A meta-analysis43 and summary of the literature44 found significantly higher levels of androstenedione in smokers compared with non-smokers, in concordance with our results, but also found higher levels of DHEAS. In our study, women smoking ≥ 25 cigarettes per day had higher mean DHEAS levels than non-smokers and women smoking fewer cigarettes, although smoking overall did not significantly contribute to the model and the trend among current smokers across cigarettes per day was not significant. Smoking might impact androgen levels by increasing their production through stimulation of the adrenal gland; nicotine has been found to increase adrenocorticotropic hormone levels.17, 41, 45 Alternatively, smoking might result in elevated androgen levels by decreasing their metabolic clearance rate; smoking has been found to inhibit both aromatase activity and enzymes that degrade androstenedione and testosterone.17, 41, 44 The general lack of association between smoking and both breast46 and ovarian47, 48 cancer may be due to the offsetting hormonal influences of this complex exposure.

Time since natural menopause was not associated with any of the androgens in our study. Previous studies also have reported null findings,29, 32, 49 although associations have been observed with androstenedione,34, 50 testosterone,50 and DHEAS38 levels in some studies. The reasons for different findings are not clear, although the significant studies tended to control for more covariates than the non-significant studies. Further research is needed to better understand the changes in hormone levels after menopause. We did not observe any substantial associations between family history of breast or ovarian cancer and any of the androgens. When a variety of factors were combined into an overall breast cancer risk score, based on the Rosner/Colditz model, we did not observe any significant associations.

Tubal ligation was associated with marginally significantly lower DHEA levels. In the only prior study of this association, women with tubal ligation had non-significantly lower androgen levels.51 While further study is needed, these data suggest that tubal ligation might decrease risk of ovarian cancer52, 53 and possibly breast cancer54, 55 in part by altering androgen levels. We found significantly lower levels of testosterone and free testosterone among women with a hysterectomy compared to women with an intact uterus. Postmenopausally, the ovaries produce 40% to 50% of circulating testosterone56, 57 so we expected significant declines among women having a hysterectomy with bilateral oophorectomy. However, the lower levels of testosterone and free testosterone were similar for women who had a hysterectomy only and those who had a hysterectomy with bilateral oophorectomy. Other studies support a reduction in testosterone levels with a simple hysterectomy, but have observed greater decreases with a bilateral oophorectomy.4951 For androgens other than testosterone, both increasing and decreasing levels have been observed.35, 49, 50 It is unclear why we observed similarly reduced testosterone levels among women with their uterus only removed and those who also had both ovaries removed, but it is unlikely to be due to measurement error. Menopausal status and reason for menopause were previously validated in this cohort.58

Our study has several strengths, including its relatively large size and the use of precise androgen assays. In addition, in a reproducibility study conducted in this population59 we found intraclass correlations over a 3-year period of 0.64 for androstenedione, 0.84 for testosterone, 0.53 for DHEA, and 0.81 for DHEAS,22 indicating that a single hormone measurement, as we have here, can reasonably characterize postmenopausal androgen levels.

Limitations of our study also need to be considered. Some exposures (e.g., alcohol) may have acute effects on hormone levels that might be missed in our study, particularly for androgens with shorter half-lives. Information on cancer risk factors was self-reported, and for some factors, such as waist and hip measurements, we were missing data for a substantial number of women. Non-differential misclassification of both cancer risk factor and androgen levels would most likely attenuate associations. Furthermore, in this cross-sectional study, it is not possible to identify the direction of the significant relationships that were observed. For instance, it is possible that cigarette smoking influences cancer risk through an effect on adrostenedione and testosterone, but it also is possible that higher levels of these hormones influence an individual's desire to smoke.

Additionally, our study population was primarily Caucasian and all women were nurses. Although this reduces the likelihood of confounding, results may not be generalizable to all women. However, while the distribution of health factors, such as cigarette smoking, may be different in our population compared with the general U.S. population, it seems likely that the associations observed for specific categories (e.g., never or current smokers) will be relevant to older women in general. Studies in more diverse populations are needed to test this hypothesis and confirm findings. Finally, although our study was large overall, we had limited numbers for specific exposures (e.g., current smokers, particularly heavy smokers).

In conclusion, we found that certain risk factors, such as BMI, alcohol intake, cigarette smoking, and hysterectomy, were associated with circulating androgen levels among postmenopausal women. However, we did not observe significant associations between many of the risk factors we examined and androgen levels. Given the relatively limited data, additional large studies are warranted to elucidate the relationship between androgen levels and risk factors for breast, endometrial, and ovarian cancers.


Supported by grants P01 CA87969 and CA49449 from the National Institutes of Health. Dr. Danforth was supported in part by a National Cancer Institute Training Grant in cancer epidemiology, CA09001. Dr. Eliassen was supported in part by Cancer Education and Career Development Grant R25 CA098566-02 from the National Cancer Institute. Dr. Colditz was supported in part by the American Cancer Society Cissy Hornung Clinical Research Professorship.


body mass index
DHEA sulfate
Nurses' Health Study
waist-to-hip ratio


Novelty/ Impact of Paper: In a cross-sectional analysis of 646 postmenopausal women in the Nurses' Health Study cohort, we examined associations between adult risk factors for breast, ovarian, and endometrial cancers and circulating androgen levels. Several risk factors, including body size, alcohol intake, cigarette smoking, and hysterectomy, were associated with androgen levels, while others, including height, time since menopause, and overall risk of breast cancer, were not.


1. Suzuki T, Miki Y, Nakamura Y, Moriya T, Ito K, Ohuchi N, Sasano H. Sex steroid-producing enzymes in human breast cancer. Endocr Relat Cancer. 2005;12:701–20. [PubMed]
2. Ho SM. Estrogen, progesterone and epithelial ovarian cancer. Reprod Biol Endocrinol. 2003;1:73. [PMC free article] [PubMed]
3. Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. 2002;11:1531–43. [PubMed]
4. Eliassen AH, Hankinson SE. Endogenous hormone levels and risk of breast, endometrial and ovarian cancers: prospective studies. Adv Exp Med Biol. 2008;630:148–65. [PubMed]
5. Kaaks R, Rinaldi S, Key TJ, Berrino F, Peeters PH, Biessy C, Dossus L, Lukanova A, Bingham S, Khaw KT, Allen NE, Bueno-de-Mesquita HB, et al. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition. Endocr Relat Cancer. 2005;12:1071–82. [PubMed]
6. 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;96:1856–65. [PubMed]
7. Zeleniuch-Jacquotte A, Shore RE, Koenig KL, Akhmedkhanov A, Afanasyeva Y, Kato I, Kim MY, Rinaldi S, Kaaks R, Toniolo P. Postmenopausal levels of oestrogen, androgen, and SHBG and breast cancer: long-term results of a prospective study. Br J Cancer. 2004;90:153–9. [PMC free article] [PubMed]
8. 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;94:606–16. [PubMed]
9. Risch HA. Hormonal etiology of epithelial ovarian cancer, with a hypothesis concerning the role of androgens and progesterone. J Natl Cancer Inst. 1998;90:1774–86. [PubMed]
10. Helzlsouer KJ, Alberg AJ, Gordon GB, Longcope C, Bush TL, Hoffman SC, Comstock GW. Serum gonadotropins and steroid hormones and the development of ovarian cancer. JAMA. 1995;274:1926–30. [PubMed]
11. Lukanova A, Lundin E, Akhmedkhanov A, Micheli A, Rinaldi S, ZeleniuchJacquotte A, Lenner P, Muti P, Biessy C, Krogh V, Berrino F, Hallmans G, et al. Circulating levels of sex steroid hormones and risk of ovarian cancer. Int J Cancer. 2003;104:636–42. [PubMed]
12. Rinaldi S, Dossus L, Lukanova A, Peeters PH, Allen NE, Key T, Bingham S, Khaw KT, Trichopoulos D, Trichopoulou A, Oikonomou E, Pera G, 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;16:23–9. [PubMed]
13. Tworoger SS, Lee IM, Buring JE, Hankinson SE. Plasma androgen concentrations and risk of incident ovarian cancer. Am J Epidemiol. 2008;167:211–8. [PubMed]
14. Lukanova A, Lundin E, Micheli A, Arslan A, Ferrari P, Rinaldi S, Krogh V, Lenner P, Shore RE, Biessy C, Muti P, Riboli E, et al. Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer. 2004;108:425–32. [PubMed]
15. Allen NE, Key TJ, Dossus L, Rinaldi S, Cust A, Lukanova A, Peeters PH, Onland-Moret NC, Lahmann PH, Berrino F, Panico S, Larranaga N, et al. Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC) Endocr Relat Cancer. 2008;15:485–97. [PubMed]
16. Jongen VH, Sluijmer AV, Heineman MJ. The postmenopausal ovary as an androgen-producing gland; hypothesis on the etiology of endometrial cancer. Maturitas. 2002;43:77–85. [PubMed]
17. Viswanathan AN, Feskanich D, De Vivo I, Hunter DJ, Barbieri RL, Rosner B, Colditz GA, Hankinson SE. Smoking and the risk of endometrial cancer: results from the Nurses' Health Study. Int J Cancer. 2005;114:996–1001. [PubMed]
18. Brenner RM, Slayden OD, Nayak NR, Baird DT, Critchley HO. A role for the androgen receptor in the endometrial antiproliferative effects of progesterone antagonists. Steroids. 2003;68:1033–9. [PubMed]
19. Rosner B, Colditz GA. Nurses' Health Study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst. 1996;88:359–64. [PubMed]
20. Rosner B, Colditz GA, Willett WC. Reproductive risk factors in a prospective study of breast cancer: the Nurses' Health Study. Am J Epidemiol. 1994;139:819–35. [PubMed]
21. Colditz GA, Rosner B. Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study. Am J Epidemiol. 2000;152:950–64. [PubMed]
22. Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ, Spiegelman D, Barbieri RL, Speizer FE. Plasma sex steroid hormone levels and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 1998;90:1292–9. [PubMed]
23. Hankinson SE, London SJ, Chute CG, Barbieri RL, Jones L, Kaplan LA, Sacks FM, Stampfer MJ. Effect of transport conditions on the stability of biochemical markers in blood. Clin Chem. 1989;35:2313–6. [PubMed]
24. 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;16:801–10. [PubMed]
25. van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab. 2000;85:3276–82. [PubMed]
26. Rosner B. Percentage Points for a generalized ESD many-outlier procedure. Technometrics. 1983;25:165–72.
27. Lukanova A, Lundin E, Zeleniuch-Jacquotte A, Muti P, Mure A, Rinaldi S, Dossus L, Micheli A, Arslan A, Lenner P, Shore RE, Krogh V, et al. Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. Eur J Endocrinol. 2004;150:161–71. [PubMed]
28. Rinaldi S, Key TJ, Peeters PH, Lahmann PH, Lukanova A, Dossus L, Biessy C, Vineis P, Sacerdote C, Berrino F, Panico S, Tumino R, et al. Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort. Int J Cancer. 2006;118:2832–9. [PubMed]
29. Lamar CA, Dorgan JF, Longcope C, Stanczyk FZ, Falk RT, Stephenson HE., Jr. Serum sex hormones and breast cancer risk factors in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2003;12:380–3. [PubMed]
30. Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, Longcope C, Stanczyk FZ, Stephenson HE, Jr., Falk RT, Miller R, Schatzkin A, Allen DS, et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst. 2003;95:1218–26. [PubMed]
31. Baglietto L, English DR, Hopper JL, MacInnis RJ, Morris HA, Tilley WD, Krishnan K, Giles GG. Circulating steroid hormone concentrations in postmenopausal women in relation to body size and composition. Breast Cancer Res Treat. 2009;115:171–9. [PubMed]
32. Cauley JA, Gutai JP, Kuller LH, LeDonne D, Powell JG. The epidemiology of serum sex hormones in postmenopausal women. Am J Epidemiol. 1989;129:1120–31. [PubMed]
33. Kaye SA, Folsom AR, Soler JT, Prineas RJ, Potter JD. Associations of body mass and fat distribution with sex hormone concentrations in postmenopausal women. Int J Epidemiol. 1991;20:151–6. [PubMed]
34. Madigan MP, Troisi R, Potischman N, Dorgan JF, Brinton LA, Hoover RN. Serum hormone levels in relation to reproductive and lifestyle factors in postmenopausal women (United States) Cancer Causes Control. 1998;9:199–207. [PubMed]
35. Nagata C, Kabuto M, Takatsuka N, Shimizu H. Associations of alcohol, height, and reproductive factors with serum hormone concentrations in postmenopausal Japanese women. Breast Cancer Res Treat. 1997;44:235–41. [PubMed]
36. Dorgan JF, Baer DJ, Albert PS, Judd JT, Brown ED, Corle DK, Campbell WS, Hartman TJ, Tejpar AA, Clevidence BA, Giffen CA, Chandler DW, et al. Serum hormones and the alcohol-breast cancer association in postmenopausal women. J Natl Cancer Inst. 2001;93:710–5. [PubMed]
37. Onland-Moret NC, Peeters PH, van der Schouw YT, Grobbee DE, van Gils CH. Alcohol and endogenous sex steroid levels in postmenopausal women: a cross-sectional study. J Clin Endocrinol Metab. 2005;90:1414–9. [PubMed]
38. Newcomb PA, Klein R, Klein BE, Haffner S, Mares-Perlman J, Cruickshanks KJ, Marcus PM. Association of dietary and life-style factors with sex hormones in postmenopausal women. Epidemiology. 1995;6:318–21. [PubMed]
39. Gavaler JS, Van Thiel DH. Hormonal status of postmenopausal women with alcohol-induced cirrhosis: further findings and a review of the literature. Hepatology. 1992;16:312–9. [PubMed]
40. Tworoger SS, Missmer SA, Eliassen AH, Spiegelman D, Folkerd E, Dowsett M, Barbieri RL, Hankinson SE. The association of plasma DHEA and DHEA sulfate with breast cancer risk in predominantly premenopausal women. Cancer Epidemiol Biomarkers Prev. 2006;15:967–71. [PubMed]
41. Manjer J, Johansson R, Lenner P. Smoking as a determinant for plasma levels of testosterone, androstenedione, and DHEAs in postmenopausal women. Eur J Epidemiol. 2005;20:331–7. [PubMed]
42. Bancroft J, Cawood EH. Androgens and the menopause; a study of 40–60-year-old women. Clin Endocrinol. 1996;45:577–87. [PubMed]
43. Law MR, Cheng R, Hackshaw AK, Allaway S, Hale AK. Cigarette smoking, sex hormones and bone density in women. Eur J Epidemiol. 1997;13:553–8. [PubMed]
44. Cassidenti DL, Pike MC, Vijod AG, Stanczyk FZ, Lobo RA. A reevaluation of estrogen status in postmenopausal women who smoke. Am J Obstet Gynecol. 1992;166:1444–8. [PubMed]
45. Yeh J, Barbieri RL. Twenty-four-hour urinary-free cortisol in premenopausal cigarette smokers and nonsmokers. Fertil Steril. 1989;52:1067–9. [PubMed]
46. Terry PD, Rohan TE. Cigarette smoking and the risk of breast cancer in women: a review of the literature. Cancer Epidemiol Biomarkers Prev. 2002;11:953–71. [PubMed]
47. Tworoger SS, Gertig DM, Gates MA, Hecht JL, Hankinson SE. Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer. Cancer. 2008;112:1169–77. [PubMed]
48. Rossing MA, Cushing-Haugen KL, Wicklund KG, Weiss NS. Cigarette smoking and risk of epithelial ovarian cancer. Cancer Causes Control. 2008;19:413–20. [PubMed]
49. Chubak J, Tworoger SS, Yasui Y, Ulrich CM, Stanczyk FZ, McTiernan A. Associations between reproductive and menstrual factors and postmenopausal androgen concentrations. J Womens Health. 2005;14:704–12. [PubMed]
50. Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, von Muhlen D. Hysterectomy, oophorectomy, and endogenous sex hormone levels in older women: the Rancho Bernardo Study. J Clin Endocrinol Metab. 2000;85:645–51. [PubMed]
51. Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab. 2005;90:3847–53. [PubMed]
52. Riman T, Nilsson S, Persson IR. Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies. Acta Obstet Gynecol Scand. 2004;83:783–95. [PubMed]
53. Tworoger SS, Fairfield KM, Colditz GA, Rosner BA, Hankinson SE. Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. Am J Epidemiol. 2007;166:894–901. [PubMed]
54. Eliassen AH, Colditz GA, Rosner B, Hankinson SE. Tubal sterilization in relation to breast cancer risk. Int J Cancer. 2006;118:2026–30. [PubMed]
55. Calle EE, Rodriguez C, Walker KA, Wingo PA, Petrelli JM, Thun MJ. Tubal sterilization and risk of breast cancer mortality in US women. Cancer Causes Control. 2001;12:127–35. [PubMed]
56. Lukanova A, Kaaks R. Endogenous hormones and ovarian cancer: epidemiology and current hypotheses. Cancer Epidemiol Biomarkers Prev. 2005;14:98–107. [PubMed]
57. Davison SL, Davis SR. Androgens in women. J Steroid Biochem Mol Biol. 2003;85:363–6. [PubMed]
58. Colditz GA, Stampfer MJ, Willett WC, Stason WB, Rosner B, Hennekens CH, Speizer FE. Reproducibility and validity of self-reported menopausal status in a prospective cohort study. Am J Epidemiol. 1987;126:319–25. [PubMed]
59. Hankinson SE, Manson JE, Spiegelman D, Willett WC, Longcope C, Speizer FE. Reproducibility of plasma hormone levels in postmenopausal women over a 2–3-year period. Cancer Epidemiol Biomarkers Prev. 1995;4:649–54. [PubMed]