Repeated serum and urinary androgen measurements in premenopausal and postmenopausal women

Micheli, Andrea; Muti, Paola; Pisani, Paola; Secreto, Giorgio; Recchione, C; Totis, A.; Fissi, R; Cavalleri, A; Panico, Salvatore; Berrino, Franco

doi:10.1016/0895-4356(91)90007-v

Cited by 32 publications

(22 citation statements)

References 14 publications

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“…However, we were generally able to detect statistically significant differences between cases and controls. Although we obtained only one blood sample from study subjects, single blood samples adequately characterize postmenopausal circulating levels of testosterone, [29][30][31] androstenedione, 29 SHBG-bound estradiol, 30 estrone 31 and estradiol (in some, 32 but not all, 30,31 studies) over a 2-yr period. We adjusted for year of blood draw to account for any possible degradation in the analytes over time and adjusted for hour of the blood draw to adjust for possible diurnal variation, particularly of the androgens.…”

Section: Discussionmentioning

confidence: 99%

Serum concentrations of estrogens, sex hormone‐binding globulin, and androgens and risk of breast cancer in postmenopausal women

Adly

Hill

Sherman

et al. 2006

Intl Journal of Cancer

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We assessed the relationship between serum concentrations of estrogens, androgens, and sex hormone-binding globulin and risk of breast cancer among postmenopausal women. Study participants provided serum prior to breast biopsy or mastectomy in 3 hospitals in Grand Rapids, Michigan between 1977 and 1987. A total of 179 subjects with localized breast cancer were compared to 152 subjects with nonproliferative breast changes that have not been associated with elevated breast cancer risk. Increasing serum concentrations of estrone and estrone sulfate were associated with increases in breast cancer risk; the odds ratios (ORs) in the fourth quartiles compared to the first were 2.3 (95% confidence interval (CI) 1.1-4.6) for both (p-trend 5 0.02 and 0.03, respectively). Estradiol and bioavailable estradiol concentrations were associated with nonstatistically significant increases in risk. Androstenediol levels were associated with risk (p-trend 5 0.01); the OR in the fourth compared to the first quartile was 2.2 (95% CI 1.0-4.6). Testosterone, dehydroepiandrosterone and androstenedione levels were not associated with increased risk. Sex hormone-binding globulin was associated with a nonsignificant decrease in risk. Associations with estrone and estrone sulfate persisted after adjustment for androstenediol (ORs for fourth compared to first quartiles were 2.0 (95% CI 0.9-4.5) and 2.2 (95% CI 1.0-4.6), respectively (p-trend 5 0.16 for both). The association with androstenediol was attenuated after adjustment for estrone (OR for fourth compared to first quartile was 1.6 (95% CI 0.7-3.6); p-trend 5 0.13). Higher serum concentrations of estrogens were associated with increased breast cancer risk in postmenopausal women. Androgen levels were not independently associated with substantially increased risk. ' 2006 Wiley-Liss, Inc.Key words: breast cancer; estrogens; androgens; androstenediol Epidemiologic, experimental and animal data strongly implicate estrogens in the etiology of breast cancer. 1 The relationship between endogenous androgen levels (testosterone, androstenedione, dehydroepiandrosterone (DHEA)) and breast cancer risk is less clear, with both epidemiologic and experimental data providing conflicting results. 2-6 A metabolite of DHEA, 5-androstene-3b, 17b-diol (androstenediol), which in vitro acts as an estrogen in estradiol-deficient medium and as an androgen in an estrogen-rich medium, has been linked to increased breast cancer risk in postmenopausal women in one study. 7 Androgens could act to stimulate the breast directly or indirectly by providing the raw material for the synthesis of estrogens in peripheral or mammary adipose tissue.In this report, we assess the relationship between serum concentrations of estrogens, sex hormone-binding globulin and androgens, including androstenediol, to risk of localized breast cancer in postmenopausal women. Women undergoing biopsy in the same hospitals as the cases but diagnosed with nonproliferative breast conditions not related to elevated risk of breast cancer served a...

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Section: Discussionmentioning

confidence: 99%

Serum concentrations of estrogens, sex hormone‐binding globulin, and androgens and risk of breast cancer in postmenopausal women

Adly

Hill

Sherman

et al. 2006

Intl Journal of Cancer

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“…Single hormone measurements in postmenopausal women have been shown to be reproducible over a 2-3 year period. They should suffice to rank subjects with regard to longterm hormone concentrations (Micheli et al 1991, Hankinson et al 1995. Unlike previously reported data (Thomas et al 1997b), we did not find any relationship between duration of blood sample storage and hormone concentrations.…”

Section: Discussionmentioning

confidence: 99%

Aromatase and breast cancer susceptibility.

Probst‐Hensch¹,

Ingles²,

Diep³

et al. 1999

Endocrine-Related Cancer

138

101

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Based on experimental and epidemiological evidence it is hypothesized that estrogen increases breast cancer risk by increasing mitotic activity in breast epithelial cells. Aromatase is crucial to the biosynthesis of estrogens and may therefore play a role in breast cancer development. Supporting data for an etiological role of aromatase in breast tumor biology are several-fold. First, the association between weight and postmenopausal breast cancer risk may be mediated by aromatase. Secondly, a pilot study found a higher aromatase expression in normal breast adipose tissue from breast cancer cases as opposed to healthy women. Thirdly, experimental data in animals suggest that aromatase activity predisposes mammary tissue to preneoplastic and neoplastic changes. In a multiethnic cohort study conducted in Los Angeles and on Hawaii we investigated (i) whether the plasma estrone to androstenedione (E1/A) ratio in different ethnic groups was associated with ethnic differences in breast cancer incidence, and (ii) whether genetic variation in the CYP19 gene encoding the P450 aromatase protein was associated with breast cancer risk. The age-and weight-adjusted ethnic specific E1/A ratios ×100 among women without oophorectomy were 7.92 in African-Americans, 8.22 in Japanese, 10.73 in Latinas and 9.29 in non-Latina Whites (P=0.09). The high E1/A ratio in Latina women was not associated with a high breast cancer incidence; in fact Latina women had the lowest breast cancer incidence in the cohort observed so far. We found no consistent association of an intronic (TTTA) n repeat polymorphism with breast cancer risk in different ethnic groups. This polymorphism was not associated with differences in the plasma E1/A ratio in a way that would predict its functional relevance. We describe a newly identified TTC deletion in intron 5 of the CYP19 gene that is associated with the (TTTA) n repeat polymorphism. Neither this polymorphism, nor a polymorphism at codon 264 in exon VII of the CYP19 gene, was associated with breast cancer. We did not identify any genetic variation in exon VIII in 54 African-American subjects. We identified rare genetic variants of unknown functional relevance in the promoter I.4 of the CYP19 gene in 3 out of 24 Latina women. Further investigation into the role of aromatase in breast cancer etiology is important, given that the Endocrine-Related Cancer (1999) 6 165-173 potential use of aromatase inhibitors as breast cancer chemopreventives depends on these results.

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“…To our knowledge, only one study has been published so far on the reproducibility of urinary sex steroid measurements over time in post-menopausal women [15]. In this previous study, 60 women who participated as controls in a case-control study were invited to give a second 24-hour urine sample approximately 1 year after the first sample.…”

Section: Discussionmentioning

confidence: 99%

“…The basic requirement for the accurate assessment of relative risk in epidemiological studies is that subjects be ranked accurately by their average, long-term hormone levels. While several studies have been published on the reproducibility and validity of hormone measurements in blood over time [10][11][12][13], few have addressed the reproducibility and validity of these measurements in urine samples [14,15].…”

Section: Introductionmentioning

confidence: 99%

Reproducibility over time of measurements of androgens, estrogens and hydroxy estrogens in urine samples from post-menopausal women

et al. 2002

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Abstract. Sex steroid concentrations in urine samples from post-menopausal women have been associated with risk of various chronic diseases. The basic requirement for the assessment of risk in such largescale epidemiological studies is that subjects be ranked accurately by their average, long-term hormone levels. We examined the reproducibility over time of measurements of urinary testosterone (T), 5a-androstane-3a, 17b-diol (ADIOL), estrone (E 1 ), estradiol (E 2 ), 2-hydroxy estrone and 2-hydroxy estradiol, (2(OH)-E), 16a-hydroxyestrone (16a(OH)-E 1 ) and the ratio of 2(OH)-E and 16a(OH)-E 1 , in a representative sub-sample of post-menopausal women (n ¼ 43) participating in an ongoing prospective cohort study. Women collected three first morning urine voids on different occasions, with average time difference between the first and the third urine sample of 5.1 years. T, ADIOL, E 1 and E 2 were measured by radio immunoassay after enzymatic hydrolysis, solidphase extraction and HPLC purification of the samples, while 2(OH)-E and 16a(OH)-E 1 were assayed by solid-phase enzyme immunoassay after enzymatic hydrolysis. Intra-class correlation co-efficients (ICCs) over time were very good for T (r ¼ 0.85), acceptable for E 2 , E 1 and ADIOL (r > 0.55), but low for 2(OH)-E, 16a(OH)-E 1 and their ratio (r < 0.46). The adjustment for creatinine concentrations did not increase these correlations.Key words: Androgens, Estrogens, Hydroxy estrogens, Post-menopausal women, Reproducibility, Urine Abbreviations: ADIOL = 5a-androstane-3a, 17b-diol; E 2 = estradiol; E 1 = estrone; 2(OH)-E = 2-hydroxy estrone and 2-hydroxy estradiol; 16a(OH)-E 1 = 16a-hydroxyestrone; T = testosterone

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Repeated serum and urinary androgen measurements in premenopausal and postmenopausal women

Cited by 32 publications

References 14 publications

Serum concentrations of estrogens, sex hormone‐binding globulin, and androgens and risk of breast cancer in postmenopausal women

Serum concentrations of estrogens, sex hormone‐binding globulin, and androgens and risk of breast cancer in postmenopausal women

Aromatase and breast cancer susceptibility.

Reproducibility over time of measurements of androgens, estrogens and hydroxy estrogens in urine samples from post-menopausal women

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