Endogenous sex hormones and subsequent breast cancer in premenopausal women

Andrea Micheli, Paola Muti, Giorgio Secreto, Vittorio Krogh, Elisabetta Meneghini, Elisabetta Venturelli, Sabina Sieri, Valeria Pala, Franco Berrino

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at -80°C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol-glucoronide, progesterone, 17-OH-progesterone, sex hormone-binding globulin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fifty-five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11-7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% Cl = 0.15-1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalInternational Journal of Cancer
Volume112
Issue number2
DOIs
Publication statusPublished - Nov 1 2004

Fingerprint

Gonadal Steroid Hormones
Breast Neoplasms
Menstrual Cycle
Progesterone
Follicle Stimulating Hormone
Luteinizing Hormone
Testosterone
Hormones
Confidence Intervals
Hyperandrogenism
Sex Hormone-Binding Globulin
Dehydroepiandrosterone Sulfate
Menstruation
Androstenedione
Corpus Luteum
Serum
Body Mass Index
Cohort Studies
Multivariate Analysis
Hemorrhage

Keywords

  • Breast cancer
  • Cohort study
  • Hormones
  • Premenopausal women

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Micheli, A., Muti, P., Secreto, G., Krogh, V., Meneghini, E., Venturelli, E., ... Berrino, F. (2004). Endogenous sex hormones and subsequent breast cancer in premenopausal women. International Journal of Cancer, 112(2), 312-318. https://doi.org/10.1002/ijc.20403

Endogenous sex hormones and subsequent breast cancer in premenopausal women. / Micheli, Andrea; Muti, Paola; Secreto, Giorgio; Krogh, Vittorio; Meneghini, Elisabetta; Venturelli, Elisabetta; Sieri, Sabina; Pala, Valeria; Berrino, Franco.

In: International Journal of Cancer, Vol. 112, No. 2, 01.11.2004, p. 312-318.

Research output: Contribution to journalArticle

Micheli, A, Muti, P, Secreto, G, Krogh, V, Meneghini, E, Venturelli, E, Sieri, S, Pala, V & Berrino, F 2004, 'Endogenous sex hormones and subsequent breast cancer in premenopausal women', International Journal of Cancer, vol. 112, no. 2, pp. 312-318. https://doi.org/10.1002/ijc.20403
Micheli, Andrea ; Muti, Paola ; Secreto, Giorgio ; Krogh, Vittorio ; Meneghini, Elisabetta ; Venturelli, Elisabetta ; Sieri, Sabina ; Pala, Valeria ; Berrino, Franco. / Endogenous sex hormones and subsequent breast cancer in premenopausal women. In: International Journal of Cancer. 2004 ; Vol. 112, No. 2. pp. 312-318.
@article{c81c7ae85852402b97c73017a9f3d61e,
title = "Endogenous sex hormones and subsequent breast cancer in premenopausal women",
abstract = "Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at -80°C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol-glucoronide, progesterone, 17-OH-progesterone, sex hormone-binding globulin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fifty-five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95{\%} confidence interval (CI) = 1.11-7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95{\%} Cl = 0.15-1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95{\%} CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.",
keywords = "Breast cancer, Cohort study, Hormones, Premenopausal women",
author = "Andrea Micheli and Paola Muti and Giorgio Secreto and Vittorio Krogh and Elisabetta Meneghini and Elisabetta Venturelli and Sabina Sieri and Valeria Pala and Franco Berrino",
year = "2004",
month = "11",
day = "1",
doi = "10.1002/ijc.20403",
language = "English",
volume = "112",
pages = "312--318",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Endogenous sex hormones and subsequent breast cancer in premenopausal women

AU - Micheli, Andrea

AU - Muti, Paola

AU - Secreto, Giorgio

AU - Krogh, Vittorio

AU - Meneghini, Elisabetta

AU - Venturelli, Elisabetta

AU - Sieri, Sabina

AU - Pala, Valeria

AU - Berrino, Franco

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at -80°C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol-glucoronide, progesterone, 17-OH-progesterone, sex hormone-binding globulin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fifty-five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11-7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% Cl = 0.15-1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.

AB - Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at -80°C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol-glucoronide, progesterone, 17-OH-progesterone, sex hormone-binding globulin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fifty-five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11-7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% Cl = 0.15-1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.

KW - Breast cancer

KW - Cohort study

KW - Hormones

KW - Premenopausal women

UR - http://www.scopus.com/inward/record.url?scp=4544286153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544286153&partnerID=8YFLogxK

U2 - 10.1002/ijc.20403

DO - 10.1002/ijc.20403

M3 - Article

C2 - 15352045

AN - SCOPUS:4544286153

VL - 112

SP - 312

EP - 318

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 2

ER -