Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi


CiteScore 2017: 2.48

SCImago Journal Rank (SJR) 2017: 1.021
Source Normalized Impact per Paper (SNIP) 2017: 0.830

Online
ISSN
1868-1891
See all formats and pricing
More options …
Volume 35, Issue 1

Issues

Dehydroepiandrosterone and/or its metabolites: possible androgen receptor antagonistic effects on digitized mammographic breast density in normal breast tissue of postmenopausal women

Eva Lundström
  • Division for Obstetrics and Gynecology, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kjell Carlström
  • Division for Obstetrics and Gynecology, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sabine Naessen
  • Division for Obstetrics and Gynecology, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gunnar Söderqvist
  • Corresponding author
  • Division for Obstetrics and Gynecology, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden, Phone: +46 8 517 700 00, Fax: +46 8 318114
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-08-25 | DOI: https://doi.org/10.1515/hmbci-2018-0036

Abstract

Background

Androgens, notably testosterone inhibit breast cell proliferation and negative correlations between free testosterone (fT) and breast cell proliferation as well as mammographic density have been described. Dehydroepiandrosterone (DHEA) is reported to be a partial androgen antagonist in breast tumor cells in vitro. Our aim was to investigate if circulating DHEA had any effects on the association between circulating fT and mammographic density in vivo in the normal postmenopausal breast.

Methods

We measured visual and digitized mammographic density and serum DHEA, testosterone, sex-hormone-binding globulin and calculated fT in 84 healthy untreated postmenopausal women.

Results

Significant negative correlations between fT and both visual and digitized mammographic density were strengthened when the median DHEA level decreased from 10.2 to 8.6 nmol/L. Thereafter, correlations became weaker again probably due to decreasing fT levels and/or sample size. There were no correlations between mammographic density and DHEA, at any of the DHEA concentration ranges studied. Serum levels of fT and DHEA were positively correlated.

Conclusion

Our findings demonstrate that circulating DHEA and/or its metabolites counteract the inhibitory action of fT on mammographic breast density.

Keywords: dehydroepiandrosterone sulfate; mammographic density; normal breast; postmenopausal women; testosterone

References

  • [1]

    Birrell SN, Bentel JM, Hickey D, Riciardelli C, Weger MA, Horsfall DI, et al. Androgens induce divergent proliferative response in human breast cell lines. J Steroid Biochem Mol Biol. 1995;52:459–67.CrossrefGoogle Scholar

  • [2]

    Isakson E, von Schoultz E, Odlind V, Söderqvist, G, Csemiczky G, Carlström K, et al. Effects of oral contraceptives on breast epithelial proliferation. Breast Cancer Res Treat. 2001;65:163–9.CrossrefPubMedGoogle Scholar

  • [3]

    Hofling M, Lundström E, Azavedo E, Svane G, Lindén-Hirschberg A, von Schoultz B. Testosterone addition during postmenopausal therapy: effects on mammographic breast density. Climacteric. 2007;10:155–63.PubMedCrossrefGoogle Scholar

  • [4]

    Hofling M, Löfgren L, von Schoultz E, Carlström K, Söderqvist G. Associations between serum testosterone levels, cell proliferation and progesterone receptor content in normal and malignant breast tissue. Gynecol Endocrinol. 2008;24:405–10.Web of SciencePubMedCrossrefGoogle Scholar

  • [5]

    Gammon MD, Thompson WD. Polycystic ovaries and the risk of breast cancer. Am J Epidemiol. 1991;134:818–24.CrossrefPubMedGoogle Scholar

  • [6]

    McCulloch DR, Akl P, Samaratunga H, Herington AC, Odorico DM. Expression of the disintegrin metallo-protease, ADAM-10, in prostate cancer and its regulation by dihydrotestosterone, insulin-like growth factor I and epidermal growth factor in the prostate cancer cell model LNCaP. Clin Cancer Res. 2004;10:314–23.CrossrefGoogle Scholar

  • [7]

    Edwall L, Carlström K, Fianu-Jonasson A. Endocrine status and markers of collagen synthesis and degradation in serum and urogenital tissue from women with and without stress urinary incontinence. Neurourol Urodynam. 2007;26:410–5.CrossrefWeb of ScienceGoogle Scholar

  • [8]

    Davies ME, Gumucio JP, Sugg KB, Bedi A, Mendias CL. MMP inhibition as a potential method to augment the healing of skeletal muscle and tendon extracellular matrix. J Appl Physiol. 2013;115:884–91.Web of ScienceCrossrefPubMedGoogle Scholar

  • [9]

    Hulboy DL, Rudolph LA, Matrisian LM. Matrix metalloproteinases as mediators of regulatory function. Mol Hum Reprod. 1997;3:27–45.CrossrefGoogle Scholar

  • [10]

    Lundström E, Conner P, Naessén S, Löfgren L, Carlström K, Söderqvist G. Estrone a partial estradiol antagonist in the normal breast. Gynecol Endocrinol. 2015;31:747–9.Web of ScienceCrossrefPubMedGoogle Scholar

  • [11]

    Chen F, Knecht K, Birzin E, Fisher J, Wilkinson H, Mojena M, et al. Direct agonist/antagonist functions of dehydroepiandrosterone. Endocrinology. 2005;146:4568–76.CrossrefPubMedGoogle Scholar

  • [12]

    Lundström E, Christow A, Kersemaekers W, Svane G, Azavedo E, Söderqvist G, et al. Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density. Am J Obstet Gynecol. 2002;186:717–22.CrossrefPubMedGoogle Scholar

  • [13]

    Lundström E, Lindén Hirschberg A, Söderqvist G. Digitized assessment of mammographic breast density – effect of continuous combined therapy, tibolone and black cohosh compared to placebo. Maturitas. 2011;70:361–4.CrossrefGoogle Scholar

  • [14]

    Lundström E, Söderqvist G, Svane G, Azawedo E, Olovsson M, von Schoultz E, et al. Digitized assessment of mammographic breast density in patients who received low dose intrauterine levo-norgestrel in continuous combination with oral estradiol valerate: a pilot study. Fertil Steril. 2006;85:989–95.CrossrefGoogle Scholar

  • [15]

    Hofling M, Carlström K, Svane G, Azavedo E, Klosterboer H, von Schoultz B. Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone-binding globulin and free testosterone levels – an association with mammographic density. Gynecol Endocrinol. 2005;20:110–5.PubMedCrossrefGoogle Scholar

  • [16]

    Taieb J, Mathian B, Millot F, Patricot MC, Mathieu E, Queyrel N, et al. Testosterone measured by 10 immunoassays and by isotope-dilution gas chromatography–mass spectrometry in sera from 116 men, women and children. Clin Chem. 2003;49:1381–95.PubMedCrossrefGoogle Scholar

  • [17]

    Carlström K, Brody S, Lunell NO, Lagrelius A, Möllerström G, Pousette A, et al. Dehydroepiandrosterone sulfate and dehydroepiandrosterone in serum: age and sex-related differences. Maturitas. 1988;10:297–306.CrossrefGoogle Scholar

  • [18]

    Eklund E, Berglund B, Labrie F, Carlström K, Ekström L, Hirschberg AL. Serum androgen profile and physical performance in women Olympic athletes. Br J Sports Med. 2017;51:1301–8.Web of SciencePubMedCrossrefGoogle Scholar

  • [19]

    Södergård R, Bäckström T, Shanbhag V, Carstensen H. Calculation of free and bound fractions of testosterone and estradiol-17β to plasma proteins at body temperature. J Steroid Biochem. 1982;16:801–10.PubMedCrossrefGoogle Scholar

  • [20]

    Naessen T, Sjogren U, Bergquist J, Larsson M, Lind L, Kushnir MM. Endogenous steroids measured by high-specificity liquid chromatography-tandem mass spectrometry and prevalent cardiovascular disease in 70-year-old men and women. J Clin Endocrinol Metab. 2010;95:1889–97.Web of SciencePubMedCrossrefGoogle Scholar

  • [21]

    Zumoff BV, Bradlow HL. Sex difference in the metabolism of dehydroisoandrosterone sulfate. JCEM. 1980;51:334–6.Google Scholar

  • [22]

    Crilly RG, Francis RM, Nordin BE. Steroid hormones, ageing and bone. Clin Endocrinol Metab. 1981;10:115–39.PubMedCrossrefGoogle Scholar

  • [23]

    Markiewicz L, Gurpide E. C19 adrenal steroids enhance prostaglandin F2α output by human endometrium in vitro. Am J Obstet Gynecol. 1988;159:500–4.CrossrefPubMedGoogle Scholar

  • [24]

    Matsuoka LY, Wortsman J, Lifrak ET, Parker LN, Mehta RG, Parker LN. Effect of isotretinoin in acne is not mediated by adrenal androgens. J Am Acad Dermatol. 1989;20:128–9.PubMedCrossrefGoogle Scholar

  • [25]

    Longcope C. Dehydroepiandrosterone metabolism. J Endocrinol. 1996;150:125–7.Google Scholar

  • [26]

    McNamara KM, Moore NL, Hickey TE, Sasano H, Tilley WD. Complexities of androgen receptor signaling in breast cancer. Endocr Relat Cancer. 2014;21:161–81.CrossrefGoogle Scholar

  • [27]

    Montt-Guevara MM, Shortrede JE, Giretti MS, Giannini A, Mannella P, Russo E, et al. Androgens regulate T47D cells motility and invasion through actin cytoskeleton remodeling. Front Endocrinol. 2016;7:136.Web of ScienceGoogle Scholar

  • [28]

    Tamimi RM, Hankinson SE, Chen WY, Rosner B, Colditz GA. Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Arch Intern Med. 2006;166:1483–9.PubMedCrossrefGoogle Scholar

  • [29]

    Glaser RL, Dimitrakakis C. Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozole: a prospective, observational study. Maturitas. 2013;76:342–9.PubMedCrossrefWeb of ScienceGoogle Scholar

About the article

aDeceased (May 5, 2018. Obituary will be published separately).


Received: 2018-05-29

Accepted: 2018-07-02

Published Online: 2018-08-25


Author Statement

Research funding: This study was supported by grants from the Swedish Cancer Society, the Swedish Research Council (project No. 5982), the Karolinska Institutet Research Funds and NV ORGANON, Oss, The Netherlands.

Conflict of interest: All authors declare no conflict of interest.

Informed consent: Informed consent has been obtained from all individuals included into the study.

Ethical approval: The research results related to human use complied with all the relevant national regulations and institutional policies, was performed in accordance to the tenets of the Helsinki Declaration and has been approved by the local institutional review board.


Citation Information: Hormone Molecular Biology and Clinical Investigation, Volume 35, Issue 1, 20180036, ISSN (Online) 1868-1891, DOI: https://doi.org/10.1515/hmbci-2018-0036.

Export Citation

©2018 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Comments (0)

Please log in or register to comment.
Log in