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Effects of pre-and postmenopausal use of exogenous hormones on receptor content in normal human breast tissue: A randomized study
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health. (Gynekologisk endokrionologi/Naessén)
Karolinska Institute, Stockholm, Sweden.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Women's and Children's Health. (Gynekologisk endokrinologi/Naessén)
Karolinska Institute, Stockholm, Sweden.
2008 (English)In: Gynecological Endocrinology, ISSN 0951-3590, Vol. 24, no 8, 475-480 p.Article in journal (Refereed) Published
Abstract [en]

Objective. To examine the effects of exposure to endogenous and exogenous hormones on estrogen receptor- (ER) and progesterone receptor (PR) levels in normal human breast tissue. Methods. In a randomized study of women scheduled for mammary reduction plasty (n = 81), ER and PR content in breast parenchyma was analyzed in premenopausal (n = 49) and postmenopausal (n = 16) women. Premenopausal women were randomized to surgery in the follicular or luteal phase of the menstrual cycle or after oral contraceptive treatment for 2 months. Postmenopausal women were randomized to sequential or estrogen-only therapy for 2 months prior to surgery. Results. ER content was higher in parous than in nulliparous (p = 0.009) premenopausal women and displayed a positive association with age (rs = 0.51, p = 0.0002). Compared with premenopausal women in the follicular phase, postmenopausal women had higher ER content (p = 0.040) whereas premenopausal women on oral contraception had lower ER (p = 0.048) and PR (p = 0.007) content. Smokers had lower PR content than non-smokers (p = 0.02). Conclusion. In the present study ER content was higher in parous than in non-parous women and associated with premenopausal age. Short-term oral contraceptives yielded lower ER and PR contents. Postmenopausal estrogen/progestogen combined therapy yielded lower PR content than estrogen-only therapy.

Place, publisher, year, edition, pages
2008. Vol. 24, no 8, 475-480 p.
Keyword
Estrogen receptor-a, human breast tissue, oral contraceptives, postmenopausal, progesterone receptor, premenopausal
Research subject
Identifiers
URN: urn:nbn:se:uu:diva-86532DOI: 10.1080/09513590802234204ISI: 000260457200010OAI: oai:DiVA.org:uu-86532DiVA: diva2:117376
Available from: 2008-12-03 Created: 2008-11-12 Last updated: 2011-05-04Bibliographically approved
In thesis
1. Effects of Endogenous and Exogenous Hormones on the Female Breast: With Special Reference to the Expression of Proteoglycans
Open this publication in new window or tab >>Effects of Endogenous and Exogenous Hormones on the Female Breast: With Special Reference to the Expression of Proteoglycans
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aims to study the effects of endogenous and exogenous hormones and mammographic breast density (BD) on cellular markers in non-cancerous female breast tissue. Women on the waiting list for breast reduction plastic surgery were recruited (n = 79), and randomized to 2 months of hormone therapy or no therapy before surgery. The women had a mammogram and a needle biopsy 2 months before surgery and tissue samples were obtained at the operation.

In premenopausal women, estrogen receptor (ER)α levels were associated with age (p = 0.0002), were similar in the follicular and luteal phases of the menstrual cycle and were higher in parous than in nulliparous women (p = 0.009). Current smokers had lower PR levels than non-smokers (p = 0.019). Women on oral contraception had lower ERα (p = 0.048) and PR (p = 0.007) levels than women in the follicular phase. The ERα levels did not differ significantly between postmenopausal estrogen and estrogen-progestogen users, but PR levels were lower among estrogen-progestogen users (p = 0.03).

We found lower expression of the genes for decorin and syndecans 1 and 4 in the luteal phase than in the follicular phase, among parous women. Protein levels of the androgen receptor, syndecan-4 and decorin was lower in premenopausal women who were using oral contraceptives (OC) than in those in the follicular phase (p = 0.002 - 0.02), whereas no significant differences between OC use and the luteal phase were found.

In premenopausal women, BD was negatively associated with age and body mass index but was similar for the menstrual phases. Breast density was associated with genetic expression of the androgen receptor and remained significant after adjustment for age (rs = 0.56; p = 0.04). After adjustement for age, breast density was also marginally associated with expression of the caspase 3 gene (0.55; 0.053). However, protein levels of caspase 3 was negatively associated (-0.61; 0.03).

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 651
Keyword
breast tissue, proteoglycans, mammographic density, oral contraceptives, androgen receptor, proliferation, apoptosis, extracellular matrix, premenopausal
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-147793 (URN)978-91-554-8018-9 (ISBN)
Public defence
2011-04-14, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2011-03-23 Created: 2011-02-28 Last updated: 2011-05-04Bibliographically approved

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