41 results on '"Söderqvist, G"'
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2. p53 expression in breast and endometrium during estrogen and tamoxifen treatment of surgically postmenopausal cynomolgus macaques
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Isaksson, E., Cline, J.M., Skoog, L., Söderqvist, G., Wilking, N., von Schoultz, E., and von Schoultz, B.
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- 1999
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3. The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology
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Engman, M., Skoog, L., Söderqvist, G., and Gemzell-Danielsson, K.
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- 2008
4. Mammary Gland
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Söderqvist, G., primary and Schoultz, B. Von, additional
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- 1999
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5. Regional Distribution of Proliferating Cells and Hormone Receptors in the Mammary Gland of Surgically Postmenopausal Macaques
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von Schoultz B, Cline Jm, Lambert Skoog, and Söderqvist G
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medicine.medical_specialty ,medicine.drug_class ,Ovariectomy ,Mammary gland ,Estrogen receptor ,Medroxyprogesterone Acetate ,Biology ,Mammary Glands, Animal ,Internal medicine ,Progesterone receptor ,medicine ,Animals ,Medroxyprogesterone acetate ,Horses ,Receptor ,Antibodies, Monoclonal ,Nuclear Proteins ,Obstetrics and Gynecology ,Antigens, Nuclear ,Estrogens ,medicine.disease ,Postmenopause ,Menopause ,Macaca fascicularis ,Ki-67 Antigen ,Endocrinology ,medicine.anatomical_structure ,Receptors, Estrogen ,Reproductive Medicine ,Estrogen ,Hormone receptor ,Female ,Receptors, Progesterone ,Cell Division ,medicine.drug - Abstract
Objective: To define the relative proliferative response and hormone receptors status in ten sites in the mammary gland of surgically postmenopausal cynomolgus macaques given hormone replacement therapy. Methods: Surgical postmenopausal cynomolgus macaques were given either no treatment (n = 4), conjugated equine estrogens (CEE, n = 4), or combined therapy with CEE and medroxyprogesterone acetate (n = 4). The drugs were administered in the diet, at doses equivalent on a caloric basis to 0.625 mg/woman/day for CEE and 2.5 mg/woman/day for medroxyprogesterone acetate. Immunostaining of mammary sections was done for estrogen receptor, progesterone receptor, and the proliferation marker Ki-67 MIB-1 (MIB). Comparisons were made between central and peripheral gland, by quadrant, left versus right, and with respect to distance from the nipple within each quadrant. Result: There were no significant differences in hormone receptor or MIB expression within different sites within the gland. Conclusions: In the surgically postmenopausal, hormone-treated macaque, regional differences in estrogen and progesterone receptors and MIB staining are not apparent. The assumption of homogeneity throughout the gland makes aspiration cytology and multiple biopsy studies feasible in this species.
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- 1997
6. Digitized assessment of mammographic breast density – Effects of continuous combined hormone therapy, tibolone and black cohosh compared to placebo
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Lundström, E., primary, Hirschberg, A.L., additional, and Söderqvist, G., additional
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- 2011
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7. Effects of oral contraceptives on breast epithelial proliferation
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Isaksson, E, von Schoultz, E, Odlind, V, Söderqvist, G, Csemiczky, G, Carlström, K, Skoog, L, von Schoultz, B, Isaksson, E, von Schoultz, E, Odlind, V, Söderqvist, G, Csemiczky, G, Carlström, K, Skoog, L, and von Schoultz, B
- Published
- 2001
8. A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolone and continuous combined estrogen–progestogen treatment
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Conner, P., primary, Christow, A., additional, Kersemaekers, W., additional, Söderqvist, G., additional, Skoog, L., additional, Carlström, K., additional, Tani, E., additional, Mol-Arts, M., additional, and von Schoultz, B., additional
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- 2004
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9. Mammographic breast density during hormone replacement therapy: effects of continuous combination, unopposed transdermal and low-potency estrogen regimens
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Lundström, E., primary, Wilczek, B., additional, von Palffy, Z., additional, Söderqvist, G., additional, and von Schoultz, B., additional
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- 2001
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10. Breast epithelial proliferation in postmenopausal women evaluated through fine-needle-aspiration cytology
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Conner, P., primary, Skoog, L., additional, and Söderqvist, G., additional
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- 2001
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11. F115 Effects of estrogens, tamoxifen, progestins, androgens and dietary soy on the mammary gland and endometrium of macaques
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Cline, JM, primary, Söderqvist, G, additional, Foth, D, additional, Römer, T, additional, and von Schoutz, B, additional
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- 1996
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12. F174 The influence of menstrual cycle phase on proliferation of breast epithelial cells in vivo
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Söderqvist, G, primary, Isaksson, E, additional, Carlström, K, additional, von Schoultz, B, additional, Tani, E, additional, and Skoog, L, additional
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- 1996
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13. Hormonal regulation of the normal breast
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Von Schoultz, B., primary, Söderqvist, G., additional, Cline, M., additional, von Schoultz, E., additional, and Skoog, L., additional
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- 1996
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14. Mammographic breast density during hormone replacement therapy: differences according to treatment.
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Lundström, E, Wilczek, B, von Palffy, Z, Söderqvist, G, and von Schoultz, B
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BREAST ,MAMMOGRAMS ,COMPARATIVE studies ,ESTROGEN ,HORMONES ,RESEARCH methodology ,MEDICAL cooperation ,PROGESTATIONAL hormones ,RESEARCH ,THERAPEUTICS ,EVALUATION research ,ANATOMY - Abstract
Objective: Our purpose was to investigate the effects of various hormone replacement regimens on mammographic breast density.Study Design: Mammographic density was recorded in women participating in a population-based screening program. All women were nonusers of hormone replacement therapy at first mammogram and thereafter reported continuous use of the same treatment: estrogen alone (n = 50) or estrogen in cyclic (n = 75) or continuous (n = 50) combination with progestogen. Mammographic density was quantified according to the Wolfe classification.Results: An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy (52%) than among those receiving cyclic (13%) and estrogen-only (18%) treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. There was little change in mammographic status during long-term follow-up.Conclusion: Regimens of hormone replacement therapy were shown to have different effects on the normal breast. There is an urgent need to clarify the biologic nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk. [ABSTRACT FROM AUTHOR]- Published
- 1999
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15. Proliferation of breast epithelial cells in healthy women during the menstrual cycle.
- Author
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Söderqvist, G, Isaksson, E, von Schoultz, B, Carlström, K, Tani, E, and Skoog, L
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BREAST ,CELL division ,COMPARATIVE studies ,EPITHELIAL cells ,SEX hormones ,RESEARCH methodology ,MEDICAL cooperation ,MENSTRUAL cycle ,MONOCLONAL antibodies ,RESEARCH ,EVALUATION research - Abstract
Objective: Our objective was to assess proliferation in normal breast epithelial cells from healthy women during the follicular and luteal phases of the menstrual cycle.Study Design: We analyzed the proliferation marker Ki-67/MIB-1 by immunocytochemical methods in breast epithelial cells procured through fine needle aspiration biopsy from 47 healthy volunteers. Differences were assessed by Wilcoxon rank sum tests, and correlations were determined by Spearman's rank correlation coefficient.Results: The proportion of KI-67/MIB-1-positive cells was higher in the luteal phase (2.04%) than in the follicular phase (1.66%). The values in women aged < 35 years were 2.29% and 1.13%, respectively (p = 0.003). In ovulating women with two aspirates during the same menstrual cycle the percentage of proliferating cells increased from the follicular phase (1.3%) to the luteal phase (2.4%) (p < 0.04). Proliferation was positively correlated with serum progesterone levels the day of aspiration (r = 0.34, p < 0.05).Conclusion: The fine needle aspiration biopsy technique is a valuable tool for in vivo studies of cell proliferation in the normal breast. Data clearly suggest a proliferative action of progesterone. [ABSTRACT FROM AUTHOR]- Published
- 1997
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16. Regional distribution of proliferating cells and hormone receptors in the mammary gland of surgically postmenopausal macaques.
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Cline, Mark, Söderqvist, Gunnar, von Schoultz, Bo, Skoog, Lambert, Cline, J M, Söderqvist, G, von Schoultz, B, and Skoog, L
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- 1997
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17. Effects of Estradiol/Micronized Progesterone vs. Conjugated Equine Estrogens/Medroxyprogesterone Acetate on Breast Cancer Gene Expression in Healthy Postmenopausal Women.
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Lalitkumar PGL, Lundström E, Byström B, Ujvari D, Murkes D, Tani E, and Söderqvist G
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- Humans, Female, Progesterone adverse effects, Estrogens, Conjugated (USP) pharmacology, Estradiol, Postmenopause, Estrogen Replacement Therapy adverse effects, Risk Factors, Gene Expression, Medroxyprogesterone Acetate therapeutic use, Neoplasms drug therapy
- Abstract
Recent studies suggest estradiol (E
2 )/natural progesterone (P) confers less breast cancer risk compared with conjugated equine estrogens (CEE)/synthetic progestogens. We investigate if differences in the regulation of breast cancer-related gene expression could provide some explanation. This study is a subset of a monocentric, 2-way, open observer-blinded, phase 4 randomized controlled trial on healthy postmenopausal women with climacteric symptoms (ClinicalTrials.gov; EUCTR-2005/001016-51). Study medication was two 28-day cycles of sequential hormone treatment with oral 0.625 mg CEE and 5 mg of oral medroxyprogesterone acetate (MPA) or 1.5 mg E2 as percutaneous gel/day with the addition of 200 mg oral micronized P. MPA and P were added days 15-28/cycle. Material from two core-needle breast biopsies in 15 women in each group was subject to quantitative PCR (Q-PCR). The primary endpoint was a change in breast carcinoma development gene expression. In the first eight consecutive women, RNA was extracted at baseline and after two months of treatment and subjected to microarray for 28856 genes and Ingenuity Pathways Analysis (IPA) to identify risk factor genes. Microarray analysis showed 3272 genes regulated with a fold-change of >±1.4. IPA showed 225 genes belonging to mammary-tumor development function: 198 for CEE/MPA vs. 34 for E2 /P. Sixteen genes involved in mammary tumor inclination were subject to Q-PCR, inclining the CEE/MPA group towards an increased risk for breast carcinoma compared to the E2 /P group at a very high significance level ( p = 3.1 × 10-8 , z -score 1.94). The combination of E2 /P affected breast cancer-related genes much less than CEE/MPA.- Published
- 2023
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18. Androgens impact on psychopathological variables according to CPRS, and EDI 2 scores: In women with bulimia nervosa, and eating disorder not otherwise specified.
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Söderqvist G and Naessén S
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- Humans, Female, Androgens, Testosterone, Dihydrotestosterone, Bulimia Nervosa, Feeding and Eating Disorders
- Abstract
Bulimia nervosa (BN) is characterized by binge eating, compensatory behavior, over-evaluation of weight and shape, which often co-occur with symptoms of anxiety and depression. Depression is the most common comorbid diagnosis in women with eating disorders. The role of androgens in the pathophysiology of depression has been recognized in recent years. However, the research on psychopathological comorbidity and androgen levels in bulimic disease is sparse. This study aimed to investigate, if there were any correlations between the androgens, testosterone (T), dehydroepiandrosterone sulphate (DHEAS), androstenedione (A4), 5α-dihydrotestosterone, (5α-DHT), and test scores of psychopathological variables, in women with bulimia nervosa (BN), eating disorder not otherwise specified of purging subtype (EDNOS-P) assessed by CPRS, and EDI 2. Women with DSM-IV diagnosis of BN (n = 36), EDNOS-P (n = 27), and healthy control subjects (n = 58) evaluated for fifteen psychopathological variables, i.a. depressive symptoms, impulsivity, personal traits, as well as serum androgen levels. All women were euthyroid, and polycystic ovarian syndrome (PCOS) diagnosis was excluded. Although androgen levels were almost equal for all three groups, significant correlations between core psychopathological symptoms (9/15) of bulimia nervosa and the most potent endogenous androgen, 5α-DHT, was found only in the EDNOS-P group. The role of 5α-DHT in women is not fully elucidated. Both animal and human studies have shown that the brain is able to locally synthesize steroids de novo and is a target of steroid hormones. Maybe these results can be interpreted in the light of differences in androgen receptor variability, metabolism and origin of T and 5α-DHT., Competing Interests: Declaration of interest The authors report no declarations of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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19. Progestogen addition with low-dose levonorgestrel intrauterine system in menopausal hormone treatment gives less normal breast tissue proliferation than oral norethisterone acetate or medroxyprogesterone acetate.
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Lundström E, Virijevic I, and Söderqvist G
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- Administration, Oral, Aged, Cell Proliferation, Female, Humans, Levonorgestrel administration & dosage, Levonorgestrel therapeutic use, Mammary Glands, Human pathology, Medroxyprogesterone Acetate administration & dosage, Medroxyprogesterone Acetate adverse effects, Medroxyprogesterone Acetate therapeutic use, Middle Aged, Norethindrone Acetate administration & dosage, Norethindrone Acetate adverse effects, Norethindrone Acetate therapeutic use, Progestins administration & dosage, Progestins therapeutic use, Uterus, Breast Neoplasms etiology, Estrogen Replacement Therapy adverse effects, Levonorgestrel adverse effects, Mammary Glands, Human drug effects, Progestins adverse effects
- Abstract
Background The impact of hormones on the development of breast cancer is despite extensive studies, incompletely understood. Combined estrogen-progestogen treatment augments the risk for breast cancer beyond that of estrogen alone, according to numerous studies. The role of breast cell proliferation as a promoter in the development and growth of breast cancer is well recognized. Materials and methods Seventy-nine patients from three randomised trials were subject to a re-analysis of breast cell proliferation: (1) 22 women received continuous combined treatment with oral estradiol (E2) 2 mg/norethisterone acetate (NETA) 1 mg once daily for 3 months. (2) Thirty-seven women received 2 months of sequential treatment with oral conjugated equine estrogens (CEE) 0.625 mg daily combined with medroxyprogesterone acetate (MPA) 5 mg for 14/28 days of each cycle. (3) Twenty women received oral estradiol-valerate (E2V) 2 mg daily combined with levonorgestrel (LNG) intrauterine system (IUS), 20 μg/24 h for 2 months. Fine needle aspiration (FNA) (studies 1 and 3) and core needle biopsy (CNB) (study 2) were used for the assessment of breast cell proliferation. Results There were no baseline proliferation differences, but at the end of treatment there was a highly significant between-group difference for E2V/LNG IUS versus the other two groups (p = 0.0025). E2/NETA and CEE treatments gave a 4-7-old increase in proliferation during treatment (p = 0.04) and (p = 0.007), respectively, which was absent in the E2V/LNG group, showing a significant correlation with insulin-like growth factor binding protein-3 (IGFBP-3) serum levels. Conclusion E2V in combination with very low serum concentrations of LNG in the IUS gives no increase in proliferation in the normal breast.
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- 2020
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20. So similar and so different: Circulating androgens and androgen origin in bulimic women.
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Naessén S, Söderqvist G, and Carlström K
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- Adult, Female, Gonadotropins, Pituitary metabolism, Humans, Menstruation Disturbances complications, Ovarian Follicle physiology, Androgens blood, Bulimia Nervosa blood, Dehydroepiandrosterone Sulfate blood, Dihydrotestosterone blood, Luteinizing Hormone blood, Sex Hormone-Binding Globulin analysis, Testosterone blood
- Abstract
Hyper androgen state frequently can be diagnosed in bulimic women. Eating disorder not otherwise specified (EDNOS) recognized as a less severe form of bulimia nervosa (BN). The objective of the study was to determine whether androgen levels and androgen origin differs in bulimic women compared to control subjects. Forty-six women with bulimia nervosa (BN), 31 with eating disorder not otherwise specified, purging type (EDNOS P) and 56 matched healthy controls were studied with respect to serum testosterone (T), 5alpha-dihydrotestosterone (DHT), sex hormone-binding globulin (SHBG), deyhydroepiahndrosterone sulfate (DHEAS) and luteinizing hormone (LH) and to ovarian morphology. Despite all groups had almost identical androgen and SHBG levels; there were differences in the origin of circulating T and DHT. Correlation analysis suggest major differences in the formation of circulating testosterone (T) and 5α-dihydrotestosterone (DHT) with BN being more like the control subjects with peripheral formation from 4-androsterne-3,17-dione (A-4), dehydroepiandrosterone sulfate (DHEAS) and also from T. While in EDNOS group a possible direct ovarian T secretion and a DHEAS modulating action of androgens on pituitary gonadotropin secretion is present. The origin of circulating T and DHT differs between bulimics. Our findings do probably not reflect direct actions of circulating DHT on pituitary LH secretion in the women with EDNOS, but rather the effect of A-4, T via conversion to DHT in the central nervous system, indicating psych/endocrine differences between the two groups of bulimic women., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2019
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21. Kjell Carlström (1940-2018).
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Söderqvist G and Lundström E
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- 2018
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22. Dehydroepiandrosterone and/or its metabolites: possible androgen receptor antagonistic effects on digitized mammographic breast density in normal breast tissue of postmenopausal women.
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Lundström E, Carlström K, Naessen S, and Söderqvist G
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- Aged, Breast diagnostic imaging, Female, Humans, Mammography, Middle Aged, Breast Density, Dehydroepiandrosterone blood, Postmenopause blood, Testosterone blood
- 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.
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- 2018
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23. Estrone - a partial estradiol antagonist in the normal breast.
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Lundström E, Conner P, Naessén S, Löfgren L, Carlström K, and Söderqvist G
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- Aged, Breast Density, Breast Neoplasms chemically induced, Breast Neoplasms diagnostic imaging, Contraceptives, Oral adverse effects, Drug Combinations, Estradiol adverse effects, Estradiol pharmacology, Estriol adverse effects, Estrogen Replacement Therapy adverse effects, Female, Humans, Mammography, Middle Aged, Norethindrone adverse effects, Norethindrone pharmacology, Breast drug effects, Breast Neoplasms blood, Contraceptives, Oral pharmacology, Estradiol blood, Estriol pharmacology, Estrogen Antagonists blood, Estrone blood, Mammary Glands, Human abnormalities, Norethindrone analogs & derivatives
- Abstract
Oral hormone replacement therapy (HRT) based on estradiol-17β (E2) greatly increases circulating estrone (E1) levels. E1 is an estrogen receptor agonist but may also be a partial E2 antagonist. We investigated the effects of circulating E1 on the association between circulating E2 and the increase in mammographic density (∂MD) in 46 healthy post-menopausal women treated with E2 2 mg and norethisterone acetate 1 mg daily. MD and serum E1 and E2 were measured before and after 6 months of treatment. At high E1 levels, ∂MD showed significant positive correlations leading to increase (∂-values) in both E1 and E2. Lowering the upper serum E1 limit strengthened the correlations to ∂E2 while the significant correlations to ∂E1 disappeared. E1 at high concentrations may act as a partial E2 antagonist also in the normal breast in vivo and disturb relationships between circulating E2 and biological estrogen effects. When investigating the relations between circulating steroids and their effects, structurally related compounds, which may act as partial antagonists, have to be considered, at least when they are present in higher concentrations.
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- 2015
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24. Megestrol acetate may stimulate the production of insulin-like growth factor 1 in breast tissues of women with breast cancer.
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Fahlén M, Löfgren L, von Schoultz E, Naessén S, Carlström K, and Söderqvist G
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- Aged, Breast metabolism, Breast Neoplasms metabolism, Female, Humans, Middle Aged, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Sex Hormone-Binding Globulin metabolism, Antineoplastic Agents, Hormonal therapeutic use, Breast drug effects, Breast Neoplasms drug therapy, Insulin-Like Growth Factor I metabolism, Megestrol Acetate therapeutic use, Tamoxifen therapeutic use
- Abstract
Background: In women with breast cancer who were treated with either continuous tamoxifen alone or sequential tamoxifen followed by megestrol acetate (MA), we demonstrated significant positive associations between the breast tumor estrogen receptor (ER) and an increase in serum sex hormone-binding globulin (SHBG) during tamoxifen treatment. We interpreted this as "ER uniformity" in different tissues, e.g., breast, liver. No other associations with ER were found. In the same study, the breast tumor progesterone receptor (PR) was determined. Our aim was to see if there were any associations between PR and endocrine changes during MA treatment., Methods: The breast tumor PR before treatment and serum insulin-like growth factor I (∂IGF-1), steroids, steroid-binding proteins, and insulin before and during treatment were measured in 17 postmenopausal women with breast cancer who were treated sequentially with tamoxifen 40 mg/day followed by MA 160 mg/day in alternating 3-month periods., Results: During MA treatment periods, the levels of IGF-1 and insulin increased significantly, whereas the levels of androgens, SHBG, corticosteroid-binding globulin, and cortisol decreased significantly. Significant positive correlations were found between the PR content and increments in ∂IGF-1 but not between PR and any other endocrine change., Conclusions: PR expression in human liver is very weak, but malignant and normal breast tissues secrete considerable amounts of growth hormone and IGF-1 in vitro and in vivo. This activity is stimulated by progestogens. The association between PR and ∂IGF-1 may therefore reflect a direct PR-mediated action of MA on malignant and normal human breast tissues in vivo.
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- 2013
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25. Percutaneous estradiol/oral micronized progesterone has less-adverse effects and different gene regulations than oral conjugated equine estrogens/medroxyprogesterone acetate in the breasts of healthy women in vivo.
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Murkes D, Lalitkumar PG, Leifland K, Lundström E, and Söderqvist G
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- Administration, Cutaneous, Administration, Oral, Adult, Breast Density, Breast Neoplasms epidemiology, Breast Neoplasms prevention & control, Cell Proliferation drug effects, Estradiol administration & dosage, Estradiol therapeutic use, Estrogens, Conjugated (USP) administration & dosage, Estrogens, Conjugated (USP) therapeutic use, Female, Gels, Gene Expression Profiling, Humans, Ki-67 Antigen genetics, Ki-67 Antigen metabolism, Mammary Glands, Human abnormalities, Mammary Glands, Human cytology, Mammary Glands, Human metabolism, Medroxyprogesterone Acetate administration & dosage, Medroxyprogesterone Acetate therapeutic use, Middle Aged, RNA, Messenger metabolism, Risk Factors, Sweden epidemiology, Estradiol adverse effects, Estrogen Replacement Therapy adverse effects, Estrogens, Conjugated (USP) adverse effects, Gene Expression Regulation drug effects, Mammary Glands, Human drug effects, Medroxyprogesterone Acetate adverse effects, Postmenopause
- Abstract
Gene expression analysis of healthy postmenopausal women in a prospective clinical study indicated that genes encoding for epithelial proliferation markers Ki-67 and progesterone receptor B mRNA are differentially expressed in women using hormone therapy (HT) with natural versus synthetic estrogens. Two 28-day cycles of daily estradiol (E2) gel 1.5 mg and oral micronized progesterone (P) 200 mg/day for the last 14 days of each cycle did not significantly increase breast epithelial proliferation (Ki-67 MIB-1 positive cells) at the cell level nor at the mRNA level (MKI-67 gene). A borderline significant beneficial reduction in anti-apoptotic protein bcl-2, favouring apoptosis, was also seen followed by a slight numeric decrease of its mRNA. By contrast, two 28-day cycles of daily oral conjugated equine estrogens (CEE) 0.625 mg and oral medroxyprogesterone acetate (MPA) 5 mg for the last 14 days of each cycle significantly increased proliferation at both the cell level and at the mRNA level, and significantly enhanced mammographic breast density, an important risk factor for breast cancer. In addition, CEE/MPA affected around 2,500 genes compared with just 600 affected by E2/P. These results suggest that HT with natural estrogens affects a much smaller number of genes and has less-adverse effects on the normal breast in vivo than conventional, synthetic therapy.
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- 2012
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26. Effects of percutaneous estradiol-oral progesterone versus oral conjugated equine estrogens-medroxyprogesterone acetate on breast cell proliferation and bcl-2 protein in healthy women.
- Author
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Murkes D, Conner P, Leifland K, Tani E, Beliard A, Lundström E, and Söderqvist G
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- Administration, Oral, Biopsy, Breast cytology, Breast metabolism, Breast Neoplasms epidemiology, Breast Neoplasms prevention & control, Cell Division drug effects, Contraceptive Agents, Female administration & dosage, Contraceptive Agents, Female adverse effects, Estrogen Replacement Therapy methods, Estrogens administration & dosage, Estrogens adverse effects, Estrogens, Conjugated (USP) administration & dosage, Female, Humans, Medroxyprogesterone Acetate administration & dosage, Prospective Studies, Risk Factors, Breast drug effects, Estrogen Replacement Therapy adverse effects, Estrogens, Conjugated (USP) adverse effects, Medroxyprogesterone Acetate adverse effects, Proto-Oncogene Proteins c-bcl-2 metabolism
- Abstract
In a prospective, randomized clinical study 77 women were assigned randomly to receive sequential hormone therapy with either conventional oral conjugated equine estrogens (0.625 mg) with the addition on 14 of the 28 days of oral medroxyprogesterone acetate (5 mg) or natural E(2) gel (1.5 mg) with oral micronized P (200 mg) on 14 of the 28 days of each cycle. Because oral conjugated equine estrogens-medroxyprogesterone acetate induced a highly significant increase in breast cell proliferation in contrast to percutaneous E(2)-oral P with a difference between therapies approaching significance, the former therapy has a marked impact on the breast whereas natural percutaneous E(2)-oral micronized P has not., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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27. Mechanisms for differential effects between natural progesterone and synthetic progestogens on normal breast tissue.
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Söderqvist G
- Abstract
Both epidemiological studies and experimental data on normal breast tissue suggest increased cancer risk, proliferation and mammographic breast density (MD) during hormone therapy (HT) containing synthetic progestogens in traditional doses, and the relative risk or RR is approximately 1.5-3 (for women treated vs. untreated with the above therapies), proliferation levels of normal breast epithelial cells of around 10% and increase in MD in up to around 50% of women during treatment. Dose-response relationships have been inferred by correlations between progestogens as levonorgestrel, norethisterone acetate and medroxyprogesterone acetate on the one hand and proliferation and/or MD on the other hand, and of indications of lower relative risk of breast cancer with modern low or ultra-low dose HT. In contrast, natural progesterone endogenously during the menstrual cycle has a weak effect and exogenous estrogen in combination with oral micronized progesterone in HT has shown to yield an indifferent effect on proliferation. Furthermore, in epidemiological studies such as the French E3N cohort, these combinations have not shown any risk increase for breast cancer for at least 5 years of treatment. Experimental data supporting or not supporting the view that the main proliferative mechanism for natural progesterone is through binding to its nascent progesterone receptors is discussed as well as the pros and cons that the non-physiological higher proliferation levels induced by synthetic progestogens is mainly mediated through interaction with potent growth factors and their paracrine and/or cell signaling pathways.
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- 2010
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28. Associations between serum testosterone levels, cell proliferation and progesterone receptor content in normal and malignant breast tissue in postmenopausal women.
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Hofling M, Löfgren L, von Schoultz E, Carlström K, and Söderqvist G
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- Antibodies, Antinuclear, Antibodies, Monoclonal, Biopsy, Fine-Needle, Breast Neoplasms blood, Estrogen Replacement Therapy, Estrone blood, Female, Humans, Immunoenzyme Techniques, Ki-67 Antigen immunology, Middle Aged, Progesterone therapeutic use, Receptors, Estrogen analysis, Sex Hormone-Binding Globulin analysis, Breast Neoplasms chemistry, Breast Neoplasms pathology, Cell Division, Postmenopause, Receptors, Progesterone analysis, Testosterone blood
- Abstract
Progestogens and progesterone receptors (PR) may play an important role in increased breast proliferation following combined estrogen/progestogen hormone therapy, while androgens may counteract this effect. In 50 untreated healthy postmenopausal women and 48 untreated postmenopausal breast cancer patients, we measured serum levels of testosterone (T), sex hormone-binding globulin (SHBG), estrone (E(1)) and adrenal androgens; and additionally, in the breast cancer patients, cortisol and corticosteroid-binding globulin and endocrine data related to breast proliferation (assessed using the Ki-67/MIB-1 monoclonal antibody) and PR levels (determined by enzyme immunoassay) in the breast cancer tissue. In the healthy women the percentage of MIB-1(+) cells showed significant negative correlations with serum levels of total T, calculated free T (fT) and the fT/E(1) ratio; while in the breast cancer patients PR content showed significant negative correlations with fT level, the fT/E(1) ratio and the T/SHBG ratio. No other correlations were found in any of the groups. Our findings in healthy women confirm previous reports of an antiproliferative effect of androgens in breast tissue and our finding in breast cancer patients suggests that this antiproliferative effect may be mediated via downregulation of PR.
- Published
- 2008
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29. Digitized assessment of mammographic breast density in patients who received low-dose intrauterine levonorgestrel in continuous combination with oral estradiol valerate: a pilot study.
- Author
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Lundström E, Söderqvist G, Svane G, Azavedo E, Olovsson M, Skoog L, von Schoultz E, and von Schoultz B
- Subjects
- Administration, Oral, Aged, Breast cytology, Cell Proliferation, Drug Administration Schedule, Drug Combinations, Estradiol administration & dosage, Female, Humans, Middle Aged, Pilot Projects, Prospective Studies, Breast drug effects, Estradiol analogs & derivatives, Estrogen Replacement Therapy methods, Levonorgestrel administration & dosage, Mammography methods, Radiographic Image Enhancement methods, Radiographic Image Interpretation, Computer-Assisted methods, Uterus
- Abstract
Objective: To perform a pilot study of the effects on the breast by low-dose intrauterine progestogen combined with estrogen., Design: A prospective pilot study., Setting: University hospital., Patient(s): Twenty postmenopausal women without any previous breast disorder., Intervention(s): Women were treated with a low-dose intrauterine system releasing 20 microg/24 hours of levonorgestrel in continuous combination with 2 mg of oral E2 valerate. The effects on mammographic breast density, breast cell proliferation, and hormonal levels were followed for 18 months., Main Outcome Measure(s): Change in mammographic breast density and breast cell proliferation. Correlations with levels of hormones, growth factors, and binding proteins., Result(s): Three women showed an apparent increase in density. For the remaining 17 women the changes were only a few percent. Digitized assessment of density showed strong correlations with visual classification scales (rs = 0.96-0.97). There was no increase in proliferation as expressed by the percentage of MIB-1-positive breast cells in fine-needle aspiration biopsies. Increase in breast density displayed a positive correlation with patients age (rs = 0.52) and an inverse relationship with levels of E2 (rs = -0.50) and free T (rs = -0.50)., Conclusion(s): Low-dose intrauterine administration progestogen may develop into an attractive alternative for hormonal therapy in postmenopausal women as endometrial protection may be achieved at very low systemic levels.
- Published
- 2006
- Full Text
- View/download PDF
30. Lessons to be learned from clinical studies on hormones and the breast.
- Author
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Söderqvist G and von Schoultz B
- Subjects
- Breast cytology, Cell Proliferation drug effects, Female, Humans, Breast drug effects, Estrogen Replacement Therapy, Gonadal Steroid Hormones pharmacology
- Abstract
Estrogen is a well-known mitogen in human breast epithelium but the action of progestogen is complex and incompletely understood. During the last years, accumulating data from animal, clinical and observational studies suggest a proliferative effect in breast tissue when progestogen is added to estrogen. Findings in surrogate markers like breast density add to clinical and epidemiological reports indicating that continuous combined HRT may carry a higher risk of breast cancer than treatment with estrogen alone. Whether the results are valid for all progestogens remains to elucidated. It is also clear that not all women respond in the same way to the same treatment and the biological basis for the marked individual variation in breast response has to be clarified. Further knowledge about the role of androgens and of the impact of different treatment regimens is important and prospective randomized clinical studies are needed.
- Published
- 2004
- Full Text
- View/download PDF
31. Mammographic breast density, hormones, and growth factors during continuous combined hormone therapy.
- Author
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Conner P, Svane G, Azavedo E, Söderqvist G, Carlström K, Gräser T, Walter F, and von Schoultz B
- Subjects
- Breast drug effects, Estradiol administration & dosage, Estradiol blood, Estrone blood, Female, Humans, Nandrolone administration & dosage, Norethindrone administration & dosage, Norethindrone Acetate, Sex Hormone-Binding Globulin metabolism, Testosterone blood, Estrogen Replacement Therapy, Growth Substances blood, Hormones blood, Mammography, Nandrolone analogs & derivatives, Norethindrone analogs & derivatives
- Abstract
Objective: To study the effect on mammographic breast density of two different continuous combined regimens for hormone therapy., Design: Randomized clinical study., Setting: University hospital., Patient(s): Postmenopausal women without any previous history of breast disorder., Intervention(s): The women received either estradiol valerate/dienogest or estradiol/norethisterone acetate. Mammograms and venous blood samples were obtained at baseline and after 6 months., Main Outcome Measure(s): Change in mammographic breast density. Correlations with levels of hormones, growth factors, and binding proteins., Result(s): An increase in mammographic density was recorded in approximately 50% of the women, and there were no differences between treatments. Increased density showed a positive correlation with estradiol, estrone, and sex hormone-binding globulin and showed a negative association to free T. Among hormonal factors, levels of free T were the most important for predicting increased density., Conclusion(s): Continuous combined hormone therapy with different progestogens has a marked impact on the breast.
- Published
- 2004
- Full Text
- View/download PDF
32. Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density.
- Author
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Lundström E, Christow A, Kersemaekers W, Svane G, Azavedo E, Söderqvist G, Mol-Arts M, Barkfeldt J, and von Schoultz B
- Subjects
- Biopsy, Needle, Double-Blind Method, Estradiol administration & dosage, Estradiol adverse effects, Estrogen Receptor Modulators therapeutic use, Humans, Norethindrone administration & dosage, Norethindrone adverse effects, Norethindrone Acetate, Norpregnenes therapeutic use, Placebos, Prospective Studies, Breast pathology, Estrogen Receptor Modulators adverse effects, Estrogen Replacement Therapy adverse effects, Mammography, Norethindrone analogs & derivatives, Norpregnenes adverse effects, Postmenopause
- Abstract
Objective: Our purpose was to compare the effects of tibolone, continuous combined hormone replacement therapy, and placebo on mammographic breast density., Study Design: A prospective, randomized, double-blind placebo-controlled study was performed. A total of 166 postmenopausal women were equally randomized to receive tibolone 2.5 mg, estradiol 2 mg/norethisterone acetate 1 mg (E(2)/NETA), or placebo. Mammograms were performed at baseline and after 6 months of treatment. Mammographic density was quantified according to the Wolfe classification and by the percentage area of the breast that had a dense pattern., Results: An increase in mammographic density was much more common among women receiving continuous combined hormone replacement therapy (46%-50%) than among those receiving tibolone (2%-6%) and placebo (0%) treatment. The difference between E(2)/NETA and placebo was highly significant (P <.001). Treatment with tibolone did not differ from that with placebo. The relative risk of an increase in breast density for E(2)/NETA versus tibolone was found to be 8.3 (95% CI 2.7-25.0)., Conclusion: An increase in mammographic density should be regarded as an unwanted side effect of hormone replacement therapy. In contrast to estrogen/progestogen treatment, tibolone seems to exert little stimulation of breast tissue.
- Published
- 2002
- Full Text
- View/download PDF
33. Effects of oral contraceptives on breast epithelial proliferation.
- Author
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Isaksson E, von Schoultz E, Odlind V, Söderqvist G, Csemiczky G, Carlström K, Skoog L, and von Schoultz B
- Subjects
- Adolescent, Adult, Antigens, Nuclear, Biomarkers analysis, Biopsy, Needle, Breast drug effects, Case-Control Studies, Female, Humans, Ki-67 Antigen, Middle Aged, Progesterone blood, Breast cytology, Cell Division drug effects, Contraceptives, Oral, Combined pharmacology, Nuclear Proteins metabolism
- Abstract
The association between oral contraceptive (OC) use and breast cancer is not fully understood. Estrogen is a known mitogen to breast epithelial cells, but there is still a controversy about the effect of added progestogens. Fine needle aspiration (FNA) biopsies were used to assess epithelial proliferation in normal breast tissue from 106 healthy premenopausal women with and without oral contraceptives. In 26 women biopsies were performed before and after 2 months of OC use. Proliferation, expressed as percentage of Ki-67/MIB-1 positive cells, was correlated to endogenous progesterone, androgenic/anabolic compounds and exogenous progestogen. We found a higher proliferation (p = 0.03) in OC users compared to non users, with mean values of 4.8% and 2.2%, respectively. There was a positive correlation between proliferation and progesterone levels in non-users and with serum levonorgestrel concentrations in women using OCs containing this progestogen (rs = 0.43, p = 0.02). Women using OCs had significantly lower serum androgen levels compared to naturally cycling women and free testosterone levels displayed an inverse relation to breast epithelial proliferation. There was a marked variation in the response to exogenous sex steroids. In certain women after 2 months of OC use, the percentage of MIB-1 positive cells was as high as 40-50%. The results add to the growing evidence that progestogens may be mitogenic in breast tissue. Increased proliferation during hormonal contraception should be regarded as an unwanted and potentially hazardous side effect. Efforts should be made to define hormonal contraceptive regimens which minimize breast epithelial proliferation and to identify those women with the most pronounced proliferative response.
- Published
- 2001
- Full Text
- View/download PDF
34. Assessment of hormonally active agents in the reproductive tract of female nonhuman primates.
- Author
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Cline JM, Söderqvist G, Register TC, Williams JK, Adams MR, and Von Schoultz B
- Subjects
- Animals, Female, Genitalia, Female pathology, Genitalia, Female physiology, Genitalia, Female drug effects, Gonadal Steroid Hormones physiology, Primates physiology
- Abstract
Using the ovariectomized macaque model of postmenopausal women's health, we investigated the effects of long-term treatments (5 weeks-3 years) with estradiol, conjugated equine estrogens (CEE), esterified estrogens, progestins such as medroxyprogesterone acetate (MPA) and nomegestrol acetate, CEE + MPA, tamoxifen, soybean phytoestrogens (SPEs), a variety of putative selective estrogen receptor modulators (SERMs), and androgens. Agents tested were selected on the basis of beneficial effects on arteries and/or bone. Doses were scaled on a caloric or serum-concentration basis to approximate human clinical doses. We evaluated endometrial and mammary gland histopathology and morphometry and used immunohistochemistry to evaluate cell proliferation and expression of estrogen receptor alpha and progesterone receptor (PR). Both estradiol and CEE induced endometrial hyperplasia. MPA antagonized epithelial proliferation induced by CEE in endometrium and induced pseudodecidual stromal hyperplasia in some animals. Tamoxifen induced endometrial polyps, cystic hyperplasia, stromal fibrosis, and PR expression but not Ki-67 expression. SPEs were not estrogenic at dietary doses and antagonized estrogen-induced proliferation in the endometrium and breast. Nandrolone induced mucometra and an adenomyosis-like change. The potential SERM 17 alpha dihydroequilenin did not have uterotrophic or mammotrophic effects. In general, experimental findings in macaques have been predictive of outcomes in human clinical trials of the same agents.
- Published
- 2001
- Full Text
- View/download PDF
35. Expression of sex steroid receptors and IGF-1 mRNA in breast tissue--effects of hormonal treatment.
- Author
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Isaksson E, Sahlin L, Söderqvist G, von Schoultz E, Masironi B, Wickman M, Wilking N, von Schoultz B, and Skoog L
- Subjects
- Adult, Aged, Breast cytology, Breast drug effects, Cell Division, Estradiol blood, Female, Humans, Insulin-Like Growth Factor I metabolism, Mammaplasty, Middle Aged, Postmenopause, Premenopause, Progesterone blood, Prolactin blood, RNA, Messenger genetics, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Breast metabolism, Estrogen Replacement Therapy, Insulin-Like Growth Factor I genetics, Receptors, Estrogen genetics, Receptors, Progesterone genetics, Transcription, Genetic
- Abstract
The mechanisms behind increased breast tissue proliferation and a possibly increased breast cancer risk in women using hormonal contraception (HC) and hormonal replacement therapy (HRT) are incompletely understood. We analyzed breast tissue from 20 premenopausal and seven postmenopausal women undergoing reduction mammoplasties for estrogen receptor (ER) and progesterone receptor (PR) content as well as mRNA levels for ER, PR and insulin-like growth factor-1 (IGF-1). The receptor values were correlated to IGF-1 mRNA concentrations and levels of steroid and peptide hormones and SHBG. In women using HC, we found significantly lower ER values (p = 0.02) but non-significantly lower ER mRNA levels compared to those in naturally cycling women. PR and PR mRNA were no different. Women on HC displayed a higher breast tissue proliferation (p = 0.05) expressed as Ki-67, MIB-1 positivity, which was correlated with IGF-1 mRNA (r(s) = 0.82, p = 0.04). Since the concentration of sex steroid receptors in breast tissue is comparatively low and steroid receptors are down-regulated during hormonal treatment, mechanisms other than direct sex steroid receptor action are likely to be present. Our results suggest a role for IGF-1 in the proliferative response of breast tissue during exogenous hormonal treatment.
- Published
- 1999
- Full Text
- View/download PDF
36. 17Beta-hydroxysteroid dehydrogenases in normal human mammary epithelial cells and breast tissue.
- Author
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Miettinen M, Mustonen M, Poutanen M, Isomaa V, Wickman M, Söderqvist G, Vihko R, and Vihko P
- Subjects
- 17-Hydroxysteroid Dehydrogenases genetics, Adult, Blotting, Northern, Cell Line, Female, Gene Expression Regulation, Enzymologic, Humans, In Situ Hybridization, Middle Aged, RNA, Messenger isolation & purification, 17-Hydroxysteroid Dehydrogenases analysis, Breast enzymology, Epithelial Cells enzymology
- Abstract
17Beta-hydroxysteroid dehydrogenase activity represents a group of several isoenzymes (17HSDs) that catalyze the interconversion between highly active 17beta-hydroxy- and low activity 17-ketosteroids and thereby regulate the biological activity of sex steroids. The present study was carried out to characterize the expression of 17HSD isoenzymes in human mammary epithelial cells and breast tissue. In normal breast tissues 17HSD types 1 and 2 mRNAs were both evenly expressed in glandular epithelium. In two human mammary epithelial cell lines, mRNAs for 17HSD types 1, 2 and 4 were detected. In enzyme activity measurements only oxidative 17HSD activity, corresponding to either type 2 or type 4 enzyme, was present. The role of 17HSD type 4 in estrogen metabolism was further investigated, using several cell lines originating from various tissues. No correlation between the presence of 17HSD type 4 mRNA and 17HSD activity in different cultured cell lines was detected. Instead, oxidative 17HSD activity appeared in cell lines where 17HSD type 2 was expressed and reductive 17HSD activity was present in cells expressing 17HSD type 1. These data strongly suggest that in mammary epithelial cell lines the oxidative activity is due to type 2 17HSD and that oxidation of 17beta-hydroxysteroids is not the primary activity of the 17HSD type 4 enzyme.
- Published
- 1999
- Full Text
- View/download PDF
37. Effects of sex steroids on proliferation in normal mammary tissue.
- Author
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Söderqvist G
- Subjects
- Animals, Breast drug effects, Cell Division, Estrogens therapeutic use, Female, Humans, Progestins therapeutic use, Receptors, Estrogen drug effects, Receptors, Progesterone drug effects, Risk Factors, Breast cytology, Breast Neoplasms chemically induced, Contraceptives, Oral, Combined adverse effects, Contraceptives, Oral, Hormonal adverse effects, Estrogens pharmacology, Hormone Replacement Therapy adverse effects, Progestins pharmacology
- Abstract
Numerous women are treated with a combination of oestrogen and progestogen for contraception and hormone replacement therapy worldwide. A possible increased risk of cancer in target organs has been discussed vividly for many years. While oestrogens are clearly mitogenic for breast epithelial cells, there has been considerable uncertainty about the effects of progestogens. This article reviews current knowledge on this field, including our own data. Oestrogen receptors are down-regulated during the luteal phase, while progesterone receptors remain at a high level throughout the menstrual cycle. According to most studies, in vivo proliferation of normal breast epithelial cells is higher during the luteal phase in the vast majority of women. Normal breast tissue can convert oestrone sulphate to oestradiol. A negative correlation between the levels of circulating oestradiol and the enzyme converting oestrone into oestradiol suggests a local regulatory mechanism of tissue oestradiol formation. Serum progesterone levels correlate positively with sulphatase activity while 19-norsteroid progestogens may be inhibitory. We found that long-term continuous combined hormonal treatment with conjugated equine oestrogens and medroxyprogesterone acetate induced a proliferative response in the breasts of surgically postmenopausal macaques. The effect of combined treatment was more pronounced than that of oestrogen treatment alone. Both endogenous progesterone and exogenous progestogens increase proliferation of breast epithelial cells. Exogenous progestogens down-regulate both oestrogen and progesterone receptors. Oestrogen and progestogens may have both direct and indirect stimulating effects on proliferation. The finding of a positive correlation between insulin-like growth factor I messenger RNA and proliferation found in hormonally treated women with low receptor levels suggests the possibility of nonreceptor-mediated effects of sex steroids on proliferation, which needs to be investigated further.
- Published
- 1998
38. 17Beta-hydroxysteroid dehydrogenase type 1 in normal breast tissue during the menstrual cycle and hormonal contraception.
- Author
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Söderqvist G, Poutanen M, Wickman M, von Schoultz B, Skoog L, and Vihko R
- Subjects
- Adult, Estradiol blood, Female, Gonadal Steroid Hormones blood, Humans, Linear Models, Middle Aged, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Reference Values, Steroids blood, 17-Hydroxysteroid Dehydrogenases metabolism, Breast enzymology, Contraceptives, Oral, Hormonal therapeutic use, Mammaplasty, Menstrual Cycle physiology
- Abstract
Our purpose was to assess 17beta-hydroxysteroid dehydrogenase (17HSD) type 1 protein expression in normal breast tissue during the menstrual cycle and hormonal contraception. We analyzed 17HSD type 1 protein expression by immunohistochemistry during the regular menstrual cycle (n = 12) and hormonal contraception (n = 7) in women undergoing reduction mammoplasty. 17HSD type 1 protein was detected in normal breast epithelial cells throughout the menstrual cycle and in all women using hormonal contraception. Mean 17HSD type 1 staining intensity was higher in alveolar epithelial cells in women using hormonal contraception (2.14) than in untreated women (1.25; P < 0.04). For ducts, this difference approached significance (2.29 vs. 1.41; P = 0.06). There was a negative correlation between serum estradiol (E2) levels and 17HSD type 1 protein expression for both alveolar (r(s) = -0.68; P = 0.004) and ductal (r(s) = -0.75; P = 0.002) breast epithelial cells. Enhanced 17HSD type 1 protein expression might increase the conversion to E2 in normal breast tissue during hormonal contraception. The negative correlation between serum E2 levels and 17HSD type 1 suggests this enzyme to be one of the regulatory mechanisms of intratissue E2 concentration in normal breast tissue.
- Published
- 1998
- Full Text
- View/download PDF
39. Metabolism of estrone sulfate by normal breast tissue: influence of menopausal status and oral contraceptives.
- Author
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Söderqvist G, Olsson H, Wilking N, von Schoultz B, and Carlström K
- Subjects
- Adolescent, Adult, Aged, Breast Neoplasms metabolism, Endometrial Neoplasms metabolism, Estradiol metabolism, Estrone metabolism, Female, Humans, Middle Aged, Postmenopause physiology, Premenopause physiology, Progesterone blood, Tritium, Breast metabolism, Contraceptives, Oral adverse effects, Estrone analogs & derivatives, Menopause physiology
- Abstract
The metabolism of [3H]estrone sulfate ([3H]E1S) was studied in normal breast tissue from 10 premenopausal women without oral contraceptives (OC), in 12 OC users and in 9 untreated postmenopausal women. [3H]E1S was converted into estrone ([3H]E1) and estradiol-17 beta ([3H]E2) by tissue samples from all three groups of women, with only minor formation of other unconjugated compounds. The rate of [3H]E2 formation was significantly higher in premenopausal women without OC than in postmenopausal women. Among premenopausal women, OC users had a significantly lower rate of total hydrolysis and of [3H]E1 formation than non-users. The rate of total hydrolysis of [3H]E1S in normal breast tissue from all three groups of women was similar to that in muscle, but the rate of [3H]E2 formation was ten times higher. Both total hydrolysis rate and rate of [3H]E2 formation were significantly lower in normal breast tissue than in breast carcinoma and in normal and neoplastic endometrium. The specific ability of normal breast tissue to convert E1S into the terminal biologically active estrogen E2 may be important for estrogenic stimulation of the breast in subjects with low circulating E2 levels. The lower rate of E1 formation in OC users may reflect an inhibitory effect of the progestagen compound in such preparations.
- Published
- 1994
- Full Text
- View/download PDF
40. Effects of female sex steroids on breast tissue.
- Author
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von Schoultz B, Söderqvist G, Tani E, and Skoog L
- Subjects
- Breast metabolism, Estrogens pharmacology, Female, Humans, Menstrual Cycle metabolism, Progesterone pharmacology, Receptors, Estrogen drug effects, Receptors, Estrogen metabolism, Receptors, Progesterone drug effects, Receptors, Progesterone metabolism, Breast drug effects, Gonadal Steroid Hormones pharmacology
- Published
- 1993
- Full Text
- View/download PDF
41. Estrogen and progesterone receptor content in breast epithelial cells from healthy women during the menstrual cycle.
- Author
-
Söderqvist G, von Schoultz B, Tani E, and Skoog L
- Subjects
- Adult, Biopsy, Needle, Epithelium metabolism, Female, Follicular Phase physiology, Humans, Luteal Phase physiology, Middle Aged, Breast metabolism, Menstrual Cycle physiology, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism
- Abstract
Objective: Our objective was to analyze the presence of estrogen and progesterone receptors in breast epithelial cells from healthy women during the follicular and luteal phase of the menstrual cycle., Study Design: We analyzed estrogen receptor and progesterone receptor variations in breast epithelial cells procured through fine-needle aspiration biopsy from 42 healthy volunteers during the menstrual cycle using immunocytochemical receptor analysis. Differences were assessed by chi 2 test and the Wilcoxon rank sum tests., Results: Estrogen receptor was detected more often in women aspirated in the follicular (68%) than in the luteal (32%) phase (p < 0.001); progesterone receptor was detected in around 80% in both phases. In ovulating women who were aspirated twice during the same menstrual cycle the proportion of estrogen receptor-positive cells was reduced from 20% to 4% (p < 0.02); the progesterone receptor values were 17% and 24%., Conclusion: Our data indicate an important difference in progesterone receptor variation in the breast as compared with the endometrium.
- Published
- 1993
- Full Text
- View/download PDF
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