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  • Author: Kjell Carlström x
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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.

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.