Lowering oral contraceptive norethindrone dose increases estrogen and progesterone receptor levels with no reduction in proliferation of breast epithelium: A randomized trial Journal Article


Authors: Hovanessian-Larsen, L.; Taylor, D.; Hawes, D.; Spicer, D. V.; Press, M. F.; Wu, A. H.; Pike, M. C.; Pearce, C. L.
Article Title: Lowering oral contraceptive norethindrone dose increases estrogen and progesterone receptor levels with no reduction in proliferation of breast epithelium: A randomized trial
Abstract: Background: This study was conducted to compare breast epithelial-cell proliferation and estrogen and progesterone receptor levels in women taking one of two oral contraceptives (OCs) containing the same dose of estrogen but different doses of the progestin norethindrone (NET). Study Design: Thirty-three women were randomly assigned 1:1 to one of two OCs with 35-mcg ethinylestradiol (EE2) but different doses of NET - 1 or 0.4 mg. At the end of the active pill phase of the third OC cycle, a breast biopsy was performed and the percentages of epithelial cells of the terminal duct lobular units were measured for Ki67 (MIB1), progesterone receptors A and B (PRA and PRB, respectively), and estrogen receptor α (ERα). Results: The biopsies from 27 women had sufficient epithelium for analysis. The percentages of cells positive for PRA, PRB and ERα were approximately double with the lower progestin dose (PRA: p=.041; PRB: p=.030; ERα: p=.056). The Ki67 percentage was not reduced with the lower progestin dose (12.5% for 0.4-mg NET vs. 7.8% for 1.0-mg NET). Conclusions: The increase in PRA-, PRB- and ERα-positive cells with the 60% lower progestin dose OC appears likely to account for its failure to decrease breast-cell proliferation. This breast-cell proliferation result is contrary to that predicted from the results of lowering the medroxyprogesterone acetate dose in menopausal hormone therapy. © 2012 Elsevier Inc.
Keywords: immunohistochemistry; adult; clinical article; controlled study; human tissue; drug dose reduction; ki 67 antigen; cell proliferation; randomized controlled trial; dose-response relationship, drug; breast epithelium; receptors, progesterone; hormonal therapy; estrogen receptor; progesterone receptor; menopause; ubiquitin-protein ligases; oral contraception; breast biopsy; medroxyprogesterone acetate; mammary glands, human; gestagen; estrogen receptor alpha; breast duct; combined oral contraceptives; contraceptives, oral, combined; ethinyl estradiol; breast epithelial cells; progestin dose; proliferation markers; ethinylestradiol; ethinylestradiol plus norethisterone acetate; mestranol plus norethisterone; biopsy, large-core needle; image-guided biopsy; norethindrone
Journal Title: Contraception
Volume: 86
Issue: 3
ISSN: 0010-7824
Publisher: Elsevier Inc.  
Date Published: 2012-09-01
Start Page: 238
End Page: 243
Language: English
DOI: 10.1016/j.contraception.2011.12.015
PROVIDER: scopus
PMCID: PMC3355208
PUBMED: 22325110
DOI/URL:
Notes: --- - "Export Date: 4 September 2012" - "CODEN: CCPTA" - "Source: Scopus"
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MSK Authors
  1. Malcolm Pike
    141 Pike