title: 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.
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.
authors: Department of Obsterics and Gynecology, Södertälje Hospital, Södertälje, Sweden.
authors: Daniel
authors: D
authors: Murkes
authors: P G L
authors: PG
authors: Lalitkumar
authors: Karin
authors: K
authors: Leifland
authors: Eva
authors: E
authors: Lundström
authors: Gunnar
authors: G
authors: Söderqvist
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000071060:Breast Density; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005782:Gels; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D042361:Mammary Glands, Human / Q000002:abnormalities / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D017698:Postmenopause; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D004966:Estrogens, Conjugated (USP); D005782:Gels; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D004958:Estradiol; D017258:Medroxyprogesterone Acetate