A microarray study on the effect of four hormone therapy regimens on gene transcription in whole blood from healthy postmenopausal women.
BACKGROUND
Postmenopausal hormone therapy is associated with many diseases and conditions, e.g., cardiovascular diseases and asthma, but the underlying molecular mechanisms are incompletely understood. The aim of the current study was to investigate the effect of four different postmenopausal hormone therapy regimens on gene transcription.


METHODS
Twenty-four healthy postmenopausal women (six women in four groups) were randomly allocated to conventional-dose 17β-estradiol/norethisterone acetate (NETA), low-dose 17β-estradiol/NETA, tibolone, or raloxifene hydrochloride. RNA was isolated from whole blood before and after 6weeks of treatment. The changes in mRNA were assessed with a microarray chip.


RESULTS
The genes FKBP5, IL13RA1, TPST1, and TLR2 were up-regulated and among the most significantly changed genes in the groups treated with conventional-dose 17β-estradiol/NETA and tibolone. Up-regulation of TPST1 was associated with reduction of tissue factor pathway inhibitor in plasma. Nine biological pathways were associated with conventional-dose 17β-estradiol/NETA, most significantly the pathways for asthma, toll-like receptor signaling, cell adhesion molecules, and MAPK signaling. Transcriptional changes with false discovery rate below 0.10 were found in 10 genes in the conventional-dose 17β-estradiol/NETA group, 7 genes in the tibolone group, and zero genes in the women on low-dose 17β-estradiol/NETA. No genes or pathways were associated with raloxifene treatment.


CONCLUSIONS
The difference between low-dose and conventional-dose17β-estradiol/NETA indicates an effect of dose on transcriptional response. Several genes and pathways related to cell adhesion molecules and immunity related cell surface receptors were influenced by conventional-dose 17β-estradiol/NETA.
Department of Haematology, Oslo University Hospital, Oslo, Norway. a.e.a.dahm@medisin.uio.no
Anders E A
AE
Dahm
Anette L
AL
Eilertsen
Jelle
J
Goeman
Ole Kristoffer
OK
Olstad
Reidun
R
Ovstebø
Peter
P
Kierulf
Marie-Christine
MC
Mowinckel
Grethe
G
Skretting
Per Morten
PM
Sandset
D000368:Aged; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D004967:Estrogens / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000494:pharmacology / Q000627:therapeutic use*; D009652:Norpregnenes / Q000494:pharmacology / Q000627:therapeutic use*; D017698:Postmenopause / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*
D004338:Drug Combinations; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009652:Norpregnenes; C418365:estradiol, norethindrone drug combination; D020849:Raloxifene Hydrochloride; D004958:Estradiol; C027385:tibolone; D009640:Norethindrone