Postmenopausal estrogen and progestin effects on the serum proteome.
BACKGROUND
Women's Health Initiative randomized trials of postmenopausal hormone therapy reported intervention effects on several clinical outcomes, with some important differences between estrogen alone and estrogen plus progestin. The biologic mechanisms underlying these effects, and these differences, have yet to be fully elucidated.


METHODS
Baseline serum samples were compared with samples drawn 1 year later for 50 women assigned to active hormone therapy in both the estrogen-plus-progestin and estrogen-alone randomized trials, by applying an in-depth proteomic discovery platform to serum pools from 10 women per pool.


RESULTS
In total, 378 proteins were quantified in two or more of the 10 pooled serum comparisons, by using strict identification criteria. Of these, 169 (44.7%) showed evidence (nominal P < 0.05) of change in concentration between baseline and 1 year for one or both of estrogen-plus-progestin and estrogen-alone groups. Quantitative changes were highly correlated between the two hormone-therapy preparations. A total of 98 proteins had false discovery rates < 0.05 for change with estrogen plus progestin, compared with 94 for estrogen alone. Of these, 84 had false discovery rates <0.05 for both preparations. The observed changes included multiple proteins relevant to coagulation, inflammation, immune response, metabolism, cell adhesion, growth factors, and osteogenesis. Evidence of differential changes also was noted between the hormone preparations, with the strongest evidence in growth factor and inflammation pathways.


CONCLUSIONS
Serum proteomic analyses yielded a large number of proteins similarly affected by estrogen plus progestin and by estrogen alone and identified some proteins and pathways that appear to be differentially affected between the two hormone preparations; this may explain their distinct clinical effects.
Pitteri
Sharon J
SJ
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109, USA.
Hanash
Samir M
SM
Aragaki
Aaron
A
Amon
Lynn M
LM
Chen
Lin
L
Busald Buson
Tina
T
Paczesny
Sophie
S
Katayama
Hiroyuki
H
Wang
Hong
H
Johnson
Melissa M
MM
Zhang
Qing
Q
McIntosh
Martin
M
Wang
Pei
P
Kooperberg
Charles
C
Rossouw
Jacques E
JE
Jackson
Rebecca D
RD
Manson
Joann E
JE
Hsia
Judith
J
Liu
Simin
S
Martin
Lisa
L
Prentice
Ross L
RL