Effects of estradiol with oral or intravaginal progesterone on risk markers for breast cancer in a postmenopausal monkey model.
OBJECTIVE
To evaluate the effects of oral estradiol given with either oral or intravaginal micronized progesterone (P4) on risk biomarkers for breast cancer in a postmenopausal monkey model.


METHODS
This experiment was a two-way crossover study in which 20 ovariectomized adult female cynomolgus macaques were treated (in equivalent doses for women) with oral estradiol (1 mg/d) + oral micronized P4 (200 mg/d) or intravaginal P4 delivered by Silastic rings (6- to 10-mg/d release rate). Hormone treatments lasted 2 months and were separated by a 1-month washout period. The primary outcome measure was breast epithelial proliferation.


RESULTS
Serum P4 concentrations were significantly greater in subjects receiving oral P4 (10.9 ng/mL) compared with intravaginal P4 (3.8 ng/mL) at 2 to 3 hours after oral dosing (P<0.0001) but not at 24 to 28 hours after oral dosing (2.9 ng/mL for oral P4 vs 3.2 ng/mL for intravaginal P4 at 2 months, P=0.19). Serum estradiol concentrations were significantly lower after oral P4 than after intravaginal P4 (P<0.05 for all time points). Oral P4 resulted in significantly decreased body weight (-2.5%) compared with intravaginal P4 (+3.6%) (P=0.0001). Markers of breast proliferation, sex steroid receptor expression, and endometrial area did not differ significantly between oral P4 and intravaginal P4 treatments (P>0.1 for all).


CONCLUSIONS
Despite different pharmacodynamic profiles, oral and intravaginal P4 had similar effects on biomarkers in the postmenopausal breast.
Wood
Charles E
CE
Department of Pathology/Section on Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA. chwood@wfubmc.edu
Sitruk-Ware
Regine L
RL
Tsong
Yun-Yen
YY
Register
Thomas C
TC
Lees
Cynthia J
CJ
Cline
J Mark
JM
D000282:Administration, Intravaginal; D000284:Administration, Oral; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000166:cytology / Q000187:drug effects*; D001943:Breast Neoplasms / Q000139:chemically induced / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D018592:Cross-Over Studies; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D008252:Macaca fascicularis; D010052:Ovariectomy; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*
D014408:Biomarkers, Tumor; D011374:Progesterone; D004958:Estradiol