Effects of estradiol with oral or intravaginal progesterone on risk markers for breast cancer in a postmenopausal monkey model
Wood,Charles E.; Sitruk-Ware,Regine; Tsong,Yun-yen; Register,Thomas C.; Lees,Cynthia J.; Cline,J.Mark
Menopause 14(4): 1-9
Publication date: 2007
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.
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.
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 G 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 G 0.05 for all time points). Oral P4 resulted in significantly decreased body weight (j2.5%) 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 9 0.1 for all).
Despite different pharmacodynamic profiles, oral and intravaginal P4 had similar effects on biomarkers in the postmenopausal breast.