ABSTRACT

Wood, Charles E., Régine Sitruk-Ware, Yun-yen Tsong, Thomas C. Register, Cynthia J. Lees, and J. Mark Cline. 2007. "Effects of estradiol with oral and intravaginal progesterone on risk markers for breast cancer in a postmenopausal monkey model," Menopause 14(4): 639–647.  

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.

Design
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 two months and were separated by a one-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 2–3 hours after oral dosing (P < 0.0001) but not at 24–28 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.

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