Coadministration of nomegestrol acetate does not diminish the beneficial effects of estradiol on coronary artery dilator responses in nonhuman primates (Macaca fascicularis).
OBJECTIVE
Our purpose was to examine the effect of coadministered nomegestrol acetate on estradiol-induced dilator responses of coronary arteries.


METHODS
In this prospective randomized trial, ovariectomized monkeys were fed a moderately atherogenic diet for 3 months while being treated with (1) no hormone replacement (control, n = 12), (2) estradiol (1.5 mg/d equivalent) added to the diet (n = 12), or (3) estradiol (1.5 mg/d equivalent) plus nomegestrol acetate (3.75 mg/d equivalent) (n = 12) added to the diet. Effects of treatment were measured with analysis of variance. Post hoc analyses were done by multiple comparison tests with Bonferroni corrections.


RESULTS
Constrictor responses of epicardial coronary arteries (measured with quantitative angiography) and decreased coronary blood velocity (measured with Doppler ultrasonography) to acetylcholine (10(-6) mol/L) were less in the estradiol-treated monkeys (with or without cotreatment with nomegestrol acetate) than in the untreated monkeys (P <.05). Typical estrogenic responses were induced by estradiol in the endometrium (ie, increased proliferation [Ki-67 expression] [P <.04] and increased hormone receptor expression). These effects were antagonized by nomegestrol acetate.


CONCLUSIONS
Although nomegestrol acetate has typical progestin-like effects on the uterus, it does not diminish the beneficial effects of estrogen on acetylcholine-induced dilator responses of coronary arteries.
Williams
J K
JK
Department of Comparative Medicine of Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Cline
J M
JM
Honoré
E K
EK
Delansorne
R
R
Paris
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008252:Macaca fascicularis; D008535:Megestrol; D009649:Norpregnadienes / Q000494:pharmacology*; D010052:Ovariectomy; D011446:Prospective Studies; D014463:Ultrasonography; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D004338:Drug Combinations; D009649:Norpregnadienes; D014665:Vasodilator Agents; D004958:Estradiol; C038501:nomegestrol acetate; D008535:Megestrol; D000109:Acetylcholine