Antiproliferative effects of low-dose micronized progesterone.
OBJECTIVE
To study the pharmacodynamic effects of oral micronized P on endometrial maturation.


METHODS
This was a controlled, open, parallel group, pilot study.


METHODS
The experiment was performed in an outpatient academic clinical research unit.


METHODS
Twelve healthy, P-challenged, estrogen-primed, postmenopausal women participated in the study.


METHODS
Patients were given 300 mg micronized P daily (8:00 A.M.) or twice (8:00 A.M. and 4:00 P.M.) daily from study days 1 through 14 after estrogen priming for 30 days. Blood samples were taken at 0, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after the 8:00 A.M. dose on study day 1 and 14 and again at 8:00 and 9:30 A.M. on days 3 and 5 fasting, days 7 and 9 after a fatty meal, and day 11 after a high fiber meal. Endometrial biopsies were taken on day 1 and 14.


METHODS
Progesterone concentrations were measured. Endometrial biopsies were studied for effects on histology, glycogen content of glands, ribosomal RNA, and nuclear estrogen receptors in glands, surface epithelium, and stroma.


RESULTS
Day 1 and 14 P kinetics were similar for 8 hours. Dose-dependent increases in glandular glycogen, decrease in ribosomal RNA, and decrease in nuclear estrogen receptors were demonstrated.


CONCLUSIONS
Oral micronized P can induce antiproliferative changes in the human endometrium at doses lower than those required for transformation of the endometrium to a full secretory state.
Kim
S
S
Department of Obstetrics and Gynecology, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, USA.
Korhonen
M
M
Wilborn
W
W
Foldesy
R
R
Snipes
W
W
Hodgen
G D
GD
Anderson
F D
FD
D002455:Cell Division / Q000187:drug effects; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D011374:Progesterone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012313:RNA / Q000032:analysis
D011374:Progesterone; D012313:RNA