PERIPHERAL PROGESTERONE (P) LEVELS AND ENDOMETRIAL RESPONSE TO VARIOUS DOSAGES OF VAGINALLY ADMINISTERED P IN ESTROGEN-PRIMED WOMEN

Objective: To compare the pharmacokinetics and pharmacodynamics of 100 mg/d, 200 mg/d, and 400 mg/d (200 mg two times per day) of P administ ered vaginally for 14 days to estrogen-primed postmenopausal women. De sign: Randomized, open-label, three-way crossover study. Setting: Two university-based investigative sites. Patient(s): Twenty healthy postm enopausal women with histologically normal endometria. Intervention(s) : Oral 17 beta-E-2 was given each day of a 28-day cycle; a P vaginal s uppository was inserted daily according to the randomization schedule during days 15-28 of each cycle; blood samples were collected; an endo metrial biopsy was obtained on day 25; and patients were crossed over to the next treatment cycle after a washout period of at least 30 days . Main Outcome Measure(s): Mean P blood levels, endometrial dating/con version. Result(s): There was good vaginal absorption of P for all dos ages. Endometrial conversion occurred in all 200- and 400-mg/d P-dosed cycles, whereas the 100-mg/d dosage failed to convert primed endometr ia consistently. There also was a significantly increased tendency for earlier bleeding and spotting with the 100-mg/d dosage. Conclusion(s) : Both the 200- and 400-mg/d dosage regimens consistently convert an e strogen-primed endometrium, and yield appropriate endometrial dating a nd bleeding patterns. However, the 400-mg/d dosage attains the highest sustained blood levels and may be the best dosage regimen for further study. (C) 1997 by American Society for Reproductive Medicine.