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 administered vaginally for 14 days to estrogen-primed postmenopausal women.


METHODS
Randomized, open-label, three-way crossover study.


METHODS
Two university-based investigative sites.


METHODS
Twenty healthy postmenopausal women with histologically normal endometria.


METHODS
Oral 17 beta-E2 was given each day of a 28-day cycle; a P vaginal suppository was inserted daily according to the randomization schedule during days 15-28 of each cycle; blood samples were collected; an endometrial 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.


METHODS
Mean P blood levels, endometrial dating/conversion.


RESULTS
There was good vaginal absorption of P for all dosages. Endometrial conversion occurred in all 200- and 400-mg/d P-dosed cycles, whereas the 100-mg/d dosage failed to convert primed endometria consistently. There also was a significantly increased tendency for earlier bleeding and spotting with the 100-mg/d dosage.


CONCLUSIONS
Both the 200- and 400-mg/d dosage regimens consistently convert an estrogen-primed endometrium, and yield appropriate endometrial dating and bleeding patterns. However, the 400-mg/d dosage attains the highest sustained blood levels and may be the best dosage regimen for further study.
Pasquale
S A
SA
University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, New Brunswick 08901-1977, USA.
Foldesy
R G
RG
Levine
J P
JP
Bachmann
G A
GA
Blackwell
R E
RE
D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D001706:Biopsy; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000033:anatomy & histology / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D014592:Uterine Hemorrhage
D011374:Progesterone; D004958:Estradiol