PHARMACOKINETICS AND ENDOMETRIAL EFFECTS OF THE VAGINAL ADMINISTRATION OF MICRONIZED PROGESTERONE IN AN OIL-BASED SOLUTION TO POSTMENOPAUSAL WOMEN

Objective: To study the pharmacokinetics of the transvaginal absorptio n of 100 mg micronized P from an oil-based solution in postmenopausal women before and after the estrogenization of the vaginal mucosa and t o evaluate the endometrial effects of 10 days of once daily P vaginal administration. Design: Prospective clinical trial. Setting: Universit y Medical School. Patients: Nine postmenopausal women undergoing hormo ne replacement therapy. Interventions: A micronized P (100 mg) oil-bas ed solution currently available on the market for IM use was administe red vaginally by means of a Teflon cannula without the aid of a specul um. Subsequently, the women received 4 weeks 0.1 mg/d transdermal E(2) treatment combined on the last 10 days with the once daily vaginal ad ministration of P in the same way as before. Main Outcome Measures: At the first (before estrogen) and second (during estrogen therapy) P ad ministrations, P serum levels were measured at time 0, and then after 15, 30, 45, 60, 120, 240, 480, and 1440 minutes. Endometrial samples w ere collected at the end of treatment. Results: After the first admini stration, a mean Cmax of 5.40 +/- 0.92 ng/mL (mean +/- SD) was reached at a Tmax of 45 minutes (range 30 to 480 minutes). The serum concentr ations returned to their initial values after 24 hours. The second P a dministration reached a mean Cmax of 5.30 +/- 1.04 ng/mL at a Tmax of 60 minutes (range 30 to 240 minutes); after 24 hours, the serum P leve ls still were significantly higher than at baseline and at the same ti me after the first administration. None of the women complained of sig nificant vaginal losses. No signs of vaginal phlogosis or irritation w ere observed. In all subjects, histologic evaluation showed clear endo metrial secretory changes. Conclusions: The daily vaginal administrati on of one vial of micronized P for 10 days allowed useful serum P leve ls to be reached, especially after estrogen therapy, and induced clear secretory changes in the endometrium.