Effects of the repetitive administration of progesterone by nasal spray in postmenopausal women

OBJECTIVE: To study the effects of 10 days of nasal spray P treatment on P serum levels and the endometrium. DESIGN: Prospective. SETTING: University Medical School. PATIENTS: Eight postmenopausal women received oral conjugated estrogens at a daily dose of 0.625 mg for 4 weeks immediately before vaginal surgery for prolapse. For the first 9 of the last 10 days the patients also received a nasal spray dosage of 11.2 mg P three times a day; on the 10th day they received only one dose. MAIN OUTCOME MEASURES: Blood samples were taken at 8:00 A.M. on treatment days 1, 3, 5, 7, 10, and 11 to follow P serum concentration levels. Endometrial samples for histologic examination were collected before P administration and immediately after surgery to evaluate the end-organ effect. RESULTS: Mean P serum levels increased sixfold after 9 days of nasal spray P administration [from 0.612 +/- 0.280 ng/mL (1.958 +/- 0.896 nmol/L) to 3.925 +/- 1.553 ng/mL (12.560 +/- 4.970 nmol/L)] and declined thereafter, returning to the before treatment levels 24 hours after the last administration. In all subjects, the first histologic evaluation showed proliferative endometrium; the second showed clear secretive changes. CONCLUSIONS: Repetitive nasal spray P administration for 10 days in postmenopausal women led to increasing P serum levels and, when the estrogen stimulation was adequate, to secretory changes in the endometrium (end-organ effect).