Influence of the Maturity of the Vaginal Epithelium upon the Absorption of Vaginally Administered Estradiol-17β and Progesterone in Postmenopausal Women

Abstract

Serum concentrations of estradiol-17Β and its metabolites estrone (unconjugated) and total estrone (mainly estrone sulfate) and of progesterone were measured before and after application of one vaginal suppository containing 250 µg estradiol-17Β and l0mg progesterone to 10 previously unsubstituted healthy postmenopausal women with normal pretreatment serum steroid levels. Vaginal hormone cytology was performed prior to administration of the estrogen-progesterone combination. An atrophic vaginal mucosa was found in 5 and a moderate proliferation in the other 5 women. A significant association was found between proliferation and pretreatment values of estrone, but not with other steroids. There was a clear, significant association between steroid absorption kinetics and the condition of the vaginal mucosa as indicated by cytological data: significantly higher absorption was found in women with an atrophic vaginal mucosa.

Association of Vaginal Estradiol Tablet With Serum Estrogen Levels in Women Who Are Postmenopausal

“…A more recent study of a vaginal estradiol softgel also showed an initial concentration spike in the hours after first administration of the medication, but a lower spike after several weeks of treatment, and no significant increase in mean circulating estradiol concentrations . A more recent study suggested that there may be greater absorption of topical hormonal preparations initially, when the mucosa is thinner and more friable . We found a suggestion of greater influence of the vaginal estradiol use on serum estradiol concentrations in women with lower starting estradiol concentrations and longer duration since menopause, which would support the hypothesis that there is greater absorption with a thinner vaginal mucosa; however, the elevations in our trial were measured at 12 weeks.…”

“… 2 , 27 A more recent study suggested that there may be greater absorption of topical hormonal preparations initially, when the mucosa is thinner and more friable. 28 We found a suggestion of greater influence of the vaginal estradiol use on serum estradiol concentrations in women with lower starting estradiol concentrations and longer duration since menopause, which would support the hypothesis that there is greater absorption with a thinner vaginal mucosa; however, the elevations in our trial were measured at 12 weeks. We could not assess initial transient spikes as have others.…”

Estrogens and the urogenital tract

“…These levels were achieved after one single dose on an atrophic vaginal mucosa. With continuous treatment using this dosage an even lower serum level of estradiol is to be expected, however, as the $2 Actu Obstet Gvnecol Scand 72 (1993) Supplement 157 absorption of estrogens is less effective in the more mature vaginal mucosa than in the atrophic one (51,177,178). Dickerson et al (179) also tested an estradiol vaginal cream with 0.2 mg 17P-estradiol, but administered it for 14 days.…”