Efficacy of estradiol vaginal cream in postmenopausal women

Abstract

In a recent comparison of estradiol and conjugated estrogen creams,6 single intravaginal doses of both estrogens were well absorbed by postmenopausal women. Only the estradiol cream led to plasma estrone and estradiol levels of premenopausal women. Symptoms of menopause have largely been attributed to a decrease in estrogen secretion, a normal process of aging. While the question of the best mode of therapy is controversial, physiological replacement would be a logical choice for postmenopausal vasomotor symptoms and vaginal mucosa atrophy. Our study was conducted to determine estrogen levels achieved after nightly vaginal administration of estradiol cream for 14 days and to evaluate it in the treatment of postmenopausal signs and symptoms. Materials and methodsThe patients were postmenopausal for at least 1 yr and had vasomotor or vaginal symptoms of estrogen deficiency. They received no estrogen or medications which could interfere with estrogen assays for at least 1 mo prior to the study. The study followed a double-blind parallel design. On a random assignment 20 patients received estradiol vaginal cream 0.01% (0.2 mg 17,8-estradiol) and 10 patients received conjugated estrogen cream (1.25 mg conjugated estrogens). An intravaginal dose of 2 gm of cream was administered at bedtime for 14 consecutive days. Patients returned for evaluation of their therapy on day 8 (12 hr after their seventh dose) and day 15 (12 hr after their fourteenth dose).Efficacy of the creams was measured by the maturation indices of the vaginal epithelium cells and severity ratings of vaginal and vasomotor symptoms at each visit. Patients were asked to record the number of vasomotor symptoms per day, and the severity of the hot flashes, 502

Urogenital Atrophy: Prevention and Treatment

“…65 In seven elderly women (70-93 yrs) daily vaginal conjugated equine estrogen 0.625 mg/day cream resulted in estradiol and estrone concentrations on day 14 similar to those in the follicular phase. 63 Intravaginal micronized estradiol cream 0.2 mg produced estradiol concentrations of 60 31 to 70 32 pg/ml and estrone concentrations of 37 31 to 90 32 pg/ml. In five premenopausal women undergoing hormonal uterine stimulation for embryo transfer, estradiol 2-mg oral tablets inserted vaginally produced higher estradiol concentrations (2344 vs 279 pg/ml) than 2-mg tablets taken orally by five other women.…”

“…Estrogens can partially or completely restore vaginal cytology, 22-24, 26, 28-37, 39, 40, 42, 43, 45-48, 50, 51, 53, 57 decrease vaginal pH to premenopausal levels, 22, 24, 37-39, 41, 43-45, 48-50 increase vaginal fluid secretions, 22, 24 mucosa thickness, 27,30,52 blood flow, 9,22,24 and sensorimotor response, 11 restore vaginal flora similar to premenopausal conditions, 27,30,44,59 and provide symptomatic relief. 21, 25, 29, 30, 32, 34, 37, 39-43, 45, 47-50, 53-59 Additional benefits are relief of other menopause symptoms, such as hot flushes, 25,31,32,40 improvements in urinary frequency and incontinence, 13,37,43,44,[47][48][49][50] and positive effects on bone density, 60 fractures, 60 and lipids. 28 Several issues are related to systemic absorption and duration of estrogen concentrations with estrogen products administered for various durations.…”

“…Whereas most studies measured similar or higher concentrations from the beginning to end of therapy, 31,32,35 hypothesized as due to increased vascularization, a few studies reported less absorption over time, hypothesized as the effect of more normal mucosa later in treatment. 32,46,51,63 However, estrone and estradiol concentrations in studies reporting decreased absorption over time were still above baseline and improved or cured urogenital atrophy or dryness. 32 Cautions, contraindications, and progestin need for oral and intravaginal estrogens are the same except for the estradiol vaginal ring and tablet and potentially newer and investigational ultra-lowestrogen products.…”

“…32,46,51,63 However, estrone and estradiol concentrations in studies reporting decreased absorption over time were still above baseline and improved or cured urogenital atrophy or dryness. 32 Cautions, contraindications, and progestin need for oral and intravaginal estrogens are the same except for the estradiol vaginal ring and tablet and potentially newer and investigational ultra-lowestrogen products.…”

“…The same regimen produced symptom relief and improvements in vaginal cytology in postmenopausal patients after 8-15 days. 31,32 Conjugated equine estrogen and estradiol vaginal creams were compared in two small, randomized studies in postmenopausal women. 31,32 After 2 weeks of estradiol 0.2 mg or conjugated equine estrogen 1.25 mg/day, no significant differences were found between groups in vaginal mucosa appearance, mucosal cytology, dryness, or hot flushes.…”