estrone-sulfate and Uterine-Hemorrhage

To establish the optimum oral daily dose of micronized medroxyprogesterone acetate, given in combination with a fixed oral dose of estrone (E1) sulfate as hormone replacement therapy, that provides endometrial protection and induces cessation of vaginal bleeding.. This multicenter, randomized, double-blind study was conducted for 2 years. Five hundred sixty-eight postmenopausal women were randomized to take E1 sulfate 1.25 mg daily and one of three doses of medroxyprogesterone acetate (2.5, 5, or 10 mg) daily. Any vaginal bleeding was recorded by patients in a daily diary, and endometrial biopsies were performed at entry into the study and at 3, 12, and 24 months.. Forty-two percent of all women reported some bleeding at month 3 of therapy. However, by month 6, 76.5, 80.1, and 80.9% of women were amenorrheic in the 2.5-, 5-, and 10-mg medroxyprogesterone acetate groups, respectively. Over time, the percentage of women with no bleeding increased in each group, and by 24 months 91.5, 89.9, and 94.3% were amenorrheic in the 2.5- and 10-mg medroxyprogesterone acetate groups, respectively. Approximately 10% of women continue to have some bleeding, regardless of the dose of medroxyprogesterone acetate. There were no statistically significant differences in the number of women with bleeding at any time point between the three groups. There were no cases of endometrial hyperplasia reported in the study population over the 2 years.. All three studied doses of medroxyprogesterone acetate, given in combination with 1.25 mg of E1 sulfate, provide adequate endometrial protection and render approximately 80% of women amenorrheic by 6 months of therapy.

Topics: Adult; Biopsy, Needle; Double-Blind Method; Endometrium; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Estrone; Female; Humans; Medroxyprogesterone Acetate; Middle Aged; Postmenopause; Progesterone Congeners; Uterine Hemorrhage

To compare two different continuous regimens of estrogens: conjugated estrogens or estrone sulfate with medroxyprogesterone acetate (MPA). To evaluate the impact of these two regimens on bleeding pattern, endometrial histology, lipid metabolism, and climacteric symptoms.. Prospective, open label, single center, randomized trial.. The menopause clinic, Centre Universitaire de Santé de l'Estrie, Université de Sherbrooke, Quebec, Canada.. Fifty-nine postmenopausal women seeking treatment for symptomatic menopause.. Patients were randomized to two groups. Both groups received 2.5 mg/d MPA plus 0.625 mg/d conjugated estrogens (group A: 31 patients) or 0.625 mg/d estrone sulfate (group B: 28 patients). Lipid metabolism, endometrial biopsies, and endometrial thickness (measured by vaginal ultrasound) were determined at 52 and 104 weeks.. Six women (10%) withdrew from the study (irregular bleeding and side effects). Fifty-three patients completed the study. Amenorrhea was produced in 92.6% and 96.1% by 52 weeks, and 100% by 104 weeks for groups A and B, respectively. Endometrial atrophy was observed by histology in 92.4% by 52 weeks and in 100% by 104 weeks in both groups. The correlation between an endometrial thickness (vaginal ultrasound) of < or = 4 mm and histologic diagnosis of endometrial atrophy was found in 41 of 53 patients. In both groups the climacteric symptoms were improved and the lipid profile showed a beneficial effect.. No significant difference was found between the two continuous regimens. Amenorrhea and atrophic endometrium occurred in 92.4% after 52 weeks of treatment. A favorable change in lipid metabolism even with the addition of MPA to estrogens was noted. Irregular bleeding was reduced and the long-term compliance with the continuous regimen was high (90%).

Topics: Blood Pressure; Drug Combinations; Endometrium; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Estrone; Female; Humans; Lipids; Medroxyprogesterone Acetate; Middle Aged; Postmenopause; Progesterone Congeners; Prospective Studies; Ultrasonography; Uterine Hemorrhage

A placebo-controlled randomized clinical trial was conducted in six centres to compare the effects of a 14 day treatment with either 50 micrograms ethinyl oestradiol daily or 2.5 mg oestrone sulphate daily, on depot medroxyprogesterone acetate (DMPA)-induced prolonged bleeding. Out of 1035 women admitted to the study, 278 requested treatment and were given ethinyl oestradiol (n = 90), oestrone sulphate (n = 91) or placebo (n = 97). Ethinyl oestradiol was successful in stopping the bleeding episode in 93% of cases, compared with oestrone sulphate and placebo which had success rates of 76 and 74% respectively. However, the relative advantage of ethinyl oestradiol was marginal, with an average reduction of 1 bleeding day and 3 spotting days compared with the other two groups. Immediately after treatment, women given ethinyl oestradiol had less bleeding but a more unpredictable pattern than the other two groups. In the long term, there were no differences between the bleeding patterns or the discontinuation rates for any reason in the three groups, and the most important single reason for discontinuation in those groups remained 'menstrual problems'. In summary, the study showed that treatment of DMPA-induced prolonged bleeding with ethinyl oestradiol had a limited short-term effect but no beneficial effect on the acceptability of DMPA as a contraceptive method. Treatment with oestrone sulphate was no different from placebo.. The findings of a multicenter clinical trial challenge the practice of estrogen treatment of the prolonged or irregular vaginal bleeding associated with depot medroxyprogesterone acetate (DMPA) contraceptive use. Included in the study were 1035 DMPA users (mean age, 27 years) from Alexandria, Egypt; Bangkok, Thailand; Chiang Mai, Thailand; Jakarta, Indonesia; Karachi, Pakistan; and Manila, Philippines. 456 (44%) of these women experienced a bleeding episode lasting more than 7 days during their first 6 months of DMPA use. Of these, only 278 (61%) requested treatment. These 278 women were randomly allocated to receive 50 mcg of ethinyl estradiol (n = 90), 2.5 mg of estrone sulfate (n = 91), or placebo (n = 97) daily for 14 days. The treatment stopped the bleeding episode for 93% of women in the ethinyl estradiol group, 76% of those in the estrone sulfate group, and 74% of women receiving a placebo. The ethinyl estradiol advantage was marginal, however. On average, women treated with ethinyl estradiol had their bleeding episode shortened by 1 bleeding day and 3 spotting days. Immediately after treatment, women given ethinyl estradiol had less bleeding and spotting days than their counterparts in the 2 other groups, but demonstrated a more unpredictable pattern, including a greater range of lengths of bleeding/spotting-free intervals. Three months after treatment, there were no differences between the 3 groups in vaginal bleeding patterns.

Topics: Adolescent; Adult; Contraceptive Agents, Female; Double-Blind Method; Estradiol Congeners; Estrogens, Conjugated (USP); Estrone; Ethinyl Estradiol; Female; Humans; Medroxyprogesterone Acetate; Menstruation; Time Factors; Treatment Outcome; Uterine Hemorrhage

Topics: Estrogens; Estrone; Female; Hemostasis; Humans; Menorrhagia; Metrorrhagia; Uterine Hemorrhage