medrogestone and Uterine-Hemorrhage

The aim of this study was to compare the incidence of women presenting irregular bleeding episodes following 9 months of treatment with a low dose continuous combined hormone replacement therapy consisting of estradiol (E(2)) and norethisterone acetate (NETA) versus a sequential hormone replacement therapy consisting of conjugated equine estrogens (CEE) and medrogestone (MG). Secondary aims were to establish the relationship between menopausal age and the occurrence of irregular bleeding for both therapies and to assess the efficacy of both therapies in alleviating menopausal symptoms.. This was a stratified and randomised, open label study conducted with late peri and postmenopausal women at 35 sites in Austria and Germany. A total of 446 women were randomly allocated into two cohorts based on time since last bleeding and then stratified to either a low dose continuous combined therapy consisting of 1 mg E(2) and 0.5 mg NETA for 28 days or a sequential therapy consisting of 0.625 mg CEE for 28 days and 5 mg MG for the final 14 days. Bleeding and menopausal complaints were continuously assessed. Treatments were administered for 9 lunar months.. The incidence rate of women presenting irregular bleeding episodes including spotting during cycle 9 was 12.2% with 1mgE(2)/0.5mgNETA and 25.8% with 0.625mgCEE/5mgMG (P = 0.0014). In the group of postmenopausal women (time since last bleeding > or = 12 months) the incidence of irregular bleeding during cycle 9 was 11.0% for 1mgE(2)/0.5mgNETA and 25.0% for 0.625mgCEE/5mgMG). In the group of late perimenopausal women (time since last bleeding 6-11 months) the incidence of irregular bleeding was similar for both treatments at cycle 3, but markedly less in patients with 1mgE(2)/0.5mgNETA at cycle 6 and 9, being significantly different compared to patients with 0.625mgCEE/5mgMG at cycle 6 (P < 0.05). The cumulative rate of amenorrhea (no bleeding or spotting) achieved with 1mgE(2)/0.5mgNETA was 89% for the postmenopausal women and 83.7% for the late perimenopausal women. Both treatments relieved menopausal complaints equally effective.. Regarding the occurrence of irregular bleeding, the low dose continuous combined therapy was superior to the sequential therapy (0.625mgCEE/5mgMG). The low dose continuous combined E(2)/NETA regimen is also suitable for late perimenopausal women since more than 80% of the women had no bleeding or spotting after 9 months of treatment.

Topics: Adult; Aged; Austria; Cohort Studies; Drug Administration Schedule; Drug Therapy, Combination; Estradiol; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Germany; Hot Flashes; Humans; Medrogestone; Menopause; Middle Aged; Norethindrone; Norethindrone Acetate; Prospective Studies; Treatment Outcome; Uterine Hemorrhage

In this study menopausal symptoms, endometrial histology, uterine bleeding pattern, plasma lipid concentrations, bone mineral loss, body weight and blood pressure have been evaluated in postmenopausal women who received continuous conjugated equine estrogens and medrogestone over a 1 year treatment period. By the third month of therapy we detected a significant (p < 0.01) improvement in postmenopausal symptomatology. At the 6th and 12th month, endometrial biopsy specimens revealed atrophic endometrium in all women. Uterine bleeding episodes were observed especially during the first months of treatment. Amenorrhoea was found in all patients only after 8 months of therapy. By the 6th month of therapy, we observed a significant (p < 0.01) decrease of plasma cholesterol and low-density lipoprotein cholesterol levels. Instead, plasma high-density lipoprotein and triglycerides concentrations didn't show significant variation from baseline values. No significant changes in bone mineral density could be detected after 12 months of treatment. Body weight and blood pressure were not significantly altered from baseline. This study suggests that continuous conjugated equine estrogens plus medrogestone treatment appears to be an interesting and safe manner to administer postmenopausal hormone replacement therapy. This regimen could represent a good alternative to sequential estroprogestin therapy in women who do not tolerate withdrawal bleeding.

Topics: Amenorrhea; Atrophy; Biopsy; Dose-Response Relationship, Drug; Endometrial Hyperplasia; Endometrium; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Female; Humans; Lipoproteins; Medrogestone; Middle Aged; Osteoporosis, Postmenopausal; Triglycerides; Uterine Hemorrhage