Efficacy of a selective COX-2 inhibitor for controlling irregular uterine bleeding in DMPA users. Long-interval treatment regimen with a desogestrel-containing oral contraceptive. A two-year double-blind controlled study of the clinical effect of combined and sequential postmenopausal replacement therapy and steroid metabolism during treatment. Continuous combination oral contraceptive pills to eliminate withdrawal bleeding: a randomized trial. Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate. Oestrogen treatment for increased bleeding in Norplant users: preliminary results. Extended regimens of the contraceptive vaginal ring: a randomized trial. Bleeding patterns after immediate vs. conventional oral contraceptive initiation: a randomized, controlled trial. Menstrual reduction with extended use of combination oral contraceptive pills: randomized controlled trial. Bleeding patterns and patient acceptability of standard or continuous dosing regimens of a low-dose oral contraceptive: a randomized trial. Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: a randomized comparative dose-ranging study. A low-dose start in hormone replacement therapy provides a beneficial bleeding profile and few side-effects: randomized comparison with a conventional-dose regimen. The impact of using a partially randomised patient preference design when evaluating alternative managements for heavy menstrual bleeding. Clinical assessment of treatments for prolonged bleeding in users of Norplant implants. Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT. Low-dose oral contraceptive to re-induce menstrual bleeding in amenorrheic women on DMPA treatment: a randomized clinical trial. Cycle control, quality of life and acne with two low-dose oral contraceptives containing 20 microg ethinylestradiol. Immediate versus delayed treatment of perimenopausal bleeding due to benign causes by balloon thermal ablation. Effects of two different regimens of continuous hormone replacement therapy on endometrial histopathology and postmenopausal uterine bleeding. Vaginal estrogen supplementation during Depo-Provera initiation: a randomized controlled trial. Randomized placebo-controlled trial of CDB-2914 in new users of a levonorgestrel-releasing intrauterine system shows only short-lived amelioration of unscheduled bleeding. Prospective, randomised study with three HRT regimens in postmenopausal women with an intact uterus. A comparative 2-year study of the effects of sequential regimens of 1 mg 17beta-estradiol and trimegestone with a regimen containing estradiol valerate and norethisterone on the bleeding profile and endometrial safety in postmenopausal women. Bleeding pattern and cycle control with an estradiol-based oral contraceptive: a seven-cycle, randomized comparative trial of estradiol valerate/dienogest and ethinyl estradiol/levonorgestrel. A pilot study to assess the effect of three short-term treatments on frequent and/or prolonged bleeding compared to placebo in women using Implanon. Optimizing continuous-combined hormone replacement therapy for postmenopausal women: a comparison of six different treatment regimens. Clinical comparison of two low-dose oral contraceptives, Minulet and Mercilon, in women over 30 years of age. Comparison of efficacy, cycle control, and tolerability of two low-dose oral contraceptives in a multicenter clinical study.
This double-blind, placebo-controlled study was conducted to evaluate the efficacy of valdecoxib and placebo for controlling irregular uterine bleeding in depot-medroxyprogesterone acetate (DMPA) users.
                A total of 51 DMPA users were enrolled. All subjects in the study had abnormal bleeding and were randomly divided into two groups. One group totaling 22 received valdecoxib, 40 mg, once a day for 5 days, and placebos were given to another 24 in the same manner; 5 subjects dropped out from the study. Analysis of the number of treatment days required for stopping the bleeding episode, percentage of women whose bleeding was stopped in 7 days, total number of bleeding-free days and length of the bleeding-free interval after the initial treatment was determined in the first and the fourth weeks.
                The percentage of the subjects whose bleeding was stopped during the first week after the initial treatment and the mean value of the bleeding-free days during the 28 days of the follow-up period were significantly higher in the valdecoxib group than in the placebo group (77.3% vs. 33.3%, p<.01; and 17.8 days vs. 11.5 days, p<.05, respectively). The mean duration of treatment days required for stopping the bleeding episode in the valdecoxib-treated group was 1.7 days, and the mean duration of the bleeding-free interval in valdecoxib-treated group was 18.6 days.
                Valdecoxib was more effective than placebo in the short-term control of irregular bleeding in DMPA users. The mechanism of nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of endometrial bleeding is likely from COX-2 inhibition. A randomized multicenter study was performed in order to investigate the acceptance of a low-dose OC (30 micrograms of ethinyloestradiol and 150 micrograms of desogestrel), using a 9 weeks on and 1 week off schedule (prolonged regimen, n = 198), compared to a traditional 3 weeks on, 1 week off schedule (standard regimen, n = 96). Haemoglobin and blood pressure remained the same in both groups during the study. No significant differences were found in body weight changes between the two groups. There was significantly more breakthrough bleeding and spotting in the group with prolonged regimen than in the group with standard regimen, but both breakthrough bleeding and spotting decreased during the trial. Irregular bleeding was significantly less in women who were already using OC, compared to "new starters." No serious side effects occurred. Significantly more women stopped the trial because of bleeding problems in the group with prolonged regimen, while there were significantly more women who stopped the trial because of headache in the group with standard regimen. After completing 12 months, or after premature withdrawal from the study, each women completed a questionnaire. Sixty-three per cent of the women preferred the studied alternative and twenty-six per cent preferred the traditional OC. A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered. To compare bleeding profiles of a traditional 28-day oral contraceptive pill cycle with continuous administration.
                After a 28-day run-in cycle, women were randomized to either 28-day cycles (21 active pills and a pill-free week) or continuous use of the same 20 microg ethinyl estradiol/100 microg levonorgestrel formulation for 12 study cycles (336 days). The number of bleeding and spotting days were measured by daily diary. A subset underwent cycle 1 (n = 16), and nine (n = 14) pelvic ultrasound and endometrial histology sampling. Blood pressure, weight, hemoglobin, and adverse events were measured at revisit. The sample size with 80% power to detect a 67% reduction in bleeding days required 27 subjects in each arm.
                Of the 79 subjects randomized, 28 (70%) of the 28-day cycle and 32 (82%) of the continuous-use subjects completed the entire study (P =.6). With continuous use, 49%, 68%, and 88% of women reported no bleeding during cycles 2, 6, and 12, respectively. Amenorrhea or infrequent bleeding was present in 68% of continuous users during cycles 1-3 and increased to 88% during cycles 10-12. Spotting during cycle days 1-21 increased initially with continuous use but reduced over time, and by 9 months was less than the spotting reported by cyclic users. Adverse events, blood pressure, weight, and hemoglobin findings were similar between groups.
                Extension of the 28-day oral contraceptive cycle to continuous use with a low-estrogen dose combination oral birth control pill resulted in significantly fewer bleeding days. This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms.
                The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study.
                All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group.
                All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern. A clinical study was conducted to assess the effects of oestrogen in controlling increased endometrial bleeding problems in the first year of Norplant use. Three treatment groups were studied: (i) 50 micrograms ethinyl oestradiol (EE); (ii) a combined pill containing 30 micrograms EE and 150 micrograms levonorgestrel (LNG); and (iii) placebo. Based on menstrual diary records, women with prolonged, frequent or irregular bleeding, as defined by World Health Organization criteria, were randomly allocated to one treatment for 21 days. A first endometrial biopsy was taken before commencing treatment and a second biopsy at either day 14 or 21 of treatment. Following treatment, all subjects kept a menstrual diary card for 90 days. In this preliminary study, 48 subjects had completed the full 90 day post-treatment record. Within 21 days of EE treatment, the number of bleeding/spotting days was reduced significantly (P < 0.02). In the 90 days following treatment, the administration of EE and EE + LNG significantly decreased the number of bleeding/spotting days (P < 0.05). There was no reduction in the number of bleeding/spotting episodes in the EE and EE + LNG groups, but the length of each bleeding/spotting episode was significantly shorter (P < 0.05). Histopathological findings of endometrium on day 0 revealed consistent progestogenic effects, and there was no apparent change in response by day 14 or 21 of EE or EE + LNG treatment. The results of this study confirm the clinical effectiveness of EE and EE + LNG for the treatment of irregular, frequent and prolonged bleeding in Norplant users. To compare the bleeding patterns and tolerability of 3 different extended ring regimens with those of the standard 28-day cycle with 21 days of contraceptive vaginal ring use followed by 7 ring-free days.
                Following a run-in 28-day ring cycle, women were randomized to 1 of 4 regimens: monthly (28-day cycle), every other month (49-day cycle), every third month (91-day cycle), or continuous (364-day cycle). Treatment duration was 1 year. Daily bleeding diary, interval visit questionnaire, and examination data were collected.
                A total of 561 women were enrolled, 429 were subsequently randomized, and 289 (67.4%) women completed the entire year. All schedules were well tolerated and acceptable to women, but study completion rates were higher for the shorter cycles. Bleeding days were reduced with postponement of the withdrawal bleeding (ring-free) week, but spotting days increased. For example, women using the continuous or 364-day ring cycle reported a median of zero bleeding days but 10-12 days of spotting during the first 3 months of extended use. Unscheduled bleeding during ring use was the lowest with the traditional 28-day cycle. Adverse events, blood pressure, body weight, and laboratory findings were comparable over the 4 treatment groups.
                The combination vaginal contraceptive ring can be used for extended cycles to alter the bleeding schedule. Women willing to tolerate some spotting might choose the longer extensions to have fewer menstrual periods.
                I. To compare bleeding patterns after immediate vs. conventional oral contraceptive (OC) initiation.
                Randomized controlled trial.
                University-based clinic.
                One hundred thirteen women initiating combination OCs.
                Participants received a 4-month supply of a monophasic 35-microg ethinyl E(2) (EE) OC and a bleeding diary, were randomized to immediate or conventional OC start, underwent monthly telephone follow-up, and after 90 days returned the diary and completed an exit interview.
                Total number of bleeding-spotting days, using the World Health Organization 90-day reference period method. Comparisons were made by trial assignment (immediate vs. conventional) and cycle day of OC initiation (day 8+ vs. days 1-7).
                There was no significant difference in the number of bleeding-spotting days (mean difference: -0.5 days; 95% CI: -3.4 to 2.3) or any other bleeding parameter between the immediate and conventional starters, or days 1-7 and day 8+ starters.
                Immediate start of OCs does not induce bleeding patterns different from conventional starting regimens. Concern about adverse bleeding patterns should not be considered a justification for instructing women to wait until menses before starting OCs. To compare a traditional 28-day cycle to an extended 49-day cycle of the 30 microg ethinyl estradiol (E2)/300 microg norgestrel monophasic birth control pill regimen.
                Ninety subjects randomized to either 28-day cycles with 21 active pills or 49-day cycles with 42 active pills for a prospective open label trial over four 84-day reference periods or trimesters. Bleeding, pill taking, and symptom diaries were completed. The sample size with 80% power to detect a 40% reduction in bleeding days required 24 subjects in each arm.
                Of the 90 women, 24 subjects (54.5%) on the 28-day cycle and 29 (63%) on the 49-day cycle completed the entire study (P =.41). There were no statistically significant differences between the two groups in demographics or continuation rates. There was a significant reduction in bleeding days in the experimental arm beginning in the first trimester (28-day = 10.9, 49-day = 6.4 mean days of bleeding, P <.001) and continuing to the fourth trimester (28-day = 11.3, 49-day = 5.8 mean days, P =.005). The number of spotting days was similar between both schedules in the first trimester (28-day = 4.8, 49-day = 3.7 mean days, P =.24) and continued into the fourth trimester (28-day = 3.4, 49-day = 2.9 mean days, P =.30). Annual expenditure for hygiene products was significantly less for extended use subjects (28-day = $41.45, 49-day = $17.54 spent, P <.001).
                Extension of the 28-day oral contraceptive (OC) cycle to a 49-day cycle resulted in fewer bleeding days and no increase in mean spotting days or bleeding episodes. The purpose of this study is to compare bleeding patterns and acceptability of a contraceptive regimen of combined 20 microg ethinyl estradiol/100 microg levonorgestrel taken with and without a hormone-free interval. Thirty-two women desiring oral contraception were randomized to six 28-day cycles (standard group) or 168 days without a pill-free interval (continuous group). Participants kept a daily bleeding calendar documenting bleeding events (none, spotting or required sanitary protection) and side effects (headache, nausea, breast tenderness, depression, premenstrual syndrome and bloating). Primary outcome was number of bleeding days. Secondary outcomes included bleeding days requiring sanitary protection, amenorrhea, patient acceptability of bleeding patterns, method satisfaction and affective side effects. There were no differences in the baseline characteristics of the two groups. Although total bleeding days were fewer in the continuous group (mean = 25.9 vs. 34.9 days), this result did not reach statistical significance. However, women in the continuous group reported significantly fewer bleeding days that required protection (18.4 vs. 33.8 days, p < 0.01), and were more likely to have amenorrhea. Although both groups reported a high level of satisfaction with bleeding patterns and side effect profiles, women in the continuous group reported significantly fewer days of bloating (0.7 vs. 11.1 days, p = 0.04), and menstrual pain (1.9 vs. 13.3 days, p < 0.01). Continuous use of 20 microg ethinyl estradiol/100 microg levonorgestrel is associated with less bleeding requiring protection, and more amenorrhea than standard administration. Taken with or without a hormone-free interval, this oral contraceptive formulation is highly acceptable with regard to bleeding patterns and side effect profile. The continuous group had fewer light and moderate bleeding days, less bloating and menstrual pain. For patients who are seeking these results, this method may be more desirable. We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E(2)V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E(2)) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study.
                440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E(2)V+2.5 mg MPA; 1 mg E(2)V+5 mg MPA; or 2 mg of E(2)+1 mg NETA. After the first 6 months, the E(2)V dose was increased to 2 mg in both E(2)V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits.
                Significantly fewer bleeding days were experienced in the first 3 months by women taking E(2)V/MPA compared with women taking E(2)/NETA. When the dose of E(2)V was increased in the E(2)V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E(2)/NETA group compared with either of the E(2)V/MPA groups. The overall continuation rates ranged from 70 to 86%.
                These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E(2)V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT. To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT.
                An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control.
                The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported.
                Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control. To identify the advantages and disadvantages of using a partially randomised patient preference design rather than a conventional randomised controlled design when evaluating alternative managements for heavy menstrual bleeding.
                Randomised controlled comparison of two clinical trial designs with subsequent follow up of the cohorts of women generated.
                Women attending a general gynaecology clinic for the first time because of heavy menstrual bleeding.
                Partially randomised patient preference clinical trial design and conventional randomised controlled design.
                Overall participation; participation in randomised clinical trial of medical management compared with transcervical surgical resection of the endometrium; prognostic characteristics (socio-demographic and Short Form 36) of clinical trial groups; outcomes (clinical and Short Form 36) of clinical trial groups.
                Overall, more women participated in the partially randomised patient preference design (130/135 vs 97/138; difference 27%, 95% CI 18% to 34%) but there was no difference in the numbers who agreed to be randomised (90/135 vs 97/138; difference-3%, 95% CI-15% to 7%). Women who chose medical management tended to have better general health, to be less restricted by their menstrual problems, with fewer having been previously treated by their general practitioner. Those who chose transcervical resection of the endometrium had all tried medical management and had higher bleeding scores. Follow up satisfactions and acceptability rates, and Short Form 36 scores were highest after transcervical resection of the endometrium, whether chosen or randomised. Acceptability and a desire to continue the same treatment was greater among those who chose medical management than those randomly allocated it.
                Use of the partially randomised patient preference design did not affect recruitment to the randomised controlled trial suggesting that a conventionally designed trial would not be biased by motivational factors in this context. Data from the preference groups informed the generalisability of the results but did tend to confirm conclusions that anyway reasonably followed from the randomised controlled trial. The extra resource implications of using the partially randomised patient preference design were significant reflecting the additional 40% who participated and the extra analyses entailed. The effectiveness of three drugs in controlling prolonged bleeding in the first year of NORPLANT implants use was tested. The drugs were levonorgestrel (L-Ng, 0.03 mg twice a day for 20 days), ethinylestradiol (EE, 0.05 mg per day for 20 days) and ibuprofen (Ib, 800 mg three times a day for 5 days) and were given orally. A control group received a placebo (PL, one pill of lactose for 20 days). Treatment should start each time a woman experienced eight consecutive days of bleeding or spotting. The 183 volunteers were not aware of the drug administered. A daily record of bleeding and spotting and of treatment intake was maintained. One-hundred-forty women completed the study period; 60 never used the prescribed treatment. Women treated with the three test drugs had significantly fewer bleeding and spotting days during the treated month and also throughout the study year than women using the placebo. The mean number of bleeding plus spotting days per actually treated subject in the first year was 77, 94, 101 and 129 days for the EE, Ib, L-Ng and PL groups, respectively. The administration of EE might help in the management of prolonged bleeding during the first year of NORPLANT implants use. To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas.
                In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared.
                Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size.
                The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE-MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE-MPA therapy, at the doses used here, promote fibroid growth. Depot medroxy progesterone acetate (DMPA) is one of the most reliable contraceptive methods with a failure rate less than 0.3 percent. It is injected every three months and Although it has many advantages over many other hormonal contraceptives, But a major disadvantage of it is bleeding disorders which comprise most of the discontinuance reasons. Our Aim was to study bleeding complications of DMPA when used as a contraceptive in Ardabil district and clinical trial of LD and Ethynil oestradiol in controlling these complications.
                All the 917 women who referred to ardabil's health centers for having a DMPA injection for the first time, were entered into a longitudinal study. Those complaining of menstrual cessation were entered into a double blinded randomized clinical trial. Data were collected by means of 9 questionnaires 7 of them used for descriptive and 2 for clinical trial study. Data was analyzed by SPSS statistical package.
                Those DMPA users with a cesarean section history had a higher chance of bleeding complications. Four hundred forty-four of the 917 women receiving the injection discontinued using it before the end of the study period. The main reason for discontinuation (in 70%) was irregular menstrual bleedings and menstrual cessation. In the clinical trial of women with bleeding cessation, 70% of those receiving the LD-OC pill experienced menstrual bleedings again, compared with only 22.7% in the placebo group. The discontinuation rate in the drug group was lower than in the placebo group as well (p < 0.05).
                Treating menstrual cessation caused by DMPA with LDs, improves the complication and decreases the discontinuance rate. Poor cycle control and tolerability can be reasons for irregular pill intake. This study compared the tolerability of two low-dose oral contraceptives and their effect on cycle control.
                In this open, group-comparative, randomized multicenter trial in Germany and the Netherlands, women received either 20 microg ethinylestradiol plus 150 microg desogestrel (20EE/DSG; n = 500) or 20 microg ethinylestradiol plus 100 microg levonorgestrel (20EE/LNG; n = 498) for six treatment cycles. Cycle control, dysmenorrhea and premenstrual syndrome (PMS) were assessed using diary cards. Tolerability was assessed using the self-administered questionnaires Psychological General Well-Being Index (PGWBI) and the Profile of Mood States (POMS). Acne was assessed by objective (acne counts) and subjective (no, moderate, mild, severe) acne scoring of the facial area at baseline and treatment cycles 1, 3 and 6.
                A total of 404 (78.1%) and 384 (75.3%) women in the 20EE/DSG and 20EE/LNG groups, respectively, completed the trial. The occurrence rate of irregular bleeding and spotting was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.18 vs. 0.13; p < 0.05). The mean number of bleeding-spotting days per cycle was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.63 vs. 0.48; p < 0.05). Early withdrawal bleeding was more frequent with 20EE/LNG (0.15 vs. 0.08; p < 0.005), whereas continued withdrawal bleeding was more frequent with 20EE/DSG (0.32 vs. 0.45; p < 0.001); absence of withdrawal bleeding was comparable (0.06 vs. 0.04, respectively). Thirteen subjects in the 20EE/LNG group and three in the 20EE/DSG group discontinued due to unacceptable bleeding (p < 0.05). Dysmenorrhea and PMS decreased comparably in both groups. There were no differences between groups for the mean total scores of PGWBI or POMS at all time-points. Fewer acne lesions were counted with 20EE/DSG vs. 20EE/LNG after six cycles (p < 0.05). The subjective acne scores supported this finding.
                20EE/DSG provided better cycle control than 20EE/LNG with less treatment discontinuation due to unacceptable bleeding. There were no apparent differences between the two groups regarding tolerability and quality of life. There was less acne with 20EE/DSG.
                Copyright 2004 Elsevier Inc. To compare the effectiveness and safety of thermal balloon ablation without pretreatment with endometrium-thinning agents compared with delayed ablation with pretreatment for women with perimenopausal menorrhagia.
                Prospective, randomized, controlled trial (Canadian Task Force classification I).
                Hospital-based ambulatory medical center.
                Thirty women age 46 to 51 years with severe enough perimenopausal menorrhagia to make them candidates for either hysterectomy or endometrial ablation. Two patients with submucosal myomas and six who had undergone cesarean section were included.
                Thirteen patients were randomly assigned to be treated within 30 days and received a single intramuscular administration of gonadotropin releasing hormone (GnRH) analog; 17 women were allocated to be treated within 3 days of enrollment without uterine preparation. A thermal balloon was inserted transcervically under general anesthesia, and after inflation in the endometrial cavity with 5% dextrose in water, was heated to 87 degrees C for 8 minutes.
                Immediate and long-term major and minor complications and success rates were analyzed. Bleeding patterns and mean duration of menstrual flow were compared between groups at 6-month follow-up. No major intraoperative or postoperative complications occurred in either group, including the women who had recently undergone hysteroscopic myomectomy or had a history of cesarean section. Minor side effects were similar in both groups, and did not exceed 5%. Overall, at 6-month follow-up, 7 women were amenorrheic, 20 hypomenorrheic, and 3 eumenorrheic. No significant differences were noted between women treated with immediate or delayed ablation in either the distribution of bleeding patterns or days of flow per cycle (mean +/- SEM 1.8 +/- 0.42 vs 2.1 +/- 0.75 days, respectively).
                This pilot study suggests that prompt treatment of perimenopausal menorrhagia with thermal balloon endometrial ablation is as effective and safe as deferred therapy combined with GnRH analog as an endometrium-thinning agent. In light of our results, the theory that previous cesarean section and presence of small submucosal myomas constitute relative contraindications for the procedure merits further consideration. (J Am Assoc Gynecol Laparosc 6(2):145-150, 1999) To compare the effects of frequently used two different regimens of combined continuous hormone replacement therapy; 0.625 mg conjugated equine estrogen (CEE) + 2.5 mg medroxyprogesterone acetate (MPA) and 1 mg 17beta estradiol (E2) + 0.5 mg norethindrone acetate (NETA), on endometrial histopathology and postmenopausal uterine bleeding.
                Two hundred and forty-six outpatient subjects aged 41-57 years were enrolled in the study conducted at the menopause clinic between November 2003 and November 2004. One hundred and thirty-nine patients were assigned to receive 0.625 mg conjugated equine estrogen + 2.5 mg medroxyprogesterone acetate (CEE/MPA), whereas 107 patients were to receive 17beta estradiol + 0.5 mg norethindrone acetate (E2/NETA). Inclusion criteria of the study were: normal values of endometrial thickness at basal evaluation, women with intact uterus, at least 12 months of amenorrhea, normal vaginal smear, bilateral mammography and biochemical blood parameters. All women were questioned every 3 months for vaginal bleeding/spotting. Endometrial sampling was performed by Pipelle catheter in the 12th month of therapy.
                For the first 3 months, vaginal bleeding/spotting rate for the CEE/MPA group was 38.7%, whereas it was higher (45%) in the E2/NETA group. For the second 3-month period, vaginal bleeding/spotting frequencies were 41.1 and 37.8%, respectively. In the third 3-month period 30.6 and 29.6%, and in the fourth 3-month period, 18.5 and 12.5% of the patients reported vaginal bleeding or spotting. None of the results of endometrial sampling have shown findings of cancer histopathology.
                Compared to CEE/MPA regimen, E2/NETA therapy has not shown more favorable effects on postmenopausal bleeding abnormalities. Irregular endometrial proliferation was seen more with the E2/NETA regimen. Irregular bleeding is often cited as the reason for discontinuation of depot-medroxyprogesterone acetate (DMPA) after the first injection. Estrogen supplementation during DMPA initiation may decrease bleeding and improve continuation.
                This prospective, randomized, controlled trial evaluated estrogen supplementation during DMPA initiation. Women initiating DMPA were randomized to receive an estradiol vaginal ring for 3 months versus DMPA alone. Bleeding diaries and questionnaires at three and 6 months assessed bleeding, continuation and ring acceptability.
                Seventy-one participants enrolled; 49 completed the first follow-up period. The median number of bleeding or spotting days was 16 in the estrogen ring group (n=26) versus 28 in the DMPA alone group (n=23) (p=.19). Seventy-seven percent of the intervention group received a second injection compared with 70% in the DMPA alone group (p=.56). For each additional day of bleeding and/or spotting reported, women were 3% less likely to receive a second injection (OR 0.97, 95% CI 0.94-0.99). Acceptability of the vaginal ring was high among those in the intervention group.
                Vaginal estrogen supplementation during DMPA initiation is acceptable to women and may decrease total bleeding.
                Copyright 2010 Elsevier Inc. All rights reserved. The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive. However, during early months of use unscheduled vaginal bleeding is common, sometimes leading to discontinuation. This study aimed to determine whether intermittent administration of progesterone receptor modulator CDB-2914 would suppress unscheduled bleeding during the first 4 months after insertion of the LNG-IUS.
                CDB-2914 150 mg, in divided doses, or placebo tablets, were administered over three consecutive days starting on Days 21, 49 and 77 after LNG-IUS insertion, in a double-blind randomized controlled trial of women aged 19-49 years, newly starting use of LNG-IUS. Daily bleeding diaries were completed for 6 months, and summarized across blocks as percentage days bleeding/spotting (BS%).
                Of 69 women randomized to receive CDB-2914, and 67 placebo, 61 and 55, respectively, completed the trial. BS% decreased with time in both arms, but showed a much steeper treatment-phase gradient in the placebo arm (P < 0.0001), so that a benefit of CDB-2914 in the 28 days after first treatment (-11% points, 95% CI -19 to -2), converted to a disadvantage by 64 days after the third treatment (+10% points, 95% CI 1-18).
                The effect of CDB-2914 on BS% was initially beneficial but then by third treatment was disadvantageous. Nevertheless, only 3% (4/136) of all women discontinued LNG-IUS. These findings give insight into possible mechanisms and suggest future research directions. ISRCTN Trial no. ISRCTN58283041; EudraCT no. 2006-006511-72. To compare compliance, symptom control, bleeding patterns, lipid and biochemical changes in postmenopausal women treated with three regimens of HRT.
                In a prospective, randomised, group comparative study, with 165 patients, the effects on the aforementioned parameters, as well as treatment compliance and side effects were studied with oral tibolone 2.5 mg per day, with cyclic combined regimen of transdermal oestrogen and progestogen (transdermal patch of 17beta-oestradiol 50 microg/day during 14 days and transdermal patch of 17beta-oestradiol 50 microg/day plus 0.25 mg/day NETA during the following 14 days), and with intermittent progesterone regimen (transdermal 17beta-oestradiol 50 microg/day and oral micronised natural progesterone 200 mg twice a week). Statistical analysis was carried out using the Fisher-test, analysis of the variance (ANOVA) and the Bouferoni test.
                Ten women dropped out of the tibolone group, 11 dropped out of the intermittent dosing group and 21 dropped out of the cyclid combined group. Irregular bleeding occurred at more rates in the cyclid combined group. Similar reductions in climacteric symptoms were found in the three groups. No differences were observed with respect to biochemical analysis.
                Efficacy and safety of the three treatment regimens being comparable, but the patients in our study preferred those that did not produce bleeding episodes. To compare the bleeding profiles and endometrial protection of two sequential regimens of 17beta-estradiol (17beta-E2) and trimegestone (TMG) with a sequential estradiol valerate (E2V)/norethisterone (NET) regimen.
                This was a randomized, double-blind, multicenter study conducted in eight countries in healthy, postmenopausal women with an intact uterus. A total of 1218 women were enrolled into the initial 1-year study (13 cycles), and subsequently 531 of these received treatment for a further year (26 cycles). Treatment regimens were 1 mg 17beta-E2 on days 1-14 and 1 mg 17beta-E2/0.125 mg TMG or 1 mg 17beta-E2/0.25 mg TMG on days 15-28, and 1 mg E2V on days 1-16 and 1 mg E2V/1 mg NET on days 17-28.
                Mean percentage of women reporting onset of withdrawal bleeding episodes during the week following discontinuation of progestogen was higher in the 1 mg 17beta-E2/0.25 mg TMG group than in the other two treatments, showing a more efficient progestogen effect on the endometrium and good predictability of bleeding onset with this treatment. The mean numbers and average lengths of bleeding episodes were similar in the three treatment groups. Overall, the bleeding profile was more favorable with 1 mg 17beta-E2/0.25 mg TMG than with the lower-dose TMG preparation. Both of the TMG regimens demonstrated a good protective effect on endometrial proliferation, with the 0.25 mg TMG dose showing a lower incidence of proliferative endometrium.
                The 1 mg 17beta-E2/0.25 mg TMG regimen showed an adequate protection of the endometrium, with an overall favorable bleeding profile. This study compared the bleeding pattern, cycle control and safety of an oral contraceptive (OC) comprising estradiol valerate/dienogest (E2V/DNG; administered using a dynamic dosing regimen) with a monophasic OC containing ethinyl estradiol 20 mcg/levonorgestrel 100 mcg (EE/LNG). E2V releases estradiol (E2), which is identical to endogenously produced 17beta-estradiol.
                This was a randomized, multicenter, double-blind, double-dummy trial lasting seven cycles in healthy women aged 18-50 years.
                Overall, 798 women were randomized and received allocated treatment (399 per group). There were significantly fewer bleeding/spotting days reported by women who received E2V/DNG than those who received EE/LNG [17.3+/-10.4 vs. 21.5+/-8.6, respectively, p<.0001, Reference Period 1 (Days 1-90); and 13.4+/-9.vs. 15.9+/-7.1, respectively, p<.0001, Reference Period 2 (Days 91-180)]. Through Cycles 1-7, the occurrence of scheduled withdrawal bleeding per cycle was 77.7-83.2% with E2V/DNG and 89.5-93.8% with EE/LNG (p<.0001 per cycle). The duration and intensity of scheduled withdrawal bleeding were reduced with E2V/DNG vs. EE/LNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5%-18.6%) and EE/LNG (9.9%-17.1%) (p>.05 per cycle). No unintended pregnancies occurred with E2V/DNG, but there was one unintended pregnancy with EE/LNG. Adverse drug reactions occurred in 10.0% and 8.5% of women taking E2V/DNG and EE/LNG, respectively. Overall, 79.4% of women were satisfied with E2V/DNG and 79.9% with EE/LNG.
                A novel OC composed of E2V/DNG is associated with an acceptable bleeding profile that is comparable to that of an EE-containing OC. The major side-effect of progestogen-only contraception is disruption of menstrual bleeding patterns, which can lead to a high incidence of early discontinuation. The aim of this study was to compare three treatments with placebo on the duration and recurrence of frequent and/or prolonged bleeding in Implanon users.
                Women between the ages of 18 and 45 years, who had used Implanon for > or =3 months and were experiencing prolonged or frequent bleeding patterns, were recruited at four Australian sites. Subjects were randomized to treatment using computer-generated random number table if they met the World Health Organization criteria for prolonged and/or frequent bleeding in the previous 90 days [Belsey, E.M., Pinol, A.P.Y. and Taskforce on Long-Acting Systemic Agents for Fertility Regulation, World Health Organization (1997) Contraception 55,57-65]. Treatments were: (1) mifepristone 25 mg given twice on day 1 followed by 4 days of twice daily placebo; (2) mifepristone 25 mg given twice on day 1 followed by 4 days of ethinyl estradiol (EE) 20 microg in the morning and placebo at night; (3) doxycycline 100 mg twice daily for 5 days; and (4) placebo twice daily for 5 days. Analysis was by intention to treat. The primary endpoint was the number of days of bleeding and spotting immediately following initiation of the 5 day course of each active therapy compared with placebo.
                A total of 179 women was assigned to treatment. Both mifepristone in combination with EE and doxycycline alone were significantly more effective in stopping an episode of bleeding {mean 4. 3 days [confidence interval (CI) 3.5-5.2], and 4.8 days (CI 3.9-5.8) respectively} than mifepristone alone or placebo [5.9 days (CI 4.8-7.2) and 7.5 days (CI 6.1-9.1) respectively]. No effect on subsequent bleeding patterns was observed in any treatment group.
                Both mifepristone plus EE and doxycycline alone were significantly more effective than placebo in terminating an episode of bleeding in women with prolonged and/or frequent bleeding using Implanon. We believe that the observed reduction in the number of bleeding days by almost 50% compared to placebo in both the mifepristone combination group and the doxycycline group demonstrates a clinically significant improvement in bleeding patterns and that further trials are needed to compare different combinations of therapy as well as multiple dosing regimens in order to establish which is the most effective treatment option. The effect of repeat administration or combinations of these preparations on long-term bleeding patterns requires further investigation. We sought to determine the optimum estradiol valerate-medroxyprogesterone acetate regimens for efficacy and safety.
                We performed a 24-month, randomized, double-blind phase II study. Four hundred nineteen women who were postmenopausal for at least 3 years were placed in six parallel treatment groups and received 1 or 2 mg estradiol valerate with either 2.5 or 5 mg medroxyprogesterone acetate. In two groups the dose of estradiol valerate was increased from 1 to 2 mg estradiol valerate after 6 months.
                A marked improvement of climacteric symptoms was observed, and most women had no bleeding even during the first 3 months of treatment. The best bleeding pattern was achieved with 1 mg estradiol valerate and 2.5 or 5 mg medroxyprogesterone acetate, and in most groups the bleeding pattern improved over time. No cases of hyperplasia were observed.
                All regimens alleviated climacteric symptoms and provided excellent bleeding control, even during the early weeks of treatment. A choice of various dose combinations offers flexibility of dosing, thus enabling therapy to be tailored to the needs of individual women. A comparative study of two low-dose oral contraceptives, gestodene (GES) 75 mcg/ethinyl oestradiol (EE) 30 mcg and desogestrel (DES) 150 mcg/EE 20 mcg, was conducted in women over 30 years of age. This randomised, open-label study was organised in Denmark, Italy, New Zealand and United Kingdom. A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles. The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline. However, the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment. The mean age (+/- SD) was 35 +/- 4 years in the GES/EE group and 35 +/- 5 years in the DES/EE group. The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group, data for 2796 cycles. There were no pregnancies on medication with either preparation. The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6. Irregular bleeding between withdrawal bleeds occurred in 10% of GES/EE and 18.5% of DES/EE cycles. Absence of all bleeding was reported in 29 (1%) and 63 (2%) cycles, respectively. The incidence of missed pills was low in both groups (11% of cycles). No significant differences were observed in cycle length or withdrawal bleeding episode length. Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE. However, for both preparations, the mean intensity was close to light bleeding. No clinically significant differences were noted in weight, blood pressure, Papanicolaou smears or laboratory data. Sixty-eight (13.5%) subjects in the GES/EE group and 64 (12.8%) in the DES/EE group discontinued before the end of the study. Among them, 37 (7%) and 40 (8%) in the respective groups withdrew because of adverse reactions. There was no difference between groups in terms of primary reasons for withdrawal. The most frequently reported complaints that led to discontinuation in both groups were headache, nausea and metrorrhagia. Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group. These results show excellent cycle control, efficacy and very low rate of side effects with both GES/EE and DES/EE. These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause. This study compares the contraceptive reliability, cycle control, and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene (EE/GSD) or 150 micrograms of desogestrel (EE/DSG). Women received the trial preparations daily for 21 days, followed by a 7-day pill-free interval. Contraceptive efficacy, cycle control, and tolerability were evaluated over a period of 12 cycles. Efficacy data of 14,700 treatment cycles (EE/GSD: 7299; EE/DSG: 7401) were obtained from 1476 women (EE/GSD, n = 740; EE/DSG, n = 736). Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding. The spotting rates in both treatment groups decreased from 35.1% (EE/GSD) and 37.5% (EE/DSG) in the first treatment cycle to approximately 10% in the fourth treatment cycle. The spotting incidence as percent of the total number of cycles was 12.7% for EE/GSD and 14.3% for EE/DSG. The breakthrough bleeding incidence was 5.2% of all cycles for EE/GSD and 6.0% of all cycles for EE/DSG. For 84.7% of the cycles in the gestodene group and for 82.5% of the cycles in the desogestrel group, neither spotting nor breakthrough bleeding were recorded. Overall, the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG. However, the difference was not statistically significant. Amenorrhea was recorded in 2.7% of the cycles with EE/GSD and in 2.9% with EE/DSG. Both preparations were well tolerated and showed a similar pattern of adverse events. More than 83% of the women in both groups either did not gain weight or lost more than 2 kg. Both preparations had a beneficial effect on dysmenorrhea. Both regimens provided reliable contraception and good cycle control. The incidence of adverse events was relatively low and both preparations were well tolerated.
Some women may benefit from the interventions described, particularly with cessation of current bleeding. Several regimens offer promise in regulating bleeding, but findings need to be reproduced in larger trials. The results of this review do not support routine clinical use of any of the regimens included in the trials, particularly for long-term effect.