Dose-response and withdrawal effects on climacteric symptoms after hormonal replacement therapy. A placebo-controlled therapeutic trial. A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms. Two hormone replacement therapy (HRT) regimens for middle-eastern postmenopausal women. Initial 17beta-estradiol dose for treating vasomotor symptoms. A 1-year comparison of the efficacy and clinical tolerance in postmenopausal women of two hormone replacement therapies containing estradiol in combination with either norgestrel or trimegestone. Dose-response analysis of effects of tibolone on climacteric symptoms. Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. [Influence of hormone replacement therapy on the quality of life in postmenopausal women with hypertension].
Out of a sample of 162 early post-menopausal women, aged 45-54 yr, 131 completed a placebo-controlled study to investigate the effect of sex hormones on mild climacteric symptoms with special reference to the dose-response relationship and withdrawal effects. The women were followed up for 42 mth under four different study programmes. All the women were examined every 3 mth and a blind assessment made of the menopausal index estimated according to Kupperman et al. The data revealed a highly significant reduction in climacteric symptoms in the hormone-treated women as compared with the placebo group (P less than 0.001), a highly significant dose relationship between climacteric symptoms and treatment with 4, 2 and 1 mg oestradiol, respectively (P less than 0.001), a highly significant and dose-dependent rebound phenomenon after withdrawal of hormone treatment (P less than 0.001)--which levelled off after 6 mth following withdrawal--and complete relief of hot flushes with the two highest doses of oestradiol (4 and 2 mg oestradiol). It is concluded that sex hormones have a beneficial effect in post-menopausal women with even mild symptoms. To compare the effects of two postmenopausal regimens on menopausal symptoms, bleeding episodes, side effects and acceptability.
                Double-blind, randomised controlled trial.
                Twenty-nine sites in Denmark, nine in Norway and six in Sweden.
                Four hundred and thirty-seven postmenopausal women with menopausal complaints. None of these women had had a hysterectomy.
                Daily treatment with tibolone 2.5 mg (n = 218) or 17beta-oestradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA) (n = 219).
                Hot flushes, sweating episodes, vaginal dryness, assessment of sexual life and bleeding patterns; at baseline and after 4, 12, 24 and 48 weeks.
                Treatment with either preparation significantly reduced mean scores for hot flushes, sweating episodes and vaginal dryness. The overall discontinuation rate was 28% (tibolone 25%, E2/NETA 31%; P = 0.14), mostly during the first six months. There was a markedly lower cumulative incidence of bleeding or spotting episodes with tibolone compared with E2/NETA (P < 0.0001), mainly during the first six treatment cycles.
                Both tibolone and E2/NETA effectively alleviate menopausal symptoms. However, tibolone caused significantly fewer bleeding or spotting episodes, which were reflected by lower overall rates of bleeding, as well as lower drop-out rates due to bleeding. Most previous studies designed to evaluate the efficacy of hormone replacement therapy (HRT) have been carried out in Europe, North America and Australia, involving Caucasian women for 6 months or less.
                To evaluate the 12-month effects of two different HRT regimens on postmenopausal symptoms of Middle-Eastern women.
                Hundred healthy Libyan women with postmenopausal symptoms, 12 months or more since their last menstrual period, were enrolled in a 12-month prospective study. Participants were randomly prescribed one of the two formulations, 50 in each group. These regimens were a continuous regimen of tibolone 2.5 mg oral tablets and a continuous regimen of 17beta-oestradiol sequentially combined with dydrogesterone (2/10 mg) oral tablets. The presence and severity of short- and intermediate-term symptoms were reported at 0, 3, 6 and 12 months of treatment. Observed symptoms were hot flushes, night sweating, palpitations, insomnia, depression, nervousness, loss of memory, vaginal dryness, loss of libido and joint pain.
                Forty-nine women (98%) in each group completed the 12-month study period. Participants, in the two groups, experienced a significant improvement within the first 3 months of treatment. The observed symptoms were completely relived by the sixth month without any significant difference between the two groups. Improvements were sustained over the 12-month period of the study. HRT users showed their acceptance to the two regimens.
                Tibolone and 17beta-oestradiol/dydrogesterone oral tablets were effective and safe to treat short- and intermediate-term symptoms in Middle-Eastern postmenopausal women, within 6 months, and with no significant differences between the groups. Thus, the use of HRT to relieve menopausal symptoms is highly recommended, at least in this region. To compare the efficacy of different doses of 17beta-estradiol (E2) for relief of vasomotor symptoms in menopausal women.
                This was a randomized, double-masked, placebo-controlled, 12-week study in which 333 menopausal women with moderate or severe hot flushes were assigned to treatment with 0.25 mg, 0.5 mg, 1 mg, or 2 mg oral micronized 17beta-E2, or placebo. The number and severity of hot flushes were recorded daily.
                There was a significant linear correlation between increased dosage of 17beta-E2 and decreased moderate to severe hot flushes per week (P <.001). Rapid reduction in moderate to severe hot flushes was only achieved with 1 and 2 mg, showing a significant difference from placebo at week 4 (P <.05). At week 4, half the women on placebo had reduced moderate to severe hot flushes of at least 52%; the corresponding figures were 56%, 69%, 86%, and 91% for 0.25, 0.5, 1, and 2 mg, respectively. At week 12, all doses except 0.25 mg were significantly better than placebo for reducing moderate to severe hot flushes (P <.001). Although there were no significant differences, twice as many women in the 2-mg group discontinued treatment due to adverse events, compared with the placebo group.
                Oral micronized 17beta-E2 showed a dose-response effect for reducing moderate and severe hot flushes in menopausal women. 17beta-E2 1 mg appeared to be the most useful initial dose. This double-blind, randomized, multi-center study compared the efficacy and clinical tolerance of a combined formulation containing 2 mg estradiol (E2) and 0.5 mg trimegestone (TMG) with a standard hormone replacement therapy containing estradiol valerate (E2V) and norgestrel (NG) in the treatment of climacteric symptoms. The study was conducted over 13 cycles, each of 28 days, and involved 634 subjects, of whom 481 completed the study. The primary efficacy variable was the percentage of subjects who showed at least a 50% reduction from baseline in the mean daily number of hot flushes in cycle 3. This was observed in 98.5% of the subjects in the E2 + TMG group and 93.3% of the subjects in the E2V + NG group (95% confidence interval of the difference, -8.6, -1.9). Significant differences in favor of the E2 + TMG combination were observed in the reduction in the mean daily number and severity of hot flushes, and in the percentage of subjects who had hot flushes at baseline but no hot flushes during treatment. There were no significant differences between the treatments in the Kupperman index and in urogenital signs or symptoms. Treatment with the E2 + TMG combination was well tolerated and the incidences of adverse events were similar in the two treatment groups. Breast pain was the main adverse event, possibly related to treatment that resulted in discontinuation. The mean number of bleeding days per cycle was significantly lower with the E2 + TMG combination than with the E2V + NG combination. The incidences of endometrial hyperplasia were low and comparable in both treatment groups. It was concluded that the E2 + TMG combination was either equivalent or superior to the E2V + NG combination in the treatment of hot flushes and other climacteric symptoms, and that its bleeding profile was favorable. To assess the clinically optimal tibolone dose for the relief of climacteric complaints.
                A randomised, double blind, placebo-controlled trial.
                Twenty-eight centres in Norway, The Netherlands, Sweden and Finland.
                Seven hundred and seventy-five healthy postmenopausal women were randomised to tibolone in a daily dose of 0.625, 1.25, 2.5 or 5.0 mg or placebo for 12 weeks.
                At baseline, and after 4, 8 and 12 weeks, hot flushes, sweating, vaginal bleeding and adverse experiences were recorded.
                Change in frequency and intensity of hot flushes and sweating over 12 weeks.
                From week four onwards, 2.5 and 5.0 mg tibolone were significantly more effective than placebo, regarding the frequency of hot flushes and sweating (P < 0.001), whereas the 0.625 mg dose was not significantly different from placebo during the study. The frequency of hot flushes with the 1.25 mg dose was statistically significantly different from placebo, only from week eight onwards. The incidence of dropouts due to insufficient therapeutic effect was much higher in the tibolone 1.25 mg group (9.5%) than in the 2.5 (1.9%) and 5.0 mg (1.3%) groups. A dose-related increase in incidence of vaginal bleeding or spotting was observed (P < 0.0001). Bleeding incidence in the 5.0 mg dose group was about twice as high as in the 2.5 mg dose group. There was no difference in incidence of adverse experiences between the 2.5- and the 1.25 mg dose group.
                A daily dose of 2.5 mg tibolone is the clinically optimal dose for the treatment of climacteric complaints in postmenopausal women. To evaluate the effects of hormone therapy (HT) on cognition and subjective quality of life (QoL) in recently postmenopausal women with cognitive complaints.
                Cognitive Complaints in Early Menopause Trial (COGENT) was a randomized, double-blind, placebo-controlled, multicenter, pilot study of 180 healthy postmenopausal women aged 45 to 55 years, randomly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months. Outcome measures included memory, subjective cognition, QoL, sexuality, and sleep, which were assessed at baseline and month 4.
                The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women's Health Initiative. There were no differences between groups on any cognitive or QoL measures, except for an increase in sexual interest and thoughts with HT. Modest negative effects on short- and long-term verbal memory approached significance (p < 0.10). Women with baseline vasomotor symptoms (VMS) showed a decrease in VMS and an improvement in general QoL, but no cognitive benefit vs placebo.
                With the power to detect an effect size of >or=0.45, this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women. The objective of this study was to evaluate the efficacy of fluoxetine and black cohosh in the treatment of women with postmenopausal symptoms. A total of 120 healthy women with menopausal symptoms were recruited to this prospective study with a follow-up period of 6 mo. They were randomly assigned to 1 of 2 groups and were treated with fluoxetine or black cohosh. After entry into the study, patients were examined at the first, second, third, and sixth months of the treatment period. The women kept diaries in which they reported the daily number and intensity of hot flushes and night sweats. In addition, at the beginning and end of the third month, they completed questionnaires consisting of a modified Kupperman Index, Beck's Depression Scale, and a RAND-36 Quality-of-Life Questionnaire. Statistically significant differences were noted in the Kupperman Index and Beck's Depression Scale at the end of the third month in both groups compared with baseline values. In the black cohosh group, the Kupperman Index decreased significantly compared with that in the fluoxetine group by the end of the third month. On the other hand, in the fluoxetine group, Beck's Depression Scale decreased significantly compared with that in the black cohosh group. Monthly scores for hot flushes and night sweats decreased significantly in both groups; however, black cohosh reduced monthly scores for hot flushes and night sweats to a greater extent than did fluoxetine. At the end of the sixth month of treatment, black cohosh reduced the hot flush score by 85%, compared with a 62% result for fluoxetine. By the sixth month of the study, 40 women had discontinued the study--20 (33%) in the fluoxetine group and 20 (33%) in the black cohosh group. Compared with fluoxetine, black cohosh is more effective for treating hot flushes and night sweats. On the other hand, fluoxetine is more effective in improvements shown on Beck's Depression Scale. The effect of hormone replacement therapy (HRT) on the quality of life in women with hypertension is still not clear. Thus, the aim of the study was to assess the effect of hormone replacement therapy on quality of life in postmenopausal women with essential hypertension by using a battery of standardized questionnaires.
                The study population consisted of 53 women (mean age 50.9 +/- 6.3 years) with mild and moderate essential hypertension (mean duration 6.4 +/- 6.4 years). The postmenopausal status was defined as the absence of menstrual blood loss during > 6 months and blood estradiol concentration < 50 pg/ml, accompanied by follicle-stimulating hormone (FSH) levels > 21 U/I. Twenty seven women were blindly randomised to transdermal hormone replacement therapy (HRT) and received 17-beta-estradiol and noretisterone acetate, TTS. Twenty six women were randomly selected as controls. The subjects were evaluated at baseline (after 2 weeks' wash-out from hypotensive drug period) and after three months of HRT using self-administered standardized quality of life questionnaires: the Psychological General Well-being Index (PGWB) and the Subjective Symptoms Assessment Profile (SSA-P).
                No differences were found in blood pressure values, heart rate, body mass index and distribution of body fat tissue between women receiving HRT and controls at baseline and after 3 months of follow-up. There were no significant differences in the baseline total PGWB score as well as in its subscale between two groups. Similarly, the frequency and intensity of subjective symptoms assessed by SSA-profile were the same in both groups at baseline. After 3 months, a significant improvement in PGWB total score was observed in women receiving HRT. This effect was due to improvement in anxiety, positive well-being and vitality. Moreover, emotional distress, symptoms of flushing, sweating and trembling hands also diminished and sexual capacity improved in women treated with HRT.
                A three-month hormone replacement therapy in hypertensive postmenopausal women slightly improves the general well-being, seems to decrease emotional tension, increase sexual capacity and markedly relieves some vasomotor symptoms.
Oral HT is highly effective in alleviating hot flushes and night sweats. Therapies purported to reduce such symptoms must be assessed in blinded trials against a placebo or a validated therapy because of the large placebo effect seen in well conducted randomised controlled trials, and also because during menopause symptoms may fluctuate and after menopause symptoms often decline. Withdrawals due to side-effects were only marginally increased in the HT groups despite the inability to tailor HT in these fixed dose trials. Comparisons of hormonal doses, product types or regimens require analysis of trials with these specific "within study" comparisons.