A pilot study of the effects of phytoestrogen supplementation on postmenopausal endometrium. The effects of soy protein containing phytoestrogens on menopausal symptoms in postmenopausal women. A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts. High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial. Hormone therapy in women in the menopause transition. Randomised, double-blind, placebo-controlled trial of effects on body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium. Effects of dietary phytoestrogens in postmenopausal women. Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial. Two hormone replacement therapy (HRT) regimens for middle-eastern postmenopausal women. A randomized, double-blind, placebo-controlled, crossover study on the effect of oral oestradiol on acute menopausal symptoms. Comparison of Pueraria lobata with hormone replacement therapy in treating the adverse health consequences of menopause. Gonadotropin-releasing hormone analogue (goserelin) plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Efficacy of sustained-release vaginal oestriol in alleviating urogenital and systemic climacteric complaints. Do combinations of 1 mg estradiol and low doses of NETA effectively control menopausal symptoms? Monophasic estrogen-progestogen therapy and sexuality in postmenopausal women. Is oestrogen therapy effective in the treatment of menopausal depression? A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women. Effects of "natural oestrogen" replacement therapy on menopausal symptoms and blood clotting. Continuous oestrogen-progestogen treatment and serum lipoproteins in postmenopausal women. The effect of estradiol vaginal tablet and conjugated estrogen cream on urogenital symptoms in postmenopausal women: a comparative study. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial. Evaluation of low-dose estrogen and progestin therapy in postmenopausal women. A double-blind, prospective study of sequential versus continuous therapy. Comparison of four continuously administered progestogen plus oestradiol combinations for climacteric complaints. Gonadotropin-releasing hormone analogue plus hormone replacement therapy for the treatment of endometriosis: a randomized controlled trial. Constant estrogen, intermittent progestogen vs. continuous combined hormone replacement therapy: tolerability and effect on vasomotor symptoms. 17 beta-estradiol and norethisterone acetate in low doses as continuous combined hormone replacement therapy.
This study was designed to assess endometrial histology in postmenopausal women not taking hormone replacement therapy, to evaluate side effects and efficacy of phytoestrogens in treating menopause-associated symptoms, and to determine whether 6 months of phytoestrogen supplementation altered endometrial histology.
                We performed a prospective, double-blinded, randomized, placebo-controlled trial comparing the effects of 6 months of dietary phytoestrogen supplementation versus placebo in postmenopausal women. Baseline endometrial biopsies were performed and, if adequate, nonhyperplastic, noncancerous, and nonovulatory, subjects were randomly assigned to receive daily placebo or soy cereal supplementation for 6 months. Study subjects completed baseline and weekly dietary, symptom, and side effect logs. Repeat endometrial biopsies were obtained at 6 months.
                Subjects were recruited from January 1998 through June 2000. Twenty-seven subjects were randomized, and 19 completed the study. One (3.7%) baseline endometrial sample was weakly proliferative. All other baseline and final biopsies were consistent with atrophic, inactive endometrium. The maximum risk of endometrial stimulation with phytoestrogens is 35%. Hot flushes, night sweats, and vaginal dryness were significantly less severe at the final week of the study compared with baseline in the placebo group. Insomnia was more common in the treated group. There were no other statistically significant differences in symptoms or side effects.
                Phytoestrogens did not cause stimulation of the endometrium. Insomnia was more frequent over the 6-month study in the soy group, whereas hot flushes, night sweats, and vaginal dryness improved from baseline in the placebo group but not in the soy group. To analyze the impact of soy protein dietary supplements containing phytoestrogens on menopausal symptoms in healthy postmenopausal women.
                A double-blind, placebo-controlled trial was conducted in 94 healthy postmenopausal women aged 50-75 years, with 44 randomized to soy supplements containing 118 mg of isoflavones (daidzein, genistein, glycitein and their respective glycosides), and 50 to an identically presented casein placebo. A validated questionnaire on menopausal symptoms was administered at baseline and at 3 months of treatment. Compliance was assessed by high-performance liquid chromatography assay of urinary phytoestrogens. Statistical analysis was completed using non-parametric statistical methods and multivariate analysis.
                At baseline 80% of women recruited were experiencing menopausal symptoms, although symptom severity was mild. Those consuming phytoestrogen supplements had 13- and 17-fold increases in urinary excretion of genistein and daidzein, respectively, with no change in the placebo group. Active soy supplements did not significantly alter either individual symptoms or specific symptom category scores when compared to placebo. Within-group comparisons revealed that the active group reported a significant improvement in vaginal dryness (p = 0.01), libido (p = 0.009), facial hair (p = 0.04) and dry skin (p = 0.027). However, similarly, those on placebo reported an improvement in libido (p = 0.015), facial hair (p = 0.014) and dry skin (p = 0.011) but not vaginal dryness.
                In this group of 94 older postmenopausal women with a high frequency of mild menopausal symptoms, 3 months of soy supplements containing phytoestrogens did not provide symptomatic relief compared with placebo. To examine the efficacy of a hop extract enriched in 8-prenylnaringenin (8-PN, the phytoestrogen in hops, Humulus lupulus L.) on relief of menopausal discomforts.
                A prospective, randomized, double-blind, placebo-controlled study over 12 weeks with 67 menopausal women, who were administered a hop extract standardized on 8-PN (100 or 250 microg). The responses were determined by means of a modified Kupperman index (KI) and a patients' questionnaire.
                All groups, including placebo, showed a significant reduction of the KI both after 6 weeks and after 12 weeks. The hop extract at 100 microg 8-PN was significantly superior to placebo after 6 weeks (P=0.023) but not after 12 weeks (P=0.086). No dose-response relationship could be established, as the higher dose (250 microg) was less active than the lower dose both after 6 weeks and after 12 weeks. Still, a trend for a more rapid decrease of KI was noticed for both active groups as compared to placebo. In particular, the decrease in hot flush score (isolated from the KI) was found significant for both treatment groups after 6 weeks (P<0.01) with respect to placebo. Results of the patients' questionnaire were consistent with those of the KI, with the most pronounced effects being observed for the 100-microg treatment.
                Daily intake of a hop extract, standardized on 8-PN as a potent phytoestrogen, exerted favorable effects on vasomotor symptoms and other menopausal discomforts. Hop-derived prenylated flavonoids may provide an attractive addition to the alternative treatments available for relief of hot flushes and other menopausal discomforts. To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study.
                A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate.
                Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted.
                A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates. To determine whether hormone treatment of women during the menopause transition induces changes in body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium.
                Prospective, randomised, placebo-controlled, double-blind, 12-month study, with crossover at 6 months.
                Outpatient clinic of a city hospital.
                105 apparently healthy women in the menopause transition (40-52 years), with menstrual function, who were experiencing minor menopausal symptoms, were selected from the general population by advertising.
                Active arm--oral conjugated oestrogens (0.625 mg daily) and cyclic medroxyprogesterone acetate (10 mg daily) on Day 14-27 of each menstrual cycle; placebo arm--placebos of both medications.
                Excess change from baseline associated with active compared with placebo treatment for all variables; effect of order of treatment.
                Baseline biochemical values were similar for both treatment-order groups, but baseline blood pressures and body weights were higher in the group receiving placebo first. With treatment, there were no differences in overall values for body weight and blood pressure (P > 0.4), and order of treatment had no significant influence (P > 0.3). There were no differences in total and low density lipoprotein cholesterol levels, overall or with order of treatment. Active treatment increased high density lipoprotein (HDL) cholesterol levels (overall and when placebo was given first; P = 0.001), and triglyceride levels (when active treatment was given first; P = 0.03). There was no overall treatment effect, but a significant order-of-treatment effect, on antithrombin III activity (mean levels were decreased by active treatment to a greater extent when it was given first; P = 0.02). The endometrium showed only physiological changes regardless of treatment.
                The lack of significant excess change in anthropometry, lipoprotein levels, antithrombin III activity, and endometrial histology in women given hormone treatment compared with placebo is reassuring. The increase in HDL cholesterol level is an extra benefit. Our study provides conclusive evidence that hormone treatment does not produce weight gain in women during the menopause transition. The aim of this study was to test the hypothesis that increased dietary intake of phytoestrogens reduces the health impact of the menopause. To test this hypothesis, a double-blind, randomized, entry-exit, cross-over study was conducted to assess the effects of three dietary manipulations--soy and linseed diets (high in phytoestrogens) and a wheat diet (low in phytoestrogens). Postmenopausal women were recruited and randomly assigned to one of the three dietary regimens. Urinary phytoestrogen concentrations, hot flush rate, vaginal smears, bone mineral density and bone mineral content were assessed for two 12-week periods. Comparative analysis showed no significant differences, but, when analyzed separately, groups consuming high phytoestrogen diets had between 10 and 30 times higher urinary excretion of phytoestrogens compared to those consuming the low phytoestrogen diet (p < 0.01). Study participants consuming soy, linseed and wheat diets had a 22% (not significant, n.s.), 41% (p < 0.009) and 51% (p < 0.001) reduction in hot flush rate; a 103% (p < 0.04), 5.5% (n.s.) and 11% (n.s.) increase in vaginal cytology maturation index; and a 5.2% (p < 0.04), 5.2% (n.s.) and 3.8% (n.s.) increase in bone mineral content, respectively. No changes were detected in bone mineral density. The differential effects of high phytoestrogen dietary manipulations on outcomes may represent tissue-specific responses to isoflavones and lignans contained in soy and linseed, respectively. Whilst health outcome measures were not significantly different between groups, the data obtained from separate analysis suggest that phytoestrogens in soy and linseed may be of use in ameliorating some of the symptoms of menopause. Furthermore, the significant decrease in hot flush rate in the wheat group cannot be attributable to phytoestrogens measured in this study. Due to subject variability, larger studies are still needed to evaluate population benefit. Clinical trials demonstrating increased risk of cardiovascular disease and breast cancer among women randomized to hormone replacement therapy have increased interest in other therapies for menopausal symptoms. Dietary supplements containing isoflavones are widely used as alternatives to hormonal therapies for hot flashes, but there is a paucity of data supporting their efficacy.
                To compare the efficacy and safety of 2 dietary supplements derived from red clover with placebo in symptomatic menopausal women.
                Randomized, double-blind, placebo-controlled trial of menopausal women, aged 45 to 60 years, who were experiencing at least 35 hot flashes per week. The study was conducted between November 1999 and March 2001 at 3 US medical centers and included women who were recently postmenopausal (mean [SD], 3.3 [4.5] years since menopause) experiencing 8.1 hot flashes per day. Women were excluded if they were vegetarians, consumed soy products more than once per week, or took medications affecting isoflavone absorption.
                After a 2-week placebo run-in, 252 participants were randomly assigned to Promensil (82 mg of total isoflavones per day), Rimostil (57 mg of total isoflavones per day), or an identical placebo, and followed-up for 12 weeks.
                The primary outcome measure was the change in frequency of hot flashes measured by participant daily diaries. Secondary outcome measures included changes in quality of life and adverse events.
                Of 252 participants, 246 (98%) completed the 12-week protocol. The reductions in mean daily hot flash count at 12 weeks were similar for the Promensil (5.1), Rimostil (5.4), and placebo (5.0) groups. In comparison with the placebo group, participants in the Promensil group (41%; 95% confidence interval [CI], 29%-51%; P =.03), but not in the Rimostil group (34%; 95% CI, 22%-46%; P =.74) reduced hot flashes more rapidly. Quality-of-life improvements and adverse events were comparable in the 3 groups.
                Although the study provides some evidence for a biological effect of Promensil, neither supplement had a clinically important effect on hot flashes or other symptoms of menopause. 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. Acute menopausal symptoms occur less frequently in Asian than in Caucasian women. Oestrogen replacement therapy has been shown to be effective in controlling acute symptoms in Caucasians, but the effect of oestrogens is not well documented in Asian women. A randomized, double-blind, placebo-controlled, crossover study of the effect of oral oestradiol on the incidence of acute menopausal symptoms was conducted in 83 Hong Kong Chinese women who had experienced a surgical menopause. Although there was a significant increase in the oestradiol concentration with treatment compared with placebo (P < 0.001), there were no significant differences in the reporting of symptoms between the treatment and placebo groups. There is no obvious explanation for this apparent lack of effect of oestrogen on acute menopausal symptoms in Chinese women. Whilst it may be related to the generally low incidence of symptoms or to a higher dietary intake of phytoestrogens in Chinese women, further studies are necessary to explain these findings. Pueraria lobata (PL) is used as a traditional Chinese herbal remedy for menopausal symptoms, as well as an ingredient in preparations for conditions affecting menopausal women, such as osteoporosis, coronary heart disease, and some hormone-dependent cancers. The scientific basis for its action may be its action as a phytoestrogen.
                To examine the effects of PL in comparison with hormone replacement therapy (HRT) on lipid profile, sex hormone levels, bone turnover markers, and indices of cognitive function. For the study, 127 community-living, postmenopausal women aged 50 to 65 years were randomized to receive HRT (n = 43), PL (equivalent to 100 mg isoflavone; n = 45), or no treatment (n = 39) for 3 months. The following measurements were carried out at baseline and after 3 months for all participants: menopausal symptoms questionnaire; neuropsychological tests covering memory, attention, motor speed, and word-finding ability; quality of life (SF36); lipid profile; urinary deoxypyridinoline; dietary phytoestrogen intake and urinary phytoestrogen; estradiol; follicle-stimulating hormone; and luteinizing hormone.
                Only participants in the HRT group showed a mean reduction in cholesterol and low-density lipoprotein cholesterol that was significantly different from that of the control group. No significant changes in lipid profile or follicle-stimulating hormone and luteinizing hormone were observed in the PL group compared with the controls. However, both the HRT and PL groups showed an improvement in Mini-Mental State Examination score and attention span compared with the case of participants receiving no treatment. HRT and PL had different effects on cognitive function; HRT improved delayed recall, whereas flexible thinking seemed improved in the PL group.
                This study was unable to demonstrate a scientific basis for the use of PL for improving the health of postmenopausal women in general. However, the effect of PL on cognitive function deserves further study. To determine whether treatment of endometriosis with a GnRH analogue (GnRH-a; goserelin) combined with continuous estrogen and progestogen hormone replacement therapy (HRT) would prevent the hypoestrogenic effects, including loss of bone density, while maintaining efficacy for treatment of endometriosis.
                Randomized controlled trial.
                Fifty premenopausal women with laparoscopically diagnosed endometriosis (revised American Fertility Score for endometriosis implants equal to four or greater) and significant symptoms of dysmenorrhoea, dyspareunia, and other pelvic pain.
                Patients were randomized to receive either goserelin alone, 3.6 mg SC depot every 4 weeks for 24 weeks, or goserelin, 3.6 mg SC depot every 4 weeks for 24 weeks, plus HRT (25 micrograms transdermal 17 beta E2 daily and 5 mg medroxyprogesterone acetate orally daily) for 20 weeks commencing with the second goserelin injection.
                There was a significant reduction in the extent of pelvic endometriosis in both groups, with no difference between the groups. Both groups experienced an improvement in symptoms and signs, again with no difference between groups. Hypoestrogenic side effects of hot flushes and loss of libido were significantly less in the group that received HRT. The amount of bone mineral density loss was significantly less in the HRT group at the lumbar spine, although it was not prevented completely.
                The addition of HRT to GnRH-a for the treatment of endometriosis did not reduce the efficacy of treatment, and adverse hypoestrogenic effects were decreased, although not abolished. In a double-blind, placebo-controlled study, 109 patients suffering from local and vasomotor postmenopausal complaints were randomly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol (E3) or a placebo. The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially, followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period. The effectiveness of the therapy was assessed on the basis of questionnaires (Kupperman index for vasomotor complaints and an original urogenital index for local complaints) and gynaecological examinations which included assessments of vaginal cytology, vaginal pH and Döderlein bacilli. To rule out induced endometrial proliferation, endometrial biopsies were performed in 50 women before and after the study. The vaginal depot (E3) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints, including hot flushes. Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation. Taking into account the minimal rate of adverse effects, the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints. This study compared two continuous-combined hormone replacement therapy (HRT) formulations, 1 mg estradiol (E2)/0.25 mg norethisterone acetate (NETA) and 1 mg E2/0.5 mg NETA, with placebo, with regard to the efficacy for vasomotor symptom relief in menopausal women.
                A total of 119 women aged 45-61 years with moderate and severe hot flushes and with amenorrhea for at least 3 months were randomly assigned to 12 weeks' treatment with 1 mg E2/0.25 mg NETA, 1 mg E2/0.5 mg NETA or placebo. The number and severity of hot flushes, as well as any vaginal bleeding, were recorded on a daily basis. The Kupperman Menopausal Index, Greene Climacteric Scale and visual analog scales for various symptoms were assessed before and after treatment. Subpopulation analysis according to menopausal status was performed.
                Both combinations significantly reduced the number and severity of hot flushes, compared to placebo. A reduction of approximately 85% in vasomotor symptomatology occurred in the two combination groups by week 4 of treatment, and this was further diminished throughout the study to approximately 97% reduction by week 12. At the end of the study, 85% of the women receiving 1 mg E2/0.5 mg NETA and 71% of the women receiving 1 mg E2/0.25 mg NETA were considered to the clinically adequate responders to treatment. Both combinations were associated with significant improvements, compared to placebo, in visual analog scales for overall general condition, Kupperman Menopausal Index, and Greene Climacteric vasomotor and psychological subscales. While both combinations resulted in similar bleeding profiles in postmenopausal women, the combination of 1 mg E2/0.5 mg NETA resulted in the lowest incidence of bleeding in late perimenopausal women.
                The combinations of 1 mg E2/0.25 mg NETA and 1 mg E2/0.5 mg NETA rapidly relieve vasomotor symptoms and are efficacious in the majority of menopausal women, including those with severe hot flushes. This study aimed to evaluate the effects of monophasic estrogen-progestogen therapy on the sexuality and climacteric symptoms of postmenopausal women.
                A prospective, randomised, double-blind, crossover, placebo-controlled, single-centre study was carried out over a total of 12 consecutive months in 40 postmenopausal women with an intact uterus who had no contraindications to hormone therapy. Patients received 17beta-estradiol 2mg in combination with norethisterone acetate 1mg (Cliane) daily for 6 months or one placebo tablet daily for 6 months. The tablets were identical in appearance. After 6 months, the groups were crossed over and the patients were followed up for another 6 months. The groups were homogenous with respect to age, height, bodyweight, body mass index and race. For the statistical analysis, the group receiving hormone therapy was referred to as group A and the placebo group was designated group B, irrespective of the placebo/hormone therapy sequence.
                In group A there were fewer hot flashes (F=22.85, p<0.01) and an improvement in sexual interest (F=5.55, p<0.05). The sequence in which the medication was received resulted in a statistically significant difference with respect to dyspareunia (F=9.65, p<0.01) and satisfaction with the duration of penetration (F=6.58, p<0.05). In the intrapatient analysis of variation with respect to orgasmic capability and the presence of dialogue with partner regarding the couple's sexual life, whether the placebo was taken prior to or following hormone therapy was significant (F=17.12, p<0.001 and F=7.10, p<0.05, respectively).
                Monophasic estrogen-progestogen therapy has a beneficial effect on sexuality and on hot flashes in postmenopausal women. Fifty-five depressed menopausal patients took part in a randomized double-blind cross-over trial using ;Harmogen' (piperazine oestrone sulphate) and placebo. The Beck depression inventory, hot flush counts, and patients' subjective assessment of well-being were used to assess clinical status. Hormonal, biochemical and coagulation profiles were carried out. Hot flushes improved significantly on oestrogen compared with placebo. Depression scores and well-being showed significant and equal improvement on oestrogen and placebo. Significant improvement in flushes in patients on placebo was observed in the first half of the trial but did not occur in the second half, in patients who had previously taken oestrogen. No significant changes occurred in biochemistry. Coagulation tests showed acceleration of the prothrombin time in patients taking ;Harmogen' compared with those on placebo. Piperazine oestrone sulphate is a relatively weak but safe oestrogen preparation, effective in treatment of vasomotor symptoms but no more effective than placebo in the treatment of depression. The purpose of this study was to evaluate the isolated and associated effects of estrogen therapy (estradiol valerate 1 mg/d orally) and physical exercise (moderate aerobic exercise, 3 h/wk) on health-related quality of life (HRQOL) and menopausal symptoms among women who had undergone hysterectomy.
                A 6-month, randomized, double-blind, placebo-controlled clinical trial with 44 postmenopausal women who had undergone hysterectomy. The interventions were physical exercise and hormone therapy (n = 9), being sedentary and hormone therapy (n = 14), physical exercise and placebo (n = 11), and being sedentary and placebo (n = 10). HRQOL was assessed by a Brazilian standard version of the Medical Outcome Study Short-Form Health Survey and symptoms by Kupperman Index at baseline and after 6 months.
                There was a decrease in symptoms in all groups, but only groups who performed physical exercise showed an increase in quality of life. Analysis of variance showed that changes in physical functioning (P = 0.001) and bodily pain (P = 0.012) scores over the 6-month period differed significantly between women who exercised and women who were sedentary, regardless of hormone therapy. Hormone therapy had no effect, and there was also no significant association between physical exercise and hormone therapy in HRQOL.
                Physical exercises can reduce menopausal symptoms and enhance HRQOL, independent of whether hormone therapy is taken. In a double-blind study on the value of equine ("natural") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months' hormone treatment followed by three months' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended. Serum lipids and lipoproteins were examined in 44 healthy postmenopausal women every 3 months during 1 year of treatment with either continuous oestrogen-norethisterone acetate or placebo. Total serum cholesterol and LDL-cholesterol levels were reduced by approximately 15% and 20% (P less than 0.001), respectively in the hormone group but were unchanged in the placebo group. Serum triglycerides levels remained constant in both groups. HDL-cholesterol levels were significantly reduced by approximately 10% in the hormone group but significant reductions of 5-10% also occurred in the placebo group so that differences between the two groups were only significant after 3 months of treatment. Vaginal bleedings were experienced during the first 3 months by eight of the 21 women receiving hormones, but in only one woman after 9 months of therapy. The addition of norethisterone acetate to postmenopausal oestrogen therapy in clinically relevant doses had no adverse effects on lipoproteins as previously reported, even though administered continuously. Moreover, the low frequency of bleeding with continuous oestrogen-progestogen therapy would make this an appropriate alternative in postmenopausal replacement therapy. To compare the effects of estradiol vaginal tablet with conjugated estrogen cream on urogenital symptoms, vaginal health index, vaginal cytology, endometrial thickness, and plasma estradiol level in postmenopausal women.
                Fifty-three women with urogenital symptoms were randomized to local vaginal treatment of 25 microg estradiol tablet or 1 g of conjugated estrogen cream for 12 weeks. They were assessed for urogenital symptoms, vaginal health index, vaginal cytology, endometrial thickness and estradiol level.
                Forty-eight women completed the treatment. Both groups showed improvement of urogenital symptoms, vaginal health index, and vaginal cytology after the first 4 weeks of treatment. Conjugated estrogen cream showed superior efficacy in alleviating vaginal dryness and dyspareunia. Two cases of endometrial proliferation were noted.
                Estradiol vaginal tablet and conjugated estrogen cream were effective in treating urogenital symptoms, the restoration of normal vaginal epithelium and reduction of vaginal pH in postmenopausal women. However, 2 cases of endometrial proliferation were noted. The primary aim was to assess whether the use of an isoflavone extract containing 40 mg or 160 mg of total isoflavones affects the frequency of menopausal flushes and other symptoms. The secondary aims were assessments of possible effects on menopause symptom scores and biological measures of estrogen activity.
                A randomized, double-blind, placebo-controlled prospective trial of 37 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period. The women were randomized to three treatment groups: placebo, 40 mg or 160 mg, delivered in tablet form.
                There was no significant difference in the incidence of flushes between the three groups at trial conclusion. There was no difference between the groups in Greene Menopause Symptom Scores, vaginal pH, levels of follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG) or total cholesterol, liver function or blood parameters. A statistically significant increase in high-density lipoprotein (HDL) cholesterol of 18.1% (p = 0.038) occurred in the 40-mg group.
                A large placebo response and inadvertent use of dietary isoflavones in the placebo group may have obscured a significant change in flushing frequency. Previous uncontrolled studies claiming a beneficial effect of foods with a high isoflavone content on menopausal symptoms may have been confounded by a large placebo response. 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. In this prospective, double-blind study, we evaluated the efficacy and safety of low-dose estrogen and progestin replacement therapy in 36 postmenopausal women who were administered oral medroxyprogesterone acetate (MPA) cyclically or continuously in combination with conjugated equine estrogen (CEE) 0.625 mg daily. In the sequential group, MPA (5.0 mg) was administered daily for 12 days of each 25-day treatment cycle. In the two continuous groups, MPA was administered without interruption at a daily dose of either 2.5 mg or 5.0 mg for 12 treatment cycles. Of the 36 women in the study, 29 women completed the one-year protocol. The clinical and metabolic responses were assessed before and every three cycles during the 12 cycles of treatment. Endometrial biopsies and lumbar bone density scans were performed before and during the last week of the 12th treatment cycle. Vasomotor and urogenital symptoms improved in all women. Cyclic menstrual bleeding occurred in all patients on sequential therapy, and proliferative endometrium was noted in two of these women. All patients in both continuous treatment groups experienced amenorrhea after the fifth cycle of therapy, and all endometrial biopsies were atrophic or inactive. From the 3rd through the 12th month of cycle, favorable lipid and lipoprotein changes occurred in all treatment groups. Lumbar bone mineral density improved significantly (P < .05) by an average of 6.41% in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) Sixty women with climacteric complaints who had not menstruated for at least 1 year were randomly allocated to receive one of four hormonal replacement regimens. All four formulations were administered daily and continuously and each contained 2 mg of micronized oestradiol-17 beta in combination with either norethisterone acetate 1 mg (group A) or 0.5 mg (group B) or megestrol acetate 5 mg (group C) or 2.5 mg (group D). The clinical efficacy was the same although the alleviation of vasomotor symptoms was somewhat slower in those women receiving preparation A. The endometrium was atrophied in nearly all biopsies. Irregular uterine bleeding was almost entirely confined to the earlier phase of the study and was substantially less with the formulation containing 1 mg norethisterone acetate. It is concluded that a continuous oestradiol-progestogen combination can be used for long-term treatment of climacteric complaints in postmenopausal women and that after 4 months the clinical efficacy is the same irrespective of the type and dose of progestogen administered. The aim of this study was to determine whether or not continuous combined HRT used with GnRH-a for the treatment of endometriosis can prevent hypoestrogenic side effects associated with GnRH-a.
                Forty premenopausal women with laparoscopically proven endometriosis entered the study. The patients were randomized into two groups. Group I (n = 19) received 3.75 mg i.m. leuprolide acetate (LA) every 4 weeks for 24 weeks. Group II (n = 21) received 3.7 mg LA combined with 1.25 mg oral conjugated equine estrogen (CEE) and 5 mg oral medroxyprogesterone acetate (MA).
                Total revised AFS score as well as total pelvic pain scores decreased significantly (P < .001) in both groups. However, a statistically significant difference of hot flushes and sweating was reported by women receiving LA + HRT as compared to those treated with LA alone (P < .001). Furthermore, the bone loss at the lumbar spine was 4.2% in group I compared to 0.9% in group II at the end of the study.
                This study suggests that 1.25 mg CEE + 5 mg MA is effective in preventing hypoestrogenic side effects caused by GnRH-a, while the treatment of endometriosis is not impaired. To compare the efficacy and tolerability of a novel oral constant estrogen plus intermittent progestogen hormone replacement therapy (HRT) regimen to a continuous combined HRT regimen in postmenopausal women.
                Subjects were randomly assigned to receive treatment with either constant 17beta-estradiol (E2), 1 mg, plus intermittent norgestimate (NGM) 90 microg (3 days off, 3 days on) (n=221) or E2 2 mg/norethisterone acetate (NETA) 1 mg (n=217) for 1 year. Treatments were evaluated based on the incidence of hot flushes and uterine bleeding.
                Both regimens had similar bleeding profiles and provided comparable vasomotor symptom relief. However, breast discomfort and edema were experienced by twice as many subjects who received E2/NETA.
                The constant E2/intermittent NGM regimen was well tolerated and possesses similar efficacy compared with a continuous combined E2/NETA regimen and may be considered whenever HRT without withdrawal bleeding is deemed appropriate. To evaluate low doses of 17 beta-estradiol (E2) and norethisterone acetate (NETA) as continuous combined hormone replacement therapy (HRT) in their effects on vasomotor symptoms, bleeding episodes, endometrial histology and mastalgia.
                Sixty postmenopausal women were randomly allocated to three treatment groups and were given 1 mg E2 and 0.25 mg NETA (A), 1 mg E2 and 0.5 mg NETA (B) and 2 mg E2 and 1.0 mg NETA (C) in daily doses. The treatment period was 1 year.
                A similar statistically significant reduction of climacteric symptoms (P < 0.05) was found in all groups. Bleedings, mainly as spottings, occurred most commonly during the first treatment months. Fewer bleeding episodes and a higher percentage of amenorrhea was noted in group B compared to the other groups but did not reach statistical significance. All endometrial biopsies showed atrophy. Women in group A and B had less severe mastalgia (P < 0.05) compared to group C, given higher doses of steroids.
                Postmenopausal women taking 1 mg of E2 plus 0.5 mg NETA as continuous combined HRT reported a marked reduction of climacteric complaints and good bleeding control. No endometrial proliferation was detected after 1 year of treatment. This type of therapy may be beneficial especially for elderly women, in whom bleeding may be annoying.
There is no evidence of effectiveness in the alleviation of menopausal symptoms with the use of phytoestrogen treatments.