Benefits of soy germ isoflavones in postmenopausal women with contraindication for conventional hormone replacement therapy

Objective: To evaluate the effects of isoflavones on vasomotor symptoms and blood lipids in postmenopausal women with contraindication for conventional hormone replacement therapy (HRT). Methods: This prospective, double-blind and placebo-controlled study included 50 postmenopausal women randomly divided into two groups: 25 women on soy germ isoflavones (60 mg per day, capsules) and 25 women on placebo. Inclusion criteria included: non-vegetarian, non-asian women whose last menstruation dated at least 12 months prior to the beginning of the study, with FSH>40 mIU/ml, hot flushes and contraindication for HRT, not using tamoxifen or antibiotic and no disease of the gastrointestinal tract. For 6 months, the Kupperman menopausal index (KMI), the vaginal cytological maturation value (MV) and both hormonal and lipid profiles were assessed. The t-test and analysis of variance (ANOVA) were employed to compare the two groups. Results: In both groups, a decreased KI rate was observed. However, isoflavone was significantly superior to placebo in reducing hot flushes (44% versus 10%, respectively) (P<0.05). After 6 months, the isoflavone group showed increased estradiol levels with unchanged FSH, LH, and vaginal cytology, and a reduction of 11.8% in LDL and an increase of 27.3% in HDL (P<0.05). In the placebo group, just a reduction in MV was observed after 6 months (P<0.05). Conclusions: Soy germ isoflavone exerted favorable effects on vasomotor symptoms and lipid profile, showing itself to be an interesting alternative therapy for the postmenopausal women with contraindication for conventional HRT.     

Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal women: a multicenter, double-blind, randomized, placebo-controlled study

OBJECTIVE: To determine the safety and efficacy of an oral soy isoflavone extract for relief of menopausal hot flushes. DESIGN: This was a double-blind, randomized, parallel group, outpatient, multicenter (15 sites) study. A total of 177 postmenopausal women (mean age = 55 years) who were experiencing five or more hot flushes per day were randomized to receive either soy isoflavone extract (total of 50 mg genistin and daidzin per day) or placebo. Physical examinations and endometrial and biochemical evaluations were performed upon admission and completion. Body weight, symptoms, and safety were evaluated at all visits. RESULTS: Relief of vasomotor symptoms was observed in both groups. Decreases in the incidence and severity of hot flushes occurred as soon as 2 weeks in the soy group, whereas the placebo group experienced no relief for the first 4 weeks. Differences between evaluable subjects in both groups were statistically significant over 6 weeks (p = 0.03). Over 12 weeks, between-group differences approached significance (p = 0.08). Endometrial thickness evaluated by ultrasound, lipoproteins, bone markers, sex hormone-binding globulin and follicle-stimulating hormone, and vaginal cytology did not change in either group. CONCLUSIONS: Soy isoflavone extract was effective in reducing frequency and severity of flushes and did not stimulate the endometrium. Soy isoflavone extracts provide an attractive addition to the choices available for relief of hot flushes.     

Effects of a standardized soy extract on hot flushes: a multicenter,double-blind,randomized, placebo-controlled study

OBJECTIVE: To investigate the effect of an oral soy isoflavone extract (Phytosoya) on hot flushes in menopausal women. DESIGN: The study was conducted on outpatients according to a multicenter, randomized, double-blind, placebo-controlled, parallel-group design. A total of 75 patients in natural or surgical menopause suffering from at least seven hot flushes per day were randomized to receive during 4 months either soy isoflavone extract (total of 70 mg genistin and daidzin per day) or placebo. RESULTS: There is evidence to suggest that 16 weeks of treatment with soy extract can help reduce the mean number of hot flushes per 24 hours in menopausal women. Withdrawals during this trial made it difficult to obtain an unbiased estimate of the true treatment effect, but numerous sensitivity analyses lend support to the suggestion that taking soy extract can be beneficial in the treatment of hot flushes. In particular, women taking soy extract had a 38% reduction in the mean number of hot flushes by week 4 and a 51% reduction by week 8. By the end of week 16, patients taking soy extract had a 61% reduction in their daily hot flushes versus a 21% reduction obtained with the placebo. "Responders" (defined as patients whose hot flushes were reduced by at least 50% at the end of treatment period) were 65.8% in the soy extract group and 34.2% in the placebo group ( < 0.005). CONCLUSION: Soy isoflavone extract may help to reduce the frequency of hot flushes in climacteric women and provides an attractive addition to the choices available for relief of hot flushes.     

Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study

OBJECTIVE: The aim of this study was to evaluate the effects of isoflavone on the climacteric symptoms (Kupperman Menopausal index), vaginal pH, vaginal cytology (vaginal maturation index) and endometrium (evaluated by ultrasound and biopsy) in postmenopausal women. METHODS: It was a single-center, 6-month, randomized, double-blind, estrogen-controlled trial. Seventy-nine women were randomly assigned to one of the two treatment groups: isoflavone (n=40): 300 mg of the standardized soy extract with a medium dose of 120 mg isoflavones/day as glycoside and aglycone (60 mg twice a day), or estrogen (n=39): one capsule of 0.625 mg conjugated equine estrogens and other capsule with glucose 0.625 mg (placebo). RESULTS: After treatment, there was a decrease in the symptomatology in both estrogen and isoflavone groups. There was a significant decrease in vaginal pH, an increase in superficial vaginal cells and endometrium proliferation after 3 and 6 months of treatment in the estrogen group, but no differences were observed in the isoflavone group for these variables. CONCLUSIONS: We concluded that the daily standardized soy extract with 120 mg isoflavones' effect on symptoms was similar to that from estrogen. Soy isoflavone has no effect on endometrium and vaginal mucosa during the treatment.     

Clinical effects of a standardized soy extract in postmenopausal women: a pilot study

OBJECTIVE: This double-blind, randomized study was aimed at evaluating comparatively, in postmenopausal women, the activity of a standardized soy extract (SOYSELECT) and placebo when given alone or in combination with conjugated equine estrogens (CEE) on early climacteric symptoms. Lipid profile, pituitary hormones, osteocalcin and endothelin levels, and vaginal and endometrial parameters were also evaluated. DESIGN: Participants in the control group were given placebo, and participants in the treated group were given 400 mg/day of a standardized soy extract, corresponding to 50 mg/daily of isoflavones. After 6 weeks of treatment, CEE was also then given to each participant at a dose of 0.625 mg/day for 4 weeks. At the end of this period, soy and placebo treatment were suspended, and, until the end of the study (week 12), participants were administered 10 mg/day of medroxyprogesterone acetate in association with CEE (0.625 mg/day). RESULTS: When compared with pretreatment data, on week 6 of the study, a significant (p < 0.01) reduction in the mean number of hot flushes per week was observed in participants who were receiving the standardized soy extract, whereas a more marked relief was observed in both soy and placebo groups during CEE administration. Concurrently, the severity of hot flushes, assessed by means of the Greene climacteric scale, was also reduced in the soy group participants (p < 0.001, by paired t-test). No soy-related changes were observed on vaginal cytology, endometrial thickness, uterine artery pulsatility index, or metabolic and hormonal parameters tested. Finally, CEE-related changes on genital tract, uterine vascular compartment, and pituitary hormones were not modified by soy treatment. CONCLUSIONS: SOYSELECT may be a safe and efficacious therapy for relief of hot flushes in women who refuse or have contraindications for hormone replacement therapy.     

Chilliness: a vasomotor symptom in Japan

OBJECTIVE: To examine the differences between biomedical and Japanese women's concepts of vasomotor symptoms and the relationships between the symptom of chilliness (hieshō) and menopause status, other vasomotor symptoms, and environmental factors such as soy isoflavone intake and exposure in Japan. DESIGN: Participants were healthy Japanese women, aged 45 to 55, living in Kyoto and Fukushima prefectures, divided into menopausal groups based on menstrual patterns. Women recalled 82 general health symptoms during the previous 2 weeks and collected finger-prick dried blood spots and matched 24-hour dietary records, which were analyzed, respectively, for isoflavone concentration by high-performance liquid chromatography coulometric electrode array detection and for soy isoflavone intake using a Japanese phytochemical database. RESULTS: An examination of kōnenki (Japanese for climacteric) symptoms suggests that chilliness (hieshō), which was reported by 29.3% of participants compared with a range of 3.0% to 22.1% for hot flushes, constitutes an important vasomotor symptom. Chilliness prevalence differed significantly between premenopausal and other menopausal status groups, with positive correlations with other estrogen-influenced sexual-vasomotor symptoms and negative correlations with isoflavone concentrations. Negative correlations with soy isoflavone intake were also found for sweating, although not for nobose and hoteri (two Japanese terms for hot flush). CONCLUSIONS: Chilliness seems to be a more important vasomotor symptom than hot flushes and sweats in Japanese women and may reflect differing thermoregulatory physiology, possibly influenced by dietary soy.     

Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms

PURPOSE: This study was conducted to investigate the efficacy of black cohosh (Cimicifuga racemosa) and St. John's wort (Hypericum perforatum) in women with climacteric symptoms, and to assess their effects on vaginal atrophy, hormone levels, and lipid profiles. MATERIALS AND METHODS: In this double-blind randomized, placebo-controlled, multicenter study, 89 peri- or postmenopausal women experiencing climacteric symptoms were treated with St. John's wort and black cohosh extract (Gynoplus), Jin-Yang Pharm., Seoul, Korea) or a matched placebo for 12 weeks. Climacteric complaints were evaluated by the Kupperman Index (KI) initially and at 4 and 12 weeks following treatment. Vaginal maturation indices, serum estradiol, FSH, LH, total cholesterol, HDL- cholesterol, LDL-cholesterol, and triglyceride levels were measured before and after treatment. From the initial 89 participants, 77 completed the trial (42 in the Gynoplus group, 35 in the placebo group). RESULTS: Baseline characteristics were not significantly different between the two groups. Mean KI scores and hot flushes after 4 and 12 weeks were significantly lower in the Gynoplus group. Differences in superficial cell proportion were not statistically significant. HDL levels decreased in the control group from 60.20 +/- 16.37 to 56.63 +/- 12.67, and increased in the Gynoplus group from 58.32 +/- 11.64 to 59.74 +/- 10.54; this was statistically significant (p=0.04). CONCLUSION: Black cohosh and St. John's wort combination was found to be effective in alleviating climacteric symptoms and might provide benefits to lipid metabolism.     

Polyunsaturated fatty acids (PUFAs) might reduce hot flushes: an indication from two controlled trials on soy isoflavones alone and with a PUFA supplement

OBJECTIVES: To investigate the effect on hot flushes of a soy isoflavone extract alone (Study A) and with the addition of a supplement of polyunsaturated fatty acids, PUFAs (Study B). METHODS: Subjects were postmenopausal women (29 in Study A, 28 in Study B) with more than five troublesome hot flushes per day. Both studies were double-blind randomized placebo-controlled trials with cross-over design, of 24-week duration. After a 2-week observation period, they were randomized to receive two capsules per day providing 60mg of isoflavones or placebo for 12 weeks; thereafter, women who had taken isoflavones were given placebo for a second 12-week period, and vice-versa. Women in the Study B were given also two capsules per day containing a PUFA supplement for the entire 24-week test period. RESULTS: Both studies showed the isoflavone extract to have no greater efficacy on hot flushes than the placebo. During the 24 weeks of the Study B there was a progressive and highly significant reduction in the number of hot flushes, independent of whether the women had begun with isoflavones or with placebo. CONCLUSION: In these two trials the isoflavone extract did not show greater efficacy on the hot flushes than the placebo. The reduction of hot flushes observed in the Study B might be due to the PUFA supplement. PUFAs, particularly Omega (Omega) 3-fatty acids, could reduce hot flushes through their influence on neuronal membranes and/or the modulation of the neurotransmitter function and the serotoninergic system. Studies specifically designed to document the action of PUFAs on hot flushes would be welcome.     

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study

OBJECTIVE: To evaluate in a 12-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium. DESIGN: A total of 389 participants met the main study criteria and were randomly assigned to receive the phytoestrogen genistein (n=198) or placebo (n=191). About 40% of participants in both groups did not suffer from hot flushes, and the evaluation was performed in a subgroup of 247 participants (genistein, n=125; placebo, n=122). Reductions from baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells. RESULTS: There were no significant differences in age, time since menopause, body mass index, and vasomotor symptoms between groups at baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). The effect was already evident in the first month and reached its peak after 12 months of genistein therapy (-56.4% reduction in the mean number of hot flushes). Furthermore, there was a significant difference between the two groups at each evaluation time (1, 3, 6, and 12 months). No significant difference was found in mean endometrial thickness and maturation value score between the two groups, either at baseline or after 12 months. CONCLUSIONS: The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on endometrium.     

Efficacy and safety of oral estriol for managing postmenopausal symptoms

OBJECTIVE: to assess the therapeutic efficacy and safety of oral estriol for the treatment of climacteric symptoms in postmenopausal women. METHODS: 68 postmenopausal women with climacteric symptoms received oral estriol, 2 mg/day, daily for 12 months. We evaluated the degree of climacteric complaints with estriol therapy; serum levels of gonadotropins, estradiol (E2) and lipids; biochemical markers of bone metabolism; blood pressure; and side effects both at baseline and during treatment. Climacteric symptoms were assessed according to the menopausal index (MI), a version of the Kupperman index that had been modified for Japanese women. RESULTS: oral estriol therapy significantly reduced total MI scores. The greatest relief was noted for hot flushes, night sweats, and insomnia. Estriol treatment significantly lowered serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations but did not affect any of the other parameters (lipids, bone, liver and blood pressure) during the study period. Slightly vaginal bleeding occurred in 14.3% of those who underwent natural menopausal women. Histologic evaluation of the endometrium and ultrasound assessment of the breasts following 12 months of estriol treatment found normal results in all women. CONCLUSION: Estriol is a safe and effective alternative for relieving climacteric symptoms in postmenopausal Japanese women.     

Effect of soy isoflavone protein and soy lecithin on endothelial function in healthy postmenopausal women

OBJECTIVE: To assess the effects of soy isoflavone protein concentrate and soy lecithin on endothelial function, measured as flow-mediated dilation (FMD) of the brachial artery in healthy postmenopausal women. DESIGN: This was a randomized, double-blind, placebo-controlled crossover trial with 25 participants (mean age, 61 years; body mass index, 25.46 kg/m2). The women underwent endothelial function testing at baseline and after 4 weeks of randomly assigned treatment with intervening 4-week washout periods. Treatment assignments included soy isoflavone protein (25 g/day) and soy lecithin (20 g/day), soy isoflavone protein (25 g/day) and placebo lecithin, placebo protein and soy lecithin (20 g/day), and double placebo. FMD and serum lipid levels were assessed at baseline and the end of each 4-week treatment phase. RESULTS: Twenty-two women completed the trial. No statistically significant (P > 0.05) difference was seen in FMD between treatment groups. A trend was suggested with FMD highest after treatment with soy protein plus lecithin (7.50 +/- 9.85), followed by soy protein (5.51 +/- 10.11), soy lecithin (5.35 +/- 6.13), and lowest after placebo (4.53 +/- 7.84). Soy isoflavone protein and soy lecithin significantly increased the high-density lipoprotein/low-density lipoprotein ratio (soy isoflavone protein plus soy lecithin, 0.64 +/- 0.19, P < 0.0001; soy isoflavone protein plus placebo lecithin, 0.58 +/- 0.17, P = 0.0058; placebo protein plus soy lecithin, 0.65 +/- 0.18, P < 0.0001) relative to the baseline value (0.49 +/- 0.15). CONCLUSIONS: In this sample of healthy postmenopausal women, soy isoflavone protein and soy lecithin significantly improved the lipid profile. A favorable influence on endothelial function could not be confirmed.     

Efficacy of citalopram on climacteric symptoms

OBJECTIVE: The aim of this study was to evaluate the efficacy of citalopram for climacteric symptoms and to assess the combined effect of citalopram and hormone therapy (HT) on climacteric symptoms in women inadequately responsive to HT alone. DESIGN: The study included 100 postmenopausal women who were allocated into one of four groups: (1) citalopram, (2) placebo, (3) citalopram+HT, or (4) placebo+HT. The women who were unable or unwilling to take HT were randomly placed in groups 1 and 2. The women who were inadequately responsive to HT were randomly placed in groups 3 and 4. The initial dose of citalopram was 10 mg/day in groups 1 and 3. After 1 week, the dose was increased to 20 mg/day. After starting the medication, follow-up visits took place during the fourth and eighth weeks of treatment. During the first and eighth weeks, women completed two questionnaires: a modified Kupperman index and the Menopause-Specific Quality of Life Questionnaire. RESULTS: Mean hot flash scores significantly improved in all groups (P<0.05). The reduction rates were 37% in group 1, 13% in group 2, 50% in group 3, and 14% in group 4. Psychosocial complaints and mean values on the Kupperman index significantly decreased in all groups (P<0.05). Physical well-being significantly improved in groups 1, 3, and 4 (P<0.05). The decrease in all scores was significantly greater in groups 1 and 3 compared to groups 2 and 4 (P<0.01). CONCLUSION: Citalopram is an effective alternative treatment option for patients who do not want to take HT for the alleviation of climacteric symptoms. Adjuvant treatment with a selective serotonin reuptake inhibitor increases the effectiveness of HT for the treatment of climacteric symptoms in women who had responded inadequately to HT.     

Efficacy and tolerability of a new 7-day transdermal estradiol patch versus placebo in hysterectomized women with postmenopausal complaints

OBJECTIVES: To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch (Fem7, Merck KGaA, Germany) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo. DESIGN: A multicentre, randomized, double-blind study with an initial screening phase (phase I), a 3-month double-blind placebo-controlled phase (phase II) and a 3-month open follow-up phase (phase III). METHODS: 186 patients were randomized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up (total duration; 6 months). The changes in Kupperman Index (primary efficacy variable), hot flushes and urogenital symptom score were studied from baseline to the end of the study. In addition, skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy. RESULTS: A reduction in Kupperman Index was observed in both groups, and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo (last value vs. baseline P = 0.0006). From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group. The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase (mean weekly hot flush reduction at the end of the placebo-controlled treatment phase: -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo, P = 0.0025). The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1-3 and 4-7. Subjective acceptance of the 7-day-Estradiol patch was good and 72.4% of patients who took active medication throughout the study were willing to consider continuing its use. CONCLUSIONS: The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women, with a rapid onset of action and 7-day duration of therapeutic effect. Although a placebo effect was observed, the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period.     

Gabapentin for the management of hot flushes: a case series

OBJECTIVE: To audit the effectiveness of the anticonvulsant gabapentin on hot flushes in postmenopausal women. DESIGN: This was an open case series involving 11 postmenopausal women who were willing to take gabapentin for the relief of their hot flushes and were willing to keep a diary recording the number and intensity of their hot flushes, both before and during treatment. Gabapentin was started at a dose of 300 mg, to be taken at night, and the women were instructed to increase the dose up to 1,200 mg, according to symptom behavior. RESULTS: Eleven women agreed to participate for on average 53.22 days (range, 2-79 days), but two discontinued participation-one before starting treatment and one after 2 days-so there are complete data sets for nine women. Gabapentin was found to be extremely effective in reducing hot flush activity (P < 0.001; Fig. 1). A significant reduction in symptoms was observed with a dose of 300 mg/day (P < 0.001). Scores on the Green Climacteric Scale were significantly improved from a mean of 25.72 (range, 12-42) to 19.25 (range, 13-31; P < 0.001). Palpitations (P = 0.001), panic attacks (P = 0.0001), mood (P = 0.023), muscle and joint pains (P = 0.021), and paresthesias and loss of sensation in the extremities (P = 0.001) were also shown to improve with treatment. CONCLUSIONS: In the present case series, gabapentin was well tolerated and could be a valuable alternative for the treatment of hot flushes in women with contraindications to hormonal replacement therapy. It would be particularly beneficial for women in whom aches and pains and paresthesias are also a significant feature of the climacteric syndrome.     

Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo

OBJECTIVES: To investigate the effectiveness and safety of a red clover isoflavone dietary supplement (Promensil, Novogen Ltd., Australia) versus placebo on the change in hot flush frequency in postmenopausal women. METHODS: In this randomized, double blind, placebo-controlled trial 30 women with more than 12 months amenorrhoea and experiencing more than five flushes per day were enrolled. All received single blind placebo tablets for 4 weeks and were subsequently randomized to either placebo or 80 mg isoflavones for a further 12 weeks. Efficacy was measured by the decrease in number of hot flushes per day and changes in Greene Climacteric Scale Score. RESULTS: During the first 4 weeks of placebo the frequency of hot flushes decreased by 16%. During the subsequent double blind phase, a further, statistically significant decrease of 44% was seen in isoflavones group (P<0.01), whereas no further reduction occurred within the placebo group. The Greene score decreased in the active group by 13% and remained unchanged in the placebo group. CONCLUSION: In this study, treatment with 80 mg isoflavones (Promensil) per day resulted in a significant reduction in hot flushes from baseline. At the end of the study there was a significant decrease in hot flushes of 44% between the active and placebo group, demonstrating the effectiveness of Promensil in the management of hot flushes.     

Efficacy and tolerability of estradiol 1 mg and drospirenone 2 mg in postmenopausal Korean women: a double-blind, randomized, placebo-controlled, multicenter study

Objectives

The aim of this study was to demonstrate that the therapeutic efficacy of an estradiol 1 mg/drospirenone 2 mg (E2/DRSP) preparation is superior to a placebo in postmenopausal Korean women with hot flushes and other climacteric symptoms, and to demonstrate that this treatment is both safe and tolerable.

Methods

This was a double-blind, randomized, placebo-controlled, multicenter study over four 28-day treatment cycles. A total of 158 subjects were screened and 90 women were randomized into two treatment groups (E2/DRSP group, n = 45; placebo group, n = 45). The primary efficacy parameter was the individual relative change of hot flushes. The secondary efficacy parameters such as other climacteric, urogenital symptoms and vaginal bleeding patterns were also evaluated, and the occurrence of any adverse events was noted. In addition, physical, gynecological examinations and laboratory analyses were performed at the beginning and end of the study.

Results

The mean number of hot flushes per week during treatment weeks 3–16 decreased by 48.1% during treatment with placebo, and by 84.4% during treatment with E2/DRSP (p < 0.001). The E2/DRSP combination also reduced the incidence and intensity of menopausal symptoms in postmenopausal women. Most of adverse events was mild or moderate degree of intensity. None of the parameters measured in the study, including laboratory analyses, physical and gynecological examinations, vital signs, and weight, led to any concerns of safety.

Conclusions

The E2 1 mg/DRSP 2 mg combination tested in the study was efficacious and safe in the treatment of hot flushes and other climacteric symptoms in postmenopausal Korean women.     

Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study

OBJECTIVE: Nonhormonal treatment of postmenopausal symptoms is a subject of great interest today. The results of studies on selective serotonin reuptake inhibitors (SSRIs) are promising, but long-term results do not exist. The objective of this study was to evaluate the efficacy of citalopram and fluoxetine in the treatment of physical and psychological menopausal symptoms and their effects on psychosocial and sexual well being in symptomatic postmenopausal women. DESIGN: One hundred fifty healthy women suffering from menopausal symptoms were recruited to this placebo-controlled double-blind study with a follow-up period of 9 months. They were randomized into three groups receiving placebo, fluoxetine, or citalopram. The initial dose was 10 mg of both fluoxetine and citalopram, and it was increased to 20 mg at 1 month and to 30 mg at the 6-month visit. The main outcome measures were hot flushes and Kupperman index. The RAND-36 Quality of Life questionnaire, Beck's Depression Scale, and the McCoy Female Sexuality Questionnaire were used at every control visit. RESULTS: There were no statistically significant differences between the groups in respect to number of hot flushes, Kupperman index, or Beck's Depression Scale, although there was a tendency in all these parameters in favor of SSRIs versus placebo. Insomnia improved significantly in the citalopram group versus placebo. Discontinuation rates at nine months were 40% in the placebo group, 34% in the fluoxetine group and 34% in the citalopram group. CONCLUSIONS: Compared with placebo, citalopram and fluoxetine have little effect on hot flushes and cannot therefore be recommended for the treatment of menopausal symptoms, if vasomotor symptoms are the main complaint. Whether the improvement of insomnia by means of citalopram affects the quality of sleep needs further investigation.     

Isoflavone-rich or isoflavone-poor soy protein does not reduce menopausal symptoms during 24 weeks of treatment

OBJECTIVE: We examined the change in menopausal symptoms in response to 24 weeks of isoflavone-rich (80.4 mg/day) and isoflavone-poor (4.4 mg/day) soy protein isolate treatment in perimenopausal women. DESIGN: In this double-blind 24-week study, 69 women were randomized to treatment: isoflavone-rich soy protein (n = 24), isoflavone-poor soy protein (n = 24), or whey protein control (n = 21). A Menopausal Index was used to assess change in hot flushes and night sweats, as well as other symptoms, at baseline, week 12, and week 24. RESULTS: Repeated measures analysis of variance indicated no treatment effect on change in hot flush (p = 0.18) and night sweat (p = 0.92) frequency, whereas there was a significant decline in hot flush (p = 0.0003) and night sweat (p = 0.0007) frequency with time in all treatment groups. Chi2 analyses indicated no treatment effect on severity of hot flushes or night sweats at any time point, as well as no treatment effect on frequency or severity of other vasomotor symptoms. At the completion of the study, we found no treatment effect on retrospective perception of frequency, duration, or severity of hot flushes or night sweats. Since time had a significant effect on symptoms with all groups reporting a decline in overall symptoms, this indicated either a placebo effect or simply an improvement in symptoms during the study. CONCLUSION: In this study, we found no evidence that isoflavone-rich or isoflavone-poor soy protein provided relief of vasomotor or of other menopausal symptoms.     

Efficacy and tolerability of estraderm MX, a new estradiol matrix patch

Objectives: To assess the efficacy and tolerability of a new matrix patch delivering 0.05 mg estradiol per day (Estraderm MX 50) in postmenopausal women with moderate to severe postmenopausal symptoms. Methods: A multicenter, double-blin, randomized, between-patient, placebo controlled trial in 109 postmenopausal women was carried out. Patches were applied twice weekly for 12 weeks. Patients were assessed at 4, 8 and 12 weeks of treatment. The primary efficacy variable was change from baseline in mean number of moderate to severe hot flushes (including night sweats) per 24 h during the last 2 weeks of treatment. Other variables included Kupperman Index, local and systemic tolerability. Plasma concentrations of estradiol (E2), estrone (E1) and estrone sulfate (E1S) were determined before and after treatment. Results: Estraderm MX was significantly superior to placebo (P < 0.001) in reducing mean number of moderate to severe hot flushes (including night sweats) per 24 h after 4, 8 and 12 weeks of treatment. The estimate of treatment group differences after 12 weeks was 4.2 hot flushes (95% confidence interval: 2.6–5.5). Estraderm MX also significantly reduced Kupperman Index at all time points compared to placebo (P < 0.001). Estraderm MX induced increases in mean E2, E1 and E1S plasma levels as expected (E2: baseline 2.7 pg/ml, 12 weeks 38.9 pg/ml; E1: baseline 18.8 pg/ml, 12 weeks 41.6 pg/ml; E1S: baseline 235.6 pg/ml, 12 weeks 765.1 pg/ml). Overall rates of adverse experiences were similar for Estraderm MX and placebo. The number of patients reporting skin irritation was low and similar in both groups. Conclusions: Estraderm MX 50, a new matrix patch, offers an effective and well tolerated dosage form for transdermal delivery of 0.05 mg E2 per day.     

Effect of raloxifene and low-dose percutaneous 17β-estradiol on menopause symptoms and endometrium—A randomized controlled trial

Objective

To investigate the effects on climacteric symptoms and endometrium of percutaneous low-dose 17β-estradiol associated with raloxifene in postmenopausal women.

Design

randomized placebo-controlled study.

Method

Fifty-two postmenopausal women with moderate to severe hot flushes were randomized to receive either 60 mg raloxifene (RLX; n = 20), 0.5 mg percutaneous 17β-estradiol associated to 60 mg raloxifene (RLX + E₂; n = 16) or placebo (PLC; n = 16). Climacteric symptoms (Kupperman index) and vaginal bleeding were evaluated. At baseline and at the end of the study endometrial thickness was measured and endometrial samples were collected for histological study.

Results

At baseline, the mean Kupperman index was 23.7 ± 1.8 in RLX group, 22.9 ± 1.9 in RLX + E₂ group and 22.6 ± 1.9 in the placebo group (NS). After 3 months, there was a significant reduction in Kupperman index mean values in both groups, but no statistical difference was observed between groups. However, RLX + E₂ and placebo were significantly superior to RLX in reducing hot flush severity (p < 0.05). Endometrial thickness did not change in both groups. The association of percutaneous low-dose 17β-estradiol to raloxifene was not associated with proliferation of endometrium neither in hysteroscopies nor in endometrial biopsies at the third month of treatment. No vaginal bleeding was reported during the study.

Conclusions

The association of percutaneous low dose of 17β-estradiol with raloxifene exerted favorable effects on hot flushes severity of postmenopausal women, providing a safe profile in endometrium at least in short-term therapy.