Mechanism of network pharmacology of Erzhi Pill and Erxian Decoction in treating climacteric syndrome with "treating the same disease with different methods": A review.

Network pharmacology and molecular docking methods were used in the present study to clarify the molecular mechanism of two traditional Chinese medicine prescriptions of climacteric syndrome. Based on oral availability and drug similarity, the main active components of Erzhi Pill and Erxian Decoction were screened through the platform of traditional Chinese medicine system pharmacology. The target database of climacteric syndrome was established by using GENECARD, OMIM, PharmGKB, Targets and Drugbank. The "component - target" network diagram was constructed using Cytoscape software (version 3.8.2). Topology analysis, module analysis, and GO and KEGG enrichment analyses were used to explore the core target and action pathway of Erzhi Pill-Erxian Decoction for treating climacteric syndrome of same disease with different treatments. There were 16 active components and 103 corresponding targets found in Erzhi Pill; 69 active components and 121 corresponding targets were found in Erxian Decoction; and 100 potential targets were found in Erzhi Pill and Erxian Decoction. Through network analysis, topology and module analysis, TP53, AKT1, Jun, ESR1, IL1B, CASP3, MMP9, PTGS2, HIF1A, MYC and EGFR could be considered as potential targets of the 2 prescriptions for alleviating climacteric syndrome. The effects of Erzhi pill and Erxian Decoction on climacteric syndrome are mainly in the pathway of lipid and atherosclerosis, AGE-RAGE signaling pathway and PI3K-Akt signaling pathway in diabetic complications. The active components in Erzhi Pill - Erxian Decoction, such as quercetin, show considerable potential as a candidate drug for the treatment of climacteric syndrome.

Long-term effects of a combination of isoflavones, agnus castus and magnolia extracts on climacteric symptoms and cardiometabolic risk profile in postmenopausal women.

OBJECTIVE: To evaluate the long-term effects of a combination of isoflavones, agnus castus and magnolia extracts (combined isoflavone compound [CIC]) on climacteric symptoms and cardiometabolic risk in symptomatic postmenopausal women. METHODS: This interventional, prospective study evaluated climacteric symptoms, mood and sleep disorders using the 21-item Greene Climacteric Scale (GCS) and 7-item Insomnia Severity Index (ISI) questionnaires; and cardiovascular, metabolic and thrombotic risk markers at baseline (T0) and after 12 months of CIC treatment (T1). RESULTS: In healthy postmenopausal women (N = 71), 12-month CIC treatment significantly reduced patient-reported vasomotor symptoms (100% vs. 17%), mood disorders (67% vs. 25%) and sleep disorders (89% vs. 19%%) (all p < .001) compared with baseline; and significantly improved GCS psychological, somatic, and vasomotor domain scores and ISI sleep disturbance scores (all p < .05). CIC significantly reduced systolic (p = .022) and diastolic blood pressure (p < .001), and heart rate (p < .001); glucose concentrations (p = .018), HOMA index (p = .013), and ALT (p = .035), homocysteine (p = .005) and NT-proBNP (p = .003) levels. CONCLUSIONS: Long-term CIC therapy improved vasomotor symptoms, mood disorders, sleep disorders, hemodynamic measurements and cardiometabolic risk markers in healthy postmenopausal women. CLINICALTRIALS.GOV IDENTIFIER: NCT03699150.

Climacteric symptoms more severe in 2010 than in 2000 - experience of Finnish women aged 52-56 years not now or previously on menopausal hormone therapy.

OBJECTIVES: To analyze and compare the experience of climacteric symptoms and their associations with sociodemographic and health-related characteristics in two cohorts of Finnish women aged 52-56 years, born ten years apart and not now or previously on menopausal hormone therapy (MHT). STUDY DESIGN: Nationwide population-based time-trend study with a large number of participants (n = 1986 + 1988). MAIN OUTCOME MEASURES: The experience of climacteric symptoms was assessed by 12 commonly used menopause-related symptoms. RESULTS: Women aged 52-56 experienced more moderate or severe symptoms and fewer mild symptoms in 2010 than in 2000. Being unemployed or inactive was associated with more severe symptoms (P = 0.007), but employment status had no effect on the relative odds estimates. CONCLUSIONS: The influence of the birth cohort and time-period effects as well as work-related factors on the experience of climacteric symptoms in women not now or previously on MHT needs further research, particularly since the change in the experience of symptoms found in this study occurred within only ten years.

Moderate Consumption of Beer (with and without Ethanol) and Menopausal Symptoms: Results from a Parallel Clinical Trial in Postmenopausal Women.

The menopausal transition can be a challenging period for women's health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms (p-value AB vs. Control: 0.009; p-value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.

Effects of peripheral oxytocin administration on body weight, food intake, adipocytes, and biochemical parameters in peri- and postmenopausal female rats.

Recent studies have revealed that the administration of oxytocin has beneficial effects on the regulation of body weight, food intake, and metabolic functions, especially in obese individuals. Obesity is common in women after the menopause and drives many components of metabolic syndrome. Weight gain in menopausal women has been frequently reported. Although obesity and associated metabolic disorders are frequently observed in peri- and postmenopausal women, there are few medical interventions for these conditions. In this study, we evaluated the effects of chronic oxytocin administration on appetite, body weight, and fat mass in peri- and postmenopausal female rats. Sixteen naturally premenopausal or menopausal rats were intraperitoneally injected with oxytocin (1,000 µg/day) for 12 days. The daily changes in their body weight and food intake were measured at the same time as the oxytocin and vehicle injections. Intraperitoneally administering oxytocin for 12 days significantly reduced food intake, body weight, and visceral adipocyte size. In addition, oxytocin administration caused reductions in serum triglyceride and low-density lipoprotein-cholesterol levels, while it did not disturb hepatic or renal functions or locomotor activity. This is the first study to show the effects of oxytocin on the metabolic and feeding functions of peri- and postmenopausal female rats. Oxytocin might be a useful treatment for metabolic disorders caused by the menopause or aging.

Isoflavonas como tratamento alternativo na sintomatologia climatérica: uma revisão sistemática / Isoflavones as alternative treatment in climacteric symptomatology: a systematic review

O climatério é uma fase natural da vida da mulher que ocorre entre os 40 e 65 anos de idade e é caracterizado pela transição entre a fase reprodutiva e não reprodutiva. Neste período, devido às alterações hormonais, ocorrem alterações biológicas, endócrinas e clínicas. Sintomas vasomotores são típicos do hipoestrogenismo e podem interferir negativamente na qualidade de vida das mulheres. Este estudo teve como objetivo revisar os resultados dos estudos de intervenção que utilizaram isoflavonas na sintomatologia de mulheres climatéricas não usuárias de Terapia de Reposição Hormonal (TRH). Realizou-se uma revisão sistemática de artigos publicados entre os anos de 2008 e 2019 na base de dados PubMed. Foram encontrados 169 estudos, e considerando os critérios de inclusão, 18 artigos foram selecionados, em que houve intervenção com isoflavonas por meio de cápsulas e/ou suplementos ou alimentos para tratamento da síndrome climatérica. Foram verificados resultados positivos nos sintomas globais, com destaque para sintomas vasomotores, em mais da metade dos estudos avaliados, em que doses entre 45 mg a 160 mg diárias de isoflavonas por pelo menos 12 semanas foram administradas, especificadamente nas mulheres no período da pós-menopausa.

The climacteric is a natural phase during women’s life, which occurs between 40 and 65 years. It is characterized by the transition from their reproductive to non-reproductive phase. In this period, due to hormonal changes, biological, endocrine and clinical modifications also occur. Vasomotor symptoms are characteristic of hypoestrogenism and can negatively affect women’s quality of life. This study aimed to review the results of intervention studies which used isoflavones to treat the symptoms of climacteric women who did not undergo Hormone Replacement Therapy (HRT). A systematic review of articles published between 2008 and 2019 in the PubMed database was carried out. 169 studies were found, and considering the inclusion criteria, 18 articles were selected, in which it was described isoflavones intervention with capsules and/ or supplements or foods for the treatment of climacteric syndrome. Positive results were observed regarding to global symptoms, with emphasis on vasomotor symptoms in more than half of the studies, in which daily doses of isoflavones, between 45 mg to 160 mg, for at least 12 weeks, were administered specifically in postmenopausal women.

Hormonal therapy in menopausal transition: implications for improvement of health-related quality of life.

The study aim was to assess scores of the Menopause Rating Scale (MRS) among women who use and desire to use hormonal therapy (HT), as well as to evaluate factors contributing to HT use and desire to use HT among women in menopausal transition. A total of 513 mid-aged women participated in the study. Data were collected using socio-demographic questionnaire, MRS and Beck Depression Inventory. The prevalence of current HT use was 9.7%, while 4.5% of women who did not use HT expressed a desire to start using HT. The MRS cutoff score for HT use was 10.5 and 11.5 among those who desire to use HT. Living in the central city districts, having lower body mass index, younger age at menopause, more gynecological illnesses, and worse MRS were associated with HT use. Living in the central city districts, having fewer births, more gynecological and chronic illnesses and having more depressive symptoms were associated with the desire to use HT. Mid-aged women who perceive their quality of life as poor due to climacteric symptoms should be advised to consider HT to improve their health status and everyday functioning.

Evaluación del Tratamiento Homeopático de Mujeres en Climaterio entre los 45 y 60 años con la Menopause Rating Scale (MRS) / Treatment Evaluation Homeopathic Women in Climacteric between 45 and 60 years old with Menopause Rating Scale (MRS)

La terapia hormonal es el tratamiento convencional para contrarrestar síntomas propios del climaterio; sin embargo, algunas mujeres tienen contraindicada esta terapia debido a los efectos adversos que provoca. El objetivo de este estudio fue evaluar la utilidad del tratamiento homeopático durante el climaterio con el uso de la Menopause Rating Scale (MRS) o Escala de Calificación Menopáusica. El estudio incluyó a 31 mujeres, sin problemas cardiacos, sin terapia de reemplazo hormonal y sin antecedentes de cáncer, a quienes se les aplicó el cuestionario de la MRS para obtener un puntuaje antes del tratamiento. Para determinar el tratamiento se utilizó el repertorio electrónico Radar 10.0 para Windows, con el objetivo de repertorizar los síntomas característicos de cada paciente y determinar el medicamento similar. El medicamento fue prescrito en dinamizaciones 30CH, indicando 5 gotas sublinguales cada 8 horas. La evaluación de los pacientes se llevó a cabo cada mes durante tres meses. Se realizó una evaluación final a los tres meses por comparación de puntajes de la escala inicial y final, a través de un análisis estadístico y utilizando la prueba de Wilcoxon. Lachesis trigonocephalus y Pulsatilla nigricans fueron los medicamentos indicados con mayor frecuencia, de acuerdo con los síntomas de cada paciente. La comparación del puntaje, antes y después del tratamiento, evidenció una reducción de síntomas con diferencia estadística, lo cual reflejó una mejoría global del 35%. Esta evidencia sugiere que el tratamiento homeopático beneficia a las mujeres en el climaterio. (AU)

Hormonal therapy is the conventional treatment for counteracting climacteric symptoms; however, this treatment is contraindicated in some women due to the adverse effects that this therapy may cause. The purpose of this study was to evaluate the usefulness of homeopathic therapy during the climacteric using the Menopause Rating Scale (MRS). The study included 31 women, without cardiac problems, history of no cancer or hormone replacement therapy; a MRS scale questionnaire was applied to these women to evaluate each symptom before to treatment. The Radar 10.0 for Windows electronic repertoire was used to repertorize the characteristic symptoms of each patient and determine the similarly. Homeopathic medication was prescribed in 30CH dynamization as 5 sublingual drops every 8 hrs. Patient evaluation took place monthly for 3 months. The evaluation of the results was performed by the comparison of scale scores through a statistical analysis using the Wilcoxon test. Lachesis trigonocephalus and Pulsatilla nigricans were the most frequent treatment indications, according to the symptoms of each patient. At the end of the homeopathic treatment, symptoms reduction was observed with statistical significance in the score, which reflects an overall improvement of 35%. This evidence suggested that homeopathic treatment benefits women in climacteric. (AU)

Medicamentos homeopáticos en el tratamiento del climaterio y la menopausia: una revisión / Homeopathic medicinal products in the treatment of climateric and menopause: a review

RESUMEN Durante el climaterio y la menopausia debido a cambios hormonales pueden presentarse en las mujeres síntomas que afectan la calidad de vida y las relaciones interpersonales. La homeopatía puede ser utilizada como terapia alternativa o complementaria en el manejo de sus síntomas proporcionando múltiples beneficios, escasos efectos secundarios, ahorro de recursos y apertura de una nueva línea para investigar. La bibliografía sobre este tema es insuficiente y se encuentra dispersa lo que dificulta la consulta por parte de los profesionales que la necesitan. Se realizó una revisión bibliográfica con el objetivo de identificar y describir los principales medicamentos homeopáticos que pueden ser utilizados para tratar los síntomas durante el climaterio y la menopausia. Los artículos se identificaron básicamente a través de la búsqueda automatizada en las bases de datos Scielo, PubMed y EBSCO, entre los meses de enero de 2017 a mayo de 2018. Se revisaron aquellos libros y artículos que por su trascendencia fueron considerados como referentes en el tema. Se escogieron 26 referencias bibliográficas que se ajustaban a los objetivos de esta investigación. Fueron identificados y descritos 22 medicamentos homeopáticos susceptibles de ser utilizados en el tratamiento de los síntomas de climaterio y menopausia por lo que puede ser una fuente útil de consulta (AU).

ABSTRACT During the climacteric and menopause, due to hormonal changes, women may present symptoms affecting life quality and interpersonal relations. Homeopathy could be used as an alternative or complementary therapy in the management of those symptoms, providing several benefits, scarce secondary effects, saving resources and opening a new research field. There is not enough bibliography on this topic and it is dispersed, making it difficult for the professional to consult it when it is necessary. A bibliographic review was carried out with the objective of identifying and describing the main homeopathic medicinal products that could be used to treat the symptoms during the climacteric and menopause. The articles were identified mainly through an automated search in Scielo, PubMed and EBSCO databases, in the period from January 2017 and May 2018. Those books and articles considered as referents in the topic because of their transcendence were reviewed. 26 bibliographic references were chosen because they complied with the objective of this research. 20 homeopathic medicinal products capable of being used in the treatment of the climacteric and menopause symptoms were identified and described, being therefore a useful consultation source (AU).

Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?

BACKGROUND: Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. RESULTS: HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). CONCLUSION: Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.

60 years of Cimicifuga racemosa medicinal products : Clinical research milestones, current study findings and current development.

Cimicifuga racemosa (CR) extracts are important worldwide as therapy for menopausal symptoms. The first medicinal product from CR has been available since 1956 (Germany, Remifemin® [Schaper & Brümmer, Salzgitter, Germany], isopropanolic extract iCR). This review describes how CR developed, via clinical studies on safety (breast, breast cancer, endometrium, liver) and efficacy, into a successful and safe medicinal product in Germany, Europe and the world. In line with developing legal frameworks for medicinal products in Germany and Europe, clinical studies on CR were observational during the 50s and 70s, and controlled studies since the 80s. The first placebo-controlled study emerged 1986. From 2000 to 2015, a total of 28 clinical studies in Europe, America and Asia were published on the efficacy of CR. In these studies, 11,073 patients received a CR-based medicinal product, 93% thereof iCR. A meta-analysis of all nine placebo-controlled studies published until 2013 confirmed the reliable efficacy of CR-based medicinal products for menopausal symptoms.

Effects of Tibolone on the Central Nervous System: Clinical and Experimental Approaches.

Hormone replacement therapy (HRT) increases the risk of endometrial and breast cancer. A strategy to reduce this incidence is the use of tibolone (TIB). The aim of this paper was to address the effects of TIB on the central nervous system (CNS). For the present review, MEDLINE (via PubMed), LILACS (via BIREME), Ovid Global Health, SCOPUS, Scielo, and PsycINFO (ProQuest Research Library) electronic databases were searched for the results of controlled clinical trials on peri- and postmenopausal women published from 1990 to September 2016. Also, this paper reviews experimental studies performed to analyze neuroprotective effects, cognitive deficits, neuroplasticity, oxidative stress, and stroke using TIB. Although there are few studies on the effect of this hormone in the CNS, it has been reported that TIB decreases lipid peroxidation levels and improves memory and learning. TIB has important neuroprotective effects that could prevent the risk of neurodegenerative diseases in postmenopausal women as well as the benefits of HRT in counteracting hot flashes, improving mood, and libido. Some reports have found that TIB delays cognitive impairment in various models of neuronal damage. It also modifies brain plasticity since it acts as an endocrine modulator regulating neurotransmitters, Tau phosphorylation, and decreasing neuronal death. Finally, its antioxidant effects have also been reported in different animal models.

Clinical trial shows lasting function of a new moisturizing cream against vaginal dryness.

Vaginal dryness and associated symptoms may occur in women of any age and are a frequent burden after menopause. The North American Menopause Society recommends long-acting non-hormonal vaginal creams as first-line therapy. A new type of such creams was developed (Remifemin® FeuchtCreme in Austria and Germany). This hormone-free cream contains hamamelis virginiana distillate and well-established vaginal cream ingredients. We explored its physical function and tolerability in an open interventional clinical trial. 20 postmenopausal women (54 to 76 years, median 60) treated their vaginal dryness using this cream once daily for 7 days and reported about their symptoms before, 4 to 8 h after first and 14 to 22 h after last application. A physician assessed tolerability and local physical function. All patients completed the study. Local physical function significantly improved from dryness at baseline (mean 4.0 ± SD 1.8) to a normal moisture level, on average (6.3 ± 2.1 after first, 6.7 ± 2.1 after last application, p = 0.0001). Subjective assessment of a feeling vaginal dryness showed a significant improvement at both times (p = 0.0001). Onset and duration of feeling moisturized were reported to be 0 to 2 min and 11.3 ± 6.9 h after application. All women reported vaginal dryness at baseline. 55 and 80% of patients reported no dryness after first application and at the end of the investigation. The cream was seen at the application site for up to 21 h. Tolerability assessments did not reveal any relevant change over time. There were four adverse events in 4 patients, all not serious and of mild intensity: urinary urgency (2), diarrhoea (1) and mild spotting after first application (1). The latter was caused by the dry surface of the applicator and was avoided by moisturizing the surface of the applicator at subsequent applications. In conclusion, these study results indicate a well-tolerated and long-acting function of this new vaginal moisturizing cream. Further clinical research in more patients will follow.

Effect of Zuogui Pill () on monoamine neurotransmitters and sex hormones in climacteric rats with panic attack.

OBJECTIVES: To explore the effects of Chinese medicine prescription Zuogui Pill (, ZGP) on monoamine neurotransmitters and sex hormones in climacteric rats with induced panic attacks. METHODS: Forty-eight climacteric female rats were randomized into 6 groups with 8 rats in each group: the control group, the model group, the low-, medium- and high-dose ZGP groups and the alprazolam group. Rats in the low-, medium- and high-dose ZGP groups were administered 4.725, 9.45, or 18.9 g/kg ZGP by gastric perfusion, respectively. The alprazolam group was treated by gastric perfusion with 0.036 mg/kg alprazolam. The control and model groups were treated with distilled water. The animals were pretreated once daily for 8 consecutive weeks. The behaviors of rats in the open fifield test and the elevated T-maze (ETM) were observed after induced panic attack, and the levels of brain monoamine neurotransmitters and the plasma levels of sex hormones were measured. RESULTS: Compared with the control group, the mean ETM escape time and the levels of 5-hydroxytryptamine (5-HT) and noradrenalin (NE) of the model group were signifificantly reduced (P<0.05), Compared with the model group, the mean ETM escape time and the 5-HT and NE levels of all the ZGP groups increased signifificantly (P<0.05 or P<0.01). However, no signifificant difference was observed in the levels of sex hormones between the groups. CONCLUSION: Pretreatment with ZGP in climacteric rats may improve the behavior of panic attack, which may be related to increased 5-HT and NE in the brain.

Does Cimicifuga racemosa have the effects like estrogen on the sublingual gland in ovariectomized rats?

BACKGROUND: Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. RESULTS: HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). CONCLUSION: Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the expression of caspase-3 caused by ovariectomy, but their effects were not identical, suggesting that both drugs confer a protective effect on the sublingual gland of ovariectomized rats, but that the specific location and mechanism of action producing these effects were different.

[Transdermal estrogen spray in therapy of postmenopausal syndrome]. / Postavení transdermálního estrogenního spreje v lécbe klimakterického syndromu.

OBJECTIVE: To show possibilities of new application method of estrogen replacement therapy - mettered-dose transdermal spray. DESIGN: Review articleResults: Transdermal spray contains 1.53 mg estradiol in one dose. It gives possibility of individual aproach in estradiol application 1, 2 or 3 doses daily. About 85% of patients showed the significant reduction of hot flushes. Perfect safety profile is predicted especially in cardiovascular point.

METFORMIN-SUSTAINED WEIGHT LOSS AND REDUCED ANDROID FAT TISSUE AT 12 MONTHS IN EMPOWIR (ENHANCE THE METABOLIC PROFILE OF WOMEN WITH INSULIN RESISTANCE): A DOUBLE BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIAL OF NORMOGLYCEMIC WOMEN WITH MIDLIFE WEIGHT GAIN.

OBJECTIVE: To assess 12-month body weight (BW) and body composition changes in normoglycemic women with midlife weight gain, after dietary and pharmacologic interventions targeting hyperinsulinemia. METHODS: EMPOWIR (Enhance the Metabolic Profile of Women With Insulin Resistance; NCT00618072) was a double-blind, placebo-controlled, 12-month trial of women with >20-pound weight gain, normal glucose tolerance test, and increased area-under-the-curve insulin. Subjects (mean ± SD, 46.7 ± 6.5 years of age; body mass index, 30.8 ± 2.8 kg/m(2); 50% white) attended 4 nutrition workshops to introduce a novel carbohydrate-modified diet (CMD) and were then randomized to one of three arms for 6 months (phase 1): CMD alone (D), or in combination with metformin (M), or metformin + rosiglitazone (MR), with rerandomization of the D group to one of the active treatment arms (phase 2, months 7 through 12). Repeated measure analysis of variance was used to assess BW at baseline, 6 months, and 12 months in 32 subjects with 12-month data; paired t tests compared baseline and 12-month dual-energy X-ray absorptiometry-derived body composition. RESULTS: Mean (±SD) BW decreased significantly at 12 months in the M arm: 85.1 ± 8.5 kg to 79.8 ± 9.0 kg (P = .0003), with 54% of variance in weight over time explained by M treatment. Mean (±SD) percent android fat decreased significantly in the M and D arms: 53.5 ± 4.8% to 49.3 ± 7.6% (P = .010) and 52.9 ± 6.2% to 48.1 ± 8.7% (P = .021). CONCLUSION: In combination with a novel carbohydrate modified diet, metformin enhanced 12-month weight loss and improved body composition in ethnically diverse normoglycemic, hyperinsulinemic women with midlife weight gain. These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies.

The menopause transition: interview with Ellen W Freeman.

Ellen W Freeman is a Research Professor in the Department of Obstetrics/Gynecology and the Department of Psychiatry at the University of Pennsylvania School of Medicine in Philadelphia (PA, USA). She directs the PMS research program and is co-director of the Human Behavior and Reproduction unit in the Department of Obstetrics and Gynecology. She received her AB in history in Smith College in Northampton, Massachusetts and her MS and PhD in social research from Bryn Mawr College in Bryn Mawr, Pennsylvania. She has published more than 200 scientific articles, book chapters, reviews and abstracts on premenstrual syndromes, perimenopause, adolescent pregnancy, infertility and related topics as well as a book on teenage pregnancy. In addition, she has lectured extensively worldwide on mood disorders and menopause in women. She is also a member of the editorial boards of Medscape, Archives of Women's Mental Health and Mental Fitness: Psychiatry, OB/GYN, Primary Care and is a Fellow in the College of Physicians of Philadelphia.