Climacteric Symptoms In Postmenopausal Women Research Articles

Efficacy and safety of a soy isoflavone extract in postmenopausal women: A randomized, double-blind, and placebo-controlled study

ObjectiveTo investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women. DesignIn this double-blind, randomized, placebo-controlled study, a total of 80 women (mean age=55.1 years), who reported 5 or more hot flush episodes per day, were randomized to receive either 250mg of standardized soy extract (Glycine max AT) a total of 100mg/day of isoflavone (n=40) or placebo (n=40). Exclusion criteria included: contra-indication for hormone therapy (HT), chronic gastrointestinal diseases, and users of HT within the preceding 6-months. For 10-months, climacteric symptoms were evaluated using a score card and the menopausal Kupperman index. Compliance and safety were also assessed. At baseline and the end of the study, lipid and hormonal profiles, as well as vaginal, mammographic and ultrasonographic parameters were measured. The t-test, Wilcoxon test and ANOVA were used in the statistical analysis. ResultsAt baseline, the mean number of hot flushes was 9.6±3.9 per day in the isoflavone group and 10.1±4.9 in the placebo group (p>0.05). After 10 months, there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo (3.1±2.3 and 5.9±4.3, respectively) (p<0.001). Kupperman index mean values showed a significant reduction in both groups. However, soy isoflavone was significantly superior to placebo, in reducing hot flush severity (69.9% and 33.7%, respectively) (p<0.001). Endometrial thickness, mammography, vaginal cytology, lipids and hormonal profile did not change in both groups. No serious adverse event related to isoflavone treatment was reported. ConclusionsThe soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance, providing a safe and effective alternative therapeutic for postmenopausal women.

Economic impact of Tibolone compared with Continuous-Combined Hormone Replacement Therapy in the management of climacteric symptoms in postmenopausal women

Background Deciding whether to treat postmenopausal women suffering from climacteric symptoms with Continuous Combined Hormone Replacement Therapy (CCHRT) has become increasingly difficult after the release of the Women's Health Initiative results. As a result, development of alternatives to CCHRT is required. Tibolone, which is a synthetic steroid that has estrogenic, progestogenic and androgenic properties, is reported to be a promising alternative. It has been used in Europe, in the same indication as CCHRT, for approximately 20 years but is not yet available in Canada. Objective We carried out a cost-utility analysis comparing a 3-year-treatment course with Tibolone 2.5 mg and conjugated equine estrogens (CEE)/medroxyprogesterone acetate (MPA) (0.625 mg/2.5 mg) in the management of postmenopausal women with climacteric symptoms. Methods A Markov model, considering persistence, vaginal bleeding and climacteric symptoms, was elaborated to compare the different options in terms of cost and Quality Adjusted Life Years (QALYs), according to a public third-party payer perspective. Results Compared with CEE/MPA, Tibolone led to an increase in cost ($485 for Tibolone versus $232 for CEE/MPA) and a slight increase in QALYs (2.08 for Tibolone versus 2.05 for CEE/MPA). Consequently, the incremental cost per QALY gained ratio was $9198. Conclusion According to the results, Tibolone seems to be a cost-effective alternative to CEE/MPA. However, those results should be interpreted with caution insofar as the difference in terms of QALY is clinically difficult to value and taking into account the limited data on Tibolone's long-term innocuity.

Mechanism‐based discovery as an approach to identify the next generation of estrogen receptor modulators

The estrogen receptor (ER) signal transduction pathway is the primary target of the hormonal therapies used for the treatment and prevention of breast cancer. Interestingly, although animal studies performed over a century ago first suggested a link between the ovaries (estrogen production) and growth of breast tumors, definition of the molecular basis for this association and its pharmaceutical exploitation has occurred relatively recently. In the realm of breast cancer chemotherapy, compounds like tamoxifen have emerged which function as antiestrogens by directly blocking the binding of estrogen(s) to their receptors in breast tumors. The aromatase inhibitors, such as letrazole and anastrazole, inhibit estrogen production while high dose progestins attenuate ER signaling by an as yet unknown mechanism. Together, these hormonal therapies have been extremely successful and have improved both mortality and morbidity in this disease. However, as we begin to fully understand the complexities of estrogen signaling, it is clear that new classes of drugs that regulate important components of this signaling pathway are going to emerge that will increase the armamentarium of the oncologist and improve overall prognosis in this disease. Estrogen-containing medicines have been marketed in the United States for the relief of climacteric symptoms in postmenopausal women since 1942 and for contraception since 1960. However, at the time of approval, little was known about the mechanism(s) underlying the biological responses to these drugs in target tissues. In the late 1950s, Elwood Jensen and colleagues identified a high affinity intracellular binding protein (now known as ER ) that was found only in estrogen-responsive tissues (1). This was followed some years later by work from Bert O’Malley’s group which demonstrated that ER was in fact a liganddependent transcription factor, whose actions dictated the cellular response to estrogens (2). These discoveries, and those of other investigators, in the early years of molecular endocrinology enabled the development of a simple model to describe the actions of estrogens in target cells, the essence of which has stood the test of time. Specifically, these models proposed that in the absence of hormone, ER resided in cells in an inactive form that underwent a biochemical “activating” event upon binding an estrogen. The agonist-bound ER was then capable of interacting with specific DNA sequences within the regulatory regions of target genes and positively or negatively regulating their transcription. By extension, it was proposed that antiestrogens, much like competitive enzyme antagonists, functioned by binding to the hormone-binding pocket of ER, thus blocking agonist access. Interestingly, there were early indications that this elegant model and proposed mechanism of action was over simplified and did not explain the full complexity of ER pharmacology. Notably, Harper and Walpole observed in their early studies of the antiestrogen tamoxifen that whereas it functioned as a potent antagonist of estrogen action in some organs, it manifested robust agonist activity in others (3). These observations were not followed up on to any great extent until the studies of Love et al. in 1992 revealed that tamoxifen, in the context of adjuvant chemotherapy for breast cancer, exhibited a paradoxical agonist activity in bone (4). Indeed, so dramatic were the results in these bone studies that it led to the rebirth of ER as a drug discovery target, this time for drugs useful for the treatment and prevention of osteoporosis. Expectedly, the heightened interest in ER modulators for osteoporosis and the accompanying advancement in our understanding of estrogen action have also had a positive impact on the development of ER modulators for breast cancer. One of the most significant advances in drug discovery efforts aimed at identifying new ER modulators is the dramatic move in recent years from empirical to predictive mechanism-based drug screens. Traditionally, discovery programs for ER modulators used receptor-binding assays as a primary screen with the subsequent use of a “predictive” secondary assay to evaluate the relative activity of selected compounds in relevant endpoints. Compounds with desired properties were then assayed in animal models of the targeted disease for efficacy. Most, if not all, of the currently approved ER modulators emerged from programs that used this general methodology. For the identification of compounds

Lack of aromatisation of the 3-keto-4-ene metabolite of tibolone to an estrogenic derivative

Tibolone is used for the treatment of climacteric symptoms in postmenopausal women. It is metabolised in a tissue-specific manner so that while some metabolites exert estrogenic effects on bone and the CNS, others are thought to protect the breast and endometrium from estrogenic stimulation. Tibolone is a 7α-methyl derivative of 19-norethynodrel. Since the introduction of synthetic progestagens for therapeutic use there has been considerable controversy as to whether they can undergo aromatisation to give rise to the potent estrogen, ethinylestradiol. In this study, we examined whether the delta-4-ene (7α-methyl norethisterone) metabolite of tibolone, which has a similar delta-4-ene A-ring structure to that of the estrone precursor, androstenedione, could undergo aromatisation to the potent estrogen, 7α-methyl ethinylestradiol. For these studies, JEG-3 choriocarcinoma cells were employed as they have a very high level of aromatase activity. TLC and HPLC procedures were developed to separate phenolic from non-phenolic compounds and were initially used to confirm that JEG-3 cells readily aromatised androstenedione to estrogens (up to 74%). The aromatisation of androstenedione to estrogens by these cells could be completely blocked with the potent aromatase inhibitor letrozole. When [ 3H] 7α-methyl norethisterone was incubated with JEG-3 cells no evidence for its conversion to [ 3H] 7α-ethinylestradiol was obtained. Radioactivity detected on the TLC plate or HPLC fractions where standard 7α-methyl ethinylestradiol was located, revealed that similar levels were present when 7α-methyl norethisterone was incubated with culture medium alone or with JEG-3 cells in the absence or presence of letrozole. From these investigations, it is concluded that 7α-methyl norethisterone does not undergo aromatisation to an estrogenic derivative.

Short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on climacteric-related symptoms in postmenopausal women: A double-blind, randomized, placebo-controlled trial

The present study aimed to evaluate the short-term effects of a combination of isoflavones, lignans and Cimicifuga racemosa on acute climacteric-related symptoms in postmenopausal women in a double-blind, randomized, placebo-controlled trial performed at the menopause clinic of our department. Eighty healthy postmenopausal women were randomly assigned to two treatment groups – one receiving the combination (group A, n = 40), the other receiving calcium supplements (group B, n = 40) – for three cycles of 28 days. Climacteric-related symptoms were evaluated by the Kupperman index (KI) at baseline and after the three cycles of treatment. At baseline no significant difference was detected in KI between groups A and B; however, after three cycles of treatment, KI was significantly (p < 0.05) lower in group A compared with baseline and with group B. We conclude that the administration of a combination of isoflavones, lignans and C. racemosa already reduces acute climacteric symptoms in postmenopausal women after 3 months of treatment. This prompt effect is probably due to the different pharmacokinetic properties of isoflavones and lignans; isoflavones are absorbed faster than lignans, while lignans are removed later. The combination of these molecules can guarantee a better reduction of postmenopausal symptoms over a 24-h period.

A study of the control of climacteric symptoms in postmenopausal women following sequential regimens of 1 mg 17β-estradiol and trimegestone compared with a regimen containing 1 mg estradiol valerate and norethisterone over a 2-year period

Objective. To compare the efficacy of two sequential 17β-estradiol (17β-E2)/trimegestone (TMG) combinations with the sequential estradiol valerate (E2V)/norethisterone (NET) regimen in relieving climacteric symptoms.Study design. This was a double-blind, randomized, multicenter study conducted among 1218 Caucasian (99%) postmenopausal women with an intact uterus in seven European countries and Israel, over 13 cycles (each of 28 days). Study duration was extended further for 13 cycles, with 531 women receiving treatment for up to 26 cycles. Treatments consisted of 1 mg 17β-E2 on days 1–14 and 1 mg 17β-E2/0.125 mg TMG or 0.25 mg TMG on days 15–28, and 1 mg E2V on days 1–16 and 1 mg E2V/1 mg NET on days 17–28.Results. Rapid and significant reductions in the mean daily number and severity of hot flushes and in the mean daily number of nocturnal sweats were established in most women with 1 mg 17β-E2/0.25 mg TMG and E2V/NET. These treatments also induced a significant improvement in the quality-of-life assessments.Conclusion. The 1 mg 17β-E2/0.25 mg TMG regimen provides rapid and effective relief of menopausal symptoms, with a reduction in the number of hot flushes ‘at least as good as’ that of the E2V/NET comparator.

Tibolone is effective for treating high levels of climacteric symptoms in postmenopausal women,

Tibolone is effective for treating high levels of climacteric symptoms in postmenopausal women,

Estradiol and drospirenone for climacteric symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled study of the safety and efficacy of three dose regimens

Method A randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of drospirenone (1, 2 or 3 mg) combined with estradiol (1 mg) in the treatment of climacteric symptoms in healthy postmenopausal women.Results The frequency of hot flushes was significantly decreased in all treatment groups (range 86–90%) in comparison to placebo (45%, p ⩽ 0.001) and remained suppressed at 16 weeks. Treatment with drospirenone and estradiol also decreased the intensity and severity of sweating, sleep problems, depression, nervousness, and urogenital symptoms. Most adverse events were mild or moderate, with similar rates observed in all groups. No serious adverse events or clinically significant laboratory abnormalities attributed to treatment occurred.Conclusion These results demonstrate that the combinations of 1, 2, and 3 mg drospirenone with 1 mg estradiol are safe and effective for the treatment of climacteric symptoms.

The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women

Evaluate the efficacy and acceptability of a novel vaginal ring delivering oestradiol acetate (Menoring) versus oral oestradiol for relief of climacteric symptoms in postmenopausal women. Prospective, multicentre, randomised, double-blind, comparator-controlled, parallel group study. Twenty-one centres in the United Kingdom. Postmenopausal women, aged <65 years experiencing > or =20 hot flushes/night sweats per week for two consecutive weeks. Patients received a vaginal ring releasing oestradiol acetate at a rate equivalent to 50 microg/day in addition to placebo tablets (vaginal ring group) or oral oestradiol 1 mg/day in addition to placebo vaginal ring (oral group) for 24 weeks. For patients with inadequate control of vasomotor symptoms, dosage was doubled at 12 weeks. Non-hysterectomised women received norethisterone 1 mg/day for 12 days in each 28 day cycle. Efficacy was assessed by change in climacteric symptoms measured by the Greene Climacteric Scale, as well as mean change in frequency of hot flushes/night sweats. A total of 159 patients were enrolled (84 vaginal ring, 75 oral). Significant improvement (P < 0.05) in mean total Greene Climacteric Scale scores in both treatment groups was observed at 12 and 24 weeks and for every subscale score including anxiety, depression and sexual dysfunction (P < 0.05). In both groups, frequency of hot flushes/night sweats was significantly reduced (P < 0.001) at 12 and 24 weeks. No significant between-group differences were noted at 12 or 24 weeks. The oestradiol vaginal ring significantly improved climacteric symptoms as measured by Greene Climacteric Scale scores and reduced the frequency of hot flushes/night sweats. Efficacy and safety of vaginal ring oestradiol were comparable with those of oral therapy. Patient evaluations of oestradiol vaginal ring tolerability and acceptability were excellent.

The effect of a novel vaginal ring delivering oestradiol acetate on climacteric symptoms in postmenopausal women

Objective Evaluate the efficacy and acceptability of a novel vaginal ring delivering oestradiol acetate (Menoring) versus oral oestradiol for relief of climacteric symptoms in postmenopausal women. Design Prospective, multicentre, randomised, double-blind, comparator-controlled, parallel group study. Setting Twenty-one centres in the United Kingdom. Population Postmenopausal women, aged <65 years experiencing ≥20 hot flushes/night sweats per week for two consecutive weeks. Methods Patients received a vaginal ring releasing oestradiol acetate at a rate equivalent to 50 μg/day in addition to placebo tablets (vaginal ring group) or oral oestradiol 1 mg/day in addition to placebo vaginal ring (oral group) for 24 weeks. For patients with inadequate control of vasomotor symptoms, dosage was doubled at 12 weeks. Non-hysterectomised women received norethisterone 1 mg/day for 12 days in each 28 day cycle. Main outcome measures Efficacy was assessed by change in climacteric symptoms measured by the Greene Climacteric Scale, as well as mean change in frequency of hot flushes/night sweats. Results A total of 159 patients were enrolled (84 vaginal ring, 75 oral). Significant improvement ( P < 0.05) in mean total Greene Climacteric Scale scores in both treatment groups was observed at 12 and 24 weeks and for every subscale score including anxiety, depression and sexual dysfunction ( P < 0.05). In both groups, frequency of hot flushes/night sweats was significantly reduced ( P < 0.001) at 12 and 24 weeks. No significant between-group differences were noted at 12 or 24 weeks. Conclusions The oestradiol vaginal ring significantly improved climacteric symptoms as measured by Greene Climacteric Scale scores and reduced the frequency of hot flushes/night sweats. Efficacy and safety of vaginal ring oestradiol were comparable with those of oral therapy. Patient evaluations of oestradiol vaginal ring tolerability and acceptability were excellent.

Effects of genistein on the endometrium: ultrasonographic evaluation

The aim of our study was to evaluate the effects of isoflavones on climacteric-related symptoms and on the endometrium in postmenopausal women ,in a prospective ,open ,randomized ,clinical trial performed at the Menopause Clinic of our Department. Seventy postmenopausal women were randomly assigned to two treatment groups receiving 12 cycles of treatment with genistein (group A) or calcium (group B). In all patients ultrasonographic endometrial thickness and Kupperman Index (KI) were evaluated at baseline and after 6 and 12 cycles of treatment. At baseline no significant difference was detected in endometrial thickness and in KI between groups A and B. After 6 and 12 cycles of treatment ,no significant difference was observed in endometrial thickness between or within groups. Endometrial thickness was lower than 5 mm in all cases before and during treatment except in two cases in group B and in one case in group A after 12 months. At 6 and 12 months ,the KI was significantly (p < 0.05) lower in group A in comparison with baseline values and group B. We conclude that genistein administration reduces climacteric symptoms in postmenopausal women and does not increase endometrial thickness.

Effects of genistein on the endometrium: ultrasonographic evaluation

The aim of our study was to evaluate the effects of isoflavones on climacteric-related symptoms and on the endometrium in postmenopausal women ,in a prospective ,open ,randomized ,clinical trial performedat the Menopause Clinic of our Department. Seventy postmenopausal women were randomly assigned to two treatment groups receiving 12 cycles of treatment with genistein (group A) or calcium (group B). Inall patients ultrasonographic endometrial thickness and Kupperman Index (KI) were evaluated at baseline and after 6 and 12 cycles of treatment. At baseline no significant difference was detected in endometrialthickness and in KI between groups A and B. After 6 and 12 cycles of treatment ,no significant difference was observed in endometrial thickness between or within groups. Endometrial thickness was lowerthan 5 mm in all cases before and during treatment except in two cases in group B and in one case in group A after 12 months. At 6 and 12 months ,the KI was significantly (p < 0.05) lower in groupA in comparison with baseline values and group B. We conclude that genistein administration reduces climacteric symptoms in postmenopausal women and does not increase endometrial thickness.

A pilot study comparing the clinical effects of Jia-Wey Shiau-Yau San, a traditional Chinese herbal prescription, and a continuous combined hormone replacement therapy in postmenopausal women with climacteric symptoms

Objectives: Interest in use of alternative remedies for managing menopausal symptoms is increasing exponentially during these years. Jia-Wey Shiau-Yau San (JWSYS), one of the traditional Chinese herbal prescriptions, is a famous herbal remedy used for the management of various menopausal-related symptoms. A randomized, controlled pilot study was performed to evaluate the clinical effects of JWSYS compared with those of a continuous combined hormone replacement therapy, Premelle ®, on quality of life in non-hysterectomized postmenopausal women. Methods: The present trial compared the effect of a l6-week treatment with JWSYS or HRT (Premelle ®) in postmenopausal women with climacteric symptoms. The Greene Climacteric Scale was used to assess the clinical effects at baseline and after 16 weeks’ treatment with either JWSYS or Premelle ®. The physiological parameters, such as follicle-stimulating hormone and estradiol levels, were also recorded at the same time points. Results: The results showed that JWSYS had a relatively lower discontinuation rate due to adverse effects, in particular the bleeding and breast tenderness. Both JWSYS and Premelle ® effectively alleviated most of the menopausal symptoms with no significant differences between treatment groups, whereas the beneficial effects of JWSYS were not mediated by hormone replacement-like effects. Moreover, JWSYS showed a good compliance and safety without estrogenic effects and metabolic alterations. Conclusions: It was suggested that JWSYS was a safe and efficacious therapy and might be an alternative choice for relief of climacteric symptoms in postmenopausal women. However, the exact efficacy and clinical roles of JWSYS have not been convincingly demonstrated in this study because of the blinding approach and some statistical concerns, and only the possibility of its efficacy has been raised. Therefore, a blinding trial with more patient numbers to evaluate the efficacy of JWSYS deserves further study.

Estradiol valerate/dienogest.

Estradiol valerate 2mg/dienogest 2mg is an oral estrogen/ progestogen formulation that has been approved throughout the European Union for the treatment of climacteric symptoms in postmenopausal women. Dienogest is a progestogen that combines the properties of both progesterone and 19-nortestosterone derivatives. It has moderate affinity for the progesterone receptor, significant antiproliferative and antiandrogenic activity, and produces secretory transformation of the endometrium. Estradiol valerate is an esterified form of natural 17beta-estradiol, the most potent endogenous human ovarian estrogen, and is hydrolysed to estradiol soon after oral administration. Results from a randomised, double-blind, multicentre trial showed that oral estradiol valerate 2mg/dienogest 2mg and estradiol valerate 2mg/dienogest 3mg once daily for 1 year were each as effective as estradiol 2mg/estriol 1mg/norethisterone acetate 1mg in the treatment of climacteric symptoms in 581 postmenopausal women; reductions from baseline in Kupperman Index scores were 78.5, 74.5 and 75.0%, respectively. The number of days without any type of bleeding was lowest in patients treated with estradiol valerate 2mg/dienogest 2mg (8.7 days), and highest in the estradiol valerate 2mg/ dienogest 3mg group (12.1 days). During the twelfth month of treatment with estradiol valerate 2mg/dienogest 2mg, the percentage of patients who reported bleeding was 14.5%. Endometrial biopsy results were similar in patients treated with estradiol valerate 2mg/dienogest 2mg, estradiol valerate 2mg/dienogest 3mg or estradiol 2mg/estriol 1mg/norethisterone acetate 1mg once daily for 1 year; 90.8, 87.4 and 87.5% of samples, respectively, contained atrophic material. Proliferative material was found in 4.2, 2.5 and 4.4% of the biopsies, respectively; there was no incidence of hyperplasia in any of the treatment groups. A noncomparative multicentre study in 1501 postmenopausal women demonstrated that adverse events associated with estradiol valerate 2mg/dienogest 2mg once daily for 48 weeks included breakthrough bleeding, mastalgia, headache, abdominal pain, hypertension, thrush, migraine, weight gain, increase in endometrial thickness and metrorrhagia.

The Effects of Estrogen Replacement Therapy on Blood Pressure, Heart Rate Variability, and Climacteric Symptoms in Postmenopausal Women

PURPOSE: Estrogen replacement therapy is indicated for the relief of hot flushes and urogenital atrophy, the prevention of osteoporosis and the reduction in risk of cardiovascular disease. The present study assessed by blood pressure, heart rate variability, and climacteric symptoms in menopausal women before treatment and at 1 month during estrogen replacement therapy. METHODS: The study sample consisted of 16 healthy menopausal women (range 49 to 59 years, mean : 53.4 years) attending menopausal clinics for the complaint of climateric symptoms at S. hospital in Chunchoen. They were all non-smokers and no patient had symptoms or evidence of cardiovascular disease. They took estrogen replacement therapy (conjugated estrogen 0.625 mg with or without medroxy progesteron 2.5mg) for 1 month. Blood pressure, heart rate variability(heart period and vagal tone) through ECG, and climacteric symptom were measured in all subjects before treatment and at 1 month during treatment. Climacteric symptom questionnaire which was developed by Neugarten et al.(1963) was modified with 20 items of question(Cronbach's alpha = 88 -.89). The data was collected from Sept. 1. 2000 to July. 30. 2001. RESULTS: There was no significant difference in mean systolic and diastolic pressure between the baseline and at 1 month during treatment. The mean heart period and vagal tone were slightly increased, but difference of mean heart period and vagal tone were not statistically significant between the baseline and at 1 month during treatment. The score of climacteric symptoms decreased significantly from the baseline after treatment. CONCLUSIONS: Even though, this study did not show that estrogen replacement therapy led decrease of blood pressure and increase heart rate variability, climacteric symptoms reduced much in all subjects after taking drugs. These results suggest that there is need to repeat study with long term period.

A Cost-Effectiveness Model of Tibolone as Treatment for the Prevention of Osteoporotic Fractures in Postmenopausal Women in Sweden

Background Osteoporosis is a major cause of morbidity and mortality in the elderly and, in particular, among postmenopausal women. Hormone replacement therapy (HRT) has been shown to protect against fractures, as well as to alleviate climacteric symptoms related to menopause. Unfortunately, HRT has a number of adverse effects and many patients are noncompliant. Tibolone, a synthetic steroid with tissue-specific estrogenic, progestogenic and androgenic effects, has been shown to prevent the loss of bone mass as well as to relieve climacteric symptoms in postmenopausal women, with fewer accompanying adverse effects.

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 (E 2) 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.

Aspectos clínicos e metabólicos de mulheres na pós-menopausa tratadas com tibolona

Objetivos: analisar a repercussão da tibolona sobre os sintomas do climatério e sobre algumas variáveis clínicas e metabólicas. Métodos: foram avaliadas 34 pacientes na pós-menopausa que foram submetidas ao tratamento com tibolona na dose de 2,5 mg/dia por 48 semanas. Foram analisados os seguintes parâmetros: peso, pressão arterial e perfis lipídico e lipoprotéico, representados pelos níveis de colesterol total, HDL-c, LDL-c, VLDL-c e triglicerídeos. Resultados: melhora relevante da sintomatologia do climatério foi demonstrada por decréscimo significativo do índice menopausal de Kupperman (p<0.001) e da freqüência média das ondas de calor (p<0.001). Estes efeitos foram observados já no primeiro mês de tratamento, mantendo-se até o final do estudo. Houve decréscimo significante nos níveis de colesterol total, triglicerídeos e VLDL-c (p<0.001). Os níveis de LDL-c apresentaram discreta redução (não-significante). Os níveis de HDL-c mostraram decréscimo significante na 24ª semana de tratamento, mas retornaram aos níveis basais na 48ª semana. Não foram observadas modificações significantes no peso e pressão arterial. Os efeitos colaterais relatados incluíram sangramento vaginal, náusea e edema, todos temporários e de intensidade leve. Conclusão: a tibolona representa uma opção para o tratamento dos sintomas climatéricos em mulheres na pós-menopausa, sem alterações relevantes no perfil lipídico e lipoprotéico.

Continuous, Combined Hormone Replacement

In Brief Objective To compare two new transdermal, continuous, combined formulations and an oral regimen of hormone replacement therapy (HRT) with respect to endometrial hyperplasia, bleeding patterns, and climacteric symptoms in postmenopausal women. Methods This was a randomized, open, parallel-group trial during 1 year in 441 postmenopausal women who received either a 10-cm2 patch of 0.025 mg estradiol (E2) and 0.125 mg norethisterone acetate, a 20-cm2 patch of 0.05 mg E2 and 0.25 mg norethisterone acetate twice weekly, or tablets of 2 mg E2 and 1 mg norethisterone acetate once daily. The efficacy variables were frequency of endometrial hyperplasia after 1 year of treatment, number of bleeding and spotting days from the fourth to sixth treatment months, relief of climacteric symptoms, and tolerability. Results The frequency of endometrial hyperplasia was no more than 2% after 1 year of treatment in all groups. One case of simple hyperplasia was detected among the women treated with 10-cm2 patches and two among those treated with oral HRT. From the fourth to sixth treatment months, amenorrhea occurred in 73%, 47%, and 66% of the women in the 10-cm2, 20-cm2, and oral HRT groups, respectively. The 10-cm2 patches and oral treatment were associated with fewer bleeding days than were the 20-cm2 patches (P < .001). During the last 3 months of the treatment year, amenorrhea was found in 100 subjects (86%) for 10-cm2 patches, 61 (65%) for 20-cm2 patches, and in 85 (79%) for oral HRT. All treatments alleviated the climacteric symptoms to a comparable extent. Conclusion In postmenopausal women, 10-cm2 patches relieved climacteric symptoms and prevented endometrial hyperplasia at least as effectively as oral HRT. Amenorrhea was induced early in a high percentage of women using 10-cm2 patches and oral HRT, and these therapies seemed to be convenient, effective, and safe for estrogen deficiency symptoms in postmenopausal women. Continuous, combined hormone replacement in a low-dose, transdermal application is equally effective and safe and induces amenorrhea to a similar extent as an oral formulation.

Continuous, combined hormone replacement: randomized comparison of transdermal and oral preparations

Objective: To compare two new transdermal, continuous, combined formulations and an oral regimen of hormone replacement therapy (HRT) with respect to endometrial hyperplasia, bleeding patterns, and climacteric symptoms in postmenopausal women. Methods: This was a randomized, open, parallel-group trial during 1 year in 441 postmenopausal women who received either a 10-cm 2 patch of 0.025 mg estradiol (E2) and 0.125 mg norethisterone acetate, a 20-cm 2 patch of 0.05 mg E2 and 0.25 mg norethisterone acetate twice weekly, or tablets of 2 mg E2 and 1 mg norethisterone acetate once daily. The efficacy variables were frequency of endometrial hyperplasia after 1 year of treatment, number of bleeding and spotting days from the fourth to sixth treatment months, relief of climacteric symptoms, and tolerability. Results: The frequency of endometrial hyperplasia was no more than 2% after 1 year of treatment in all groups. One case of simple hyperplasia was detected among the women treated with 10-cm 2 patches and two among those treated with oral HRT. From the fourth to sixth treatment months, amenorrhea occurred in 73%, 47%, and 66% of the women in the 10-cm 2, 20-cm 2, and oral HRT groups, respectively. The 10-cm 2 patches and oral treatment were associated with fewer bleeding days than were the 20-cm 2 patches ( P < .001). During the last 3 months of the treatment year, amenorrhea was found in 100 subjects (86%) for 10-cm 2 patches, 61 (65%) for 20-cm 2 patches, and in 85 (79%) for oral HRT. All treatments alleviated the climacteric symptoms to a comparable extent. Conclusion: In postmenopausal women, 10-cm 2 patches relieved climacteric symptoms and prevented endometrial hyperplasia at least as effectively as oral HRT. Amenorrhea was induced early in a high percentage of women using 10-cm 2 patches and oral HRT, and these therapies seemed to be convenient, effective, and safe for estrogen deficiency symptoms in postmenopausal women.