Menopausal Complaints Research Articles

Estrogen receptor beta and its selective ligands: an option for treatment of menopausal vasomotor symptoms?

Abstract In the human female, menopause is the permanent end of fertility, defined as occurring 12 months after the last menstrual period. During peri- and postmenopausal stages, the vast majority of women experience moderate-to-severe vasomotor symptoms, such as hot flashes and night sweats, which interfere with sleep and may be severe enough to affect quality of life. The only treatment approved by national health authorities is hormone therapy with estrogen alone or in combination with a progestagen. However, this therapeutic regimen is associated with severe side effects, such as stimulation of growth of breast cancer or cardiovascular events. Thus, there is a demand for efficient and safe alternative treatments for menopausal complaints. After the discovery of estrogen receptor beta in many organs, and confirmation of its presence in the brain, many researchers raised the question of whether ERβ-specific ligands may be novel therapeutic agents for treatment of menopausal complaints with the desirable effects of estrogen but without increased risk of tumor incidence. This minireview will briefly summarize the relevance of estrogen receptor beta and its specific ligands for the treatment of menopausal symptoms with a focus on vasomotor menopausal symptoms. At present, estrogen receptor beta-selective ligands do not seem to be active in models of prevention or reversal of osteoporosis. However, data from animal experiments suggest that estrogen receptor beta-selective ligands might be safe therapeutics for the treatment of vasomotor menopausal symptoms.

Differentiated Evaluation of Extract-Specific Evidence on Cimicifuga racemosa's Efficacy and Safety for Climacteric Complaints.

Past reviews on Cimicifuga racemosa (CR) without differentiation between extracts, quality, and indication altogether led to inconsistent data. Therefore, for the first time, we meet the requirements of the system's logic of evidence-based phytotherapy by taking into consideration extracts, pharmaceutical quality (reflected in a regulatory status as medicinal product), and indication. A literature search for clinical studies examining CR's efficacy and safety for menopausal complaints was conducted. The results were sorted by type of extract, regulatory status, and indication. Accordingly, Oxford Levels of Evidence (LOE) and Grades of Recommendation (GR) were determined. CR extracts demonstrated a good to very good safety in general, on estrogen-sensitive organs and the liver. However, only registered CR medicinal products were able to prove their efficacy. Best evidence was provided by the isopropanolic CR extract (iCR): the multitude of studies including more than 11,000 patients demonstrated consistent confirmatory evidence of LOE 1b (LOE 1a for safety) leading to GR A. The studies on the ethanolic extract BNO 1055 including more than 500 patients showed exploratory evidence of LOE 2b resulting in GR B. A positive benefit-risk profile is stated and limited to Cimicifuga racemosa products holding a marketing authorisation for treating climacteric complaints.

How are Interactions Taken into Account in Studies on Conventional and Complementary Therapies for Breast Cancer Patients with Menopausal Complaints?

Introduction: Postmenopausal symptoms in breast cancer patients undergoing antihormone treatment lead to high drop-out rates from the therapy. From the therapeutic point of view, methods of both conventional and complementary medicine are concerned. Interactions are being discussed in cases of natural substances. However, they are also relevant for conventional medical substances. The aim of this analysis is to answer the question as to what extent potential interactions are taken into account in clinical studies and reviews on supportive therapies. Materials and Methods: Clinical studies and reviews were identified by means of a systematic search and analysed with regard to the consideration of potential interactions. Results: Altogether 46 clinical studies and one Cochrane review were found. Among the 35 studies on conventional drug therapies, 5 (14 %) took possible interactions into account. Among the 17 studies on complementary medicine, there were 2 (11.7 %) such publications. The Cochrane review did not mention interactions. Discussion: For future studies in which interactions cannot be excluded, a strategy to control for their clinically relevant consequences should be developed. The present authors suggest that the use of survival and recurrence data as secondary endpoints, also for studies on purely supportive therapies, is a reasonable approach. The resulting considerations for study routines are listed thematically.

Menopausal complaints in Slovak midlife women and the impact of CYP1B1 polymorphism on their incidence

A wide variety of symptoms have been attributed to menopause, negatively influencing women's physical and psychological health. In addition to lifestyle parameters and personal history, genetic factors are considered to be the main source of this variation. This study aims to investigate the incidence of menopausal symptoms among midlife women according to their menopausal status, and to evaluate the contribution to their manifestation from CYP1B1 Leu432Val polymorphism as a predisposing factor for menopausal symptoms. The studied cohort consisted of 299 women ranging from 39 to 59 years of age. Women were recruited from the western and middle parts of Slovakia, and all participants completed a menopause-specific questionnaire and provided blood or saliva samples for genotyping. Our results indicated that all women are at risk of typical menopausal symptoms, but there is a higher number of postmenopausal women affected than premenopausal ones. Regression analysis showed that the CYP1B1 Leu/Leu genotype can increase the experience of bloated stomach and facial hair increase in all the sampled women, while the Leu/Leu genotype may increase experience of palpitations and involuntary urination in the premenopausal women. The Leu/Leu genotype may increase the experience of nausea, bloated stomach, and vaginal dryness in peri- and postmenopausal women. We determined that women with the Leu/Leu, or Leu/Val genotypes were approximately five times more likely to suffer from vaginal dryness than the Val/Val women (OR = 4.948; 95% CI, 1.259-19.447). We therefore suggest that CYP1B1 Leu432Val polymorphism could be involved in individual susceptibility to menopausal symptoms in Slovak midlife women.

Klimakterische Beschwerden über die Lebensspanne? Ergebnisse einer repräsentativen Umfrage in der deutschen Allgemeinbevölkerung

Aim of the present investigation was the assessment of magnitude and distribution of subjective menopausal complaints in the German population. Study participants included 1 350 women aged 14-92 years, completing the menopause rating scale (MRS II). A total of 22% of the women exhibited considerable/severe menopausal complaints. Symptoms as sleep problems, joint and muscular discomfort, heart discomfort and physical and mental exhaustion increased drastically with advancing age. Hot flushes/sweating were the only symptoms specifically assigned to the menopausal period. Significant predictors for the intensity of menopausal complaints were: region of living, age, level of psychic burden, somatic complaints, depression, stress and fatigue. It is concluded that menopausal symptoms referred to in the literature must be questioned to be phase specific. Further research on aetiological factors is needed.

Alternative methods for the treatment of post-menopausal troubles.

BackgroundMenopause is described as the transition from the reproductive phase of a women to the non reproductive. Changes in hormone levels might lead to complaints and health consequences especially during peri- and postmenopause. Hormone therapy has a potential damaging health risk profile and is recommended for temporal limited therapy for acute vasomotor symptoms only.ObjectiveThe present HTA-report aims to assess the effectiveness and the cost-effectiveness of alternative treatment methods for women with postmenopausal symptoms in Germany regarding patient relevant endpoints (reduction of symptoms and frequency of adverse events and improvement of quality of life).MethodsA systematic literature search was carried out in 33 relevant databases in September 2010. Citations were selected according to pre-defined criteria and were extracted and evaluated.ResultsIn the systematic research 22 studies are identified for the effectiveness evaluation, 22 primary studies and one review.High doses of isolated genistein reduce the frequency/intensity of hot flashes while low doses of genistein show no significant effect. Intake of isoflavone extract such as genistein, daidzein, glycitein in various combinations does not have an effect on improvement of cognitive function or vaginal dryness. The effect of black cohosh and hop extract for menopausal complaints cannot be determined since results are heterogenous. The combination of isoflavone, black cohosh, monk’s pepper, valerian and vitamin E has a positive effect on menopause symptoms. Ginkgo biloba shows no significant effect on menopause symptoms and cognitive improvement beside mental flexibility. Acupuncture has a significant influence on hot flashes especially in severe cases.Discussion/ConclusionNo final statement can be drawn regarding the effectiveness of alternative treatment methods due to qualitative shortcomings of included studies and a general limited availability of studies in this field. Furthermore, the generalization of the present HTA is limited due to the inclusion of only postmenopausal women.

Short-term hormone therapy improves sCD40L and endothelial function in early menopausal women: Potential role of estrogen receptor polymorphisms

ObjectiveHormone therapy (HT) has been suggested to improve vascular function and inflammation in menopausal women, although not consistently. We aimed to investigate the effects of HT on endothelial function and inflammation, especially sCD40L, in early menopausal women, and the effect of common estrogen receptor (ER) polymorphisms on vascular responses to HT. Study designEighty-four early menopausal women (<3 years in menopause) with menopausal complaints eligible for HT. Forty women received transdermal 17β-estradiol plus cyclical micronized progesterone for 3 months while 44 did not (controls). Main outcome measuresBrachial artery flow-mediated dilation (FMD) and vascular inflammation markers (sICAM, sP-Selectin and sCD40L). Genetic polymorphisms of ERα (PvuII 454-397T>C and XbaI 454-351A>G) and ERβ (AluI 1730A>G) were also assessed. ResultsThe two groups did not differ at baseline. Following HT, vasomotor complaints’ severity, blood pressure, LDL, sCD40L, sICAM and sP-Selectin decreased and FMD increased compared to controls (P<0.05 for all). ERβ AluI A allele presence was the most important independent predictor of HT-induced increase in FMD while ERα XbaI A allele was the only independent predictor of decrease in sCD40L. ConclusionsShort-term HT in early menopausal women improved endothelial function and inflammation. Specific ER polymorphisms that were found to be main determinants of HT-induced effects on endothelium could identify subgroups of women who may benefit the most from HT.

Prenylated isoflavonoids from plants as selective estrogen receptor modulators (phytoSERMs)

Isoflavonoids are a class of secondary metabolites, which comprise amongst others the subclasses of isoflavones, isoflavans, pterocarpans and coumestans. Isoflavonoids are abundant in Leguminosae, and many of them can bind to the human estrogen receptor (hER) with affinities similar to or lower than that of estradiol. Dietary intake of these so-called phytoestrogens has been associated with positive effects on menopausal complaints, hormone-related cancers, and osteoporosis. Therefore, phytoestrogens are used as nutraceuticals in functional foods or food supplements. Most of the isoflavonoids show agonistic activity towards both hERα and hERβ, the extent of which is modulated by the substitution pattern of their skeleton (i.e.-OH, -OCH(3)). Interestingly, substitutions consisting of a five-carbon prenyl group often seem to result in an antiestrogenic activity. There is growing evidence that the action of some of these prenylated isoflavonoids is tissue-specific, suggesting that they act like selective estrogen receptor modulators (SERMs), such as the well-known chemically synthesized raloxifene and tamoxifen. These so-called phytoSERMS might have high potential for realizing new food and pharma applications. In this review, the structural features of isoflavonoids (i.e. the kind of skeleton and prenylation (e.g. chain or pyran), position of the prenyl group on the skeleton, and the extent of prenylation (single, double)) are discussed in relation to their estrogenic activity. Anti-estrogenic and SERM activity of isoflavonoids was always associated with prenylation, but these activities did not seem to be confined to one particular kind/position of prenylation or isoflavonoid subclass. Few estrogens with agonistic activity were prenylated, but these were not tested for antagonistic activity; possibly, these molecules will turn out to be phytoSERMs as well. Furthermore, the data on the dietary occurrence, bioavailability and metabolism of prenylated isoflavonoids are discussed.

Mass spectrometric dereplication of nitrogen-containing constituents of black cohosh (Cimicifuga racemosa L.)

Black cohosh preparations are popular dietary supplements among women seeking alternative treatments for menopausal complaints. For decades, triterpene glycosides and phenolic acids have dominated the phytochemical and biomedical research on this plant. In this study, we provide evidence that black cohosh contains an unexpected and highly diverse group of secondary nitrogenous metabolites previously unknown to exist in this plant. Using a dereplication approach that combines accurate mass measurements, database searches and general knowledge of biosynthetic pathways of natural products, we identified or tentatively identified 73 nitrogen-containing metabolites, many of which are new natural products. The identified compounds belong to several structural groups including alkaloids, amides or esters of hydroxycinnamic acids and betains. Among the alkaloids, several classes such as guanidino alkaloids, isoquinolines and β-carbolines were identified. Fragmentation patterns for major compound classes are discussed, which provides a framework for the discovery of these compounds from other sources. Identification of alkaloids as a well-known group of bioactive natural products represents an important advance in better understanding of the pharmacological profile of black cohosh.

Menopausal symptoms and risk factors for cardiovascular disease in postmenopause

ABSTRACTObjectives Conflicting evidence indicates an increased risk for cardiovascular disease in postmenopausal women suffering from hot flushes. In this study, we tested whether, beyond hot flushes, menopausal symptoms are associated with biochemical and biophysical risk factors for cardiovascular disease.Methods Retrospective cross-sectional analysis on 951 women in surgical or physiological postmenopause, recruited at the menopause outpatient service of our university hospital between April 2002 and December 2009. The Greene Climacteric Scale and its subscales for anxiety, depression, somatic symptoms, vasomotor symptoms and sexuality were used to evaluate menopausal complaints. Blood pressure, fasting glucose and lipids levels were evaluated as risk factors for cardiovascular disease. Anthropometric parameters and those derived by remote and reproductive medical history were used as possible confounders. All data were anonymously retrieved from an electronic database.Results By multiple regression analysis, high density lipoprotein (HDL) cholesterol was inversely related to body mass index, the Greene Climacteric Scale score and years since menopause (R = 0.390; p = 0.0001). The total cholesterol/HDL cholesterol ratio was positively related to waist circumference and the Greene Climacteric Scale score (R = 0.356; p = 0.0001). Triglycerides (R = 0.353; p = 0.0001) and triglyceride/HDL cholesterol (R = 0.425; p = 0.0001) were positively related to waist circumference, the Greene Climacteric Scale score and the Greene vasomotor subscore. Glucose was positively related to waist circumference, years since menopause and the Greene Climacteric Scale score (R = 0.390; p = 0.0001). Blood pressure was not related to menopausal symptoms. The 10-year risk for cardiovascular disease calculated by the Framingham formula was related independently and directly to body mass index and the Greene Climacteric Scale score (R = 0.183; p = 0.0001).Conclusions Menopausal symptoms evaluated by a validated climacteric scale are associated with a worsening of biochemical risk factors for atherosclerosis and cardiovascular disease.

Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue.

Tibolone (Org-OD14) is the active substance of Livial®, a synthetic steroid with the structure 7α,17α-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and androgenic properties, used to treat menopausal complaints. After oral administration, tibolone is extensively metabolized into the 3α-(Org-4904) and 3β-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene (Org-OM38) isomer with progestogenic/androgenic activities, and the 3α-sulfate (Org-34322) derivative, a major biologically inactive circulating form. We compared the dose response of tibolone and its metabolites on estrone sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in normal and cancerous human breast tissues. Tissue minces were incubated with physiological concentrations of [3H]-E1S (5×10-9M) alone or in the presence of tibolone and its metabolites (concentration range: 5×10-7to 5×10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and evaluated quantitatively by thin-layer chromatography. The sulfatase activity was significantly higher in cancerous breast but strongly inhibited by tibolone and the different metabolites, whereas 3α- and 3β-hydroxy derivatives were the most potent inhibitors. This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients.

HPTLC method for the quantification of isoflavones in nutritional supplements of red clover (Trifolium pratenseL.)

Nutritional supplements of red clover (Trifolium pratense L.) have gained an increasing popularity in the western diet as an alternative treatment for menopausal complaints such as hot flashes. These effects are attributed to the present isoflavones with high amounts of formononetin, biochanin A, daidzein, glycitein and genistein. Isoflavones are nonsteroidal compounds, which are also called phytoestrogens because of their weak estrogenic effect. For the identification and quantification of these flavonoids, an HPTLC method was established. Chromatography was performed on silica gel HPTLC glass plates with dichloromethane-glacial acetic acid-ethyl acetate (12:2:1, v/v) as mobile phase leading to sufficient separation of the components. Consistent results could be achieved and an efficient distinction between different botanical supplements was possible. HPTLC analysis proved to be an inexpensive method for the quality control of red clover-based dietary supplements.

Long-term effects of the rhapontic rhubarb extract ERr 731 ® on estrogen-regulated targets in the uterus and on the bone in ovariectomized rats

The efficacy of ERr 731 ®, a commercially available extract isolated from Rheum rhaponticum, in terms of menopausal complaints like hot flushes, depression, anxiety and vaginal dryness has been proven in a two-year clinical study. Further a recent preclinical study excluded unwanted side effects on the endometrium by showing a lack of stimulation of proliferation marker genes by ERr 731 ® or its constituents in the 3-day uterotrophic assay. The present study aimed at further substantiating the safety of ERr 731 ® in terms of endometrial hyperplasia and at the same time test for potential estrogenic effects in the bone. Therefore, ovariectomized (ovx) rats were treated in a dietary long-term administration for 90 days. Hence, the modulation of proliferation in the uterus was investigated by examining the effects on the mRNA expression of proliferation marker genes ( Mki67, Pcna), on the estrogen-responsive gene C3 and on the estrogen receptors ERα and ERβ. We additionally performed densitometry analysis of the proximal tibia metaphysis using peripheral computed tomography (pQCT) and quantified bone homeostasis markers in the serum to examine potential effects on the bone. In this study design, neither an uterotrophic response nor a modulation of proliferation marker genes on mRNA level has been observed as response to the long-term application of the rhapontic extract. Furthermore, no impact of the two administered ERr 731 ® doses on the E2 deprivation-induced bone loss has been evident at the end of the study. In conclusion, the observations from previous trials regarding the endometrial safety of ERr 731 ® have been supported by our experimental findings that exclude a stimulatory activity on proliferation in the uterus in a long-term administration in the young adult rat but no effect on the bone mineral density could be observed.

Long-term effects of the rhapontic rhubarb extract ERr 731® on estrogen-regulated targets in the uterus and on the bone in ovariectomized rats

The efficacy of the commercially available extract ERr 731® from Rheum rhaponticum L. regarding attenuation of menopausal complaints like hot flushes, depression, anxiety and vaginal dryness has been proven in a two-year clinical study. Further, no undesired side effects like uterotrophy or proliferation of the endometrium became apparent while testing ERr 731® in a 3-day uterotrophic assay. The present study aimed at further substantiating the safety of application of ERr 731® regarding endometrial hyperplasia and at the same time test for potential bone sparing effects in the preclinical ovariectomized (ovx) rat model. For this purpose we performed a 90d dietary feeding study in ovx rats. The impact of exposure on uterine proliferation was investigated by assessing the mRNA levels of proliferation marker genes (Mki67, Pcna) in comparison to the expression of the mRNAs of the estrogen receptors ESR1 and ESR2 and the estrogen response gene C3. To test for potential effects on the bone, we additionally performed densitometry analysis of the proximal tibia metaphysis using peripheral computed tomography and quantified bone homeostasis marker in the serum. With this study design, neither an uterotrophic response nor a modulation of mRNA levels of proliferation markers was detected after 90d of dietary exposure with the rhapontic extract. Furthermore, no effect of the two administered doses of ERr 731® on E2 deprivation induced bone loss became apparent. In conclusion, the observations from previous trials regarding the endometrial safety of ERr 731® application were substantiated, but no effect on the Bone Mineral Density could be observed.

Assessing Risks and Benefits of Nonhormonal Treatments for Vasomotor Symptoms in Perimenopausal and Postmenopausal Women

Vasomotor symptoms (VMS); (hot flushes and night sweats) are the most common menopausal complaint for which women seek treatment. Several therapies can be considered to help manage these complaints. The objective of this review is to assess the risks and benefits of available and emerging therapeutic options for the management of menopausal VMS. A review of the literature was conducted based on relevant publications identified through a PubMed search for clinical trials of agents used in the treatment of VMS. Hormone therapy (HT) remains the most effective treatment available, but there will always remain a need for nonhormonal options. Evidence does not support the efficacy of alternative or over-the-counter products, such as phytoestrogens and black cohosh, and their long-term safety is largely unknown. There is evidence supporting the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the management of VMS from clinical trials of paroxetine, venlafaxine, and desvenlafaxine. Gabapentin appears to be effective, but the doses required may cause poor tolerability and reduced patient adherence. Data also suggest that clonidine has a modest effect at the expense of considerable adverse effects. Choosing an appropriate treatment approach for the management of VMS requires careful assessment of the riskbenefit ratio of each alternative, as well as individual patient preference.

First time proof of sage’s tolerability and efficacy in menopausal women with hot flushes

This trial aimed to assess the tolerability and efficacy of a fresh sage preparation in treating hot flushes and other menopausal complaints. Sage (Salvia officinalis) has been traditionally used to treat sweating and menopausal hot flushes, as well as to alleviate associated menopausal symptoms and as a general tonic. However, no clinical studies substantiating the use of sage in menopause have been published previously. In an open, multicenter clinical trial conducted in eight practices in Switzerland, 71 patients (intent-to-treat population [ITT], n=69; with a mean age of 56.4±4.7 years, menopausal for at least 12 months, and with at least five flushes daily) were recruited and treated with a once-daily tablet of fresh sage leaves for 8 weeks after an introductory baseline week. Parameters for the evaluation of efficacy were the change in intensity and frequency of hot flushes, and total score of the mean number of intensity-rated hot flushes (TSIRHF) as determined by diary protocol over the 2-month treatment period. Other variables included assessment of the Menopause Rating Scale (MRS) by the treating physician at baseline and after 2 months of therapy. In the ITT population there was a significant decrease in the TSIRHF by 50% within 4 weeks and by 64% within 8 weeks (P<0.0001). The mean total number of hot flushes per day decreased significantly each week from week 1 to 8. The mean number of mild, moderate, severe, and very severe flushes decreased by 46%, 62%, 79%, and 100% over 8 weeks, respectively. The MRS and its somato-vegetative, psychological, and urogenital subscales decreased significantly by 43%, 43%, 47%, and 20% respectively. The treatment was very well tolerated. A fresh sage preparation demonstrated clinical value in the treatment of hot flushes and associated menopausal symptoms.

Hot Flashes: Is the Road Even Longer Than We Thought?

Hot flashes, the most common menopausal complaint, have been reported to last from 6 months to >5 years (JW Womens Health Jun 18 2009). To understand

The Effect of Acupuncture on Postmenopausal Symptoms and Reproductive Hormones: A Sham Controlled Clinical Trial

Acupuncture is commonly used to treat menopausal symptoms and other gynaecological conditions. In this study, the authors aimed to investigate whether acupuncture has an effect on menopausal symptoms and to explore whether this effect is related to changes in hormone levels. Materials and methods A total of 53 postmenopausal women were alternately assigned into two treatment groups: acupuncture (n=27) and sham acupuncture (n=26). Menopausal symptoms were assessed using the Menopause Rating Scale (MRS). The serum oestradiol, follicular stimulating hormone (FSH) and luteinising hormone (LH) levels were measured at baseline and again after the first and last sessions. The Student t test was used for normally distributed data and the Wilcoxon signed rank test for not normally distributed data. The group differences in MRS scores were assessed using non-parametric Mann-Whitney U test. After treatment, total MRS, and the somatic and psychological subscale scores were significantly lower in the acupuncture group than the sham group (all p=0.001). The severity of hot flushes was found to be significantly decreased after treatment in acupuncture group (p=0.001). In the acupuncture group LH levels were lower and oestradiol levels were significantly higher than sham group (p=0.046 and p=0.045, respectively) after treatment, but there was no difference in FSH levels. Acupuncture was effective in reducing menopausal complaints when compared to sham acupuncture and can be considered as an alternative therapy in the treatment of menopausal symptoms.

Self‐reported cognitive functioning in postmenopausal breast cancer patients before and during endocrine treatment: findings from the neuropsychological TEAM side‐study

This study aimed to evaluate self-reported cognitive functioning of postmenopausal breast cancer patients before and during endocrine treatment compared with healthy female controls, and to investigate associations between self-reported cognitive functioning, cognitive test performance and anxiety/depression, fatigue, and menopausal complaints. Self-reported cognitive functioning, anxiety/depression, fatigue, menopausal complaints, and cognitive tests performance were assessed before (T1) and after 1 year (T2) of adjuvant endocrine treatment in postmenopausal chemotherapy-naïve breast cancer patients. Self-reported cognitive functioning was assessed by the cognitive failures questionnaire and interview questions concerning cognitive complaints. Patients participated in the TEAM-trial, a prospective randomized study investigating tamoxifen versus exemestane as adjuvant therapy for hormone-sensitive breast cancer. Identical information was obtained from healthy postmenopausal volunteers. Two measures for self-reported cognitive functioning provided the distinctive results. At T1 and T2, healthy controls reported a higher frequency of cognitive failures than patients; change over time did not differ between groups. The prevalence of cognitive complaints did not differ between the groups at T1, but change over time regarding attention/concentration complaints differed between groups, due to an increased prevalence in tamoxifen users. Self-reported cognitive functioning showed moderate associations with anxiety/depression, fatigue, and menopausal complaints. Cognitive test performance was not associated with self-reported cognitive functioning, but weakly with anxiety/depression and fatigue. Adjuvant therapy with tamoxifen and exemestane did not influence the self-reported frequency of cognitive failures. Increased attention/concentration complaints were observed in tamoxifen users, but not in exemestane users. This latter finding should be confirmed with better validated instruments.

Black cohosh (Cimicifuga racemosa) in tamoxifen-treated breast cancer patients with climacteric complaints – a prospective observational study

Objective. The antihormonal therapy of breast cancer patients with the antiestrogen tamoxifen often induces or aggravates menopausal complaints. As estrogen substitution is contraindicated, herbal alternatives, e.g. extracts of black cohosh are often used.Design. A prospective observational study was carried out in 50 breast cancer patients with tamoxifen treatment. All patients had had surgery, most of them had undergone radiation therapy (87%) and approximately 50% had received chemotherapy. Every patient was treated with an isopropanolic extract of black cohosh (1–4 tablets, 2.5 mg) for 6 months. Patients recorded their complaints before therapy and after 1, 3, and 6 months of therapy using the menopause rating scale (MRS II).Results. The reduction of the total MRS II score under black cohosh treatment from 17.6 to 13.6 was statistically significant. Hot flashes, sweating, sleep problems, and anxiety improved, whereas urogenital and musculoskeletal complaints did not change. In all, 22 patients reported adverse events, none of which were linked with the study medication; 90% reported the tolerability of the black cohosh extract as very good or good.Conclusions. Black cohosh extract seems to be a reasonable treatment approach in tamoxifen treated breast cancer patients with predominantly psychovegetative symptoms.