Side effects of low-dose tamoxifen: results from a six-armed randomised controlled trial in healthy women.

BACKGROUND: Adherence to adjuvant tamoxifen therapy is suboptimal, and acceptance of tamoxifen for primary prevention is poor. Published results indicate effect of low-dose tamoxifen therapy. Using questionnaire data from a randomised controlled trial, we describe side effects of standard and low-dose tamoxifen in healthy women. METHODS: In the KARISMA trial, 1440 healthy women were randomised to 6 months of daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. Participants completed a 48-item, five-graded Likert score symptom questionnaire at baseline and follow-up. Linear regression models were used to identify significant changes in severity levels across doses and by menopausal status. RESULTS: Out of 48 predefined symptoms, five were associated with tamoxifen exposure (hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps). When comparing these side effects in premenopausal women randomised to low doses (2.5, 5 mg) versus high doses (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose-dependent difference was seen in postmenopausal women. CONCLUSIONS: Symptoms related to tamoxifen therapy are influenced by menopausal status. Low-dose tamoxifen, in contrast to high-dose, was associated with less pronounced side effects, a finding restricted to premenopausal women. Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03346200.

Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health.

Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.

Morning chronotype is a protective factor against chemotherapy-induced hot flashes in premenopausal women with breast cancer.

PURPOSE: Adjuvant chemotherapy in patients with breast cancer often causes hot flashes, impairing quality of life. However, the chronobiological or psychiatric factors associated with the development of chemotherapy-induced hot flashes (CIHFs) remain undetermined. The purpose of this study was to investigate whether chronotype was associated with the incidence of CIHFs. METHODS: A total of 119 premenopausal women with non-metastatic breast cancer awaiting adjuvant chemotherapy after surgery without hot flashes were included. The presence of CIHF was defined as having moderate to severe hot flashes, as measured by the subscale of hot flashes in the Menopause Rating Scale, at 4 weeks after the completion of chemotherapy. Chronotype (Morning/Intermediate/Evening) was assessed with the Composite Scale of Morningness before adjuvant chemotherapy. To examine the association between chronotype and CIHF, we built logistic regression models, adjusting for age, body mass index, sleep quality, and radiation therapy. RESULTS: CIHF occurred in 50.4% of participants. Morning type was inversely associated with CIHF (reference: Intermediate type, odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16-0.94; p = 0.040) in the univariate model, and the association remained significant (OR, 0.37; CI, 0.13-0.96; p = 0.045) after adjusting for age, body mass index, sleep quality, and radiation therapy. CONCLUSIONS: Morning chronotype is a protective factor against the development of CIHF in patients with breast cancer. Chronotypes should be assessed and considered in the prediction and management of CIHF.

Design of a randomized controlled trial on the efficacy of a reproductive health survivorship care plan in young breast cancer survivors.

BACKGROUND: Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. PURPOSE: Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. METHODS: SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient. HCP outcomes are preparedness and confidence in discussing each issue. RESULTS: Among 318 YBCS screened, 57.2% underwent randomization. Mean age was 40.0 (SD 5.9), and mean age at cancer diagnosis was 35.6 (SD 5.4). Significant hot flashes, fertility-related concerns, vaginal symptoms, and inadequate contraception were reported by 50.5%, 50%, 46.7%, 62.1% of YBCS, respectively; 70.9% had multiple issues. Among 165 nominated HCPs, 32.7% enrolled. The majority of HCPs reported preparedness (68.5-90.7%) and confidence (50.0-74.1%) in discussing reproductive health issues with YBCS. HCPs were least likely to report preparedness or confidence in discussing fertility-related concerns. CONCLUSION: Conducting a trial for improving YBCS reproductive health online is feasible, providing a mechanism to disseminate evidence-based management.

Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Soy isoflavones may benefit some, but not all, menopausal women, and the ability of the women to produce equol may be the major determinant of effectiveness. We assessed the efficacy of soy isoflavones and equol for alleviating menopausal symptoms, especially vasomotor symptoms, in postmenopausal women who were equol producers and nonproducers by using systematic review and meta-analysis of randomized clinical trials (RCTs). We searched 12 English, Korean, and Chinese language scientific and medical databases. We selected all available RCTs that assessed the effect of equol, either equol itself or soy isoflavone in equol producers, on menopausal symptoms in peri- or postmenopausal women. The primary outcome was the effect on hot flashes. The severity of hot flashes was determined by the scores, and sensitivity and risk of bias analyses were conducted. Other outcomes of the review, but not meta-analysis, included depression and adverse events. Six studies (779 total subjects) met all criteria for the systematic review, 5 of those could be included in the meta-analysis (728 total subjects). Two studies included in the meta-analysis reported no statistically significant benefits of equol; the other three did report significant benefits of equol. Meta-analysis revealed a significant benefit of equol for lowering hot flash scores and revealed a generally low risk of bias. In conclusion, this study found that supplementing equol to equol nonproducers significantly lowered the incidence and/or severity of hot flashes in menopausal women.

Menopause Symptom Management in the United Kingdom.

Menopause is a complex time in a woman's life. It is an increasingly a midlife event, when health care professionals should be aiming to optimize a woman's health for the next 30 years or so. Nurses need to be able to give up-to-date information and evidence for all forms of treatment based on a background of complex and ever-changing research. This article covers the main presenting complaints and treatments, from lifestyle to hormone replacement therapy, by drawing on guidelines from national bodies.

Extended Use of Systemic Menopausal Hormone Therapy.

Because clinical trial data assessing more than 10 years of hormone therapy (HT) use are not available, providing guidance to menopausal women regarding duration of systemic HT is controversial. However, clinicians routinely encounter this issue in practice. Using available evidence and clinical experience, this chapter provides guidance for clinicians who care for patients who may be candidates for extended use of systemic HT.

Clinical Inquiries: Does exercise relieve vasomotor menopausal symptoms?

No. Exercise doesn't decrease the frequency or severity of vasomotor menopausal symptoms in perimenopausal and postmenopausal women (strength of recommendation: A, systematic review of randomized controlled trials [RCTs] and consistent RCT).

Management of Menopausal Symptoms for Women Who Are at High Risk of Thrombosis.

For women at elevated risk of thrombosis, clinicians are challenged to relieve menopausal symptoms without increasing the risk of thrombosis. Oral menopausal hormone therapy increases the risk of venous thromboembolism by 2-fold to 3-fold. Observational studies suggest less thrombotic risk with transdermal therapies and with progesterone over synthetic progestogens (progestins), but the data are limited. Beneficial nonpharmacologic therapies include cognitive behavioral therapy and clinical hypnosis, whereas beneficial nonhormonal pharmacologic therapies include selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. For treatment of the genitourinary syndrome of menopause, vaginal lubricants and moisturizers, low-dose vaginal estrogen, and intravaginal dehydroepiandrosterone are options.

The effectiveness of a group-based educational program on the self-efficacy and self-acceptance of menopausal women: A randomized controlled trial.

This study aimed to assess the effectiveness of a group-based educational training on the self-efficacy and self-acceptance of Iranian menopausal women using the PRECEDE-PROCEED model. This Randomized Controlled Trial (RCT) was conducted on 80 menopausal women in the age range of 47-55 years residing in the northeast of Iran. The participants were divided randomly into a test group (n = 40) and a control group (n = 40). We found that designing and implementation of a group-based educational training according to the PRECEDE-PROCEED model can significantly enhance the knowledge and performance of the test group with regard to self-efficacy and self-acceptance.

The advantages of hypnosis intervention on breast cancer surgery and adjuvant therapy.

BACKGROUND: In oncology, hypnosis has been used for pain relief in metastatic patients but rarely for induction of anesthesia. MATERIAL AND METHOD: Between January 2010 and October 2015, 300 patients from our Breast Clinic (Cliniques universitaires Saint-Luc, Université catholique de Louvain) were included in an observational, non-randomized study approved by our local ethics committee (ClinicalTrials.gov - NCT03003611). The hypothesis of our study was that hypnosis intervention could decrease side effects of breast surgery. 150 consecutive patients underwent breast surgery while on general anesthesia (group I), and 150 consecutive patients underwent the same surgical procedures while on hypnosis sedation (group II). After surgery, in each group, 32 patients received chemotherapy, radiotherapy was administered to 123 patients, and 115 patients received endocrine therapy. RESULTS: Duration of hospitalization was statistically significantly reduced in group II versus group I: 3 versus 4.1 days (p = 0.0000057) for all surgical procedures. The number of post-mastectomy lymph punctures was reduced in group II (1-3, median value n = 1.5) versus group I (2-5, median value n = 3.1) (p = 0.01), as was the quantity of lymph removed (103 ml versus 462.7 ml) (p = 0.0297) in the group of mastectomies. Anxiety scale was also statistically reduced in the postoperative period among the group of patients undergoing surgery while on hypnosis sedation (p = 0.0000000000000002). The incidence of asthenia during chemotherapy was statistically decreased (p = 0.01) in group II. In this group, there was a statistically non-significant trend towards a decrease in the incidence of nausea/vomiting (p = 0.1), and the frequency of radiodermitis (p = 0.002) and post-radiotherapy asthenia (p = 0.000000881) was also reduced. Finally, the incidence of hot flashes (p = 0.0000000000021), joint and muscle pain (p = 0.0000000000021) and asthenia while on endocrine therapy (p = 0.000000022) were statistically significantly decreased in group II. DISCUSSION: Hypnosis sedation exerts beneficial effects on nearly all modalities of breast cancer treatment. CONCLUSION: Benefits of hypnosis sedation on breast cancer treatment are very encouraging and further promote the concept of integrative oncology.

Reducing menopausal symptoms for women during the menopause transition using group education in a primary health care setting-a randomized controlled trial.

OBJECTIVES: Women's physical and mental ill-health shows a marked increase during menopause, which usually occurs between 45 and 55 years of age. Mental illness and somatic symptoms are common causes of long-term sick leave. Women suffer from a lack of knowledge about the menopause transition and its associated symptoms. The aim of the study was to investigate whether group education for women in primary health care (PHC) about the menopause transition can improve their physical and mental ill-health. STUDY DESIGN: This randomized controlled study was conducted in PHC and aimed to evaluate a group education programme for women aged 45-55 years, around the menopause transition. A total of 131 women were randomized to group education or no intervention. The group intervention included two education sessions with topics related to menopause. They answered two questionnaires at baseline and at four-month follow-up: the Menopause Rating Scale (MRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). MAIN OUTCOME MEASURE: Change in MRS and MADRS scores over the four months. RESULTS: The intervention group experienced a slight reduction in symptoms while the control group mostly experienced the opposite. CONCLUSION: This study showed that it was feasible to implement group education on menopause for women aged 45-55 years. THE CLINICAL TRIAL REGISTRATION NUMBER: NTC02852811.

[Risk and benefit of nutritional supplements for the treatment of postmenopausal complaints]. / Risiko und Nutzen von Nahrungsergänzungsmitteln für die Behandlung von Wechseljahresbeschwerden.

Menopause is for many females associated with an occurrence of a variety of health complaints and a decrease in quality in life. Hot flashes, sleep disturbances and a variety of other symptoms result in a strong psychological strain. Hormone replacement therapy for treatment of climacteric complaints is discussed controversially regarding associated side effects. This is a major reason to propose treatment with plant derived extracts and compounds as an alternative. Such compounds are available either as drugs but mostly as nutritional supplements. Here we have to distinguish between so-called phytoestrogens which are postulated to act via estrogen receptors such as hop extracts, soy extracts, pomegranate extracts and red clover extracts. A second group of compounds addresses postmenopausal complaints independent of estrogen receptors. This group includes yams, actaea racemosa, agnus castus, rhei radix extracts and spinach extracts. For none of the mentioned substances and extracts could a clear proven effectiveness for the treatment of postmenopausal complaints be demonstrated. In contrast, for some of the mentioned substances, for example isoflavones, there are concerns regarding side effects and safety. The free availability of such nutritional supplements results in an uncontrolled consumption. Different products were combined and consumed in doses far higher than recommend by the manufacturers.

Occurrence of climacteric symptoms in postmenopausal women after prophylactic bilateral ovariectomy.

PURPOSE OF INVESTIGATION: To analyse the quality of life in postmenopausal women after prophylactic bilateral ovariectomy depending on the time from menopause. MATERIALS AND METHODS: The study involved 252 postmenopausal women grouped according to the time from last menstruation: one to five years (group A), five to ten years (group B), and > ten years (group C). All women were ovariectomized during laparotomy performed for benign diseases of the uterus. Climacteric symptoms were measured with the Kupperman Index one day before and three months after surgery. RESULTS: Highly significant age differences and no substantial BMI differences were demonstrated among the study groups. Before and after surgery climacteric symptoms were reported by 17.06% and 57.8% of women, respectively. After surgery, group A women significantly more often had hot flushes, sweating, nervousness, and sleep disorders, the women in group B significantly more often reported sleep disorders, nervousness, and sweating, and the women in group C significantly more often complained of nervousness. CONCLUSION: In postmenopausal women, ovaries play the most important role during the first ten years from the last menstruation.

Beneficios de la soja en la salud femenina / Benefits of soy in women's health

Desde hace varias décadas, se ha desarrollado un gran interés por el papel de los fitoestrógenos como alternativa a la terapia hormonal sustitutiva. De hecho, numerosos estudios han determinado los efectos de las isoflavonas de soja sobre la sintomatología climatérica al reducir significativamente la frecuencia e intensidad de los sofocos. Este resultado se ha observado también sobre la salud cardiovascular. El objetivo de este trabajo ha sido revisar los estudios publicados, principalmente ensayos clínicos aleatorizados y controlados sobre el efecto de las isoflavonas en los síntomas climatéricos y su repercusión en la calidad de vida de la mujer, así como en otros marcadores de salud. Tras una revisión de metaanálisis y ensayos clínicos recientes, se ha obtenido evidencia de la eficacia del consumo de isoflavonas en la reducción de los sofocos con una mejora de la calidad de vida, en la disminución del riesgo cardiovascular por optimización del perfil lipídico, y en la mejoría de la densidad mineral ósea y otros marcadores de resorción ósea. La mayoría de los autores concluyen en el efecto favorable de un consumo regular de isoflavonas de soja sobre la salud y la calidad de vida de la mujer peri y postmenopáusica (AU)

A great interest has been developed last decades on the role of phytoestrogens as an alternative to hormone replacement therapy. In fact, numerous studies have shown the effects of soy isoflavones on climacteric symptomatology by significantly reducing the frequency and intensity of hot flashes, as well on cardiovascular health. The aim of this paper was to review the last studies, mainly randomized controlled trials, on the effect of isoflavones on climacteric symptoms and their impact on women’s quality of life, as well as on other health markers. Following a review of meta-analyzes and recent clinical trials, evidence has been obtained of the efficacy of isoflavones use in reducing hot flashes, improving the quality of life, lowering the cardiovascular risk by optimizing lipid profile, and Improving bone mineral density and other markers of bone resorption. Most of the authors concluded on the favorable effect of regular consumption of soy isoflavones on the health and quality of life of peri and postmenopausal women (AU)

A Nonhormonal Treatment for Moderate to Severe Vasomotor Symptoms of Menopause.

It is estimated that up to 80% of women experience symptoms related to declining estrogen levels that occur with menopause. The most common bothersome symptoms reported by women during and after this transition are vasomotor symptoms, which can include hot flashes, flushing, night sweats, and sleep disturbances. These symptoms are the most common reason women seek care during menopause. Until recently, the mainstay of treatment and symptom relief has been estrogen supplementation. In 2013, the U.S. Food and Drug Administration approved paroxetine, a low-dose selective serotonin reuptake inhibitor, as the first nonhormonal treatment for moderate to severe vasomotor symptoms of menopause. This article provides an overview of the use of paroxetine to treat vasomotor symptoms of menopause, including potential adverse reactions, special considerations for use, and implications for nursing practice.