Eficacia y seguridad de una alternativa a la terapia hormonal de la menopausia: extracto purificado de polen / Efficacy and safety of an alternative to menopausal hormone therapy: purified cytoplasm of pollen

Los síntomas vasomotores (SVM) se encuentran entre los síntomas más comunes de la transición a la menopausia. Más del 70% de las mujeres de mediana edad informan SVM en algún momento durante la transición a la menopausia, y para un tercio de las mujeres los SVM son muy frecuentes o graves. Muchas mujeres recurren a terapias naturales para tratar los SVM. Esta revisión se centra en una de esas opciones naturales: el extracto purificado de polen (Serelys®). Se realizó una búsqueda e identificación de artículos publicados hasta octubre de 2022 recopilados de sistemas de búsqueda electrónicos, como Google Scholar, MEDLINE, PubMed y Scopus. Las palabras de búsqueda fueron “Vasomotor symptoms”, “menopause” AND “pollen”. Los estudios preclínicos señalan un mecanismo de acción en su implicación sobre el sistema serotoninérgico, así como su unión a los receptores de dopamina. Los estudios clínicos demuestran la seguridad y el efecto positivo sobre los SVM.

Vasomotor symptoms (VMS) are among the most common symptoms of the menopausal transition. More than 70% of middle-aged women report VMS at some point during the menopausal transition, and for a third of women, VMS is very common or severe. Many women turn to natural therapies to treat VMS. This review focuses on one such natural option, purified pollen extract (Serelys®). The information available until October 2022 was collected via the library and electronic search systems such as Google Scholar, MEDLINE, PubMed, and Scopus. The search words were: “Vasomotor symptoms”, “menopause” AND “pollen”. Preclinical studies point to a mechanism of action in its involvement in the serotonergic system, as well as its binding to dopamine receptors. Clinical studies demonstrate the safety and positive effect on VMS.

Guideline No. 422a: Menopause: Vasomotor Symptoms, Prescription Therapeutic Agents, Complementary and Alternative Medicine, Nutrition, and Lifestyle

Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence. Perimenopausal and postmenopausal women. Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment. Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002­2020, and MeSH search terms were specific for each topic developed through the 7 chapters. The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Intended Audience physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population.

Rheum rhaponticum Root Extract Improves Vasomotor Menopausal Symptoms and Estrogen-Regulated Targets in Ovariectomized Rat Model.

Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb Rheum rhaponticum L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERß receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (Tskin) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E2 withdrawal helped maintain body temperature similarly to E2 alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERß in the hypothalamus of OVX rats, as well as in ERα/ß cell-based reporter assays. These data validate the OVX/Tskin rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.

Nonpharmacological therapies for the management of menopausal vasomotor symptoms in breast cancer survivors.

PURPOSE: Breast cancer affects millions of women worldwide, and for many, therapy results in treatment-induced menopause. Menopausal symptoms in breast cancer survivors are often more severe, frequent, and of greater duration compared with natural menopause. Hot flushes and night sweats pose a significant burden for many women, with limited therapeutic options as menopausal hormone therapy is contraindicated. Guidelines recommend non-hormonal pharmacological agents including clonidine, gabapentin, and some antidepressants. However, some women may be reluctant to use medications due to concerns about side effects. The aim of this narrative review was to appraise recent evidence for nonpharmacological treatments for vasomotor symptoms in breast cancer survivors including cognitive behavioural therapy, hypnosis, yoga, mindfulness, acupuncture, and lifestyle changes. METHODS: A literature search was conducted. Studies were included if they were randomised and involved breast cancer survivors and nonpharmacological treatments for menopausal vasomotor symptoms. RESULTS: Twelve studies met the criteria, and three studies of exercise in healthy menopausal women were included. Cognitive behavioural therapy reduces menopausal symptoms and perceived impact of hot flushes and night sweats in breast cancer survivors and is cost effective. The efficacy of hypnosis as a treatment for menopausal vasomotor symptoms in women with breast cancer is supported by two randomised controlled trials. Yoga and acupuncture may reduce vasomotor symptom frequency and/or burden. Studies of exercise as an intervention for vasomotor symptoms in healthy menopausal women have not shown benefit. CONCLUSION: Evidence for nonpharmacological interventions supports cognitive behavioural therapy and hypnosis in the management of vasomotor symptoms in breast cancer survivors.

Non-contact imaging of peripheral hemodynamics during cognitive and psychological stressors.

Peripheral hemodynamics, measured via the blood volume pulse and vasomotion, provide a valuable way of monitoring physiological state. Camera imaging-based systems can be used to measure these peripheral signals without contact with the body, at distances of multiple meters. While researchers have paid attention to non-contact imaging photoplethysmography, the study of peripheral hemodynamics and the effect of autonomic nervous system activity on these signals has received less attention. Using a method, based on a tissue-like model of the skin, we extract melanin [Formula: see text] and hemoglobin [Formula: see text] concentrations from videos of the hand and face and show that significant decreases in peripheral pulse signal power (by 36% ± 29%) and vasomotion signal power (by 50% ± 26%) occur during periods of cognitive and psychological stress. Via three experiments we show that similar results are achieved across different stimuli and regions of skin (face and hand). While changes in peripheral pulse and vasomotion power were significant the changes in pulse rate variability were less consistent across subjects and tasks.

Chronic Sildenafil Treatment Improves Vasomotor Function in a Mouse Model of Accelerated Aging.

Aging leads to a loss of vasomotor control. Both vasodilation and vasoconstriction are affected. Decreased nitric oxide-cGMP-mediated relaxation is a hallmark of aging. It contributes to vascular disease, notably hypertension, infarction, and dementia. Decreased vasodilation can be caused by aging independently from cardiovascular risk factors. This process that can be mimicked in mice in an accelerated way by activation of the DNA damage response. Genetic deletion of the DNA repair enzyme ERCC1 endonuclease in mice, as in the case of Ercc1Δ/- mice, can be used as a tool to accelerate aging. Ercc1Δ/- mice develop age-dependent vasomotor dysfunction from two months after birth. In the present study we tested if chronic treatment with sildenafil, a phosphodiesterase 5 inhibitor that augments NO-cGMP signaling, can reduce the development of vasomotor dysfunction in Ercc1Δ/- mice. Ercc1Δ/- mice and wild-type littermates were treated with 10 mg/kg/d of sildenafil from the age of 6 to the age of 14 weeks. Blood pressure and in vivo and ex vivo vasomotor responses were measured at the end of the treatment period. Ercc1Δ/- mice developed decreased reactive hyperemia, and diminished NO-cGMP-dependent acetylcholine responses. The diminished acetylcholine response involved both endothelial and vascular smooth muscle cell signaling. Chronic sildenafil exclusively improved NO-cGMP signaling in VSMC, and had no effect on endothelium-derived hyperpolarization. Sildenafil also improved KCl hypocontractility in Ercc1Δ/- mice. All effects were blood pressure-independent. The findings might be of clinical importance for prevention of morbidities related to vascular aging as well as for progeria patients with a high risk of cardiovascular disease.

Peroxisome proliferator-activated receptor-γ mediates the antihypertensive effects of acupuncture in spontaneously hypertensive rats.

We investigated a central antihypertensive effect of acupuncture in rostral ventrolateral medulla (RVLM) in spontaneously hypertensive rats (SHRs). In total, 56 rats were randomly divided into seven groups as follows: the SHR group, SHR+acupuncture (SHR+Acu) group, SHR+nonacupuncture (SHR+Non-acu) group, GW9662+acupuncture (GW9662+Acu) group, GW9662+GW1929 group, GW9662 group, and 2% DMSO group (n = 8 per group). The whole eight Wistar-Kyoto rats were assigned to the WKY group. The acupuncture treatment lasting for 14 days was performed at the Taichong acupoint (LR3) or at a nonacupoint (non-acu) once daily. The peroxisome proliferator-activated receptor (PPAR)-γ agonist GW1929 and the PPAR-γ inhibitor GW9662 were microinjected by the brain stereotactic technique. Blood pressure was measured by the tail-cuff method. Sympathetic vasomotor activity was determined by implanting in a telemetry electrocardiogram radio transmitter. The expression of PPARs in the RVLM of the rats was detected using Western blot. We demonstrated that acupuncture attenuated blood pressure, heart rate, and sympathetic vasomotor activity in SHRs. The protein expression of PPAR-γ was significantly increased in SHRs treated with acupuncture. The antihypertensive effects of acupuncture in SHRs were abrogated by microinjection bilaterally into RVLM of GW9662. Microinjection of GW1929 mimicked the antihypertensive effect of acupuncture. PPAR-γ expression was negatively correlated with blood pressure and sympathetic vasomotor activity in SHRs treated with acupuncture. These results suggested that acupuncture promoted a central antihypertensive effect by increasing the expression of PPAR-γ in RVLM of SHRs.

[HTA and non-hormonal menopause treatment]. / HTA et traitements non-hormonaux de la ménopause.

Serotonin reuptake inhibitors, clonidine, gabapentin and pregabalin have shown moderate efficacy in menopausal disorders. The effect of phytoestrogens is reported to be modest, but the side effects are not well known.

Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial.

OBJECTIVES: In the postmenopausal period, most women suffer vasomotor symptoms (VMS). It is well-known that VMS can worsen the quality of life. Diet seems to play a relevant role in the development of VMS, but the effect of diet on VMS is mainly limited to observational studies, and analyses of nutritional supplements. The aim of this study was thus to determine the efficacy of a lactoovo- vegetarian (LOVe) diet rich in omega-3 fatty acids vs. a lacto-ovo-vegetarian diet rich in EVO (extra-virgin olive oil) in reducing VMS frequency in postmenopausal women. METHODS: A two-arms (lacto-ovo-vegetarian diet with EVO vs. lacto-ovo-vegetarian diet rich in omega-3) randomized-controlled trial with a follow-up period of 16 weeks. We considered as primary outcome the change in the Kupperman index (follow-up vs. baseline evaluation, reported as delta, D) and in its subscales. Secondary outcomes included changes in common anthropometric and biohumoral measurements. RESULTS: Among 54 women randomly assigned to a study group, 40 (mean age 55.1±5.4 years) completed the study and complied with their assigned diet. Women randomized to the omega-3 group (n=18) showed significant improvements, compared to the EVO group (n=22), in Kupperman index (Δ=-11.4±9.8 vs. -5.9±8.2; p=0.045), hot flashes (Δ=-3.3±3.4 vs. -1.3±2.6; p=0.04), and a marginally significant improvement in nervousness (Δ=-1.7±1.7 vs. -0.8±1.5; p=0.07). No significant differences were observed for the secondary outcomes. No relevant side effects were reported. CONCLUSION: After 16 weeks, a lacto-ovo-vegetarian diet rich in omega-3 reduced VMS frequency in postmenopausal women more than the lacto-ovo-vegetarian diet rich in EVO.

Prospective observational study to evaluate the efficacy and safety of the pollen extract Sérélys® in the management of women with menopausal symptoms.

Safety concerns or contraindications to the use of hormones have resulted in a rise of the use of herbal medicinal products for the management of menopausal symptoms. The pollen extract Sérélys® represents, due to its ingredients and mode of action, a new and innovative alternative for the management of these symptoms. The aim of the present study was to demonstrate the efficacy and safety of Sérélys®. A prospective, open, observational, and multicentre study was performed on 104 menopausal women. The patients received over 3 months the pollen extract Sérélys® containing the extracts PI82 and GC Fem in a dosage of twice 160 mg extract and 5 mg vitamin E. Using a validated menopausal rating score, the improvement of menopausal symptoms was recorded. A significant decrease of different menopausal symptoms was observed between the starting point of the study and after 12 weeks (p < .0001). Hot flashes were reduced by 48.5%, sleep disturbance by 50.1%, depressive mood by 51.2%, irritability by 47.9%, fatigue by 47.8%, vaginal dryness by 39.63% and muscles and joint pain by 27.4%. The pollen extract Sérélys® reduced significant menopausal symptoms showing a very low side effect profile.

Respiratory muscle training positively affects vasomotor response in young healthy women.

Vasomotor response is related to the capacity of the vessel to maintain vascular tone within a narrow range. Two main control mechanisms are involved: the autonomic control of the sympathetic neural drive (global control) and the endothelial smooth cells capacity to respond to mechanical stress by releasing vasoactive factors (peripheral control). The aim of this study was to evaluate the effects of respiratory muscle training (RMT) on vasomotor response, assessed by flow-mediated dilation (FMD) and heart rate variability, in young healthy females. The hypothesis was that RMT could enhance the balance between sympathetic and parasympathetic neural drive and reduce vessel shear stress. Thus, twenty-four women were randomly assigned to either RMT or SHAM group. Maximal inspiratory mouth pressure and maximum voluntary ventilation were utilized to assess the effectiveness of the RMT program, which consisted of three sessions of isocapnic hyperventilation/ week for eight weeks, (twenty-four training sessions). Heart rate variability assessed autonomic balance, a global factor regulating the vasomotor response. Endothelial function was determined by measuring brachial artery vasodilation normalized by shear rate (%FMD/SR). After RMT, but not SHAM, maximal inspiratory mouth pressure and maximum voluntary ventilation increased significantly (+31% and +16%, respectively). Changes in heart rate variability were negligible in both groups. Only RMT exhibited a significant increase in %FMD/SR (+45%; p<0.05). These data suggest a positive effect of RMT on vasomotor response that may be due to a reduction in arterial shear stress, and not through modulation of sympatho-vagal balance.

Effect of omega-3 supplements on vasomotor symptoms in menopausal women: A systematic review and meta-analysis.

OBJECTIVE: We aimed to investigate the effect of omega-3 supplements on relief of vasomotor symptoms among menopausal women. STUDY DESIGN: The Cochrane Library, MEDLINE, SCOPUS, EMBASE, ProQuest, Google Scholar, Web of Science, CINAHL, IranMedex and SID databases were searched until September 2017. Inclusion criteria were (1) women were experiencing vasomotor symptoms in the menopause period, (2) intervention was omega-3 supplements (3) randomized controlled trial (RCT) or quasi-RCT, and (4) outcome measures included changes in the frequency and severity of hot flush or night sweats, sleep problems and side effects. RESULTS: Three randomized controlled trials involving 483 women in the age range of 51 to 54.7 years were included in the review. Overall, the risk of bias in the included studies was moderate. All the participants were found to be blinded. Meta-analysis of the data showed no difference in the frequency and severity of hot flushes, insomnia severity, sleep quality, quality of life and adverse effects between the two groups. Compared to placebo group, women who received omega-3 supplements experienced lower frequency (mean difference: -1.82, 95% CI: -2.81, -0.83) and severity (mean difference: -.89, 95% CI: -1.25, -0.53) of night sweats. CONCLUSIONS: RCTs which investigate the impact of omega-3 supplements on vasomotor symptoms in menopausal women are scarce. A comprehensive search in a wide range of databases found only three relevant papers. Our analysis suggests that omega-3 supplements may alleviate night sweats but have no benefit in reducing hot flushes, or improving sleep quality and quality of life during the menopausal period. We recommend high quality RCTs along with a longer follow-up period to investigate this important subject, as there was insufficient evidence to conclude that omega-3 supplements are of benefit in alleviating vasomotor symptoms in menopausal women.

N-3 Polyunsatured Fatty Acids in Menopausal Transition: A Systematic Review of Depressive and Cognitive Disorders with Accompanying Vasomotor Symptoms.

Depression is one of the most important health problems worldwide. Women are 2.5 times more likely to experience major depression than men. Evidence suggests that some women might experience an increased risk for developing depression during "windows of vulnerability", i.e., when exposed to intense hormone fluctuations, such as the menopause transition. Indeed, this period is associated with different symptoms, including vasomotor, depressive, and cognitive symptoms, which have all been shown to worsen as women approach menopause. Even though hormonal therapy represents the most effective treatment, side effects have been reported by several studies. Therefore, an increased number of women might prefer the use of alternative medicine for treating menopausal symptoms. N-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) are included among these alternative treatments. We here provide a review of studies investigating the effects of n-3 LCPUFAs on hot flashes and depressive and cognitive disorders in menopausal women. The reported results are scattered and heterogeneous. In conclusion, a beneficial role of n-3 LCPUFAs in hot flashes, and depressive and cognitive symptoms related to menopausal transition is still far from conclusive.

The role of kisspeptin/neurokinin B/dynorphin neurons in pathomechanism of vasomotor symptoms in postmenopausal women: from physiology to potential therapeutic applications.

Women during perimenopausal period experience a range of symptoms, which interfere with physical, sexual, and social life. About 65-75% of symptoms connected with postmenopausal period are vasomotor symptoms (VMS), such as hot flushes and night sweats. Hot flushes are subjective sensation of heat associated with cutaneous vasodilatation and drop in core temperature. It is suspected that VMS are strongly correlated with pulsatile oversecretion of gonadotropin-releasing hormone (GnRH) and subsequently luteinizing hormone (LH). Evidence has accumulated in parallel showing that lack of negative feedback of steroid hormones synthesized in ovary causes overactivation of hypertrophied kisspeptin/neurokinin B/dynorphin (KNDy) neurons, located in infundibular nucleus. Oversecretion of both kisspeptin (KISS1) and neurokinin B (NKB), as well as downregulation of dynorphin, plays dominant role in creation of GnRH pulses. This in turn causes VMS. Administration of senktide, highly potent and selective NK3R agonist, resulted in increase of serum LH concentration, induction of VMS, increase in heart rate, and skin temperature in postmenopausal women. These finding suggest that modulation of KNDy neurons may become new therapeutic approach in the treatment of VMS.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON MENOPAUSE-2017 UPDATE.

EXECUTIVE SUMMARY This American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) Position Statement is designed to update the previous menopause clinical practice guidelines published in 2011 but does not replace them. The current document reviews new clinical trials published since then as well as new information regarding possible risks and benefits of therapies available for the treatment of menopausal symptoms. AACE reinforces the recommendations made in its previous guidelines and provides additional recommendations on the basis of new data. A summary regarding this position statement is listed below: New information available from randomized clinical trials and epidemiologic studies reported after 2011 was critically reviewed. No previous recommendations from the 2011 menopause clinical practice guidelines have been reversed or changed. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, selective estrogen-receptor modulators (SERMs), and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, SERMs, and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. New recommendations in this position statement include: 1. RECOMMENDATION: the use of menopausal hormone therapy in symptomatic postmenopausal women should be based on consideration of all risk factors for cardiovascular disease, age, and time from menopause. 2. RECOMMENDATION: the use of transdermal as compared with oral estrogen preparations may be considered less likely to produce thrombotic risk and perhaps the risk of stroke and coronary artery disease. 3. RECOMMENDATION: when the use of progesterone is necessary, micronized progesterone is considered the safer alternative. 4. RECOMMENDATION: in symptomatic menopausal women who are at significant risk from the use of hormone replacement therapy, the use of selective serotonin re-uptake inhibitors and possibly other nonhormonal agents may offer significant symptom relief. 5. RECOMMENDATION: AACE does not recommend use of bioidentical hormone therapy. 6. RECOMMENDATION: AACE fully supports the recommendations of the Comité de l'Évolution des Pratiques en Oncologie regarding the management of menopause in women with breast cancer. 7. RECOMMENDATION: HRT is not recommended for the prevention of diabetes. 8. RECOMMENDATION: In women with previously diagnosed diabetes, the use of HRT should be individualized, taking in to account age, metabolic, and cardiovascular risk factors. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; BMI = body mass index; CAC = coronary artery calcification; CEE = conjugated equine estrogen; CEPO = Comité de l'Évolution des Pratiques en Oncologie; CAD = coronary artery disease; CIMT = carotid intima media thickness; CVD = cardiovascular disease; FDA = Food and Drug Administration; HDL = high-density lipoprotein; HRT = hormone replacement therapy; HT = hypertension; KEEPS = Kronos Early Estrogen Prevention Study; LDL = low-density lipoprotein; MBS = metabolic syndrome; MPA = medroxyprogesterone acetate; RR = relative risk; SERM = selective estrogen-receptor modulator; SSRI = selective serotonin re-uptake inhibitor; VTE = venous thrombo-embolism; WHI = Women's Health Initiative.

Omega-3 versus isoflavones in the control of vasomotor symptoms in postmenopausal women.

Determine the efficacy and tolerability of omega-3 fatty acids versus soybean isoflavones in reducing the vasomotor symptoms (VMSs) frequency in postmenopausal women. A randomized, prospective, two-arm study was performed in healthy postmenopausal women aged 45-65. The two arms were: two capsules/day of omega-3 (425 mg of omega-3/capsule) administered orally (n = 38) and two tablets/day of soybean isoflavones (54.4 mg of isoflavones/tablet) (n = 30), over 16 weeks. The mean baseline frequency of moderate and severe VMSs per week in the omega-3 group was 24.56 and 23.90, respectively, and 19.65 and 19.51 in the isoflavone group. After 4 months, the reduction in moderate and severe hot flashes with omega-3 was significant (p < .001), whereas in the case of isoflavones, there was a significant difference in severe (p = .02) hot flashes after 4 months, but not in moderate hot flashes (p = .077). Omega-3 did not demonstrate significant efficacy differences versus isoflavones over time. The use of omega-3 has a beneficial effect on hot flash reduction after 4 months of treatment. This is comparable to the benefits found with soybean isoflavones after 3-4 weeks and after 4 months in severe hot flash women, but higher than those found with soybean isoflavones in moderate symptom women.

Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause.

BACKGROUND: Vasomotor symptoms (VMSs) are the hallmarks of menopause, occurring in approximately 75% of postmenopausal women in the UK, and are severe in 25%. OBJECTIVES: To identify which treatments are most clinically effective for the relief of VMSs for women in natural menopause without hysterectomy. SEARCH STRATEGY: English publications in MEDLINE, Embase, and The Cochrane Library up to 13 January 2015 were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) of treatments for women with a uterus for the outcomes of frequency of VMSs (up to 26 weeks), vaginal bleeding, and discontinuation. DATA COLLECTION AND ANALYSIS: Bayesian network meta-analysis (NMA) using mean ratios (MRs) and odd ratios (ORs). MAIN RESULTS: Across the three networks, 47 RCTs of 16 treatment classes (n = 8326 women) were included. When compared with placebo, transdermal estradiol and progestogen (O+P) had the highest probability of being the most effective treatment for VMS relief (69.8%; MR 0.23; 95% credible interval, 95% CrI 0.09-0.57), whereas oral O+P was ranked lower than transdermal O+P, although oral and transdermal O+P were no different for this outcome (MR 2.23; 95% CrI 0.7-7.1). Isoflavones and black cohosh were more effective than placebo, although not significantly better than O+P. Not only were selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) found to be ineffective in relieving VMSs, but they also had significantly higher odds of discontinuation than placebo. Limited data were available for bleeding, therefore no conclusions could be made. CONCLUSION: For women who have not undergone hysterectomy, transdermal O+P was the most effective treatment for VMS relief. TWEETABLE ABSTRACT: Which treatment best relieves menopause flushes? Results from the #NICE guideline network meta-analysis.

The Effects of Stretching Training on Cardiac Autonomic Function in Obese Postmenopausal Women.

Context • Menopause and obesity are associated with autonomic dysfunction. Unconventional exercise modalities that include an important flexibility component seem to improve cardiac autonomic function by lowering sympathetic tone and increasing vagal modulation of the heart rate (HR). Yet clear evidence of the effects of stretching training (ST) on cardiac autonomic modulation is limited. Objective • The present study intended to examine the effects of ST on HR variability (HRV) and flexibility in obese postmenopausal women. Design • The research team designed a randomized, controlled trial. Setting • The study was conducted at the Florida State University (Tallahassee, FL, USA). Participants • Twenty-four obese, postmenopausal women, aged 50-65 y with a body mass index of >30 but <40 kg/m2 participated in the study. Intervention • Participants were randomly assigned either to an ST group (n = 12) or a no-exercise control group (n = 12). The study was 8 wk in duration. Outcome Measures • Participant HRV and sit-and-reach scores (SRSs) were measured at baseline and after 8 wk of training. Results • Significant decreases occurred for the ST group between baseline and postintervention in sympathetic activity, as measured by normalized low frequency (nLF) power, and in sympathovagal balance, as measured by the ratio of the natural logarithm low frequency (LnLF) activity to the natural logarithm high frequency (LnHF) power, with P < .01 for both measures. The decreases for the ST group were significantly greater than those for the control group for the nLF and LnLF/LnHF, with P < .05 for both measures. Significant increases in vagal tone occurred for the ST group between baseline and postintervention, as measured by the normalized high frequency (nHF) power, with P < .01, and in SRS following ST, with P < .001. The increases for the ST group were significantly greater than those for the control group for the nHF and SRS, with P < .05 for both measures. The changes in SRS were correlated with the changes in the LnLF/LnHF power, with r = .65 and P < .03 negatively correlated. Conclusions • The findings indicated that ST can improve cardiac autonomic modulation by increasing vagal tone and decreasing sympathetic activity in obese postmenopausal women. The improvement in SRS partially explained the decrease in the sympathovagal balance. Because older or obese individuals have a higher risk of developing cardiovascular diseases, they could potentially benefit from ST.

Effect of age on cutaneous vasomotor responses during local skin heating.

This study examined the effect of ageing on the low-frequency oscillations (vasomotion) of skin blood flow in response to local heating (LH). Skin blood flow was assessed by laser-Doppler flowmetry on the forearm at rest (33°C) and in response to LH of the skin to both 42°C and 44°C in 14 young (24±1years) and 14 older (64±1years) participants. Vasomotion was analyzed using a wavelet transform to investigate power of the frequency intervals associated with endothelial, neural, myogenic, respiratory, and cardiac activities of the laser-Doppler signal. Laser-Doppler flux increased in both groups with LH (both d>1.8, p<0.001). Endothelial activity increased in both groups following LH to 42°C (young d=1.4, p<0.001; older d=1.2, p=0.005) and 44°C (young d=1.4, p=0.001; older d=1.5, p=0.005). Endothelial activity was higher in the young compared to older group during LH to 42°C (d=1.4, p=0.017) and 44°C (d=1.5, p=0.004). In response to LH to 42°C and 44°C, neural activity in both groups was decreased (both groups and conditions: d>1.2, p<0.001). Myogenic activity increased in the younger group following LH to 44°C (d=1, p=0.042), while in the older group, myogenic activity increased following LH to 42°C (d=1.2, p=0.041) and 44°C (d=1.1, p=0.041). Respiratory and cardiac activities increased in both groups during LH to 42°C and 44°C (All: d>0.9, p<0.017). There were no differences in wavelet amplitude between younger and older in the neural (d=0.1, p>0.7), myogenic (d=0.3, p>0.7), respiratory (d=0.4, p>0.6), and cardiac (d=0.1, p>0.7) frequency intervals. These data indicate that LH increases cutaneous endothelial and myogenic activity, while decreasing neural activity. Furthermore, ageing reduces the increase in cutaneous endothelial activity in response to LH.