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.

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.

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.

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.

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.

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.

Sudomotor and vasomotor activity during the menstrual cycle with global heating.

Many studies have reported that there are changes in sympathetic activity throughout the menstrual cycle as there are oestrogen receptor in the hypothalamus and all other parts of the sympathetic nervous system. The purpose of this study was to see whether there were variations in sympathetic activity, skin vasomotor and sweat gland sudomotor rhythms during the menstrual cycle. Eight young female subjects with a regular menstrual cycle participated in the study. Subjects were tested once during the follicular phase and once during the luteal phase. Skin blood flow and sweat rate were significantly higher in the luteal phase compared with the follicular phase (p < .05), but the frequency and magnitude of sudomotor and vasomotor rhythms were significantly greater in the follicular phase (p < .05). In contrast, spectral data showed less sympathetic activity in the luteal phase. A significant finding here is that the sudomotor rhythm of sweat glands is altered by the menstrual cycle.

The paracrine control of vascular motion. A historical perspective.

During the last quarter of the past century, the leading role the endocrine and nervous systems had on the regulation of vasomotion, shifted towards a more paracrine-based regulation. This begun with the recognition of endothelial cells as active players of vascular control, when the vessel's intimal layer was identified as the main source of prostacyclin and was followed by the discovery of an endothelium-derived smooth muscle cell relaxing factor (EDRF). The new position acquired by endothelial cells prompted the discovery of other endothelium-derived regulatory products: vasoconstrictors, generally known as EDCFs, endothelin, and other vasodilators with hyperpolarizing properties (EDHFs). While this research was taking place, a quest for the discovery of the nature of EDRF carried back to a research line commenced a decade earlier: the recently found intracellular messenger cGMP and nitrovasodilators. Both were smooth muscle relaxants and appeared to interact in a hormonal fashion. Prejudice against an unconventional gaseous molecule delayed the acceptance that EDRF was nitric oxide (NO). When this happened, a new era of research that exceeded the vascular field commenced. The discovery of the pathway for NO synthesis from L-arginine involved the clever assembling of numerous unrelated observations of different areas of knowledge. The last ten years of research on the paracrine regulation of the vascular wall has shifted to perivascular fat (PVAT), which is beginning to be regarded as the fourth layer of the vascular wall. Starting with the discovery of an adipose-derived relaxing substance (ADRF), the role that different adipokines have on the paracrine control of vasomotion is now filling the research activity of many vascular pharmacology labs, and surprising interactions between the endothelium, PVAT and smooth muscle are being unveiled.

The effect of heating rate on the cutaneous vasomotion responses of forearm and leg skin in humans.

We examined skin blood flow (SkBF) and vasomotion in the forearm and leg using laser-Doppler fluxmetry (LDF) and spectral analysis to investigate endothelial, sympathetic, and myogenic activities in response to slow (0.1 °C·10 s(-1)) and fast (0.5 °C·10 s(-1)) local heating. At 33 °C (thermoneutral) endothelial activity was higher in the legs than the forearms (P ≤ 0.02). Fast-heating increased SkBF more than slow heating (P=0.037 forearm; P=0.002 leg). At onset of 42 °C, endothelial (P=0.043 forearm; P=0.48 leg) activity increased in both regions during the fast-heating protocol. Following prolonged heating (42 °C) endothelial activity was higher in both the forearm (P=0.002) and leg (P<0.001) following fast-heating. These results confirm regional differences in the response to local heating and suggest that the greater increase in SkBF in response to fast local heating is initially due to increased endothelial and sympathetic activity. Furthermore, with sustained local skin heating, greater vasodilatation was observed with fast heating compared to slow heating. These data indicate that this difference is due to greater endothelial activity following fast heating compared to slow heating, suggesting that the rate of skin heating may alter the mechanisms contributing to cutaneous vasodilatation.

Nonhormonal management of menopause-associated vasomotor symptoms: 2015 position statement of The North American Menopause Society.

OBJECTIVE: To update and expand The North American Menopause Society's evidence-based position on nonhormonal management of menopause-associated vasomotor symptoms (VMS), previously a portion of the position statement on the management of VMS. METHODS: NAMS enlisted clinical and research experts in the field and a reference librarian to identify and review available evidence. Five different electronic search engines were used to cull relevant literature. Using the literature, experts created a document for final approval by the NAMS Board of Trustees. RESULTS: Nonhormonal management of VMS is an important consideration when hormone therapy is not an option, either because of medical contraindications or a woman's personal choice. Nonhormonal therapies include lifestyle changes, mind-body techniques, dietary management and supplements, prescription therapies, and others. The costs, time, and effort involved as well as adverse effects, lack of long-term studies, and potential interactions with medications all need to be carefully weighed against potential effectiveness during decision making. CONCLUSIONS: Clinicians need to be well informed about the level of evidence available for the wide array of nonhormonal management options currently available to midlife women to help prevent underuse of effective therapies or use of inappropriate or ineffective therapies. Recommended: Cognitive-behavioral therapy and, to a lesser extent, clinical hypnosis have been shown to be effective in reducing VMS. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS, although other selective serotonin reuptake/norepinephrine reuptake inhibitors, gabapentinoids, and clonidine show evidence of efficacy. Recommend with caution: Some therapies that may be beneficial for alleviating VMS are weight loss, mindfulness-based stress reduction, the S-equol derivatives of soy isoflavones, and stellate ganglion block, but additional studies of these therapies are warranted. Do not recommend at this time: There are negative, insufficient, or inconclusive data suggesting the following should not be recommended as proven therapies for managing VMS: cooling techniques, avoidance of triggers, exercise, yoga, paced respiration, relaxation, over-the-counter supplements and herbal therapies, acupuncture, calibration of neural oscillations, and chiropractic interventions. Incorporating the available evidence into clinical practice will help ensure that women receive evidence-based recommendations along with appropriate cautions for appropriate and timely management of VMS.

Qigong Effects on Heart Rate Variability and Peripheral Vasomotor Responses.

Population aging is occurring worldwide, and preventing cardiovascular event in older people is a unique challenge. The aim of this study was to examine the effects of a 12-week qigong (eight-form moving meditation) training program on the heart rate variability and peripheral vasomotor response of middle-aged and elderly people in the community. This was a quasi-experimental study that included the pre-test, post-test, and nonequivalent control group designs. Seventy-seven participants (experimental group = 47; control group = 30) were recruited. The experimental group performed 30 min of eight-form moving meditation 3 times per week for 12 weeks, and the control group continued their normal daily activities. After 12 weeks, the interaction effects indicated that compared with the control group, the experimental group exhibited significantly improved heart rate variability and peripheral vasomotor responses.

Vasomotor and respiratory responses evoked from the dorsolateral periaqueductal grey are mediated by the dorsomedial hypothalamus.

Activation of neurons in the dorsomedial hypothalamus (DMH) evokes increases in mean arterial pressure (MAP), sympathetic activity, heart rate (HR) and respiratory activity. Results of previous studies suggest that the DMH-evoked increases in MAP and HR are mediated by neurons within the periaqueductal grey (PAG), but a recent study has proposed that the converse is also true, i.e. that increases in MAP and HR evoked from the PAG depend upon neuronal activity in the DMH. In this study in anaesthetized rats, we examined the functional relationship between the DMH and PAG in regulating renal sympathetic nerve activity (RSNA) and respiratory activity (determined by measuring phrenic nerve activity (PNA)). Bilateral microinjections of the neuronal inhibitor muscimol into the DMH virtually abolished the increases in MAP, RSNA and PNA burst rate and amplitude evoked from the dorsolateral (dl) PAG. In contrast, multiple bilateral injections of much larger (10 times) doses of muscimol or of the local anaesthetic lignocaine into sites in the dlPAG at three different rostrocaudal levels did not reduce the magnitude or duration of the sympathetic vasomotor and respiratory responses evoked by disinhibition of neurons in the DMH. Thus, sympathetic vasomotor and respiratory responses generated from the dlPAG are dependent upon neuronal activity in the DMH, but not the converse. The results of this study together with those of previous studies indicate that the PAG regulates cardiovascular and respiratory function via both ascending projections to the DMH and descending projections to the ventral medulla, that originate from different PAG subregions.

Randomized, double-blind, placebo-controlled trial of Cimicifuga racemosa (black cohosh) in women with anxiety disorder due to menopause.

OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled, parallel group trial of the efficacy and tolerability of Cimicifuga racemosa (black cohosh) extract for the treatment of anxiety disorder due to menopause. We hypothesized that black cohosh would be superior to placebo in reducing anxiety symptoms of menopause, with a comparable tolerability profile to placebo. MATERIALS AND METHODS: Subjects were randomized to therapy with either pharmaceutical-grade black cohosh extract (n = 15) or placebo (n = 13) for up to 12 weeks. The primary outcome measure was changed over time in total Hamilton Anxiety Rating Scale (HAM-A) scores. Secondary outcomes included a change in scores on the Beck Anxiety Inventory, Green Climacteric Scale (GCS), and Psychological General Well-Being Index (PGWBI) and the proportion of patients with a change of 50% or higher in baseline HAM-A scores. RESULTS: There was neither a significant group difference in change over time in total HAM-A scores (P = 0.294) nor a group difference in the proportion of subjects with a reduction of 50% or higher in baseline HAM-A scores at study end point (P = 0.79). There was a significantly greater reduction in the total GCS scores during placebo (vs black cohosh; P = 0.035) but no group difference in change over time in the GCS subscale scores or in the PGWBI (P = 0.140). One subject (3.6%) taking black cohosh discontinued treatment because of adverse events. CONCLUSIONS: We found no statistically significant anxiolytic effect of black cohosh (vs placebo). However, small sample size, choice of black cohosh preparation, and dosage used may have been limiting factors producing negative results.

Influence of hyperbaric oxygen on blood vessel reactivity: concept of changes in conducted vasomotor response.

The actions of oxygen in the body are extremely complex, and are also involved in various signalling pathways. Hyperbaric oxygen is known to contribute to the improvement of conditions where tissue circulation is suboptimal, and has considerable usage in different treatment protocols and experimental investigations. However, the precise mechanism by which hyperbaric oxygen changes the functioning of coordinated blood vessel systems and microcirculation is still unknown. Taking into account the known facts, we suggest that hyperbaric oxygen induces changes in conducted vasomotor responses, and in that way influences vascular sensitivity and reactivity to vasodilators and vasoconstrictors. Conducted vasomotor responses are constrictions and dilations that are propagated along the vessel, leading to changes in vessel diameter on a certain distance of the initial site of vasoactive substance activity. Because these vascular responses are of substantial significance in physiological processes, their modification would subsequently cause alterations of blood vessel function and tissue perfusion that could explain observed effects of hyperbaric oxygen. We also discuss potential molecular targets of hyperbaric oxygen, investigation of which could presumably help in the eventual clarification of hyperbaric oxygen action.

Symptoms of menopause: hot flushes.

Vasomotor symptoms (VMSs) are highly prevalent during the peri- and early postmenopause. They constitute a major driver for patient self-referral for medical care. Although most women will experience an abatement of their VMS by 5 years after their final menses, women with early or surgical menopause may have worse or more persistent symptoms, and up to 16% of naturally menopausal women continue to experience VMS well after their menopause is past. Although estrogen is the most effective known therapy, it is neither appropriate nor desirable for every symptomatic woman, and nonhormonal treatments such as gabapentin, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors drugs, and the antihypertensives clonidine and alphamethyldopa may be helpful for some women. There is mounting evidence to support the ineffectiveness of many proposed complementary and alternative modalities. This review will highlight the natural history of VMS and the current medical evidence supporting various treatments.

Treatment strategies for reducing the burden of menopause-associated vasomotor symptoms.

BACKGROUND: Vasomotor symptoms (VMS), such as hot flashes and night sweats, are the most bothersome symptoms of menopause and affect an estimated 75% of women aged over 50 years. OBJECTIVE: To discuss the burden, pathophysiology, and management of menopause-associated VMS and to evaluate pharmacologic options available for the treatment of VMS, including herbal remedies, hormone replacement therapy (HRT), and nonhormonal therapies. SUMMARY: Lifestyle changes, including regulation of core body temperature, relaxation techniques, regular physical activity, weight loss, and smoking cessation may help reduce the risk of VMS and should be implemented by all women with menopause-associated VMS. The role of herbal remedies in the treatment of VMS remains unclear, as clinical trial efficacy data are inconsistent and inconclusive. Nevertheless, soy isoflavones, red clover isoflavones, black cohosh, and vitamin E are commonly used to treat VMS and may be considered in women with mild symptoms that are not controlled by lifestyle changes alone. These herbal remedies appear to be safe when used for short durations (d 6 months). HRT, consisting of estrogen (in women without a uterus) or estrogen plus progestin (in women with a uterus) is the most widely studied and most effective treatment option for relief of menopause-associated VMS and is considered the standard of care for women with moderate-to-severe VMS. HRT should be used at the lowest effective dose and for the shortest duration possible (preferably d 5 years) in women in whom the potential benefits outweigh the potential risks. Nonhormonal therapies, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, gabapentin, and clonidine, may be appropriate alternatives in women who cannot or will not use HRT for VMS relief, such as those with a history of or at risk for breast cancer. CONCLUSION: The physical and financial burden imposed by menopauseassociated VMS is immense. Optimum management of VMS includes lifestyle changes in all women and HRT in women with moderate-tosevere symptoms. Less effective herbal remedies or nonhormonal therapies may be appropriate in certain women, such as those with mild symptoms or those who cannot or will not take HRT.

Effect of coenzyme Q10 administration on endothelial function and extracellular superoxide dismutase in patients with ischaemic heart disease: a double-blind, randomized controlled study.

AIMS: This randomized controlled study was designed to determine whether oral coenzyme Q(10) (CoQ(10)) supplementation (100 mg tid) was able to improve extracellular superoxide dismutase (ecSOD) activity and endothelium-dependent (ED) vasodilation in patients with coronary artery disease (CAD). ecSOD, a major antioxidant enzyme system of the vessel wall, is reduced in patients with CAD. Moreover, there is a strong correlation between endothelium-bound ecSOD and the ED dilation of conduit arteries. CoQ(10) has been recently shown to improve the ED relaxation in diabetic patients. METHODS AND RESULTS: Thirty-eight CAD patients (33 M/5 F, mean age 55 +/- 4 years, ejection fraction 57.5 +/- 8%) were randomized into two groups. One group (n = 19) received CoQ(10) orally at doses of 300 mg/day for 1 month, whereas the other group received a placebo. On entry and after 1 month, all patients underwent brachial artery ED assessment, cardiopulmonary exercise test, and the measurement of endothelium-bound ecSOD activity. A total of 33 patients completed the study. ecSOD, ED relaxation, as well as peak VO(2) and O(2) pulse increases in the CoQ(10)-treated group were statistically greater vs. the variations in the placebo group. In particular, improvements elicited by CoQ(10) supplementation were remarkable in subjects presenting low initial endothelium-bound ecSOD and thus more prone to oxidative stress. CONCLUSION: Improvements in the ED relaxation and endothelium-bound ecSOD activity might be related to CoQ(10) capability of enhancing endothelial functionality by counteracting nitric oxide oxidation. The enhancement of peak VO(2) and of O(2) pulse is likely due to the bioenergetic effect of CoQ(10); on the other end, the improved VO(2) could also depend on the observed enhanced peripheral endothelial function.

Landmarks in understanding the central nervous control of the cardiovascular system.

In this Paton Lecture I have tried to trace the key experiments that have developed ideas on how the brain regulates the cardiovascular system. It is a personal view and inevitably, owing to constraints on space and time, I have not been able to cover areas such as the nucleus tractus solitarius and cardiac vagal neurones, although I acknowledge that some may consider the story is incomplete without them. Starting with the crucial discovery of vasomotor nerves and 'vasomotor tone', the patterns of activity in sympathetic nerves which led to the important idea of central oscillating networks of neurones are described. I discuss how this knowledge has informed current controversies on the origin of vasomotor activity in presympathetic neurones in the ventral medulla, which identify intrinsic pacemaker activity or synaptic input from multiple oscillators as prime mechanisms. I present an emerging view that the role of other regions of the brain, in particular supramedullary sites, has been underplayed. These regions are pivotal for the non-uniform distribution of cardiac output that is unique to each reflex and behavioural state. I discuss the most recent evidence for 'central command' neurones that offers a plausible explanation for how these patterns of sympathetic activity are achieved. Finally, I stress the importance of these current ideas to the understanding of pathological changes in sympathetic activity in cardiovascular diseases such as hypertension or congestive heart failure.

[Effect of soybeans and soy sauce on vasomotor symptoms during menopause]. / Efectos de la soja en los síntomas vasomotores de la menopausia.

During menopause, some women experience symptoms which can interfere with their living quality. Some of these symptoms are the so-called vasomotor symptoms which include suffocations, hot flashes, and nocturnal sweats. Up to now, the most effective remedy was hormone treatment, but a study of isoflavines, such as soybean, suggests it is possible to alleviate the disturbances caused by menopause. Due to this study we consider that the addition of isoflavines can provide benefits to women. Therefore, it is correct to include them in the field of medicines which give an alternative to estrogen therapy. However, one must bear in mind that data about the efficiency and security of alternative medicines in the treatment of menopause symptoms are not conclusive since each woman is unique and it is necessary to have consensus on an individualized health plan which permits one to carry out adequate therapeutic adjustments in accordance to the needs which occur over the entire menopause process.