Palpitation is a perceived abnormality of the heartbeat characterized by awareness of heart muscle contractions in the chest such as hard beats, fast beats, irregular beats, and/or pauses. Palpitation does not necessarily indicate a structural or functional abnormality of the heart, but it can be a symptom arising from an objectively rapid or irregular heartbeat.1
Women in the menopausal transition and postmenopausal period are affected by vasomotor symptoms (VMS), urogenital atrophy, sexual dysfunction, somatic symptoms, cognitive difficulty, sleep disturbance, and psychological problems. Some of these effects, particularly VMS and urogenital atrophy, are closely associated with estrogen deficiency, while the exact mechanisms underlying the other symptoms are not fully understood. Palpitation is one of these menopausal symptoms whose etiology is not yet completely elucidated.
Therefore, in the present study, we sought to determine the prevalence of palpitation and to investigate the factors associated with the sensation of rapid or irregular heartbeats in middle-aged women.
Study design and participants
In this cross-sectional study, we examined the medical records of a study population similar to those analyzed in our previous studies.2-6 Specifically, we retrospectively analyzed the first-visit records of 394 Japanese women aged 40 to 59 years who had enrolled in the Systematic Health and Nutrition Education Program (SHNEP) conducted at the menopause clinic of the Tokyo Medical and Dental University Hospital between November 2007 and March 2020. All middle-aged women who were enrolled in this program were referred to our clinic for treatment of their menopausal symptoms. The goals of SHNEP were to improve general health status by prescribing appropriate medications after a physician's assessment and providing advice on diet and exercise regimens after lifestyle assessment by nutritionists. Body composition, cardiovascular parameters, basal metabolism, physical fitness, and autonomic nervous system activities were measured by trained nutritionists who were employed by our institution to work exclusively for SHNEP. The questionnaires for physical and psychological symptoms and life-style were also filled by participants with the help of the nutritionists. In the beginning of our investigation, we obtained approval for the study protocol from the Tokyo Medical and Dental University Review Board and confirmed that all participants completed an informed consent form (approval number: 774). All study procedures were implemented in accordance with the Declaration of Helsinki.
Women were defined as having a menopausal transition if they had menstruated within the past 12 months but had either missed a period or experienced irregular cycles in the past 3 months. Women were defined as postmenopausal if they had not menstruated in the past 12 months.6 Women who had hysterectomy with bilateral oophorectomy were included in the postmenopausal group, whereas women who underwent hysterectomy with or without unilateral oophorectomy were excluded from the study. Women whose menopausal status was unidentified were also excluded.
Height, weight, waist circumference, and hip circumference were measured to determine body mass index and waist-to-hip ratio. Body composition, including body fat, muscle mass, water mass, and visceral fat level, were assessed using a bioimpedance analyzer (MC190-EM; Tanita, Tokyo, Japan).
Cardiovascular parameters and basal metabolism
Cardiovascular parameters, including systolic blood pressure, diastolic blood pressure, heart rate, cardio-ankle vascular index (as an indicator for atherosclerosis), and ankle-brachial pressure index (as an indicator of lower limb ischemia), were measured using a vascular screening system (VS-1000; Fukuda Denshi, Tokyo, Japan). An electrocardiogram (ECG) generated by the system was used for the assessment of arrhythmia. Resting energy expenditure was measured using an indirect calorimeter (VMB-005N; Vine, Tokyo, Japan).
Physical fitness was assessed for power, reaction time, and flexibility. Hand-grip strength was measured using a hand dynamometer (Yagami, Nagoya, Japan), twice with each hand; the larger values from each hand were used to calculate the average hand-grip strength (kgf). Participants’ reaction times were measured with the ruler drop test, using a wooden ruler 60 cm in length and weighing 110 g (Yagami, Nagoya, Japan).7 Briefly, the tester holds the ruler such that the 0-cm line is surrounded by, but not touching, the seated participant's outstretched fingers and thumb. The tester drops the ruler with arbitrary timing, the participant tries to catch it as quickly as possible, and the distance the ruler falls before being caught is recorded. The test was repeated seven times. After omitting the largest and the smallest values, the remaining five values were pooled to generate the average reaction time (ruler cm). Flexibility was measured by the sit and reach test using a flexometer (Yagami, Nagoya, Japan). The longer reach of two separate tests is defined as the participant's ante-flexion (cm).
The presence of the following lifestyle factors was also assessed: regular exercise, tea or coffee consumption of more than three cups a day, daily alcohol consumption, and smoking of more than 20 cigarettes a day.
Physical and psychological symptoms
At their initial visits, women were interviewed by physicians and nutritionists, and they provided data regarding their menopausal symptoms by completing the Menopausal Symptom Scale (MSS), the Menopausal Health Related-Quality of Life (MHR-QOL) questionnaire, and the Hospital Anxiety and Depression Scale (HADS).
Palpitation was evaluated using the MSS. The MSS has been validated and used in our previous studies, in which patients rate the severity of 10 menopausal symptoms.6,8 The questionnaire evaluates symptoms using a four-point Likert scale depending on how often each symptom affects their daily life: none (never, 0 points), mild (rarely, 1 point), moderate (sometimes, 2 points), or severe (very often, 3 points). Palpitation is listed as item four in the MSS (“rapid or irregular heartbeat”). In the final multivariate logistic regression analysis, the presence of palpitation was defined as either “moderate” or “severe” for the item.
VMS (hot flush and night sweats) were evaluated using MHR-QOL. The MHR-QOL is a modification of the Women's Health Questionnaire developed by Hunter et al9,10 and contains 38 items scored on a four-point or binary scale covering four major domains (physical health, mental health, life satisfaction, and social involvement) of a woman's health during the menopausal transition.11 The physical health domain comprised nine items that assessed somatic and VMS using a four-point Likert scale depending on how often each symptom affected their daily life: none (0-1 times a mo, 0 points); mild (1-2 times a week, 1 point); moderate (3-4 times per week, 2 points); or severe (almost every day, 3 points). The VMS score was defined as the sum of the hot flush and night sweats scores.
Depression and anxiety
Depression and anxiety were evaluated using the HADS. The HADS was developed by Zigmond and Snaith12 as a reliable instrument for screening clinically significant anxiety and depression in women visiting a general medical clinic, and it was translated into Japanese by Kitamura et al. It has seven items (odd items) comprising the anxiety subscale and another seven items (even items) comprising the depression subscale. Women respond to these items using a four-point Likert scale. Women who receive a score of 8 to 10 points are considered likely to experience anxiety or depression, and those who receive a score of 11 to 21 points are considered to be definitively experiencing anxiety or depression.
Autonomic nervous system activities
In the period between November 2007 and December 2012, we also assessed ANS activity in 198 patients. ANS activities were evaluated by analyzing the ECG R-R interval variability. The procedures for ECG measurement and power spectrum analysis of the R-R interval variability are described in detail elsewhere.13 Briefly, the participants were allowed to rest for at least 20 minutes prior to the measurement, and the ECG was then continuously monitored and recorded for 5 minutes with participants resting in the supine position. ECG measurements were always performed in the morning to avoid circadian variations. ECG data were digitized at a sampling rate of 1 kHz, and the R-R intervals were stored sequentially. Next, a power spectral analysis using a fast Fourier transformation was performed on the R-R interval series. The spectral powers were calculated for the following frequency bands: low frequency (0.03-0.15 Hz) power (LP), an indicator of both sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity; high frequency (0.15-0.5 Hz) power (HP), which reflects solely PNS activity; and total (0.03-0.5 Hz) power representing the overall ANS activity. To assess the balance between SNS and PNS activities, we used [LP]/[HP] and [HP]/[total power] as indicators of SNS and PNS activities (sympathetic nerve activity (SNA) and phrenic nerve activity (PNA)), respectively.
Continuous variables are presented as mean ± standard deviation. The differences among the 4 groups were analyzed using the one-way ANOVA, Kruskal-Wallis, and chi-square tests. The items that were not rejected by D’Agostino's K-squared test were considered to follow a normal distribution, for which a one-way ANOVA test was used. For the items rejected by D’Agostino's K-squared test, the Kruskal-Wallis test was used. The variables that significantly differed (P < 0.05) among the four groups at the univariate level were selected for multivariate logistic regression analysis. Using cut-off points for Pearson or Spearman correlation coefficients |R| of >0.9, multicollinearity was identified between the variables. The stepwise variable selection procedure was performed for variable inclusion and exclusion to determine the independent predictors of palpitation. Different models were compared based on the Bayesian information criterion. P < 0.05 was considered statistically significant. Statistical analysis was performed using GraphPad Prism version 5.02 (GraphPad Software, San Diego, CA) and JMP version 14 (SAS Institute Inc, Cary, NC).
First, participants were divided into four groups: “none,” “mild,” “moderate,” and “severe” by frequency of palpitation. The proportion of each group was as follows: none (N = 104), 26.4%; mild (N = 129), 32.7%; moderate (N = 116), 29.4%; severe (N = 45), 11.4% (Table 1). The percentages were not significantly different among the groups of women in different menopausal status (P = 0.260, chi-square test).
TABLE 1 -
The proportion of participants by severity of palpitation (N
Next, we compared these groups in terms of age, menopausal status, body composition, cardiovascular parameters, basal metabolism, physical fitness, lifestyle factors, psychological symptoms, and VMS. We found that palpitation was not associated with age, menopausal status, heart rate, prevalence of arrhythmia, ANS activity, caffeine, or alcohol consumption. The variables that significantly differed among the four groups were: 1) systolic pressure (mm Hg), 2) body ante-flexion (cm, sit-and-reach test), 3) regular exercise habits, 4) VMS score, and 5) HADS depression and anxiety subscale scores (Table 2). In other words, the more severely the women were affected by palpitation, 1) the higher their systolic blood pressure; 2) the less exercises they performed; 3) the lower they scored in the sit-and-reach test; 4) the higher they scored for VMS in MHR-QOL; and 5) the higher they scored in the HADS depression and anxiety subscales.
TABLE 2 -
Univariate comparison of background factors by severity of palpitation (N
|“Rapid or irregular heartbeat”
||None (n = 104)
||Mild (n = 129)
||Moderate (n = 116)
||Severe (n = 45)
|Age and menopausal status
| Age (y)
||51.1 ± 4.1
||51.1 ± 4.1
||50.7 ± 3.9
||51.3 ± 3.9
| Pre-/peri-/postmenopausal (%)
| Height (cm)
||157.6 ± 5.0
||158 ± 5.6
||156.7 ± 5.9
||158.2 ± 5.7
| Weight (kg)
||52.3 ± 7.6
||54.4 ± 9.9
||54.6 ± 9.0
||55.4 ± 12.4
| BMI (kg/cm2)
||21.1 ± 3.2
||21.8 ± 3.7
||22.22 ± 3.4
||22.1 ± 4.8
| Body fat (%)
||26.2 ± 6.8
||28.0 ± 7.6
||28.7 ± 7.5
||28.0 ± 9.5
| Muscle mass (kg)
||36.0 ± 2.8
||36.3 ± 3.3
||36.2 ± 3.3
||36.6 ± 3.7
| Water mass (kg)
||27.3 ± 2.7
||27.7 ± 3.4
||27.8 ± 3.3
||28.0 ± 3.7
| Waist hip ratio (%)
||86.4 ± 5.4
||87.4 ± 6.4
||87.2 ± 6.1
||87.7 ± 6.9
| Visceral fat level
||4.4 ± 2.3
||5.1 ± 2.7
||5.2 ± 2.5
||5.5 ± 3.8
| Systolic pressure (mm Hg)
||122.3 ± 16.1
||126.2 ± 17.4
||127.4 ± 18.0
||132.3 ± 19.5
| Diastolic pressure (mm Hg)
||79.2 ± 11.6
||80.7 ± 12.3
||81.3 ± 13.5
||83.2 ± 10.9
| Heart rate (/min)
||77.3 ± 11.6
||78.1 ± 12.6
||78.5 ± 13.1
||81.9 ± 14.9
| Arrythmia (%)
| Cardio-ankle vascular index
||7.449 ± 0.796
||7.564 ± 0.764
||7.37 ± 0.715
||7.518 ± 0.551
| Ankle-brachial pressure index
||1.118 ± 0.059
||1.107 ± 0.055
||1.102 ± 0.064
||1.164 ± 0.486
| Body temperature (Celsius)
||36.2 ± 0.5
||36.2 ± 0.4
||36.2 ± 0.5
||36.2 ± 0.5
| Resting energy expenditure (Kcal/d)
||1649 ± 412
||1634 ± 444
||1647 ± 494
||1599 ± 397
| Hand-grip strength (kgf)
||25.9 ± 4.5
||25.9 ± 4.4
||24.7 ± 4.9
||25.5 ± 4.0
| Reaction time (ruler cm)
||23.2 ± 4.1
||22.7 ± 4.2
||22.9 ± 3.8
||23.1 ± 4.8
| Body ante-flexion (cm)
||38.7 ± 9.5
||36.5 ± 10.7
||36.2 ± 9.3
||32.8 ± 9.6
| Regular exercise: yes/no (%)
| More than three cups of tea/coffee: yes/no (%)
| Daily alcohol consumption: yes/no (%)
| More than 20 cigarette smoking: yes/no (%)
|Physical and psychological symptoms
| VMS score (MHR-QOL)
||1.4 ± 1.9
||2.3 ± 2.1
||2.8 ± 2.1
||2.8 ± 2.2
| Depression score (HADS-D)
||5.2 ± 3.3
||6.7 ± 3.9
||7.9 ± 3.9
||8.8 ± 3.9
| Anxiety score (HADS-A)
||6.1 ± 3.3
||6.9 ± 3.4
||8.6 ± 3.6
||10.0 ± 4.1
Data are given as mean ± standard deviation or %.BMI, body mass index; HADS, Hospital Anxiety and Depression Scale; MHR-QOL, Menopausal Health-Related Quality of Life; VMS, vasomotor symptoms.
aOne-way ANOVA test.
In addition, these four groups were also compared with SNA and PNA in 198 participants. The analysis showed no association between ANS activity and palpitation (Table 3).
TABLE 3 -
The relationship between autonomic nervous system activities and palpitation (N
|“Rapid or irregular heartbeat”
||None (N = 70)
||Mild (N = 62)
||Moderate (N = 41)
||Severe (N = 25)
|Sympathetic nervous activity
||3.57 ± 5.31
||4.65 ± 9.58
||2.26 ± 2.64
||3.95 ± 5.81
|Parasympathetic nervous activity
||0.38 ± 0.20
||0.38 ± 0.23
||0.46 ± 0.24
||0.36 ± 0.22
We then divided the participants into two groups: those who were defined as having palpitation (“moderate” or “severe”) and those who were not (“none” or “mild”). We performed multivariate logistic regression analysis to determine the independent background factors associated with palpitation. The abovementioned variables that significantly differed (P < 0.05) among the four groups at the univariate level were selected for analysis, and were adjusted for each other. There was no multicollinearity between the factors. Therefore, palpitation was shown to be independently associated with VMS score (adjusted odds ratio [OR] = 1.18, 95% confidence interval [CI] = 1.07.1.31, P < 0.001) and the HADS anxiety subscale score (OR = 1.19, CI = 1.12-1.27, P < 0.001) (Table 4).
TABLE 4 -
Multivariate logistic regression analysis of background factors for the association with palpitation
||Unadjusted OR (95% Cl)
|Systolic pressure (mm Hg)
|Body ante-flexion (cm)
|Regular exercise: yes/no
|VMS score (MHR-QOL)
|Depression score (HADS-D)
|Anxiety score (HADS-A)
CI, confidence interval; HADS, Hospital Anxiety and Depression Scale; MHR-QOL, Menopausal Health-Related Quality of Life; OR, odds ratio; VMS, vasomotor symptoms.
aAdjusted for each other.
In the present study, we investigated the prevalence of and the background factors associated with, palpitation in 394 middle-aged women attending our menopause clinic. The results revealed that palpitations were not associated with age, menopausal status, heart rate, arrhythmia, ANS activity, caffeine, or alcohol consumption, but was associated with VMS and anxiety.
The historical study by Neugarten and Kraines14 identified “pounding of the heart” as one of the typical menopausal symptoms. In the Study of Women's Health Across the Nation study, Gold et al15 compared the prevalence of various menopausal symptoms in ethnically diverse groups and found that the prevalence of “heart pounding or racing” in middle-aged women varied by race and ranged from 10.3% to 28.1%.15 Likewise, Anderson et al16 investigated the frequency of various menopausal symptoms in Australian and Japanese local residents, and revealed that the percentage of women who responded to the item “heart beating quickly or strongly” as “quite a bit” or “extremely” was 7.1% in Australian women and 2.7% in Japanese women. In our study, we found that the prevalence of palpitation (“moderate” or “severe”) among middle-aged Japanese women was approximately 40%, remarkably more frequent than that of the studies by Gold or Anderson. This difference might depend on the setting of the study: community or hospital.
Among the lifestyle factors known to be associated with palpitation were excessive alcohol and caffeine consumption.17 In healthy middle-aged women, consuming two or more drinks per day (30 g or more ethanol) significantly increased the risk of atrial fibrillation compared with those having less consumption.18 Although 11.2% of our patients were habitual drinkers, less than half consumed 30 g or more ethanol per day (data not shown). The relatively low prevalence of excessive drinking may be the reason that alcohol was not a contributing factor to palpitation in the present study.
Likewise, people consuming 240 mg of caffeine per day (approximately four cups of coffee) compared with caffeine abstainers had an increased prevalence of palpitation.19 Additionally, Løchen and Rasmussen20 found a predominantly higher prevalence of palpitation among Norwegians who consumed nine or more cups of coffee a day. We calculated daily caffeine intake in our patients based on their coffee, green tea, and black tea consumption, assuming that coffee contains about 60 mg of caffeine per 100 mL, whereas green tea and black tea contain about 20 and 30 mg, respectively. According to our estimate, less than half of our patients who drank ≥ 3 cups of tea or coffee consumed 240 mg or more of caffeine. The discrepancy between our study and the previous studies that showed caffeine intake as a contributor to palpitation may be due to the ethnic difference in the styles of beverage consumption since, compared with Westerners, Japanese people generally drink green tea or black tea more often than coffee.
A review of the relationship between menopause and palpitation hypothesized that perimenopausal women had an imbalance in the autonomic control of the cardiovascular system that shifted toward sympathetic hyperactivity, which may cause palpitations in menopausal transition.21 However, in our study, menopausal status was not associated with the prevalence of palpitation, in line with the study by Ishizuka et al.22 They investigated the prevalence of a variety of menopausal symptoms in local Japanese residents grouped by menopausal status and did not find a difference in prevalence of palpitation among the groups: premenopausal, 35.8%; perimenopausal, 33.3%; postmenopausal, 34.1%.22 Furthermore, none of the ANS activity, heart rate, or arrhythmia were found to be associated with the severity of palpitation in the current study. According to previous studies, subjective symptoms of palpitation were not necessarily associated with increased heart rate or the development of arrhythmia, and electrocardiographic (Holter) monitoring showed no significant relationship between palpitation and cardiac arrhythmia in healthy individuals or patients with cardiovascular diseases.23-25 Our study showed that the relationship between severity of subjective palpitation and cardiovascular parameters was also weak in women transitioning through menopause.
VMS are commonly referred to as night sweats and hot flushes, which are experienced by up to 70% of women around menopause.26,27 To the best of our knowledge, the association of VMS with palpitation has not been reported before. Although the mechanism underlying the association between palpitation and VMS was not investigated in the present study, calcitonin gene-related peptide (CGRP), a known modulator of VMS, could be a candidate linking these two symptoms.
Several studies have shown that plasma CGRP levels are higher during the onset of a hot flush in postmenopausal women.28-30 Labastida-Ramírez et al31 also reported that fluctuations in estrogen levels modulate CGRP receptor signaling. CGRP is involved in various physiological functions, including vasodilatation and thermoregulation.32-35 The peptide could cause vasodilation either by directly stimulating adenylate cyclase in smooth muscle cells or via endothelium-dependent relaxation pathways.33,36,37 A previous study showed that function-blocking CGRP antibodies inhibit neurogenic vasodilatation without affecting heart rate in rats.38 Braasch et al39 also demonstrated a CGRP-dependent increase in firing of thermoregulatory neurons in the preoptic and anterior regions of the hypothalamus in male rats. These studies suggest that CGRP may induce VMS through both vasodilation and hyperthermic shifts in body temperature.
CGRP could also be involved in the pathogenesis of subjective palpitation. A known inducer of migraine, CGRP, was experimentally administered to the participants in a clinical trial, who complained of palpitation as a side effect of the injection.40-42 On the other hand, Mai et al43 found that there was no difference in heart rate between CGRP knockout (CGRP−/−) mice and age-matched wild-type mice. Thus, CGRP is not only related to VMS, but can also cause palpitation without altering the heart rate. Further studies are warranted to clarify the role of CGRP in linking VMS and palpitation, which could eventually unify palpitations with hot flushes and night sweats as VMS under the same mechanism.
Anxiety symptoms are among the most known menopausal symptoms, and Ishizuka et al22 reported that 57.6% of middle-aged Japanese women experienced them transitioning through menopause. According to the Study of Women's Health Across the Nation, perimenopausal increase in anxiety symptoms was more often seen in women starting with low anxiety levels in the premenopausal period, which means that the menopausal transition may confer vulnerability to anxiety in women who are not inherently anxious.44
Previous studies have not observed an association between anxiety and autonomic activity levels. The Netherlands Study of Depression and Anxiety, a cohort study investigating the long-term course of health care for depression and anxiety in the Netherlands, found no association between participants’ anxiety and cardiac autonomic variables after adjusting for antidepressant use,45,46 suggesting that anxiety may influence subjective palpitation directly rather than changing cardiac activity. For example, patients who complained of palpitation despite not having coronary heart disease or serious arrhythmia on the 24-hour ECG were significantly more likely to have panic disorder.47,48 Panic disorder is characterized by intense anxiety and is classified as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Thus, a strong sense of anxiety would cause subjective palpitations regardless of changes in autonomic activity or heart conditions.
The strength of the present study is in its adjustment for extensively investigated background factors, including age, menopausal status, body composition, cardiovascular parameters, basal metabolism, physical fitness, lifestyle factors, vasomotor, and psychological symptoms. We also evaluated the association between ANS activity and palpitation in a portion of the participants. Conversely, the study has several limitations. First, the study population was relatively small and consisted only of middle-aged Japanese women who attended our clinic. To generalize the results, the study needs to be conducted on a wider population. Second, the use of the response to a single question on the MSS to represent the dependent variable for the multivariate logistic regression analysis was not optimal. Furthermore, with a more precise measure of palpitations, such as 24-hour Holter monitoring, congruence of self-reports with physiologic monitoring would have been better assessed. Third, we did not exclude patients with underlying conditions, such as hyperthyroidism, that are known to cause palpitations. However, as we found no association between subjective palpitation and arrhythmia or increased heart rate, the inclusion was not likely to have a significant impact on the results. Lastly, the cross-sectional design of this study prevented the determination of causal relationships of vasomotor and anxiety symptoms to palpitation.
The sensation of rapid or irregular heartbeats is highly prevalent in middle-aged women. It is not associated with age, menopausal status, heart rate, arrhythmia, autonomic nervous system activity, caffeine, or alcohol consumption, but with vasomotor symptoms and anxiety.
1. Goyal A, Robinson KJ, Katta S, Sanchack KE. Palpitations, StatPearls. Treasure Island, FL: StatPearls Publishing LLC; 2020.
2. Terauchi M, Hiramitsu S, Akiyoshi M, et al. Associations between anxiety, depression and insomnia in peri- and post-menopausal women. Maturitas
3. Terauchi M, Hirose A, Akiyoshi M, Owa Y, Kato K, Kubota T. Prevalence and predictors of storage lower urinary tract symptoms in perimenopausal and postmenopausal women attending a menopause
4. Terauchi M, Hirose A, Akiyoshi M, Kato K, Miyasaka N. Feelings of unattractiveness in peri- and postmenopausal women are associated with depressed mood, poor memory and unsatisfactory sexual relationships. Climacteric
5. Odai T, Terauchi M, Hirose A, Kato K, Akiyoshi M, Miyasaka N. Severity of hot flushes is inversely associated with dietary intake of vitamin B(6) and oily fish. Climacteric
6. Terauchi M, Odai T, Hirose A, Kato K, Miyasaka N. Chilliness in Japanese middle-aged women is associated with anxiety and low n-3 fatty acid intake. Climacteric
7. Terauchi M, Obayashi S, Akiyoshi M, Kato K, Matsushima E, Kubota T. Effects of oral estrogen and hypnotics on Japanese peri- and postmenopausal women with sleep disturbance. J Obstet Gynaecol Res
8. Terauchi M, Obayashi S, Akiyoshi M, Kato K, Matsushima E, Kubota T. Insomnia in Japanese peri- and postmenopausal women. Climacteric
9. Hunter M, Battersby R, Whitehead M. Relationships between psychological symptoms, somatic complaints and menopausal status. Maturitas
10. Hunter M. The south-east England longitudinal study of the climacteric and postmenopause. Maturitas
11. Terauchi M, Hirose A, Akiyoshi M, Owa Y, Kato K, Kubota T. Subgrouping of Japanese middle-aged women attending a menopause
clinic using physical and psychological symptom profiles: a cross-sectional study. BMC Women's Health
12. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand
13. Miyasaka N, Akiyoshi M, Kubota T. Relationship between autonomic nervous system activity and bone mineral density in non-medicated perimenopausal women. J Bone Miner Metab
14. Neugarten BL, Kraines RJ. Menopausal symptoms in women of various ages. Psychosom Med
15. Gold EB, Sternfeld B, Kelsey JL, et al. Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40-55 years of age. Am J Epidemiol
16. Anderson D, Yoshizawa T, Gollschewski S, Atogami F, Courtney M. Menopause
in Australia and Japan: effects of country of residence on menopausal status and menopausal symptoms. Climacteric
17. Abbott AV. Diagnostic approach to palpitations. Am Fam Physician
18. Conen D, Tedrow UB, Cook NR, Moorthy MV, Buring JE, Albert CM. Alcohol consumption and risk of incident atrial fibrillation in women. JAMA
19. Shirlow MJ, Mathers CD. A study of caffeine consumption and symptoms; indigestion, palpitations, tremor, headache and insomnia. Int J Epidemiol
20. Løchen ML, Rasmussen K. Palpitations and lifestyle: impact of depression and self-rated health. The Nordland Health Study. Scand J Soc Med
21. Rosano GM, Rillo M, Leonardo F, Pappone C, Chierchia SL. Palpitations: what is the mechanism, and when should we treat them? Int J Fertil Womens Med
22. Ishizuka B, Kudo Y, Tango T. Cross-sectional community survey of menopause
symptoms among Japanese women. Maturitas
23. Zeldis SM, Levine BJ, Michelson EL, Morganroth J. Cardiovascular complaints. Correlation with cardiac arrhythmias on 24-hour electrocardiographic monitoring. Chest
24. Lipski J, Cohen L, Espinoza J, Motro M, Dack S, Donoso E. Value of Holter monitoring in assessing cardiac arrhythmias in symptomatic patients. Am J Cardiol
25. Barsky AJ. Palpitations, arrhythmias, and awareness of cardiac activity. Ann Intern Med
26. Gold EB, Colvin A, Avis N, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women's health across the nation. Am J Public Health
27. Politi MC, Schleinitz MD, Col NF. Revisiting the duration of vasomotor symptoms of menopause
: a meta-analysis. J Gen Intern Med
28. Valentini A, Petraglia F, De Vita D, et al. Changes of plasma calcitonin gene-related peptide levels in postmenopausal women. Am J Obstet Gynecol
29. Wyon YA, Spetz AC, Theodorsson GE, Hammar ML. Concentrations of calcitonin gene-related peptide and neuropeptide Y in plasma increase during flushes in postmenopausal women. Menopause
30. Chen JT, Shiraki M. Menopausal hot flash and calciotonin gene-related peptide; effect of Keishi-bukuryo-gan, a kampo medicine, related to plasma calciotonin gene-related peptide level. Maturitas
31. Labastida-Ramírez A, Rubio-Beltrán E, Villalón CM, MaassenVanDenBrink A. Gender aspects of CGRP in migraine. Cephalalgia
32. Iyengar S, Ossipov MH, Johnson KW. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain
33. Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev
34. Sorby-Adams AJ, Marcoionni AM, Dempsey ER, Woenig JA, Turner RJ. The role of neurogenic inflammation in blood-brain barrier disruption and development of cerebral oedema following acute central nervous system (CNS) injury. Int J Mol Sci
35. Lima WG, Marques-Oliveira GH, da Silva TM, Chaves VE. Role of calcitonin gene-related peptide in energy metabolism. Endocrine
36. Brain SD, Grant AD. Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev
37. Gray DW, Marshall I. Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide. Br J Pharmacol
38. Zeller J, Poulsen KT, Sutton JE, et al. CGRP function-blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat. Br J Pharmacol
39. Braasch DC, Deegan EM, Grimm ER, Griffin JD. Calcitonin gene-related peptide alters the firing rates of hypothalamic temperature sensitive and insensitive neurons. BMC Neurosci
40. Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J. CGRP may play a causative role in migraine. Cephalalgia
41. Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia
42. Christensen CE, Younis S, Deen M, Khan S, Ghanizada H, Ashina M. Migraine induction with calcitonin gene-related peptide in patients from erenumab trials. J Headache Pain
43. Mai TH, Wu J, Diedrich A, Garland EM, Robertson D. Calcitonin gene-related peptide (CGRP) in autonomic cardiovascular regulation and vascular structure. J Am Soc Hypertens
44. Bromberger JT, Kravitz HM, Chang Y, et al. Does risk for anxiety increase during the menopausal transition? Study of women's health across the nation. Menopause
45. Hu MX, Milaneschi Y, Lamers F, et al. The association of depression and anxiety with cardiac autonomic activity: the role of confounding effects of antidepressants. Depress Anxiety
46. Hu MX, Lamers F, Penninx B, de Geus EJC. Temporal stability and drivers of change in cardiac autonomic nervous system activity. Auton Neurosci
47. Jonsbu E, Dammen T, Morken G, Lied A, Vik-Mo H, Martinsen EW. Cardiac and psychiatric diagnoses among patients referred for chest pain and palpitations. Scand Cardiovasc J
48. Barsky AJ, Cleary PD, Coeytaux RR, Ruskin JN. Psychiatric disorders in medical outpatients complaining of palpitations. J Gen Intern Med