- Email: [email protected]
Influence of menstrual cycle on cardiac performance
Maturitas 58 (2007) 70–74
Influence of menstrual cycle on cardiac performance Kadriye Zengin, Mehmet Tokac ∗ , Mehmet Akif Duzenli, Ahmet Soylu, Nazif Aygul, Kurtulus Ozdemir Selcuk University, Meram Faculty of Medicine, Department of Cardiology, Konya, Turkey Received 13 April 2007; received in revised form 11 June 2007; accepted 14 June 2007
Abstract Objectives: The purpose of this study was to investigate the relationship between endogen sex hormone levels and myocardial performance in two different phases of menstrual cycle. Background: The relationships between cardiac performance and sex hormone levels in menstrual cycle have not yet been clearly identified. Methods: Twenty-seven women at the age of 19–42 years (mean 24.11 ± 6.02) with regular menstrual cycles (28–31 days) were enrolled in this study. Cardiac performance was evaluated by tissue Doppler imaging (TDI) derived myocardial performance index (MPI) in the menstrual and the luteal phases of the menstrual cycle. Results: Left ventricular MPI were statistically significant between the menstrual phase and luteal phase of the menstrual cycle (Inferior 0.53 ± 0.10 versus 0.44 ± 0.09, P < 0.001; Anterior 0.54 ± 0.13 versus 0.45 ± 0.10, P < 0.008; Lateral 0.50 ± 0.09 versus 0.44 ± 0.12, P < 0.03; Septum 0.54 ± 0.07 versus 0.46 ± 0.10, P < 0.005; Global 0.52 ± 0.06 versus 0.44 ± 0.09, P < 0.001). Right ventricle MPI between the two periods was also significantly different (0.49 ± 0.10 versus 0.42 ± 0.10, P < 0.01). There was a moderate correlation between estrogen levels and global MPI (r = 0.46, P = 0.001), but no correlation was found between progesterone levels and global MPI (r = 0.22, P = NS). Conclusion: We firstly demonstrated that endogen estrogen or progesterone improved the combined systolic and diastolic function in both left and right ventricle during luteal phases of menstrual cycle. Considering the previous studies and our results, estrogen may be responsible for this improvement. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Menstrual cycle; Myocardial performance index; Estrogen
1. Introduction
∗ Corresponding author at: Ebusuud Ef. Cd. Derya St. A-Blok, No.: 10 42080 Havzan, Konya, Turkey. Tel.: +90 332 223 6846; fax: +90 332 323 9930. E-mail address: [email protected] (M. Tokac).
A wide variety of biological functions are regulated by the cyclic changes in estrogen and progesterone levels during menstrual cycle of women in the reproductive age. Recent studies have shown that estrogen produces distinct effect on cardiac myocytes at physio-
0378-5122/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2007.06.002
K. Zengin et al. / Maturitas 58 (2007) 70–74
logical concentrations [1,2]. The influence of estrogen on cardiac functions has been mostly studied in animal models [1,3]. In human, however, there is little information available about the possible relationship of the endogenous estrogen changes during menstrual cycle and cardiac function. Myocardial performance index (MPI) was defined as the sum of isovolumic contraction (ICT) and isovolumic relaxation time (IRT) divided by ejection time (ET), which is a powerful index of systolic and diastolic functions at the same time [4]. It is independent of ventricular geometry and not affected by heart rate or blood pressure. Myocardial performance index is particularly a useful means of assessing global ventricular function [5]. Its prognostic value has been proved in different heart diseases in several studies [6–10]. Myocardial performance index can be obtained from pulse wave Doppler recordings, pulse wave tissue Doppler imaging (TDI) recordings, and left ventricular area waveforms obtained from acoustic quantification. Pulse wave TDI could provide a high temporal resolution and the calculation of MPI within a single cardiac cycle. The aim of the present study was to investigate the relationship between endogen sex hormone levels and myocardial performance during two different phases of menstrual cycle.
2. Methods 2.1. Study population Twenty-seven women at the age of 19–42 years (mean 24.11 ± 6.02) with regular menstrual cycles (28–31 days) were enrolled in this study. The subjects were healthy nurses with a normal physical examination, electrocardiogram, echocardiogram, and no history of cardiovascular or medical disease. All of the individuals included in this study had a history of regular cycles for at least 24 months, and the last cycle at the time of inclusion was ovulatory which was determined by measuring body temperature change every morning during the cycle. Exclusion criteria included the presence of irregular menstrual periods, pregnancy, breast-feeding, previous hysterectomy, current smoking, or the use of oral contraceptives. Informed consent was obtained from all subjects. The study was approved
71
by Selcuk University Meram Medical Faculty Ethical Committee. 2.2. Study protocol The menstrual-phase study was performed within 3–5 days of the onset of menses, which was determined by history. The luteal phase study was performed 6–8 days after ovulation, which was usually day 20–24 of the cycle. Peripheral venous blood samples were obtained from all participants to determine sex hormone levels after echocardiographic evaluation in two periods of menses. 2.3. Echocardiography All the studies were performed with an ATL HDI 5000CV (software version 10.1; Advanced Technology Laboratories, Bothell, WA) echocardiographic system equipped with variable frequency phased-array transducer (2–4 MHz with harmonic imaging feature). Echocardiographic evaluations were done in the usual manner in left lateral position. Measurements were made according to the recommendations of the American Society Echocardiography [11]. Pulse wave TDI was performed on septal, lateral, anterior, and inferior sides of mitral annulus in the left ventricle and on the free wall side of tricuspid annulus in the right ventricle at the apical 2–4 chamber view. Time intervals were measured at a sweep speed of 100 mm/s and were averaged over at least three cardiac cycles. Isovolumic contraction time was obtained between end of A wave and onset of S wave; ejection time was measured between onset and end of S wave; IRT was obtained between end of S wave and onset of E wave. Thus, the MPI was calculated (ICT + IRT)/(ET). ICT, IRT and ET from the four mitral annular regions were averaged and global left ventricular MPI was calculated using the same formula. All measurements were taken by the same examiner, who was blind to the phases of menstrual cycle of the study subjects. 2.4. Statistical analysis Continuous data are expressed as mean ± S.D. Paired sample t-test was used to compare hormonal and echocardiographic parameters in both phases of menstrual cycle. Analyses were carried out using The
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Table 1 The basic clinical and echocardiographic characteristics Characteristic
Value
Age (years) Height (cm) Weight (kg) Body mass index (kg/m2 ) Aortic dimension (cm) Left ventricular outflow tract (cm) Left atrial dimension (cm) End-diastolic dimension (cm) End-systolic dimension (cm) Ejection fraction (%)
24.1 163.0 60.6 22.9 3.0 1.8 3.0 4.3 2.4 62.8
Table 3 Left and right ventricular systolic and diastolic time intervals ± ± ± ± ± ± ± ± ± ±
6.0 60 9.1 3.0 0.3 0.1 0.3 0.3 0.4 3.8
Statistical Package for the Social Science (version 10, SPSS, Chicago, IL). A P value of <0.05 was considered as statistically significant. The correlation between estrogen and progesterone levels and MPI was determined by Pearson correlations analyze.
3. Results The basic clinical and echocardiographic characteristics for the subjects are illustrated in Table 1. Table 2 shows the serum sex hormone levels and hematological parameters for each phase of the menstrual cycle. As expected, serum progesterone, estrogen, follicle stimulating hormone (FSH) and luteinising hormone (LH) were significantly higher in the luteal phase than those in the menstrual phase (P < 0.0001, P < 0.0001, P < 0.006, P < 0.0001, respectively). There were no significant differences between the two phases with regard to hematological parameters and prolactin levels. Table 3 summarizes time intervals obtained from TDI velocities in each menstrual cycle phase. IsovoTable 2 The serum sex hormone levels and hematological parameters Menstrual phase Luteal phase Progesterone (ng/ml) 2.2 Estrogen (pg/ml) 46.9 FSH (mIU/ml) 3.7 LH (mIU/ml) 4.8 Prolactin (ng/ml) 10.9 Hemoglobin (g/dl) 12.9 Hemotokrit (%) 39.1 White blood cell (K/l) 6.7 Platelet (103 /l) 253.5
± ± ± ± ± ± ± ± ±
2.6 45.9 2.0 4.8 2.7 1.1 3.8 1.9 60.8
12.7 162.0 7.6 11.0 11.3 12.9 39.6 6.8 245.8
± ± ± ± ± ± ± ± ±
6.7 80.1 6.5 3.7 2.7 1.2 2.8 1.8 41.0
P 0.0001 0.0001 0.006 0.0001 NS NS NS NS NS
FSH, follicle stimulating hormone; LH, luteinising hormone.
Menstrual phase
Luteal phase
P
Lateral IRT (ms) ICT (ms) ET (ms)
66.2 ± 16.1 72.5 ± 14.8 276.7 ± 30.1
59.6 ± 20.7 61.7 ± 18.3 275.0 ± 24.0
NS 0.02 NS
Anterior IRT (ms) ICT (ms) ET (ms)
72.3 ± 15.0 72.1 ± 17.3 271.7 ± 34.5
62.5 ± 18.5 63.3 ± 18.7 277.3 ± 20.7
0.04 0.08 NS
Septum IRT (ms) ICT (ms) ET (ms)
71.3 ± 14.5 75.2 ± 13.5 273.3 ± 22.0
62.7 ± 16.4 64.0 ± 17.8 271.9 ± 21.2
0.04 0.01 NS
Inferior IRT (ms) ICT (ms) ET (ms)
71.5 ± 18.4 73.1 ± 14.4 272.5 ± 32.0
61.3 ± 17.9 60.8 ± 17.5 275.4 ± 24.0
0.04 0.008 NS
Right ventricle IRT (ms) ICT (ms) ET (ms)
58.5 ± 20.1 71.3 ± 15.9 262.9 ± 18.7
52.7 ± 14.6 59.8 ± 19.1 266.5 ± 19.3
NS 0.02 NS
Global left ventricular IRT (ms) 70.3 ± 11.3 ICT (ms) 73.2 ± 10.5 ET (ms) 272.8 ± 22.5
61.5 ± 14.7 62.5 ± 15.3 275.7 ± 21.9
0.01 0.005 NS
ET, ejection time; ICT, isovolumic contraction time; IRT, isovolumic relaxation time.
lumic contraction time in lateral, septal, and inferior wall of left ventricle and right ventricle free wall was significantly different between the two phases (P < 0.02, P < 0.01, P < 0.008, P < 0.02, respectively). Isovolumic relaxation time in anterior, septal, and inferior wall of left ventricle was also significantly different between the two phases (P < 0.04, P < 0.04, P < 0.04, respectively). On the otherhand, there was no significant difference in terms of ET in any left ventricular wall and right ventricle free wall between the phases. Global ICT and IRT were significantly higher in the menstrual phase compared to those in the luteal phase (P < 0.005, P < 0.01, respectively), but ET remained unchanged. Myocardial performance index values are given in Table 4. The difference in MPI between two phases of menstrual cycle calculated from four different walls of left ventricle and global left ventricular MPI was statistically significant (Inferior 0.53 ± 0.10 versus 0.44 ± 0.09, P < 0.001;
K. Zengin et al. / Maturitas 58 (2007) 70–74 Table 4 Segmental and global myocardial performance index Menstrual phase Inferior MPI Anterior MPI Lateral MPI Septum MPI Right ventricular MPI Global MPI
0.53 0.54 0.50 0.54 0.49 0.52
± ± ± ± ± ±
0.10 0.13 0.09 0.07 0.10 0.06
Luteal phase 0.44 0.45 0.44 0.46 0.42 0.44
± ± ± ± ± ±
0.09 0.10 0.12 0.10 0.10 0.09
P 0.001 0.008 0.03 0.005 0.01 0.001
MPI, myocardial performance index.
Anterior 0.54 ± 0.13 versus 0.45 ± 0.10, P < 0.008; Lateral 0.50 ± 0.09 versus 0.44 ± 0.12, P < 0.03; Septum 0.54 ± 0.07 versus 0.46 ± 0.10, P < 0.005; Global 0.52 ± 0.06 versus 0.44 ± 0.09, P < 0.001). Right ventricle MPI was also significantly different between two periods (0.49 ± 0.10 versus 0.42 ± 0.10, P < 0.01). While no correlation between progesterone levels and global MPI was found (r = 0.22, P = NS), there was a moderate correlation between estrogen levels and global MPI (r = 0.46, P = 0.001).
4. Discussion This study showed that a significant improvement in myocardial performance occurred in luteal phase, in which sex hormones are high, in healthy women who had regular menstrual cycle and did not use any drugs. To the best of our knowledge, this study was the first to evaluate cardiac performance in two phases of menstrual cycle using TDI derived MPI. It is postulated that hormonal fluctuations within the menstrual cycle phases are an important cause of the changes in cardiovascular, renal, gastrointestinal, metabolic, haematological, and immune functions in women [12]. Prior studies to investigate cardiac functions in menstrual cycle phases evaluated hemodynamic and electrophysiological changes [13–16]. They have clearly shown a change in hemodynamic and electrophysiological parameters during different phases of menstrual cycle. These changes have been mainly attributed to estrogen fluctuation during menstrual cycle [13–17]. Estrogen receptors on cardiac myocytes, which may influence contractility, have been demonstrated in experimental studies [18,19]. In addition, estrogen has a vasodilator effect on the vascular bed via nitric oxide [20]. We still need to understand
73
the effect of estrogen on cardiac performance in physiological milieu. The MPI was defined as noninvasive Doppler measurement of ventricular function, which is commonly used in the assessment of systolic and diastolic function of left and right ventricles. It has been reported that the MPI obtained by the combination of systolic and diastolic time intervals can be used in the determination of dysfunction degree. It was firstly obtained by conventional echocardiography, but the fluctuations cardiac cycle length limits its application. To avoid this limitation, the MPI can be obtained by TDI. Doppler derived MPI of left ventricle is partially preload-dependent, whereas it was demonstrated that TDI derived MPI of LV is not influenced by changes in preload and heart rate [21]. In this study, improvement in tissue Doppler derived MPI in luteal phase of menstrual cycle can be speculated to be mainly related to estrogen effects. Influence of progesterone on cardiac functions has not been investigated enough yet. However, some HRT studies demonstrated that progesterone does not change the beneficial effect of estrogen on cardiac protection, except that on lipid profile [22]. Effects of estrogen on cardiac functions have been studied in postmenopausal women, and short-term beneficial effects of estrogen were different among those studies. Fak et al. [23] observed a significant improvement of left ventricular diastolic functions after a single dose of 0.625 mg conjugated equine estrogen, whereas Aldrighi et al. [24] did not observe any changes in IRT, ejection time or MPI 90 min after a single dose of estradiol. In our study, natural increase of estrogen takes a long time, contrary to previous studies where drugs were used with respect to time and methodology. Concordant with our results, Fuenmayor et al. [25] showed a significant change in the left ventricular diastolic function during luteal phases of menstrual cycle in normal women using pulse wave Doppler derived mitral E/A ratio. Besides improvement in left ventricular diastolic functions, we demonstrated the improvements in left ventricular systolic function, global left ventricular function and right ventricular function using TDI derived time intervals. Also, this study showed that there was a moderate correlation between estrogen levels and MPI and that progesterone levels did not have such a correlation. In this study, it was demonstrated for the first time that endogen estrogen or progesterone improved the
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combined systolic and diastolic function in both left and right ventricle during luteal phases of menstrual cycle. Considering the previous studies and our results, estrogen may be responsible for this improvement. In clinical practice, these results can be important when echocardiographic evaluation was done in reproductive age women.
[12]
[13]
References [1] Nuedling S, Kahlert S, Loebbert K, et al. 17 Beta-estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in vitro and in vivo. Cardiovasc Res 1999;43:666–74. [2] Pelzer T, Schumann M, Neumann M, et al. 17 beta-estradiol prevents programmed cell death in cardiac myocytes. Biochem Biophys Res Commun 2000;268:192–200. [3] Voss MR, Stallone JN, Li M, Cornelussen RN, Knuefermann P, Knowlton AA. Gender differences in the expression of heat shock proteins: the effect of estrogen. Am J Physiol Heart Circ Physiol 2003;285:H687–92. [4] Tei C, Nishimura RA, Seward JB, Tajik AJ. Noninvasive Doppler-derived myocardial performance index: correlation with simultaneous measurements of cardiac catheterization measurements. J Am Soc Echocardiogr 1997;10:169–78. [5] Pellett AA, Tolar WG, Merwin DG, Kerut EK. The Tei index: methodology and disease state values. Echocardiography 2004;21:669–72. [6] Peltier M, Slama M, Garbi S, Enriquez-Sarano ML, Goissen T, Tribouilloy CM. Prognostic value of Doppler-derived myocardial performance index in patients with left ventricular systolic dysfunction. Am J Cardiol 2002;90:1261–3. [7] Harjai KJ, Scott L, Vivekananthan K, Nunez E, Edupuganti R. The Tei index: a new prognostic index for patients with symptomatic heart failure. J Am Soc Echocardiogr 2002;15:864–8. [8] Moller JE, Egstrup K, Kober L, Poulsen SH, Nyvad O, Torp-Pedersen C. Prognostic importance of systolic and diastolic function after acute myocardial infarction. Am Heart J 2003;145:147–53. [9] Schwammenthal E, Adler Y, Amichai K, et al. Prognostic value of global myocardial performance indices in acute myocardial infarction: comparison to measures of systolic and diastolic left ventricular function. Chest 2003;124:1645–51. [10] Dujardin KS, Tei C, Yeo TC, Hodge DO, Rossi A, Seward JB. Prognostic value of a Doppler index combining systolic and diastolic performance in idiopathic-dilated cardiomyopathy. Am J Cardiol 1998;82:1071–6. [11] Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional
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Influence of menstrual cycle on cardiac performance Kadriye Zengin, Mehmet Tokac ∗ , Mehmet Akif Duzenli, Ahmet Soylu, Nazif Aygul, Kurtulus Ozdemir Selcuk University, Meram Faculty of Medicine, Department of Cardiology, Konya, Turkey Received 13 April 2007; received in revised form 11 June 2007; accepted 14 June 2007
Abstract Objectives: The purpose of this study was to investigate the relationship between endogen sex hormone levels and myocardial performance in two different phases of menstrual cycle. Background: The relationships between cardiac performance and sex hormone levels in menstrual cycle have not yet been clearly identified. Methods: Twenty-seven women at the age of 19–42 years (mean 24.11 ± 6.02) with regular menstrual cycles (28–31 days) were enrolled in this study. Cardiac performance was evaluated by tissue Doppler imaging (TDI) derived myocardial performance index (MPI) in the menstrual and the luteal phases of the menstrual cycle. Results: Left ventricular MPI were statistically significant between the menstrual phase and luteal phase of the menstrual cycle (Inferior 0.53 ± 0.10 versus 0.44 ± 0.09, P < 0.001; Anterior 0.54 ± 0.13 versus 0.45 ± 0.10, P < 0.008; Lateral 0.50 ± 0.09 versus 0.44 ± 0.12, P < 0.03; Septum 0.54 ± 0.07 versus 0.46 ± 0.10, P < 0.005; Global 0.52 ± 0.06 versus 0.44 ± 0.09, P < 0.001). Right ventricle MPI between the two periods was also significantly different (0.49 ± 0.10 versus 0.42 ± 0.10, P < 0.01). There was a moderate correlation between estrogen levels and global MPI (r = 0.46, P = 0.001), but no correlation was found between progesterone levels and global MPI (r = 0.22, P = NS). Conclusion: We firstly demonstrated that endogen estrogen or progesterone improved the combined systolic and diastolic function in both left and right ventricle during luteal phases of menstrual cycle. Considering the previous studies and our results, estrogen may be responsible for this improvement. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Menstrual cycle; Myocardial performance index; Estrogen
1. Introduction
∗ Corresponding author at: Ebusuud Ef. Cd. Derya St. A-Blok, No.: 10 42080 Havzan, Konya, Turkey. Tel.: +90 332 223 6846; fax: +90 332 323 9930. E-mail address: [email protected] (M. Tokac).
A wide variety of biological functions are regulated by the cyclic changes in estrogen and progesterone levels during menstrual cycle of women in the reproductive age. Recent studies have shown that estrogen produces distinct effect on cardiac myocytes at physio-
0378-5122/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2007.06.002
K. Zengin et al. / Maturitas 58 (2007) 70–74
logical concentrations [1,2]. The influence of estrogen on cardiac functions has been mostly studied in animal models [1,3]. In human, however, there is little information available about the possible relationship of the endogenous estrogen changes during menstrual cycle and cardiac function. Myocardial performance index (MPI) was defined as the sum of isovolumic contraction (ICT) and isovolumic relaxation time (IRT) divided by ejection time (ET), which is a powerful index of systolic and diastolic functions at the same time [4]. It is independent of ventricular geometry and not affected by heart rate or blood pressure. Myocardial performance index is particularly a useful means of assessing global ventricular function [5]. Its prognostic value has been proved in different heart diseases in several studies [6–10]. Myocardial performance index can be obtained from pulse wave Doppler recordings, pulse wave tissue Doppler imaging (TDI) recordings, and left ventricular area waveforms obtained from acoustic quantification. Pulse wave TDI could provide a high temporal resolution and the calculation of MPI within a single cardiac cycle. The aim of the present study was to investigate the relationship between endogen sex hormone levels and myocardial performance during two different phases of menstrual cycle.
2. Methods 2.1. Study population Twenty-seven women at the age of 19–42 years (mean 24.11 ± 6.02) with regular menstrual cycles (28–31 days) were enrolled in this study. The subjects were healthy nurses with a normal physical examination, electrocardiogram, echocardiogram, and no history of cardiovascular or medical disease. All of the individuals included in this study had a history of regular cycles for at least 24 months, and the last cycle at the time of inclusion was ovulatory which was determined by measuring body temperature change every morning during the cycle. Exclusion criteria included the presence of irregular menstrual periods, pregnancy, breast-feeding, previous hysterectomy, current smoking, or the use of oral contraceptives. Informed consent was obtained from all subjects. The study was approved
71
by Selcuk University Meram Medical Faculty Ethical Committee. 2.2. Study protocol The menstrual-phase study was performed within 3–5 days of the onset of menses, which was determined by history. The luteal phase study was performed 6–8 days after ovulation, which was usually day 20–24 of the cycle. Peripheral venous blood samples were obtained from all participants to determine sex hormone levels after echocardiographic evaluation in two periods of menses. 2.3. Echocardiography All the studies were performed with an ATL HDI 5000CV (software version 10.1; Advanced Technology Laboratories, Bothell, WA) echocardiographic system equipped with variable frequency phased-array transducer (2–4 MHz with harmonic imaging feature). Echocardiographic evaluations were done in the usual manner in left lateral position. Measurements were made according to the recommendations of the American Society Echocardiography [11]. Pulse wave TDI was performed on septal, lateral, anterior, and inferior sides of mitral annulus in the left ventricle and on the free wall side of tricuspid annulus in the right ventricle at the apical 2–4 chamber view. Time intervals were measured at a sweep speed of 100 mm/s and were averaged over at least three cardiac cycles. Isovolumic contraction time was obtained between end of A wave and onset of S wave; ejection time was measured between onset and end of S wave; IRT was obtained between end of S wave and onset of E wave. Thus, the MPI was calculated (ICT + IRT)/(ET). ICT, IRT and ET from the four mitral annular regions were averaged and global left ventricular MPI was calculated using the same formula. All measurements were taken by the same examiner, who was blind to the phases of menstrual cycle of the study subjects. 2.4. Statistical analysis Continuous data are expressed as mean ± S.D. Paired sample t-test was used to compare hormonal and echocardiographic parameters in both phases of menstrual cycle. Analyses were carried out using The
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K. Zengin et al. / Maturitas 58 (2007) 70–74
Table 1 The basic clinical and echocardiographic characteristics Characteristic
Value
Age (years) Height (cm) Weight (kg) Body mass index (kg/m2 ) Aortic dimension (cm) Left ventricular outflow tract (cm) Left atrial dimension (cm) End-diastolic dimension (cm) End-systolic dimension (cm) Ejection fraction (%)
24.1 163.0 60.6 22.9 3.0 1.8 3.0 4.3 2.4 62.8
Table 3 Left and right ventricular systolic and diastolic time intervals ± ± ± ± ± ± ± ± ± ±
6.0 60 9.1 3.0 0.3 0.1 0.3 0.3 0.4 3.8
Statistical Package for the Social Science (version 10, SPSS, Chicago, IL). A P value of <0.05 was considered as statistically significant. The correlation between estrogen and progesterone levels and MPI was determined by Pearson correlations analyze.
3. Results The basic clinical and echocardiographic characteristics for the subjects are illustrated in Table 1. Table 2 shows the serum sex hormone levels and hematological parameters for each phase of the menstrual cycle. As expected, serum progesterone, estrogen, follicle stimulating hormone (FSH) and luteinising hormone (LH) were significantly higher in the luteal phase than those in the menstrual phase (P < 0.0001, P < 0.0001, P < 0.006, P < 0.0001, respectively). There were no significant differences between the two phases with regard to hematological parameters and prolactin levels. Table 3 summarizes time intervals obtained from TDI velocities in each menstrual cycle phase. IsovoTable 2 The serum sex hormone levels and hematological parameters Menstrual phase Luteal phase Progesterone (ng/ml) 2.2 Estrogen (pg/ml) 46.9 FSH (mIU/ml) 3.7 LH (mIU/ml) 4.8 Prolactin (ng/ml) 10.9 Hemoglobin (g/dl) 12.9 Hemotokrit (%) 39.1 White blood cell (K/l) 6.7 Platelet (103 /l) 253.5
± ± ± ± ± ± ± ± ±
2.6 45.9 2.0 4.8 2.7 1.1 3.8 1.9 60.8
12.7 162.0 7.6 11.0 11.3 12.9 39.6 6.8 245.8
± ± ± ± ± ± ± ± ±
6.7 80.1 6.5 3.7 2.7 1.2 2.8 1.8 41.0
P 0.0001 0.0001 0.006 0.0001 NS NS NS NS NS
FSH, follicle stimulating hormone; LH, luteinising hormone.
Menstrual phase
Luteal phase
P
Lateral IRT (ms) ICT (ms) ET (ms)
66.2 ± 16.1 72.5 ± 14.8 276.7 ± 30.1
59.6 ± 20.7 61.7 ± 18.3 275.0 ± 24.0
NS 0.02 NS
Anterior IRT (ms) ICT (ms) ET (ms)
72.3 ± 15.0 72.1 ± 17.3 271.7 ± 34.5
62.5 ± 18.5 63.3 ± 18.7 277.3 ± 20.7
0.04 0.08 NS
Septum IRT (ms) ICT (ms) ET (ms)
71.3 ± 14.5 75.2 ± 13.5 273.3 ± 22.0
62.7 ± 16.4 64.0 ± 17.8 271.9 ± 21.2
0.04 0.01 NS
Inferior IRT (ms) ICT (ms) ET (ms)
71.5 ± 18.4 73.1 ± 14.4 272.5 ± 32.0
61.3 ± 17.9 60.8 ± 17.5 275.4 ± 24.0
0.04 0.008 NS
Right ventricle IRT (ms) ICT (ms) ET (ms)
58.5 ± 20.1 71.3 ± 15.9 262.9 ± 18.7
52.7 ± 14.6 59.8 ± 19.1 266.5 ± 19.3
NS 0.02 NS
Global left ventricular IRT (ms) 70.3 ± 11.3 ICT (ms) 73.2 ± 10.5 ET (ms) 272.8 ± 22.5
61.5 ± 14.7 62.5 ± 15.3 275.7 ± 21.9
0.01 0.005 NS
ET, ejection time; ICT, isovolumic contraction time; IRT, isovolumic relaxation time.
lumic contraction time in lateral, septal, and inferior wall of left ventricle and right ventricle free wall was significantly different between the two phases (P < 0.02, P < 0.01, P < 0.008, P < 0.02, respectively). Isovolumic relaxation time in anterior, septal, and inferior wall of left ventricle was also significantly different between the two phases (P < 0.04, P < 0.04, P < 0.04, respectively). On the otherhand, there was no significant difference in terms of ET in any left ventricular wall and right ventricle free wall between the phases. Global ICT and IRT were significantly higher in the menstrual phase compared to those in the luteal phase (P < 0.005, P < 0.01, respectively), but ET remained unchanged. Myocardial performance index values are given in Table 4. The difference in MPI between two phases of menstrual cycle calculated from four different walls of left ventricle and global left ventricular MPI was statistically significant (Inferior 0.53 ± 0.10 versus 0.44 ± 0.09, P < 0.001;
K. Zengin et al. / Maturitas 58 (2007) 70–74 Table 4 Segmental and global myocardial performance index Menstrual phase Inferior MPI Anterior MPI Lateral MPI Septum MPI Right ventricular MPI Global MPI
0.53 0.54 0.50 0.54 0.49 0.52
± ± ± ± ± ±
0.10 0.13 0.09 0.07 0.10 0.06
Luteal phase 0.44 0.45 0.44 0.46 0.42 0.44
± ± ± ± ± ±
0.09 0.10 0.12 0.10 0.10 0.09
P 0.001 0.008 0.03 0.005 0.01 0.001
MPI, myocardial performance index.
Anterior 0.54 ± 0.13 versus 0.45 ± 0.10, P < 0.008; Lateral 0.50 ± 0.09 versus 0.44 ± 0.12, P < 0.03; Septum 0.54 ± 0.07 versus 0.46 ± 0.10, P < 0.005; Global 0.52 ± 0.06 versus 0.44 ± 0.09, P < 0.001). Right ventricle MPI was also significantly different between two periods (0.49 ± 0.10 versus 0.42 ± 0.10, P < 0.01). While no correlation between progesterone levels and global MPI was found (r = 0.22, P = NS), there was a moderate correlation between estrogen levels and global MPI (r = 0.46, P = 0.001).
4. Discussion This study showed that a significant improvement in myocardial performance occurred in luteal phase, in which sex hormones are high, in healthy women who had regular menstrual cycle and did not use any drugs. To the best of our knowledge, this study was the first to evaluate cardiac performance in two phases of menstrual cycle using TDI derived MPI. It is postulated that hormonal fluctuations within the menstrual cycle phases are an important cause of the changes in cardiovascular, renal, gastrointestinal, metabolic, haematological, and immune functions in women [12]. Prior studies to investigate cardiac functions in menstrual cycle phases evaluated hemodynamic and electrophysiological changes [13–16]. They have clearly shown a change in hemodynamic and electrophysiological parameters during different phases of menstrual cycle. These changes have been mainly attributed to estrogen fluctuation during menstrual cycle [13–17]. Estrogen receptors on cardiac myocytes, which may influence contractility, have been demonstrated in experimental studies [18,19]. In addition, estrogen has a vasodilator effect on the vascular bed via nitric oxide [20]. We still need to understand
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the effect of estrogen on cardiac performance in physiological milieu. The MPI was defined as noninvasive Doppler measurement of ventricular function, which is commonly used in the assessment of systolic and diastolic function of left and right ventricles. It has been reported that the MPI obtained by the combination of systolic and diastolic time intervals can be used in the determination of dysfunction degree. It was firstly obtained by conventional echocardiography, but the fluctuations cardiac cycle length limits its application. To avoid this limitation, the MPI can be obtained by TDI. Doppler derived MPI of left ventricle is partially preload-dependent, whereas it was demonstrated that TDI derived MPI of LV is not influenced by changes in preload and heart rate [21]. In this study, improvement in tissue Doppler derived MPI in luteal phase of menstrual cycle can be speculated to be mainly related to estrogen effects. Influence of progesterone on cardiac functions has not been investigated enough yet. However, some HRT studies demonstrated that progesterone does not change the beneficial effect of estrogen on cardiac protection, except that on lipid profile [22]. Effects of estrogen on cardiac functions have been studied in postmenopausal women, and short-term beneficial effects of estrogen were different among those studies. Fak et al. [23] observed a significant improvement of left ventricular diastolic functions after a single dose of 0.625 mg conjugated equine estrogen, whereas Aldrighi et al. [24] did not observe any changes in IRT, ejection time or MPI 90 min after a single dose of estradiol. In our study, natural increase of estrogen takes a long time, contrary to previous studies where drugs were used with respect to time and methodology. Concordant with our results, Fuenmayor et al. [25] showed a significant change in the left ventricular diastolic function during luteal phases of menstrual cycle in normal women using pulse wave Doppler derived mitral E/A ratio. Besides improvement in left ventricular diastolic functions, we demonstrated the improvements in left ventricular systolic function, global left ventricular function and right ventricular function using TDI derived time intervals. Also, this study showed that there was a moderate correlation between estrogen levels and MPI and that progesterone levels did not have such a correlation. In this study, it was demonstrated for the first time that endogen estrogen or progesterone improved the
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combined systolic and diastolic function in both left and right ventricle during luteal phases of menstrual cycle. Considering the previous studies and our results, estrogen may be responsible for this improvement. In clinical practice, these results can be important when echocardiographic evaluation was done in reproductive age women.
[12]
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