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The Relationship Between Serum Sex Steroid Levels and Heart Rate Variability Parameters in Males and the Effect Of Türk Kardiyol Dern Arş - Arch Turk Soc Cardiol 2010;38(7):459-465 459 The relationship between serum sex steroid levels and heart rate variability parameters in males and the effect of age Erkeklerde serum cinsiyet steroidleri ile kalp hızı değişkenliği verileri arasındaki ilişki ve yaşın etkileri M. Tolga Doğru, M.D., M. Murad Başar, M.D.,# Ercan Yuvanç, M.D.,# Vedat Şimşek, M.D., Ömer Şahin, M.D. Departments of Cardiology and #Urology, Medicine Faculty of Kırıkkale University, Kırıkkale Objectives: We evaluated the relationships between sex Amaç: Bu çalışmada cinsiyet steroidleri ile kalp hızı de- steroid levels and heart rate variability (HRV) parameters. ğişkenliği (KHD) verileri arasındaki ilişkiler araştırıldı. Study design: The study included 114 male subjects (mean Çalışma planı: Çalışmaya, kardiyolojik açıdan değerlen- age 46.6±11.3 years) presenting to our department for cardi- dirme için başvuran 114 erkek hasta (ort. yaş 46.6±11.3) ologic evaluation. Hormonal analysis included serum levels alındı. Hormon analizlerinde serumda luteinize edici hor- of luteinizing hormone, prolactin, total testosterone (TT), free mon, prolaktin, total testosteron (TT), serbest testosteron, testosterone, estradiol (E2), and dehydroepiandrosterone östradiol (E2) ve dehidroepiandrosteron sülfat (DHEA-S) sulfate (DHEA-S). Parameters of HRV were derived from düzeyleri ölçüldü. Yirmi dört saatlik Holter kayıtlarından 24-hour Holter monitoring. The associations between serum KHD parametreleri hesaplandı. Serum cinsiyet steroidleri sex steroid levels and HRV parameters were investigated in ile KHD değerleri arasındaki ilişkiler hastalar üç yaş gru- three age groups (20-39 years; 40-59 years; >60 years). buna (20-39 yaş; 40-59 yaş; >60 yaş) ayrılarak incelendi. Results: All the participants had normal biochemical re- Bulgular: Biyokimyasal sonuçlar katılımcıların tümünde sults. The three age groups were similar in terms of anthro- normal bulundu. Antropometrik ölçümler açısından üç pometric measurements. Among sex steroids analyzed, yaş grubu benzerlik gösterdi. İncelenen cinsiyet steroid- only serum DHEA-S level was significantly different among leri içinde sadece serum DHEA-S düzeyi üç yaş grubu the groups (p=0.026), showing a decreasing trend with age. arasında anlamlı farklılık göstererek (p=0.026) yaşla azal- In the evaluation of HRV, all parasympathetic activities de- ma eğilimi sergiledi. Kalp hızı değişkenliği değerlendirme- creased (for HFn, pNN50, and rMSDD: p=0.001, p=0.000, sinde, parasempatik aktiviteyi gösteren tüm veriler yaşla and p=0.000, respectively), while only LF/HF among sym- anlamlı düşüş gösterirken (HFn, pNN50 ve rMSDD için pathetic activities increased (p=0.000) with age. Partial sırasıyla p=0.001, p=0.000 ve p=0.000), sempatik aktivite correlation analysis with control of age and waist circumfer- göstergeleri arasında sadece LF/HF oranı yaşla artış gös- ence showed that TT and DHEA-S were positively correlat- terdi (p=0.000). Yaş ve bel çevresi ayarlı kısmi korelasyon ed with HFn (parasympathetic parameter), and were in neg- analizinde, TT ve DHEA-S parasempatik aktivite göster- ative correlation with LF/HF24 hours and global sympathetic gelerinden HFn ile pozitif ilişkili; sempatik aktivite göster- index (GSI) (sympathetic parameters). Serum E2 level was gelerinden LF/HF24 saat ve global sempatik indeks (GSİ) ile negatively correlated with the parasympathetic parameter negatif ilişkili bulundu. Serum E2 ise parasempatik para- of rMSSD, and positively correlated with LF/HF24 hours and metre olan rMSDD ile negatif, LF/HF24 saat ve GSİ ile pozitif GSI. Among serum sex steroids, DHEA-S was the most ilişki gösterdi. Cinsiyet steroidleri arasında otonomik fonk- correlated parameter with autonomic functions. siyonlarla en ileri ilişkiyi gösteren DHEA-S idi. Conclusion: Our results showed positive correlations Sonuç: Çalışmamızın bulguları, antropometrik faktörler- between androgens and parasympathetic activity and be- den bağımsız olarak, erkeklerde androjenlerin parasem- tween estradiol and sympathetic activity in men, indepen- patik aktivite ile, östradiolün ise sempatik aktivite ile ilişkili dent from anthropometric factors. olduğunu göstermektedir. Key words: Androgens; dehydroepiandrosterone; electrocar- Anah tar söz cük ler: Androjen; dehidroepiandrosteron; elektro- diography, ambulatory; estradiol; gonadal steroid hormones; kardiyografi, ambulatuvar; östradiol; gonodal steroid hormonu; heart rate; male; testosterone. kalp hızı; erkek; testosteron. This study was partly presented at the 28th Congress of the Société Internationale d’Urologie in Cape Town, November 12-16, 2006. Received: August 9, 2009 Accepted: November 12, 2009 Correspondence: Dr. M. Tolga Doğru. Huzur Mah., 46. Sok., Sonbahar Apt., 5/12, 06450 Ankara, Turkey. Tel: +90 312 - 472 83 36 e-mail: [email protected] 460 Türk Kardiyol Dern Arş Heart rate variability (HRV) and its computed compo- Exclusion criteria included the following clinical or nents are noninvasive, reliable, and popular indicators laboratory features: cardiac disease such as congenital for assessing the activities of the autonomic nervous heart disease, left ventricle hypertrophy or dilatation, system and are used for indirect evaluation of auto- cardiac arrhythmias or conduction problems; systemic nomic functions.[1-7] Recent studies have shown that diseases such as diabetes mellitus and hypertension, factors such as gender, sex steroid levels, age, and an- neurological problems, psychiatric diseases, mixed thropometric features may also influence autonomic connective tissue disorders, endocrinopathy such as functions.[1-6] The relationship between serum sex ste- thyroid pathology and hypogonadism; abnormal liver roid levels and autonomic functions in both genders and renal function tests, hyperlipidemia, smoking or has become an attractive area of research. alcohol use, use of medications for chronic disorders, 2 Testosterone regulates sexual maturation in fetal and obesity (BMI >28 kg/m ). and pubertal periods, and determines the sexual char- The patients were divided into three age groups acteristics and function in adulthood.[8,9] There are few as follows: 20-39 years (group 1), 40-59 years (group studies in the literature regarding the effect of sex ste- 2), and >60 years (group 3). There were 43 patients in roids levels on autonomic function and HRV. The ef- group 1 (mean age 33.9±4.9 years), 46 patients in group fect of testosterone on the autonomic neural ganglion, 2 (mean age 47.8±3.2 years), and 25 patients in group 3 particularly on the control of perineal reflexes and (mean age 66.6±4.5 years). nerve transduction pathways has been described in Biochemical and hormonal analysis. Laboratory recent years, and providing evidence that testosterone work-up involved a detailed biochemical analysis (SMA- affects parasympathetic responses and facilitates the 24) and complete blood count. Additionally, luteinizing [10-13] baroreflex response in autonomic function. These hormone, prolactin, total testosterone (TT), free testos- findings indicate that serum sex steroids, especially terone (FT), estradiol (E2), and dehydroepiandrosterone testosterone, have effects not only on sexual differen- sulfate (DHEA-S) were assayed. Non-fasting blood tiation, but also on autonomic functions of the cardio- samples were drawn between 09.00 and 10.00 hours. Se- vascular system. rum hormone levels were determined using the electro- Animal studies have shown that serum estradiol chemiluminescence immunoassay with the Roche Ele- level also influences autonomic functions.[14,15] In hu- cys 2010 immunoassay analyzer and Roche kit (Roche man studies, peripheral fat tissue, serum leptin level, Diagnostics, Indianapolis, Indiana, USA). and testosterone/estradiol ratio have been shown to Cardiologic evaluations. Patients were taken to a si- [16-18] affect sympathovagal tonus in males. These find- lent and quiet test room at 20°C and were allowed to ings suggest a primary and/or a secondary role for sex rest for 15 minutes in the supine position at the be- steroids in autonomic function. ginning of the test. Then, arterial blood pressure was The aim of the present study was to investigate measured and 12-channel ECG recordings were ob- the effect of age on the relationship between sex tained. Additionally, all the patients were evaluated steroid levels and autonomic functions. For this with posteroanterior chest radiography, exercise stress purpose, we utilized HRV as an indicator of auto- test (Quinton 4500 treadmill, Seattle, Washington, nomic functions. USA), and color Doppler echocardiography (GE Vivid 7 Pro, General Electric, Florida, USA). Finally, a Holt- PATIENTS AND METHODS er device was affixed and the starting time was set to Patients. A total of 114 male patients aged between record second sensitivity. 20 and 79 years (mean 46.6±11.3 years) were enrolled Measurement of 24-hour HRV. Heart rate variabil- into the study. All patients were admitted to the Cardi- ity parameters were derived from the recordings of ology Department for general health examination and 24-hour Holter monitoring and analyzed with the Del were evaluated with a detailed history and physical Mar-Impresario System (Del Mar-Impresario Medi- examination. Height, weight, waist, and hip measure- cal Systems, Irvine, CA, USA). Data were evaluated ments were made; body mass index (BMI) and waist/ using the HRV standards recommended by the Task hip ratio were calculated, and arterial pressures were Force Report in 1996.[7]
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