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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 38  |  Issue : 3  |  Page : 147-150

The effects of menstrual cycle on sympathetic skin response and strength–duration properties


Department of Neurology, Faculty of Medicine, Adana Dr. Turgut Noyan Research Hospital, Başkent University, Adana, Turkey

Date of Submission07-Oct-2020
Date of Decision04-Feb-2021
Date of Acceptance10-Feb-2021
Date of Web Publication20-Sep-2021

Correspondence Address:
Ahmet Onur Keskin
Department of Neurology, Adana Dr. Turgut Noyan Research Hospital, Başkent University, Ankara
Turkey
Vahide Deniz Yerdelen

Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/nsn.nsn_184_20

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  Abstract 


Background: Sympathetic control of the circulation is considerably affected by female reproductive hormones. Sudomotor function can be easily evaluated with sympathetic skin response (SSR). Although studies reveal that SSR amplitude decreases with hormone replacement therapy, the effect of estrogen on SSR is unclear. Measuring axonal excitability provides information about the physiological and physical properties of axonal ion channels and nerves. Axonal excitability tests may also give valuable information about the pathophysiology underlying neuronal disorders. In this study, we investigate the influence of female hormones, especially estrogen, on neuronal excitability and the sympathetic nervous system. Methods: SSR and strength–duration time constant (SDTC) tests were conducted on healthy women with a mean age of 26 ± 4 years with regular menstrual cycles. The tests were performed during the first 3 days of the menstrual cycle when the level of estrogen is at its lowest and 2 days before ovulation when the estrogen is at its highest level. Results: SDTC, rheobase, and the latency of SSR were found to be relatively shorter at 2 days before ovulation when compared with the values of the first 3 days of the menstrual cycle. However, the difference was not statistically significant (P > 0.05). Discussion: The SDTC and SSR values in the 2 days before ovulation and the first 3 days of the menstrual cycle did not show any significant differences. We suggested that these parameters do not affect neuronal excitability associated with varied estrogen levels. Conclusion: Further research will be required to fully understand the influence of sex hormones on the nervous system in menstrual cycles, which can suggest underlying mechanisms of various diseases that are linked with autonomic and hormonal alterations.

Keywords: Axonal excitability, menstrual cycle, strength–duration time constant, sympathetic skin response


How to cite this article:
Keskin AO, Yerdelen VD. The effects of menstrual cycle on sympathetic skin response and strength–duration properties. Neurol Sci Neurophysiol 2021;38:147-50

How to cite this URL:
Keskin AO, Yerdelen VD. The effects of menstrual cycle on sympathetic skin response and strength–duration properties. Neurol Sci Neurophysiol [serial online] 2021 [cited 2021 Dec 9];38:147-50. Available from: http://www.nsnjournal.org/text.asp?2021/38/3/147/326288




  Introduction Top


The possible relationship between estrogens and neuronal excitability was described almost 150 years ago. The autonomic changes during the menstrual cycle have been studied since the 1970s.[1] The central nervous system (CNS) is affected by hormonal changes. Thus, it has been suggested that hormones lead to variations in the functions of the autonomic nervous system (ANS) through the CNS.[2] Higher plasma catecholamine levels have been reported in the luteal phase of the menstrual cycle compared to the follicular phase.[3] Sympathetic control of the circulation is considerably affected by female reproductive hormones. Yildirir et al. investigated the heart rate variability (HRV) alternation in different phases of the menstrual cycle and reported that sympathetic activity increased in the luteal phase of the menstrual cycle compared to the follicular phase.[4] Nonetheless, the exact physiological mechanism and phenomena observed during the menstrual cycle are still not completely understood.[2],[5] Sudomotor function can be easily evaluated with sympathetic skin response (SSR). Studies have been conducted using SSR in both peripheral and CNS disorders.[2],[6],[7] Despite the peripheral pathways of the SSR are well known, information on the central pathways are limited.[6] However, SSR cannot exclude impaired sympathetic noradrenergic function conclusively.[6]

Measuring axonal excitability provides information about the physiological and physical properties of axonal ion channels and nerves. Axonal excitability tests may also give valuable information about the pathophysiology underlying neuronal disorders.[8] However, the effects of the female hormones on neuronal excitability are not fully understood. Kumar and Foster and Carrer et al. suggested that the female hormones can alter neuronal excitability.[9],[10]

Na+/K+ pump activity and axonal conduction in peripheral nerves can be evaluated with nerve excitability measurements. The strength–duration curve is a standard method to measure neuronal excitability.[11] The rheobase and the strength–duration time constant (SDTC) are the strength–duration properties of an axon.[11],[12] The SDTC is a measure of the rate at which the threshold current for a target potential declines as stimulus duration is increased.[13] The STDC is equal to chronaxie according to Weiss's formula.[14]

In this study, we aimed to demonstrate the possible differences in SSR and axonal excitability parameters during different menstrual cycle phases associated with different estrogen levels.


  Methods Top


The study included ten healthy women with regular menstrual cycles (27.3 ± 2.6 days). The mean age of volunteers was 26 ± 4 years. The participants were briefed on the purpose of the study and gave their consent to participate in the study. They also did not have any systemic or metabolic diseases or peripheral neuropathy. SSR and SDTC tests were performed during the first 3 days of the menstrual cycle when the estrogen level is at its lowest and 2 days before ovulation when estrogen is at its highest level. Ethical approval for this study was granted by the Clinical Research Ethics Committee at Baskent University.

Autonomic function tests

Electromyographic tests were performed in a silent room, while the patient was awake and comfortable. The skin temperature was maintained at >32°C. In the study, an electromyography machine with filter settings of 0.5 Hertz (Hz) for low frequency and 500 Hz for high frequency was used. The sweep speed was set at 300–500 ms per division. Palmar SSR readings were recorded using surface electrodes. The stimulating electrodes were located at the contralateral median nerve. The reference electrode was placed at the wrist, and the active electrode was placed on the palm. Pinprick, touch, unexpected acoustic stimuli, and electrical stimulation of the median nerve at 30 mA stimulus intensity were applied; four successive SSRs were recorded [Figure 1]. SSR latency was measured as the first continuous deflection from baseline, and SSR amplitude was measured from peak to peak. The mean of four SSR latencies and amplitudes was also recorded.
Figure 1: Sympathetic skin response induced by unexpected acoustic stimuli, pinprick, touching, and median nerve electrical stimulation at 30 mA stimulus intensity in an example participant

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Strength–duration properties

Electromyographic tests were performed in a silent room, and the skin temperature was maintained at >32°C. The study used an electromyography machine with the filter settings for the low frequency at 10 Hz and the high frequency at 3 kHz. Sampling time was set to 100 μs, and channel sensitivity was set at 1–5 mV division for the motor nerve conduction study. The nerve excitability tests were studied using a similar methodology as previously described.[12]

Statistics

Statistical analyses were performed with SPSS software version 23.0 (SPSS Inc., Chicago, IL, USA). Continuous variables as mean and standard deviation (SD) (if necessary, median and minimum–maximum) and categorical variables were summarized as number and percent. Wilcoxon signed–rank test was used to compare the values during the first 3 days of the menstrual cycle and the 2 days before ovulation. Quantitative data are presented as means ± SD. P < 0.05 was considered statistically significant.


  Results Top


The sensory distal latency, amplitude, and conduction velocity of the ulnar nerves were 2.1 ± 0.1 ms, 43.45 ± 6.3 μV, and 59.2 ± 2.9 m/s, respectively. The motor distal latency, amplitude, and conduction velocity elicited by stimulating at below elbow of the ulnar nerve were 2.2 ± 0.1 ms, 11.3 ± 1.8 mV, and 58.4 ± 1.8 m/s, respectively.

The latency (ms) of SSR on the first 3 days of the menstrual cycle and at 2 days before ovulation was 1496 ± 23 and 1465 ± 12 and the amplitude (μV) of SSR was 2894 ± 12 and 2876 ± 12, respectively [Table 1]. There was no significant difference between the values measured at different phases of the menstrual cycles (P > 0.05). The SDTC and rheobase for motor nerves were found to be relatively shorter during the 2 days before ovulation when compared with the values of the first 3 days of the menstrual cycle [Figure 2]. However, this difference was not statistically significant (P > 0.05).
Table 1: The values of participants at menstruation period and 2 days before ovulation

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Figure 2: (a and b) The strength-duration time consent tests of motor (a) and sensory fibers (b) of the ulnar never were performed during the first 3 days of the menstrual cycle when the level of estrogen is at the least and 2 days before ovulation when the level of estrogen is highest. The relation between stimulus duration and the value achieved by multiplying stimulus duration (charge). The strength–duration time constant is calculated as follows in this example: when y is accepted as zero, x is found by dividing 1.946 to 0.66

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  Discussion Top


Sympathetic control of the circulation is considerably affected by female reproductive hormones. Nonetheless, the exact physiological mechanism and phenomena observed during the menstrual cycle are still not completely defined.[1],[5] A review that investigated the effects of endogenous and exogenous estrogens on HRV in female participants speculated that vagal dominance on the heart decreases from the follicular phase to the luteal phase.[15] Sahiner et al. concluded that estrogens may have an inhibitory effect on the spinal cord sympathetic neurons.[16] Findings that suggest alternatives in ANS functions during the menstrual cycle are questionable. Some studies did not reveal an association, while others reported a significant increase in skin conductance, respiratory, and heart rate during the luteal phase.[1],[4],[5],[15]

SSR has been used in various pathophysiological conditions. Peripheral sudomotor innervation can be investigated with an SSR test. However, diet, physical activity, and sleep can alter sympathetic nervous system activity during the menstrual cycle.[17] A normal SSR test does not exclude the disorder in the sympathetic noradrenergic system conclusively. Dysautonomia symptoms usually indicate nerve dysfunctions other than skin sympathetic nerves.[6]

In this study, we performed SSR and SDTC tests during the first 3 days of the menstrual cycle when the estrogen level is at its lowest and 2 days before ovulation when the estrogen level is at its highest. In our study, there was no significant difference between the two menstrual cycle phases in SSR and SDTC. Although there was no significant difference, the SSR test findings 2 days before ovulation suggested a decreased neuronal excitability, which is possibly associated with a higher estrogen level. Although studies are showing that SSR amplitude decreases with hormone replacement therapy in postmenopausal women, the effect of estrogen on SSR is ambiguous.[16],[18]

There is limited data about the effects of gender on axonal excitability parameters in the literature. There are also no studies that examine axonal excitability at different phases of the menstrual cycle. Kiernan et al. evaluated axonal excitability in the sensory nerves of 50 healthy participants and reported that sensory nerve action potential amplitudes were higher, while thresholds and rheobase were lower in women compared to men.[8] Yerdelen et al. reported that the SDTC was lower in men compared to women and that the difference was more pronounced, especially under the age of 40.[13] Besides, Bae et al. reported that younger women (<50 years) had lower rheobase, greater threshold changes, and greater supernormality compared to men.[19]

Autonomic arousal and progesterone increase during the luteal phase.[1],[4],[5],[15] In our study, we compared the SSR and SDTC values when the estrogen levels were at their highest and lowest. Therefore, the effect of progesterone was minimal in this study. SSR and axonal excitability at different stages of the menstrual cycle may have ascended due to an increase in progesterone in the luteal phase. There are limitations in our study. We were unable to eliminate other factors in our study group that could affect autonomic variations, such as sleep, diet, and physical activity. In addition, the number of participants in our study was limited because of the difficulty in following the menstrual cycles of women. Further research will be required to fully understand the influence of sex hormones on the nervous system in menstrual cycles, which can suggest underlying mechanisms of various diseases that are linked with autonomic and hormonal alterations.


  Conclusion Top


Further research will be required to fully understand the influence of sex hormones on the nervous system in menstrual cycles, which can suggest underlying mechanisms of various diseases that are linked with autonomic and hormonal alterations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Charkoudian N. Influences of female reproductive hormones on sympathetic control of the circulation in humans. Clin Auton Res 2001;11:295-301.  Back to cited text no. 1
    
2.
Ozisik HI, Kamisli O, Karlidag R, Kizkin S, Ozcan C. Sympathetic skin response in premenstrual syndrome. Clin Auton Res 2005;15:233-7.  Back to cited text no. 2
    
3.
Goldstein DS, Levinson P, Keiser HR. Plasma and urinary catecholamines during the human ovulatory cycle. Am J Obstet Gynecol 1983;146:824-9.  Back to cited text no. 3
    
4.
Yildirir A, Kabakci G, Akgul E, Tokgozoglu L, Oto A. Effects of menstrual cycle on cardiac autonomic innervation as assessed by heart rate variability. Ann Noninvasive Electrocardiol 2002;7:60-3.  Back to cited text no. 4
    
5.
Kuczmierczyk AR, Adams HE. Autonomic arousal and pain sensitivity in women with premenstrual syndrome at different phases of the menstrual cycle. J Psychosom Res 1986;30:421-8.  Back to cited text no. 5
    
6.
Vetrugno R, Liguori R, Cortelli P, Montagna P. Sympathetic skin response: Basic mechanisms and clinical applications. Clin Auton Res 2003;13:256-70.  Back to cited text no. 6
    
7.
Shahani BT, Halperin JJ, Boulu P, Cohen J. Sympathetic skin response – A method of assessing unmyelinated axon dysfunction in peripheral neuropathies. J Neurol Neurosurg Psychiatry 1984;47:536-42.  Back to cited text no. 7
    
8.
Kiernan MC, Bostock H, Park SB, Kaji R, Krarup C, Krishnan AV, et al. Measurement of axonal excitability: Consensus guidelines. Clin Neurophysiol 2020;131:308-23.  Back to cited text no. 8
    
9.
Kumar A, Foster TC. 17beta-estradiol benzoate decreases the AHP amplitude in CA1 pyramidal neurons. J Neurophysiol 2002;88:621-6.  Back to cited text no. 9
    
10.
Carrer HF, Araque A, Buño W. Estradiol regulates the slow Ca2+-activated K+current in hippocampal pyramidal neurons. J Neurosci 2003;23:6338-44.  Back to cited text no. 10
    
11.
Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin Neurophysiol 2001;112:1575-85.  Back to cited text no. 11
    
12.
Yerdelen D, Ertorer E, Koç F. The effects of hypothyroidism on strength-duration properties of peripheral nerve. J Neurol Sci 2010;294:89-91.  Back to cited text no. 12
    
13.
Yerdelen D, Uysal H, Koc F, Sarica Y. Effects of sex and age on strength-duration properties. Clin Neurophysiol 2006;117:2069-72.  Back to cited text no. 13
    
14.
Geddes LA. Accuracy limitations of chronaxie values. IEEE Trans Biomed Eng 2004;51:176-81.  Back to cited text no. 14
    
15.
von Holzen JJ, Capaldo G, Wilhelm M, Stute P. Impact of endo- and exogenous estrogens on heart rate variability in women: A review. Climacteric 2016;19:222-8.  Back to cited text no. 15
    
16.
Sahiner T, Aktan E, Kaleli B, Oguzhanoglu A. The effects of postmenopausal hormone replacement therapy on sympathetic skin response. Maturitas 1998;30:85-8.  Back to cited text no. 16
    
17.
Tada Y, Yoshizaki T, Tomata Y, Yokoyama Y, Sunami A, Hida A, et al. The impact of menstrual cycle phases on cardiac autonomic nervous system activity: An observational study considering lifestyle (Diet, Physical Activity, and Sleep) among female college students. J Nutr Sci Vitaminol (Tokyo) 2017;63:249-55.  Back to cited text no. 17
    
18.
Kutlar I, Yilmaz M, Balat O. Sympathetic skin response in women receiving hormone replacement therapy. Int J Gynaecol Obstet 2004;84:181-2.  Back to cited text no. 18
    
19.
Bae JS, Sawai S, Misawa S, Kanai K, Isose S, Shibuya K, et al. Effects of age on excitability properties in human motor axons. Clin Neurophysiol 2008;119:2282-6.  Back to cited text no. 19
    


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