Effects of menstrual cycle phase: a randomized prospective observational trial

Abstract

AimWomen experience physical and psychological changes as a result of their menstrual cycle. This study aimed to investigate whether the menstrual cycle had any effect on the preoperative anxiety experienced by women who were scheduled to have an operation.MethodsOne hundred female patients who were scheduled to undergo a septorhinoplasty, and who met the inclusion criteria, were enrolled in the present study. The patients were divided into two groups according to the phase of their menstrual cycle: Group F (follicular phase) and Group L (luteal phase). The patients’ anxiety level was measured preoperatively using the State-Trait Anxiety Inventory Scale. The patients’ heart rate and blood pressure measurements were performed preoperatively as well as at 1 min, 5 min, and 10 min after intubation.ResultsThe preoperative anxiety scores of the patients in the luteal phase (41.14) were statistically significantly higher than those of the patients in the follicular phase (36.04). The blood pressure, heart rate, and peripheral oxygen saturation values were found to be similar between the two groups.ConclusionWe believe that preoperative anxiety is higher during the luteal phase of the menstrual cycle than during the follicular phase, but the hemodynamic data were similar in both phases.

Keywords

Introduction

Preoperative anxiety is a condition that can negatively affect anesthesia, surgery, and postoperative recovery.¹ In fact, it has been shown that preoperative anxiety affects patients in both cognitive and physiological ways. If such anxiety is not correctly managed, it may lead to surgical procedures being postponed or canceled, or it may result in delayed postoperative wound healing. Anxiety can arise for a number of reasons, including a patient’s concern about his/her health and surgery, uncertainty regarding possible outcomes, fear of not waking up after surgery, and fear/experience of pain. It has been suggested that preoperative anxiety might be experienced by as many as 80% of patients.^2-3 It has also been reported that anxiety directly increases a patient’s blood pressure and changes his/her pulse rate, which might lead to hemodynamic instability during anesthesia.^4-5 The menstrual cycle is a physiological event accompanied by fluctuations in certain hormones, including estrogen and progesterone.⁶ The menstrual cycle involves two basic phases, namely the follicular phase and the luteal phase.⁷ Hormonal, physical, and psychological changes occur in women as a result of the menstrual cycle. Hence, it has been suggested that there is a strong relation between the menstrual cycle and an individual’s emotional state.⁸ It has previously been established that women feel well during the first phase of the menstrual cycle, while they face emotional, physical, and behavioral difficulties toward the end of the cycle.⁹ Indeed, studies have shown that women experience anxiety, dysphoric discomfort, irritability, mood changes, depression, anger, and sleep disorders prior to menstruation.^10-11 In addition, the hemodynamic response might increase, depending on the physiological and psychological stress condition, during the luteal phase.¹² Various studies have been conducted with regard to the physiological and hemodynamic effects of the menstrual cycle. However, the effects of the different phases of the menstrual cycle on preoperative anxiety have not yet been investigated to an adequate extent. The present study hypothesizes that preoperative anxiety will vary according to the phases of the menstrual cycle. The aim of this study was hence to investigate the effects of the different phases of the menstrual cycle on preoperative anxiety in patients scheduled to have surgery

Materials and Methods

The present study was conducted among patients who were scheduled to undergo a septorhinoplasty. All prospective septorhinoplasty patients who attended the hospital for a routine preoperative examination were informed about the study. After ethical approval had been received (Ethics Committee IRB Approval Date: 17 Jan 2018, Decision number: 02) and written informed consent had been obtained from the patients, the study was initiated. After the clinical trial had been recorded, the cases were started (NCT03708679).Inclusion Criteria for the StudyPatients who did not smoke, did not drink alcohol, and did not use oral contraceptives; who did not report any irregular menstrual cycles (28±2-day menstruation cycle); who were between 18 and 45 years of age; and who were considered to be in the American Society of Anesthetics (ASA) I-II Group were included in the study.Exclusion Criteria for the StudyPatients who were determined to exhibit difficulties in communication; who reported experiencing amenorrhea, pregnancy, delirium, psychological diseases, and major depressive disorders; who had malignancy and acute kidney failure; and who were older than 45 years of age were excluded from the study.GroupsInformation regarding their menstrual cycles was obtained from all the patients. The length (days) of the menstrual cycle was counted from the first day of the last cycle. Those patients who were found to be between the 8th and 12th days of the menstrual cycle were enrolled in Group F (follicular phase), while those who were found to be between the 20th and 24th days of the menstrual cycle were enrolled in Group L (luteal phase).¹³ The follow-up of the cases and the recording of the measurements were carried out by an anesthesiologist who was unaware of the patient groups.Study ProcedureThe ages, heights, weights, and ASA scores of the patients were recorded while they were in the preoperative unit. The patients were divided into groups based on the dates of their last menstrual cycles. Standard monitoring procedures were used with all the patients, including electrocardiogram (ECG), heart rate (HR), non-invasive blood pressure (NIBP), and peripheral oxygen saturation (SpO2). After 10 minutes of resting, the patients’ hemodynamic measurements were recorded at both the 5th and 10th minutes post-resting. Instant anxiety measurements were also performed. For this, the State-Trait Anxiety Inventory for AdultsTM (STAI-AD).¹⁴ scale was used. When using this scale, scores of between one and four are awarded for each of the 20 included statements. The sum of the points awarded with regard to positive feelings (statements 1, 2, 5, 8, 10, 11, 15, 16, 19, and 20) was subtracted from the sum of the points awarded with regard to negative feelings (statements 3, 4, 6, 7, 9, 12, 13, 14, 17, and 18), with the resultant figure then being multiplied by a constant of 50. The scores for all the patients were added together to obtain the overall STAI-AD scores for the groups (Figure 1). The standard monitoring process continued after the patients were transferred to the operating room. The patients’ values were recorded before and after the induction of anesthesia, and again at the 1st, 5th, and 10th minutes after intubation. The venous vein was opened using a 20 G i.v. cannula. Then, 1 mg/kg of lidocaine, 2 μg/kg of fentanyl, 2 mg/kg of propofol, and 0.6 mg/kg of rocuronium were administered to induce anesthesia. If a maintenance dose was required, 0.5 mcg/kg of fentanyl, 0.2 mg/kg of rocuronium, and 1% of sevoflurane were used. Throughout the operation, 40% oxygen and 60% of medical air were used. The maintenance fluid required for the patients was provided with 0.9% NaCl. Once the procedure had been completed, the durations of both the surgery and the anesthesia were recorded.Statistical AnalysesThe descriptive statistics concerning the investigated characteristics were expressed as the mean, standard deviation, minimum, and maximum values for the continuous variables, while they were expressed as the number and percentage for the categorical variables. The independent t-test was employed to compare the group means for the continuous variables. The Chi-Square test was employed to determine the relation between the groups and the categorical variables. Based on the recommendations of previous studies.^15-17 the standard deviation (σ) was considered to be 2.5 due to the number of anxiety scores (STAI-AD). The effect size (d) was assumed to be 0.9, while a Z value of 1.96 was used for the 0.05 type I error rate. The sample size was determined to be 45 by using the equation for sample size calculation (n = Z2 .σ2 /d2 ) , and 50 patients were included in each group. A p-value of <0.05 was considered to be statistically significant. Statistical Package for the Social Sciences (SPSS) v. 20.0 software (IBM SPSS for Windows, SPSS Inc., Chicago, IL, USA) was used to analyze the data.

Results

A total of 100 female patients were included in the present study. The patients’ demographical data were found to be similar (p>0.05) (Table 1). The mean anxiety score for Group L was determined to be statistically significantly higher than that for Group F (p<0.05) (Figure 2). The highest anxiety scores were found to be 71 in Group L and 50 in Group F, respectively. No statistically significant differences were detected between the groups with regard to the systolic, diastolic, and mean blood pressures, heart rates or the peripheral oxygen saturation values (p>0.05). The average blood pressure values of the groups are shown in Table 2.

Discussion

This study showed that the level of preoperative anxiety was higher in the septorhinoplasty patients who were in the luteal phase of their menstrual cycle. However, it was also determined that the blood pressure, heart rate, and peripheral oxygen saturation values were similar between the two groups. Our findings are consistent with those of previous studies, which reported higher levels of anxiety during the luteal phase of the menstrual cycle.^6-7,18 Premenstrual stress, which is observed during the luteal phase of the menstrual cycle, is characterized by physical, psychological, and behavioral changes, which are believed to affect 75% of women of reproductive age.¹⁹ Previous studies have suggested that the functioning of the autonomic nervous system during the luteal phase might be related to various psychosomatic and behavioral symptoms that occur during the premenstrual period.²⁰ Kanojia et al.⁷ conducted a study among healthy young women, and they reported that the average anxiety score during the luteal phase (46.96) was higher than that during the follicular phase (40.64). In the present study, it was likewise determined that the level of preoperative anxiety was higher during the luteal phase than during the follicular phase. The results of our study are hence in line with those reported in the literature. These results are consistent with the notion of psychological changes being induced by stress and with the stress-related psychological changes reported to occur during the luteal phase of the menstrual cycle. Similar to the present study, Gonda et al.¹⁸ investigated the fluctuations in psychological symptoms that occur during the menstrual cycle. They determined that the anxiety level during the luteal period was higher than that during the follicular period. According to the utilized measurement scales, they detected psychological fluctuations, at least to some degree, in all participants. The fact that all our patients were scheduled to undergo aesthetic surgeries might have influenced both the anxiety measurements and hemodynamic reflections. The hemodynamic effects might differ in relation to different surgeries. The luteal stage, during which the estrogen and progesterone hormone levels decrease, is associated with high irritability and negative mood. Thus, ovarian steroids are considered to be important predictors of fluctuations in women’s moods during the menstrual cycle.²¹ However, several prior studies have reported there to be no change in women’s moods during the luteal phase.^22-23 Natale et al.²⁴ considered that this difference might be due to the scales employed in such studies. For instance, Redei et al.²⁵ directly compared the daily hormone measurements and the reported moods of women, and they concluded that there was no relation between the estradiol and progesterone levels and women’s moods. Schwartz et al.²⁶ measured the daily ovarian hormone levels in women and reported that women’s moods were not related to their hormone levels. They also reported that individuals’ stress level and physical health status exerted a major impact on their mood, although fluctuations in ovarian hormones had little effect. In our study, while there were differences in the anxiety scores between the groups, the blood pressure, heart rates, and peripheral oxygen saturation values were not found to differ. This caused us to consider that the increased anxiety scores did not reach a level that might affect the hemodynamics during the luteal phase. In addition, the fact that the participants in our study were young and healthy individuals might also have influenced their hemodynamic stability. It is likely that different results would be found in older individuals and those with comorbidities. Hemodynamic changes might also be observed during different phases of the menstrual cycle due to the effect of the hormones secreted during those phases.^6,13 In previous studies, it has been reported that the plasma norepinephrine levels and sympathetic activity in healthy women were found to be higher during the luteal phase than during the follicular phase.^13,27 It has also been reported that there were higher systolic blood pressure levels, as well as lower diastolic blood pressure levels, during the luteal phase due to the physiological and psychological stress that occurs during that phase impacting the hemodynamic response.¹² In our study, however, we did not find any differences between the patients’ systolic, diastolic, and mean blood pressures. This difference might be due to the fact that our patients were all healthy and young individuals. Further, our patients were all ASA I-II patients, and they did not have any comorbidities. Similar to our study, Kanojia et al.⁷ reported that the menstrual cycle only affected participants’ hemodynamics to a minimal extent, while Gonda et al.¹⁸ did not report any hemodynamic changes related to the different phases of the menstrual cycle. Various studies have investigated the effects of the menstrual cycle on anesthesia, traumatic intubation, and the hemodynamic response to laryngoscopy. Hanci et al.¹³ reported that the heart rates and blood pressures that were measured one minute after intubation were significantly higher in those patients who were in the luteal phase than in patients who were in the follicular phase. They reported that the altered hemodynamic responses observed in the face of intubation during the different menstrual cycle phases (rate pressure product [RPP]) might be associated with the increased response to plasma norepinephrine levels and sympathetic activity seen during the luteal phase. Khan et al.²⁸ however, reported that they detected more stable hemodynamic responses during the luteal phase. They also detected higher blood pressures and lower heart rates during the follicular phase. Hence, they recommended that any required surgeries should be scheduled during the luteal phase.²⁸ Yet, in a meta-analysis, it was reported that the current evidence is inadequate to determine the most appropriate phase of the menstrual cycle (luteal or follicular) during which to schedule anesthesia and surgery. The authors, therefore, stated that further randomized clinical trials were needed.²⁹

Limitations

It must be acknowledged that the present study did have a number of limitations. The fact that the majority of patients were in the third decade of life might have had an impact on the finding of similar hemodynamic results. Further, we were unable to measure the patients’ estrogen and progesterone levels in the present study. The inability to evidence the accuracy of the patients’ menstruation phases using hormonal parameters hence represents another limitation of the study. As a result, based on the results of the present study, we believe that the level of preoperative anxiety is higher during the luteal phase of the menstrual cycle than during the follicular phase, but the hemodynamic data were similar in both phases. However, more randomized studies are required to confirm our results.

Declarations

References

1. Matthias AT, Samarasekera DN. Preoperative anxiety in surgical patients: experience of a single unit. Acta Anaesthesiol Taiwan. 2012;50(1):3-6. doi:10.1016/j.aat.2012.02.004
   Article · PubMed · Google Scholar
2. Aust H, Eberhart L, Sturm T, et al. A cross-sectional study on preoperative anxiety in adults. J Psychosom Res. 2018;111:133-139. doi:10.1016/j.jpsychores.2018.05.012
   Article · PubMed · Google Scholar
3. Aust H, Rusch D, Schuster M, Sturm T, Brehm F, Nestoriuc Y. Coping strategies in anxious surgical patients. BMC Health Serv Res. 2016;16:250. doi:10.1186/s12913-016-1492-5
   Article · PubMed · Google Scholar
4. Jlala HA, French JL, Foxall GL, Hardman JG, Bedforth NM. Effect of preoperative multimedia information on perioperative anxiety in patients undergoing procedures under regional anaesthesia. Br J Anaesth. 2010;104(3):369-374. doi:10.1093/bja/aeq002
   Article · PubMed · Google Scholar
5. Bai X, Li J, Zhou L, Li X. Influence of the menstrual cycle on nonlinear properties of heart rate variability in young women. Am J Physiol Heart Circ Physiol. 2009;297(2):H765-H774. doi:10.1152/ajpheart.01283.2008
   Article · PubMed · Google Scholar
6. Fu Q, VanGundy TB, Shibata S, Auchus RJ, Williams GH, Levine BD. Menstrual cycle affects renal-adrenal and hemodynamic responses during prolonged standing in the postural orthostatic tachycardia syndrome. Hypertension. 2010;56(1):82-90. doi:10.1161/hypertensionaha.110.151787
   Article · PubMed · Google Scholar
7. Kanojia S, Sharma VK, Gandhi A, et al. Effect of yoga on autonomic functions and psychological status during both phases of menstrual cycle in young healthy females. J Clin Diagn Res. 2013;7(10):2133-2139. doi:10.7860/jcdr/2013/6912.3451
   Article · PubMed · Google Scholar
8. Akdeniz F, Karadağ F. Does menstrual cycle affect mood disorders? Turk Psikiyatri Derg. 2006;17(2):1-9.
   PubMed · Google Scholar
9. Lithgow BJ, Moussavi ZJN. Physiological differences in the follicular, luteal, and menstrual phases in healthy women determined by electrovestibulography: depression, anxiety, or other associations? 2017;76(2):72-81. doi:10.1159/000487771
   Article · PubMed · Google Scholar
10. Erden V, Yangn Z, Erkalp K, Delatioglu H, Bahçeci F, Seyhan A. Increased progesterone production during the luteal phase of menstruation may decrease anesthetic requirement. Anesth Analg. 2005;101(4):1007-1011. doi:10.1213/01.ane.0000168271.76090.63
    Article · PubMed · Google Scholar
11. Sener EB, Kocamanoglu S, Cetinkaya MB, Ustun E, Bildik E, Tur A. Effects of menstrual cycle on postoperative analgesic requirements, agitation, incidence of nausea and vomiting after gynecological laparoscopy. Gynecol Obstet Invest. 2005;59(1):49-53. doi:10.1159/000081222
    Article · PubMed · Google Scholar
12. Manhem K, Jern C, Pilhall M, Shanks G, Jern S. Haemodynamic responses to psychosocial stress during the menstrual cycle. Clin Sci (Lond). 1991;81(1):17-22. doi:10.1042/cs0810017
    Article · PubMed · Google Scholar
13. Hanci V, Yurtlu S, Hakimoglu S, et al. The effects of the menstrual cycle on the hemodynamic response to laryngoscopy and tracheal intubation. Anesth Analg. 2010;111(2):362-365. doi:10.1213/ane.0b013e3181e62984
    Article · PubMed · Google Scholar
14. Spielberger C, Gorsuch R, Lushene R, Vagg P, Jacobs G. Manual for the State-Trait Anxiety Inventory: Form Y Self-Evaluation Questionnaire. Palo Alto, CA: Consulting Psychologists Press; 1983. doi:10.53841/bpstest.2003.stai
    Article · PubMed · Google Scholar
15. Marteau TM, Bekker H. The development of a six-item short-form of the state scale of the Spielberger State-Trait Anxiety Inventory. Br J Clin Psychol. 1992;31(pt 3):301-306. doi:10.1111/j.2044-8260.1992.tb00997.x
    Article · PubMed · Google Scholar
16. Wetsch WA, Pircher I, Lederer W, et al. Preoperative stress and anxiety in day-care patients and inpatients undergoing fast-track surgery. Br J Anaesth. 2009;103(2):199-205. doi:10.1093/bja/aep136
    Article · PubMed · Google Scholar
17. Wang SM, Kulkarni L, Dolev J, Kain ZN. Music and preoperative anxiety: a randomized, controlled study. Anesth Analg. 2002;94(6):1489-1494. doi:10.1097/00000539-200206000-00021
    Article · PubMed · Google Scholar
18. Gonda X, Telek T, Juhasz G, Lazary J, Vargha A, Bagdy G. Patterns of mood changes throughout the reproductive cycle in healthy women without premenstrual dysphoric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(8):1782-1788. doi:10.1016/j.pnpbp.2008.07.016
    Article · PubMed · Google Scholar
19. Zaafrane F, Faleh R, Melki W, Sakouhi M, Gaha L. An overview of premenstrual syndrome. J Gynecol Obstet Biol Reprod (Paris). 2007;36(7):642-652
    PubMed · Google Scholar
20. Matsumoto T, Ushiroyama T, Kimura T, Hayashi T, Moritani T. Altered autonomic nervous system activity as a potential etiological factor of premenstrual syndrome and premenstrual dysphoric disorder. Biopsychosoc Med. 2007;1(1):24. doi:10.1186/1751-0759-1-24
    Article · PubMed · Google Scholar
21. Richardson JT. The premenstrual syndrome: a brief history. Soc Sci Med. 1995;41(6):761-767. doi:10.1016/0277-9536(95)00042-6
    Article · PubMed · Google Scholar
22. Almagor M, Ben-Porath YS. Mood changes during the menstrual cycle and their relation to the use of oral contraceptive. J Psychosom Res. 1991;35(6):721-728. doi:10.1016/0022-3999(91)90123-6
    Article · PubMed · Google Scholar
23. Charette L, Tate DL, Wilson A. Alcohol consumption and menstrual distress in women at higher and lower risk for alcoholism. Alcohol Clin Exp Res. 1990;14(2):152-157. doi:10.1111/j.1530-0277.1990.tb00462.x
    Article · PubMed · Google Scholar
24. Natale V, Albertazzi P. Mood swings across the menstrual cycle: a comparison between oral contraceptive users and non-users. Biol Rhythm Res. 2006;37(6):489-495. doi:10.1080/09291010600772451
    Article · PubMed · Google Scholar
25. Redei E, Freeman EW. Daily plasma estradiol and progesterone levels over the menstrual cycle and their relation to premenstrual symptoms. Psychoneuroendocrinology. 1995;20(3):259-267. doi:10.1016/0306-4530(94)00057-h
    Article · PubMed · Google Scholar
26. Schwartz DH, Romans SE, Meiyappan S, De Souza MJ, Einstein G. The role of ovarian steroid hormones in mood. Horm Behav. 2012;62(4):448-454. doi:10.1016/j.yhbeh.2012.08.001
    Article · PubMed · Google Scholar
27. Nakagawa M, Ooie T, Takahashi N, et al. Influence of menstrual cycle on QT interval dynamics. Pacing Clin Electrophysiol. 2006;29(6):607-613. doi:10.1111/j.1540-8159.2006.00407.x
    Article · PubMed · Google Scholar
28. Hussain Khan Z, Rahimi M, Kalani P, Ghorbani B. The effects of the menstrual cycle on the hemodynamic response to laryngoscopy and tracheal intubation. Tehran Univ Med J. 2014;72(4):242-248. doi:10.1097/00003643-201406001-00150
    Article · PubMed · Google Scholar
29. Kurdi MS, Ramaswamy AH. Does the phase of the menstrual cycle really matter to anaesthesia? Indian J Anaesth. 2018;62(5):330. doi:10.4103/ija.ija_139_18
    Article · PubMed · Google Scholar

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