Effect of the menstrual cycle on circulation during combined spinal-epidural anaesthesia

From adolescence to menopause, hormone levels during the menstrual cycle affect various body systems, from the cardiovascular system to the water and electrolyte balance. The periodically fluctuating hormone levels affect the endometrium, causing the menstrual cycle to be divided into three phases: menstruation, the follicular and luteal phases. Previous studies have primarily focused on the long-term effects of oestrogen and progesterone on the cardiovascular system, including the reduction in atherosclerosis, coronary heart disease and the pathogenesis and progression of hypertension. Recent studies have found that the heart rate is higher during the luteal phase than during the follicular phase, while the heart rate varies less during the luteal phase than during the follicular phase. Most of these studies focused on how hormone levels affect the body during states of rest, stress, or exercise [1‐9]; however, no report has addressed the effect of hormone levels on the circulation during body position changes or during anaesthesia. In this study, we investigated how body position changes and combined spinal-epidural anaesthesia (CSEA) affect circulatory function during the stages of the menstrual cycle.

This study investigated the cardiovascular regulation and compensation abilities after preoperatively fasting from food and water, under preoperative stress conditions, and under CSEA. No significant differences were found in the various circulatory indicators between patients in the supine position; however, when the supine position was changed to the standing position, the patients’ heart rates increased, and this effect was obvious during the luteal phase. After starting anaesthesia, both groups’ heart rates decreased; however, the heart rates of patients in the luteal phase were higher than those of patients in the follicular phase. Hypotension occurred more often in the luteal phase than in the follicular phase, and the required vasoactive drug dosage increased.

Female hormones include oestrogen and progesterone, and their receptors are widely distributed across various tissues and organs. Studies have found that the oestrogen β-receptor is widely distributed and that this receptor helps to regulate biosynthetic functions in tissues and cells, blood flow in tissues and organs, and body temperature. Conversely, progesterone plays the opposite role [10]. Oestrogen affects regulating the body’s circulation via three mechanisms: by increasing the responsiveness of endothelium-dependent bradykinin-mediated vasodilation and norepinephrine-mediated vasoconstriction, by upregulating nitric oxide (NO) synthase (this mechanism’s effect is controversial), and by regulating the sympathetic nervous system activity by affecting norepinephrine synthesis and the number and sensitivity of α-adrenergic receptors. Conversely, progesterone weakens the responsiveness of endothelium-dependent vasodilation to oestrogen.

Changes in posture cause much of the blood to be redistributed, leading to circulatory fluctuations. Perfusion in important organs decreases, exciting the sympathetic nervous system and the carotid sinus aortic arch baroreceptors, thus causing the heart rate to increase and the heart to work harder in order to more effectively circulate blood to the body [10‐13]. Similarly, CSEA inhibits the sympathetic nerves, dilating the peripheral blood vessels below the anaesthetic plane and reducing the amount of blood returning to the heart.

Although posture changes and CSEA cause similar physiological changes, i.e., a reduced amount of blood returning to the heart over a brief time, the body must make corresponding adjustments to adapt to circulatory system changes. However, compared with circulatory fluctuations caused by preoperative posture changes, CSEA causes the blood vessels in the lower limbs to dilate and weakens the compensatory and regulatory functions below the body’s anaesthetic plane. This relies more on the compensatory function above the anaesthetic plane and regulation via exogenous vasoactive substances to effectively circulate blood and oxygen to the vital organs and tissues. Therefore, differences in the body’s regulation during the different menstrual phases became more obvious, and the vasoactive drug dose (e.g., ephedrine) used in the corpus luteal group increased. In a previous study, when patients were under the influence of mental stress, the decrease in peripheral vascular resistance and the increase in cardiac work in the corpus luteal group supported our hypothesis [14]. The results of this study showed that regardless of body position changes or whether the measurement was taken during or after anaesthesia, patients’ heart rates during the luteal phase were higher than those of patients during the follicular phase, and this result was obvious in the standing position and at 30 min after anaesthesia. This result may have occurred because during the follicular phase, oestrogen inhibits the sympathetic nervous system; however, during the luteal phase, progesterone plays the opposite role by allowing oestrogen to increase sympathetic nervous system activity. Moreover, the first peak of the preovulatory oestrogen level was higher than the second peak of the postovulatory oestrogen level. In addition, oestrogen increases the sensitivity of the vasoconstriction response to the action of norepinephrine. Therefore, during the luteal phase, the vasoactive drug dose used in the patients within 30 min after anaesthesia was greater than that used during the follicular phase. We hypothesize that women have a stronger compensatory and regulatory capacity during the follicular phase, which might be because the oestrogen level during the follicular phase is higher than that during the luteal phase, and short-term circulatory fluctuations might be primarily due to the endogenous norepinephrine-mediated vasoconstriction response. Therefore, the patients’ heart rates were lower during the follicular phase than during the luteal phase, and the demand for vasoactive drugs during the follicular phase was lower than that during the luteal phase. Although the heart rates of patients in the luteal phase were slightly higher than those of patients in the follicular phase 30 min after anaesthesia, this difference is limited to statistical significance and is not clinically significant. The menstrual cycle is not a major factor in choosing the operative period. We hypothesised that the menstrual cycle may have more significance for women with circulatory complications in responding to position changes and anaesthetic effects.

Most studies have focused on the long-term effects of oestrogen on the circulatory system, and the reduced occurrence and progression of atherosclerosis, coronary heart disease, and hypertension. Recently, researchers have been paying more attention to the female hormones’ short-term regulating of the circulatory system. Mckinley et al. divided healthy premenopausal women into two groups: those in the follicular phase and those in the luteal phase. A 24-h dynamic electrocardiogram was measured, and patient heart rates and RR interval variability (RRV) were recorded. These authors concluded that heart rate during the follicular phase was lower than that during the luteal phase, and both low-frequency and high-frequency RRV were higher than their counterparts during the luteal phase, which strongly supports the hypothesis that female hormones affect cardiovascular regulation by regulating cardiac autonomic nerve function [11]. In a study on postural orthostatic tachycardia syndrome (POTS), patients were divided into two groups: the early follicular phase and the middle luteal phase. Heart rate, peripheral vascular resistance, stroke volume per stroke (SV), and cardiac output (CO) were measured for the supine and standing positions after 2 h. In a control group from the general population, no significant differences were observed in the various indicators of the two phases. Patients with POTS in the experimental group showed higher oestrogen levels during the middle luteal phase than those during the early follicular phase, and this result corresponded to increased plasma renin and aldosterone secretion, which led to increased CO, SV, and heart rates. Furthermore, standing endurance was increased, and syncope was decreased. These authors concluded that hormone level fluctuations during the menstrual cycle affect the renin-angiotensin-aldosterone system and haemodynamic stability [2]. The increased heart rate is consistent with our conclusion; however, the changes in blood pressure differed, possibly because of the defect in vascular regulatory function among patients with postural orthostatic tachycardia syndrome. Choi et al. divided the follicular phase of the menstrual cycle into the early and late follicular phases to compare the cardiovascular system responses during movement and resting. Both oestrogen and progesterone were at lower levels during the early follicular phase than during the late follicular phase. This study found that blood pressure, heart rate, SV, and CO during the early follicular phase at movement and rest were higher than those during the late follicular phase, while peripheral vascular resistance was higher during the late follicular phase. In addition, the late follicular phase was more sensitive to exogenous norepinephrine than the early follicular phase. In that study, the blood pressure, heart rate, and sensitivity to exogenous vasoactive drugs in the late follicular phase group, which showed higher oestrogen levels, were consistent with the experimental results of the current study [3]. Gordon et al. studied the responsiveness of the cardiovascular system during different menstrual cycle phases under the influence of mental stress. That experiment was divided into the early follicular, late follicular, and luteal phases. The cardiac index (CI) of the luteal phase was significantly increased compared with the other two groups, whereas the vascular resistance index (VRI) was significantly decreased. The oestrogen and adrenaline levels during the luteal and late follicular phases were both higher than those during the early follicular phase. Oestrogen does not directly affect the CI or VRI, but it affects adrenaline sensitivity, thereby indirectly affecting haemodynamic stability. These authors concluded that haemodynamic stability depends more on the sensitivity to menstrual cycle-related adrenaline than to the hormonal level [14, 15]. The early follicular phase is also part of the menstrual cycle and women normally do not undergo surgery during their menstrual period. Our experiment did not collect data on the early follicular phase; however, the increased sensitivity to epinephrine during the period with high hormone levels supports our experimental results. Krejza et al. studied the relationship between the regulatory function of the cerebral blood vessels and female hormone levels. They collected data on the 5th, 13th, and 26th day of the menstrual cycle and recorded the plasma oestrogen concentration and bilateral carotid artery blood flow under normal conditions and after intravenously injecting 1000 mg of acetazolamide. These authors concluded that the increased carotid artery blood flow was associated with the degree of increase in the plasma oestrogen concentration [16, 17]. In general, oestrogen increases the sensitivity of endogenous and exogenous vasoactive substances and enhances the regulatory capacity of the cardiovascular system.

This study had the following limitations. First, neither oestrogen nor progesterone levels were measured. Second, we did not conduct a study on the different menstrual cycles of the same participants. Instead, we selected patients who had scheduled gynaecological surgeries and divided them into groups based on their different menstrual cycles. Third, we did not measure the specific excitability indexes of the sympathetic and parasympathetic nervous systems or the plasma concentration of norepinephrine. Fourth, we cannot exclude the transient effect of ephedrine on heart rate. Fifth, this study on women without circulatory complications under CSEA at different menstrual cycle stages and fluctuations may have more significance for women with circulatory complications.

Although the effect is slight, women may be better able to compensate and tolerate circulatory fluctuations during the follicular phase than during the luteal phase.