Does Menstruation Affect Anesthesia?

The physiological factors that affect an individual’s response to anesthesia are complex and still an area of research. One such factor is the menstrual cycle, a natural and highly ubiquitous biological process affecting nearly half of the human population. Hormonal fluctuations, changes in pain perception, and other physiological changes can potentially alter the effect of anesthetic agents, as well as postoperative recovery. As such, the exploration of the impacts of menstruation on anesthesia brings up key considerations for healthcare practitioners to optimize patient care.

The menstrual cycle is classified into four slightly overlapping phases: the menstrual phase, the pre-ovulatory follicular phase, the ovulatory phase, and the post-ovulatory luteal phase. Estrogen, the primary female hormone, is at its peak during the follicular phase and remains high during ovulation and drops afterward. Progesterone, a hormone most strongly involved in menstruation and pregnancy, remains low through the follicular phase but rises during the luteal phase. During menstruation, both hormones decline due to hormonal withdrawal.¹

Throughout this cycle, including during menstruation, there are several physiological changes that are relevant to anesthesia. The luteal phase is associated with higher heart rates and systolic blood pressure, with lower diastolic pressure.² During ovulation, there is an estrogen-induced spike in nitric oxide production, which leads to an increase in cardiac output and a decrease in systemic vascular resistance, systolic, and diastolic blood pressure.³ In addition, several researchers have found pulmonary function significantly improves in the luteal phase, a phenomenon likely due to the broncho-dilatory effects of progesterone.³

Estradiol, an estrogen steroid hormone used as medication in some clinical scenarios, has shown pro-nociceptive actions, while progesterone has demonstrated anti-nociceptive qualities.⁴ Studies on altered pain perception during the menstrual cycle have assessed parameters such as cold pressor, heat and ischemic pain perception, pain inhibition, and subjective pain scores. Although the results of these studies were variable, a majority found lowered pain perception in the follicular phase and increased pain perception during the menstrual phase.³ These changes may influence injection discomfort and clinical effectiveness of local anesthetics.

In a study including 20 female patients in the follicular phase and 20 patients in the luteal phase, researchers induced anesthesia with a combination of nitrous oxide and sevoflurane. The minimum alveolar concentration (MAC) value of sevoflurane in the follicular group was significantly larger than in the luteal group. The requirement for maintaining anesthesia under sevoflurane was also higher for patients in the follicular phase. The study concludes the high progesterone levels during the luteal phase may be the cause of decreased anesthesia requirement for both induction and maintenance.⁵

Another study analyzed the responses of sixty-four adult women receiving preoperative dexmedetomidine and perioperative propofol anesthesia for elective gynecologic surgery. Bispectral index (BIS) values, a measure of consciousness, decreased fastest in luteal phase patients receiving dexmedetomidine anesthesia. This group also required the least amount of propofol to reach a BIS of 50, which is clinically considered to be a marker of full sedation.⁶ From a pharmacologic standpoint, propofol and progesterone both exert their CNS effects through direct modulation of the GABA receptor complex. On the other hand, dexmedetomidine has an anti-nociceptive effect through its influence on the α2A-adrenoceptors in the locus coeruleus.⁷ The pharmacokinetic interactions between propofol, dexmedetomidine, and progesterone may be the cause of the lower propofol requirements for luteal phase patients. Since the sedation with propofol is deeper for patients in the luteal phase, anesthesiologists who include this agent in their anesthesia plan should be aware of how this drug affects patients in the luteal phase of their menstrual cycle.

 Hormonal fluctuations related to menstruation–especially the oscillations in estrogen and progesterone–affect various physiological systems, from cardiovascular impacts to pain perception and dosage requirements for anesthesia. Research suggests that women in the luteal phase may require lower doses of anesthetic agents like propofol and sevoflurane due to the increase in progesterone. Understanding the pharmacokinetic interactions between the female sex hormones and anesthetic agents is essential for optimizing anesthesia care and ensuring patient safety.

References

1. Hanci, Volkan, et al. “Brief Report: The Effects of the Menstrual Cycle on the Hemodynamic Response to Laryngoscopy and Tracheal Intubation.” Anesthesia and Analgesia, vol. 111, no. 2, Aug. 2010, pp. 362–65. https://doi.org/10.1213/ANE.0b013e3181e62984
2. Manhem, K., et al. “Haemodynamic Responses to Psychosocial Stress During the Menstrual Cycle.” Clinical Science (London, England: 1979), vol. 81, no. 1, July 1991, pp. 17–22. https://doi.org/10.1042/cs0810017
3. Kurdi, MadhuriS, and AshwiniH Ramaswamy. “Does the Phase of the Menstrual Cycle Really Matter to Anaesthesia?” Indian Journal of Anaesthesia, vol. 62, no. 5, 2018, p. 330. https://doi.org/10.4103/ija.IJA_139_18
4. Ileri, Zehra, et al. “Effect of Menstrual Cycle on Orthodontic Pain Perception: A Controlled Clinical Trial.” Journal of Orofacial Orthopedics = Fortschritte Der Kieferorthopadie: Organ/Official Journal Deutsche Gesellschaft Fur Kieferorthopadie, vol. 77, no. 3, May 2016, pp. 168–75. https://doi.org/10.1007/s00056-016-0013-9
5. Erden, Veysel, et al. “Increased Progesterone Production During the Luteal Phase of Menstruation May Decrease Anesthetic Requirement” Anesthesia & Analgesia, vol. 101, no. 4, Oct. 2005, pp. 1007–11. https://doi.org/10.1213/01.ane.0000168271.76090.63
6. Zhou, Xiaomin, et al. “Effects of the Menstrual Cycle on Bispectral Index and Anesthetic Requirement in Patients with Preoperative Intravenous Dexmedetomidine Following Propofol Induction.” International Journal of Clinical and Experimental Medicine, vol. 7, no. 12, Dec. 2014, pp. 5663–68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307534/
7. Guo, Tian-Zhi, et al. “Dexmedetomidine Injection into the Locus Ceruleus Produces Antinociception.” Anesthesiology, vol. 84, no. 4, Apr. 1996, pp. 873-881. https://doi.org/10.1097/00000542-199604000-00015