PCOS: Autonomic Nervous System Dysregulation and Mitochondrial Issues

Women with polycystic ovary syndrome (PCOS) often have increased stress, with an exaggerated sympathetic (fight-flight-freeze-fawn) nervous system and underactive parasympathetic (stay-and-play, rest-and-digest, feed-and-breed!) nervous system. We call these findings autonomic imbalances, including reduced parasympathetic activity, which suggests a potential link to mitochondrial dysfunction. Research indicates that mitochondrial dysfunction is indeed associated with PCOS and may contribute to its pathophysiology. I am finding in my practice that many women over 35 experience mitochondrial dysfunction and it’s a critical factor not just in ovarian aging and perimenopause, but also in your general health and hormone production.

Focus on Mitochondria

Mitochondria are the cellular powerhouses that convert nutrients into energy while orchestrating vital processes like metabolism, inflammation regulation, and aging—making them the ultimate keystone for vibrant health and longevity. Mitochondria play a crucial role in cellular energy production, and their dysfunction can lead to systemic metabolic imbalances. 

Problems with mitochondria—the parts of cells that produce energy—can change how the body reacts to stress. These changes affect key systems like the stress hormone pathway and levels of inflammation in the body. Their study highlights how healthy mitochondria are essential for managing stress and keeping the body’s systems balanced. However, most of the studies on stress and mitochondria have been performed in men, leading to a gender health gap.

Studies have shown that women with PCOS have increased oxidative stress and mitochondrial dysfunction, which are linked to the progression and complications of the syndrome. Specifically, mitochondrial dysfunction in granulosa cells has been implicated in the pathogenesis of PCOS, affecting follicular development and ovarian function.

Furthermore, autonomic nervous system dysfunction in PCOS patients is characterized by increased sympathetic activity and decreased parasympathetic activity, which can impact cardiovascular health and metabolic regulation. This autonomic imbalance may be exacerbated by mitochondrial dysfunction, as mitochondria are integral to cellular energy homeostasis and reactive oxygen species (ROS) management.

What Are the Signs and Symptoms?

Common symptoms of autonomic imbalance in women with polycystic ovary syndrome (PCOS) include increased sympathetic activity and reduced parasympathetic activity. These autonomic imbalances manifest in several ways:

• Cardiovascular Symptoms: Women with PCOS often exhibit cardiovascular autonomic dysfunction, characterized by reduced heart rate variability (HRV), increased muscle sympathetic nerve activity (MSNA), and delayed heart rate recovery (HRR) after exercise. These changes indicate a dominance of sympathetic over parasympathetic activity.
• Blood Pressure Variability: There is often an exaggerated systolic blood pressure (SBP) response to exercise and a delayed recovery of SBP post-exercise, reflecting sympathetic hyperactivity.
• Metabolic Dysregulation: Autonomic imbalance in PCOS is associated with metabolic disturbances such as insulin resistance and dyslipidemia, which can further exacerbate autonomic dysfunction.
• Endothelial Dysfunction: Increased sympathetic activity and reduced parasympathetic modulation contribute to endothelial dysfunction, which is independent of obesity and metabolic disturbances.
• Altered Heart Rate Variability: Women with PCOS show lower values in HRV parameters such as SDNN (standard deviation of normal-to-normal RR intervals) and rMSSD (root mean square of successive differences), indicating reduced parasympathetic activity.

These signs and symptoms highlight the complex interplay between autonomic dysfunction and the metabolic and cardiovascular abnormalities seen in PCOS. Addressing these autonomic imbalances may be crucial for managing the broader health implications of PCOS, which I’ve written about in most of my books, especially Women, Food, and Hormones.

Action Items for Women with PCOS

To get started with autonomic and mitochondrial rehab, I recommend the following simple actions.

1. Track your HRV
2. Stop drinking alcohol
3. Perform n-of-1 experiments to see what improves HRV

Summary

Mitochondrial impairment is likely a contributing factor to the autonomic dysregulation observed in women with PCOS, affecting both metabolic and reproductive health. To learn more about mitochondrial impairment and how to address it with evidence-based approaches, be sure to register for my Friday Five.

References:

M. Picard et al., “Psychological Stress and Mitochondria: A Conceptual Framework.” Psychosomatic Medicine 80, no. 2 (2018): 126-140.

J. Zhang et al., “Polycystic Ovary Syndrome and Mitochondrial Dysfunction.” Reproductive Biology and Endocrinology: RB&E 17, no. 1 (2019):67; P. Shukla et al., “Mitochondrial Dysfunction: An Emerging Link in the Pathophysiology of Polycystic Ovary Syndrome.” Mitochondrion 52 (2020):24-39; C. Sun et al., “The Role Played by Mitochondria in Polycystic Ovary Syndrome.” DNA and Cell Biology 43, no. 4 (2024):158-174. 

Y. Wang et al., “NAD+ Deficiency and Mitochondrial Dysfunction in Granulosa Cells of Women with Polycystic Ovary Syndrome.” Biology of Reproduction 105, no. 2 (2021):371-380; Y. Gao et al., “Oxidative Stress and Mitochondrial Dysfunction of Granulosa Cells in Polycystic Ovarian Syndrome.” Frontiers in Medicine 10 (2023):1193749.

 G. Tekin et al., “Altered Autonomic Neural Control of the Cardiovascular System in Patients with Polycystic Ovary Syndrome.” International Journal of Cardiology 130, no. 1 (2008):49-55; Y. Yu et al., “The Role of the Autonomic Nervous System in Polycystic Ovary Syndrome.” Frontiers in Endocrinology 14 (2023):1295061.

Tekin, G., A. Tekin, E. B. Kiliçarslan, et al. “Altered Autonomic Neural Control of the Cardiovascular System in Patients with Polycystic Ovary Syndrome.” International Journal of Cardiology 130, no. 1 (2008): 49–55. https://doi.org/10.1016/j.ijcard.2007.08.037; Gui, J., and R. H. Wang. “Cardiovascular Autonomic Dysfunction in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.” Reproductive Biomedicine Online 35, no. 1 (2017): 113–120. https://doi.org/10.1016/j.rbmo.2017.03.018; Ollila, M. M., A. Kiviniemi, E.

Stener-Victorin, et al. “Effect of Polycystic Ovary Syndrome on Cardiac Autonomic Function at a Late Fertile Age: A Prospective Northern Finland Birth Cohort 1966 Study.” BMJ Open 9, no. 12 (2019): e033780. https://doi.org/10.1136/bmjopen-2019-033780.
 Tekin, G., A. Tekin, E. B. Kiliçarslan, et al. “Altered Autonomic Neural Control of the Cardiovascular System in Patients with Polycystic Ovary Syndrome.” International Journal of Cardiology 130, no. 1 (2008): 49–55. https://doi.org/10.1016/j.ijcard.2007.08.037.=

Ollila, M. M., et al. “Effect of Polycystic Ovary Syndrome on Cardiac Autonomic Function at a Late Fertile Age: A Prospective Northern Finland Birth Cohort 1966 Study.” BMJ Open 9, no. 12 (2019): e033780. https://doi.org/10.1136/bmjopen-2019-033780; Yu, Y., T. Chen, Z. Zheng, et al. “The Role of the Autonomic Nervous System in Polycystic Ovary Syndrome.” Frontiers in Endocrinology 14 (2023): 1295061. https://doi.org/10.3389/fendo.2023.1295061.

Lambert, E. A., et al. “Sympathetic Activation and Endothelial Dysfunction in Polycystic Ovary Syndrome Are Not Explained by Either Obesity or Insulin Resistance.” Clinical Endocrinology 83, no. 6 (2015): 812–19. https://doi.org/10.1111/cen.12803.

 de Sá, J. C., et al. “Analysis of Heart Rate Variability in Polycystic Ovary Syndrome.” Gynecological Endocrinology: The Official Journal of the International Society of Gynecological Endocrinology 27, no. 6 (2011): 443-47. https://doi.org/10.3109/09513590.2010.501881; Ji, H. R., et al. “Characteristics of Heart Rate Variability in Women with Polycystic Ovary Syndrome: A Retrospective Cross-Sectional Study.” Medicine 97, no. 38 (2018): e12510. https://doi.org/10.1097/MD.0000000000012510.