Insights into PCOS: Mitochondrial Dysfunction and Inflammation

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting many women of reproductive age. The WHO estimates that 8–13% of reproductive-aged women are affected. However, up to 70% of affected women remain undiagnosed worldwide – which is a shocking statistic. It can be poorly understood and clients are often left feeling helpless with very few options for treatment. One emerging area of research is the role of mitochondrial dysfunction in PCOS, particularly its connection to chronic inflammation.

Mitochondrial Dysfunction in PCOS

Mitochondria, the powerhouse of the cell, are crucial for energy production. In women with PCOS, mitochondrial dysfunction has been observed, leading to impaired cellular energy metabolism. This dysfunction is not only linked to the typical metabolic issues seen in PCOS, such as insulin resistance and obesity, but also plays a significant role in the overall pathophysiology of the disorder.

When mitochondria don’t function properly, they generate excessive reactive oxygen species (ROS), leading to oxidative stress. Think of an apple going brown. This oxidative stress can damage cells, particularly in the ovaries, where mitochondrial health is essential for proper follicular development and oocyte quality.

Inflammation in PCOS

Chronic low-grade inflammation is a hallmark of PCOS. Elevated levels of inflammatory markers like C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6) are commonly found in women with PCOS. This persistent inflammation exacerbates insulin resistance and contributes to the development of other metabolic conditions associated with PCOS.

The Connection Between Mitochondrial Dysfunction and Inflammation

Mitochondrial dysfunction and inflammation in PCOS create a vicious cycle where each one worsens the other. Mitochondrial dysfunction leads to increased production of ROS, which triggers oxidative stress and, subsequently, an inflammatory response. This inflammation further impairs mitochondrial function.

Additionally, mitochondrial dysfunction in PCOS can affect adipose tissue, leading to the release of pro-inflammatory cytokines and further contributing to systemic inflammation.

Therapeutic Approaches

Addressing mitochondrial dysfunction and inflammation is crucial in managing PCOS. Potential therapeutic strategies include:

  1. Antioxidants: Supplementing with antioxidants like Coenzyme Q10 and N-acetylcysteine (NAC) may help reduce oxidative stress and improve mitochondrial function. Metformin also seems to have antioxidant effects.  These have all been studied.
  2. Lifestyle Interventions: Regular exercise and a balanced diet rich in anti-inflammatory foods can help mitigate inflammation and improve mitochondrial health. Vegetables are packed with phytonutrients and form a crucial part of any dietary intervention.  A number of positive studies have come out in the past year looking at intermittent fasting as well as low-carb/ketogenic diets.
  3. Insulin Sensitizers: Medications like metformin can improve insulin sensitivity, indirectly reducing the burden on mitochondria and lowering inflammation.
  4. Mitochondria-Targeted Therapies: Emerging therapies aimed directly at improving mitochondrial function are being explored, offering hope for more effective management of PCOS.  Elamipretide and Mitotempo are primarily being used in research settings.  MitoQ, which is a supplement available in the US, has been shown in animal models to ameliorate PCOS.

Mitochondrial dysfunction and inflammation are not just contributors to PCOS; they could potentially be at the very heart of its pathophysiology. Addressing these issues head-on is crucial for those seeking lasting relief. A root medicine approach – one that integrates lifestyle changes, targeted nutrition, supplements, and medical interventions like Metformin – holds the most promise. This holistic strategy doesn’t just manage symptoms; it tackles the underlying causes, offering a path forward that empowers individuals with PCOS to manage their health successfully.

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References:

  1. Victor VM, Rocha M, Bañuls C, et al. Mitochondrial dysfunction and oxidative stress in insulin resistance. Curr Pharm Des. 2011;17(32):3998-4011.
  2. Macut D, Koić-Domjanić G, Bjekić-Macut J, et al. Mitochondrial function in women with polycystic ovary syndrome: A role of oxidative stress and insulin resistance. Arch Endocrinol Metab. 2020;64(3):331-337.
  3. González F. Inflammation in polycystic ovary syndrome: underlying mechanisms and clinical implications. Steroids. 2012;77(4):300-305.
  4. Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids. 2013;78(8):782-785.
  5. Lee MS, Lee YJ, Seo HA, et al. Mitochondria-targeted antioxidant mitotempo prevents ovarian aging. Exp Gerontol. 2021;145:111210.
  6. Lubecka N, Clebiera M, Hening E. Polycystic Ovary Syndrome and Oxidative Stress – from Bench to Bedside. Int Journal Molecular Sciences. 2023; 24(18)