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PCOS: what oxidative stress and markers are trying us to tell

Polycystic ovarian syndrome (PCOS) is the most frequently observed endocrinopathy in women of reproductive age. Although the figures vary according to diagnostic criteria, its incidence is reported between 6% and 20%. Acne, hirsutism, seborrhea, menstrual irregularities, anovulation, infertility, obesity and various metabolic alterations (eg glucose and lipids) and atherosclerotic disorders are among the symptoms and signs of this disease. Regarding the etiology of PCOS, some causal factors such as hormonal disorders, adipose dysfunction and oxidative stress have been blamed, but no definitive consensus has been reached. However, in recent years, insulin resistance (IR) has been reported to play an important role in the progression of PCOS. Fetuin-A is a glycoprotein produced in the liver and released into the plasma. It is known that it has various biological functions, including the prevention of tissue calcification and maintenance of calcium-phosphorus balance. The data obtained in recent experimental studies have shown that high levels of fetuin-A cause insulin resistance, disturbing insulin receptor signaling.

Oxidative stress has been defined as an imbalance between the formation of reactive oxygen species (ROS), which cause oxidative damage and the antioxidant defense system. The molecular damage caused by free radicals has been claimed to lead to many diseases, such as atherosclerosis, diabetes mellitus and PCOS. The most recent studies found significant positive correlations between serum fetuin-A and LH levels, the LH / FSH ratio and glucose levels, but there were no correlations between fetuin-A levels and serum FSH levels or serum markers of oxidative stress (TOS). However, the total antioxidant status (TAS) was altered. The literature contains limited data on the role of fetuin-A in patients with PCOS. Recently, some researchers have reported that fetuin-A can be a useful biochemical marker for detecting IR in patients with PCOS. A high level of fetuin-A in the body has been claimed to be linked with insulin resistance, by inhibiting the tyrosine kinase activity of insulin receptors in the liver and muscle tissues. In the end, the persistence of IR leads to hyperinsulinemia.

Increased levels of insulin have been shown to cause both an LH surge and an increase in androgen release from theca cells through ovarian insulin receptors in women with PCOS. About 50% of women with PCOS are overweight or obese and most of them have severe IR and excess androgens. In the latest published studies, there was no correlation between BMI and fetuin-A serum levels in both PCOS patient groups and healthy control subjects. Likewise, Kozakowski et al. showed that serum fetuin-A levels in lean and obese PCOS patients were not significantly different. In contrast to the latest results, they found an association between the levels of fetuin-A and the steroid DHEAS, but not the LH / FSH ratio. Higher fetuin-A levels were seen in patients with PCOS and correlations between serum fetuin-A and LH levels, LH / FSH and blood sugar. Although no consensus has been reached on the formation of oxidative stress, one theory is related to the increase in the number of mononuclear cells that develop secondarily to hyperglycemia in patients with PCOS. It has been suggested that molecular damage due to free oxygen radicals plays an important role in the etiopathogenesis of PCOS.

In a study this year (Sak et al.), The TOS and OSI (ratio of TAS to TOS) in the PCOS group were significantly higher than the control group, which is consistent with the literature. Furthermore, TAS levels, which are an indicator of antioxidant levels that actively participate in the elimination of free radicals in the body, were significantly lower in PCOS patients than in controls. There is no universally accepted treatment for PCOS, because its etiology is not clearly understood. Thus, there is a continuing need for studies on the aetiopathogenesis of this disease. Internal antioxidant defenses can be regulated or enhanced through multiple interventions. Constant physical activity, a healthy lifestyle and the elimination of unhealthy factors (eg smoking and alcohol) are a first step to avoid the accumulation of oxidative stress. The diet rich in active ingredients against ROS (polyphenols, vitamin C, vitamin E) is definitely recommended, considering that there are certain data on the involvement of oxidative stress in this pathology.

External food supplementation (antioxidant supplements) is not discouraged, as there are clinical studies on the effects of vitamin E, vitamin D, omega-3 fatty acids, zinc, selenium and melatonin, especially on the condition of insulin resistance.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Sak S et al. Clin Exp Reprod Med 2018; 45(3):116-21.

Zuo T et al. Oxid Med Cell Longev.; 2016:8589318.

Kucukaydın Z et al. J Endocr Invest 2016; 39:1139-48.

Papalou O et al. Curr Pharm Des 2016; 22:2709-22.

Kozakowski J et al. Endokrynol Pol. 2014; 65:371-76.

Enli Y et al. Gynecol Endocrinol 2013; 29:1036-39.   

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it