Study of the Effect of a Nutritional Supplement on Microbiota, Metabolic Control, Inflammatory Profile, and Quality of Life in Patients With Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is an endocrine-metabolic disorder that affects many women of reproductive age. PCOS is not just a reproductive disorder but a systemic condition, as cases of PCOS have been described even in menopause, although its prevalence in post-reproductive stages is not high. The diagnosis of PCOS is made using the Rotterdam criteria, agreed upon in 2003 by ESHRE and ASRM (European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine). According to these criteria, a patient must meet two of the following three criteria to be diagnosed with PCOS: oligo-anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian appearance.

The Rotterdam criteria are widely used but can sometimes lead to an erroneous diagnosis of PCOS. Therefore, in 2006, the AES (Androgen Excess Society) decided that, in addition to the 2003 Rotterdam criteria, hyperandrogenism-either physical or biochemical-was necessary for a PCOS diagnosis. Depending on the criteria used and the diversity of the population studied, epidemiological results can vary. Despite this variability, it is estimated that PCOS affects 6-12% of women of reproductive age.

The most common manifestations of PCOS include androgenic alopecia, hirsutism, acne, irregular cycles, or periods of amenorrhea. An ultrasound image showing polycystic ovarian morphology alone is insufficient for diagnosing PCOS. In polycystic ovaries, more than 12 follicles of 2-9 mm in size and increased ovarian volume (>10 ml) should be visualized using transvaginal ultrasound. Despite the complex and not fully understood pathophysiology of PCOS, two main types of alterations are identified.** On one hand, there is an accelerated release of gonadotropin-releasing hormone (GnRH), which leads to an increased release of luteinizing hormone (LH), resulting in greater androgen production, altered folliculogenesis, and long menstrual cycles or amenorrhea. On the other hand, there is an alteration in ovarian steroidogenesis and folliculogenesis due to increased activity of cytochrome P450c17, an enzyme involved in the synthesis of ovarian and adrenal androgens, leading to elevated androgen levels.

In 70-80% of PCOS cases, women present insulin resistance (IR), with 30-50% of these also exhibiting obesity. High body fat percentage and hyperinsulinemia play significant roles in the development and progression of PCOS. Chronically elevated insulin levels can be associated with elevated androgen levels in a bidirectional manner. Elevated insulin levels may stimulate LH production and increase the activity of the P450c17 enzyme in the ovaries and adrenal glands, resulting in reduced hepatic production of sex hormone-binding globulin (SHBG), which increases the amount of free androgens. Conversely, elevated androgens are associated with increased insulin resistance in the muscles, leading to poorer glucose uptake.

Obesity is considered an amplifying factor in the pathophysiology of PCOS. Adipose tissue is an endocrine organ, and a high amount of adipose tissue increases the production of inflammatory cytokines, which can worsen IR by interfering with glucose uptake. While 70-80% of women with PCOS have IR, there is a 20-30% subgroup without metabolic involvement. Women with PCOS who have a healthy body fat percentage also present with insulin resistance, suggesting that obesity is not the cause of PCOS.