Can PolyCystic Ovarian Syndrome (PCOS) cause weight gain?

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder that affects women of childbearing age, with prevalence rates ranging from 5-20% depending on the diagnostic criteria used (1). It is considered one of the most frequent causes of infertility (2)(4).

PCOS Symptoms and Characteristics

The diagnosis of PCOS is typically based on the presence of at least two of the following criteria: chronic ovulatory dysfunction (irregular menstrual periods or anovulation), clinical or biochemical hyperandrogenism (e.g., hirsutism or acne due to male hormone excess), and polycystic ovaries (presence of small cysts on the ovaries) observed on ultrasound (2).

PCOS is a heterogeneous syndrome, and its exact cause is not fully understood, but it is considered multifactorial, involving genetic, environmental, and metabolic abnormalities (1).

PCOS and Metabolic Issues (Insulin Resistance and Weight)

A central feature in the pathogenesis of PCOS is insulin resistance (IR) and compensatory hyperinsulinemia (3). This condition affects approximately 75% of lean women with PCOS and 95% of overweight or obese women with PCOS (11). Obesity is a significant contributing factor, with 60-70% of women with PCOS being overweight (7) (11). This increased insulin levels can lead to irregular menstrual cycles and hyperandrogenism (11).

PCOS is associated with an increased risk of several metabolic disorders and long-term health complications, including:

• Type 2 diabetes (7).
• High cholesterol (dyslipidemia) and high blood pressure (hypertension) (7).
• Cardiovascular diseases, such as atherosclerosis and myocardial infarction (7).
• Gestational diabetes mellitus (GDM) during pregnancy (17) (18).

Insulin resistance can directly and indirectly worsen PCOS symptoms (11). For instance, higher insulin levels reduce sex hormone binding globulin (SHBG) production, leading to increased free testosterone levels, which exacerbates hyperandrogenism (11) (12). Hyperinsulinemia also stimulates ovarian theca cells to overproduce androgens (11) (19). The excess body weight often seen in PCOS can also contribute to IR (6).

Weight Management in PCOS

Losing weight and maintaining a healthy weight through lifestyle changes, including diet and physical activity, are considered first-line treatments for managing PCOS (4). Weight loss can improve metabolic and hormonal profiles, facilitating the restoration of physiological conditions (21). While PCOS-related weight gain can be a challenge, even modest weight loss can help you alleviate PCOS symptoms (22).

Treatment Options for PCOS

Different treatment options for PCOS aim to improve hormonal balance, insulin sensitivity, and reproductive outcomes.

1. Inositols (Myo-inositol and D-chiro-inositol) Myo-inositol (MI) and D-chiro-inositol (DCI) are natural molecules involved in cell processes, lipid synthesis, and cell growth, and they regulate important cellular functions including gametogenesis and fertilisation (23). They are also precursors for insulin mediators (24)(25)

• Insulin Sensitivity and Hormonal Effects: Both MI and DCI act as insulin sensitisers (10).
• Inositols have shown beneficial effects in reducing insulin resistance, improving menstrual cycle regularity, and reducing hyperandrogenism in women with PCOS (27).
• Specifically, MI has been shown to decrease LH and androgen levels (29), improve the LH/FSH ratio, and reduce testosterone and androstenedione levels. It helps re-establish ovulatory menstrual cycles, particularly in obese women with PCOS, which can facilitate spontaneous pregnancies (36)(37).
• Inositols can also increase SHBG levels, which helps reduce free androgen concentrations (31).
• Myo-inositol (MI) significantly reduces fasting plasma glucose and AUC-insulin levels compared to placebo (32).

 

• Ovarian and Fertility Benefits:
• MI is abundant in follicular fluid and enhances FSH action, improving oocyte and embryo quality (10).
• Inositol supplementation has been shown to improve clinical pregnancy rates in infertile women undergoing ovulation induction (29).
• During IVF, MI can save gonadotropins in both PCOS and non-PCOS women and efficiently reduces stimulation length only in PCOS women (51).

 

• MI:DCI Ratio and "Ovarian Paradox":
• The physiological plasma ratio of MI to DCI is 40:1 (40). In PCOS women with insulin resistance, this ratio can be altered in the ovary (e.g., to 0.2:1) due to hyperinsulinemia overstimulating epimerase activity, leading to excess DCI and MI depletion in the ovary (40). This phenomenon is known as the "ovarian paradox" (40).
• Combining MI and DCI in their physiological ratio (40:1) has shown promising results in improving metabolic and reproductive parameters in PCOS (30). Some studies suggest this combination might be more effective than MI alone (61).

 

• Safety and Bioavailability: Inositols are considered safe with few side effects at recommended dosages, making them an optimal nutraceutical alternative to metformin (4). Oral absorption can be influenced by various factors, including physicochemical properties and formulation. Poor bioavailability has been suggested as a reason for "inositol resistance" in some patients (70).

2. Metformin Metformin is considered the gold standard insulin sensitizer widely used to treat insulin resistance in PCOS (4).

• Effects: Metformin improves insulin sensitivity, reduces hyperandrogenism, and can have positive effects on peripheral insulin sensitivity in both normal-weight and overweight PCOS patients (26). It can also improve lipid metabolism (74).
• Side Effects: Metformin may induce gastrointestinal side effects such as nausea, diarrhea, vomiting, and flatulence (4). These side effects often limit its use (37).
• Impact on Vitamins: Long-term use of metformin may decrease serum vitamin B12 levels (76). It can also potentially increase homocysteine levels (76). Therefore, dietary supplements rich in Vitamin B12 may be beneficial for PCOS patients on metformin therapy (85).

3. Vitamin D Vitamin D deficiency is common in PCOS (67–85% of cases) and correlates with the severity of the syndrome (1).

• Effects: Vitamin D modulates several regulatory pathways in human reproduction (17).
• It can improve ovulatory function, menstrual cyclicity, and egg quality in PCOS women (17).
• Vitamin D supplementation improves insulin resistance and the quality of embryos, leading to a higher ratio of clinical pregnancies in PCOS (89).
• Vitamin D therapy can decrease serum androgen and AMH levels in PCOS patients (93).
• Optimal Vitamin D levels correlate strongly with the likelihood of implantation and clinical pregnancy (94).
• Studies show that magnesium-zinc-calcium-Vitamin D co-supplementation can significantly reduce hirsutism and total testosterone levels in PCOS women (95)(96).
• Vitamin D aids in normalizing blood glucose levels and reducing the incidence of gestational diabetes (17).
• Considerations: Potential adverse effects of overconsumption of Vitamin D are still controversial due to a lack of long-term data on high doses in women of childbearing age (17). Long-term studies are needed regarding its supplementation during pregnancy and interference with other molecules (17).

4. Folic Acid and Vitamin B12

• Folic acid is often combined with myo-inositol in treatments for PCOS (97)(98).
• High levels of folic acid and Vitamin B12 in follicular fluid have been associated with a significantly higher probability of pregnancy (99)(100).
• Folic acid and Vitamin B12 are involved in homocysteine homeostasis (101).

5. Other Supplements

• Coenzyme Q10: Supplementation has shown beneficial effects on glucose metabolism and lipid profiles in PCOS women, including decreased fasting plasma glucose, serum insulin concentrations, and insulin resistance (102)(103).
• Magnesium, Zinc, and Calcium: Co-supplementation of magnesium, zinc, calcium, and Vitamin D has shown beneficial effects on hormonal profiles, inflammation, and oxidative stress in PCOS women, including reductions in hirsutism and total testosterone (95). Zinc also plays a key antioxidant role and is important for oocyte maturation and embryo quality (105)(106).
• Alpha-lipoic acid (ALA): ALA improves insulin resistance and has been suggested as beneficial in PCOS treatment, especially when combined with myo-inositol (107). However, its influence on reproductive hormones is less clear, and its benefits appear primarily restricted to metabolic features in insulin-resistant PCOS women (107).
• Melatonin: Higher levels of melatonin in follicular fluid were associated with an increased probability of pregnancy in infertile women undergoing ICSI (99)(100).

In summary, PCOS is a common and complex condition often characterized by insulin resistance, abnormal hormone levels (especially androgens), and challenges with fertility and weight management. While metformin is a common treatment, inositols are emerging as a promising and safe alternative or co-treatment due to their positive effects on metabolic, hormonal, and reproductive outcomes. Supplementation with Vitamin D, folic acid, and Vitamin B12 can also play a crucial role in improving outcomes for women with PCOS.