PCOS and Insulin Resistance

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Anovulatory infertility is a prominent feature of women with Polycystic Ovary Syndrome, seen in as many as 80% of these women. Lifestyle intervention, with as little as 5% weight reduction, is considered first line treatment for overweight and obese PCOS women, due to its health, metabolic, reproductive and psychological benefits. Pharmaceutical ovulation induction treatments include letrozole, clomiphene citrate and metformin, and combination of clomiphene citrate and metformin as first-line agents. Gonadotrophins may also be given as first-line pharmacologic therapy provided there is close ultrasound monitoring, counselling on cost and potential risk of multiple pregnancy. Second-line therapy for ovulation induction include gonadotrophins and laparoscopic ovarian drilling. IVF-ICSI is considered third-line treatment for anovulatory infertility when first or second-line agents have failed. The role of bariatric surgery and in-vitro maturation will likewise be discussed.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during their reproductive ages, which is generally shows with oligo/amenorrhea, anovulatory cycles, clinical o biochemical hirsutism, polycystic ovaries and, in a significant percentage of cases, insulin resistance. PCOS is associated with significant metabolic consequences, including increased risk of impaired glucose tolerance and type 2 diabetes mellitus, atherogenic dyslipidemia, systemic inflammation due to increased secretion of pro-inflammatory factors by adipose tissue, non-alcoholic fatty liver disease, hypertension and potential coagultion disorders. PCOS affects quality of life and can worsen anxiety and depression either due to its symptoms or due to the diagnosis of a chronic disease. Treatment aim in PCOS include optimising healthy weight, improving underlying hormonal disturbances, prevention of future reproductive and metabolic complications, and improving quality of life.

The first and most effective therapy for metabolic dysfunction typically consists of lifestyle modifications including a diet and exercise regimen. Lifestyle treatment may improve a number of anthropometric markers in women with PCOS. A 5% to 10% weight loss is considered clinically significant and is associated with metabolic, reproductive and psychological health benefits. Insulin resistance is a key aetiological factor in PCOS, associated with increasing severity of PCOS. Lifestyle modifications may improve insulin resistance independent of weight loss, as demonstrated in the general population. Studies have shown that Lifestyle intervention may also improve quality of life scores in the domains of emotions and infertility in PCOS. As such, there is a strong rationale for lifestyle interventions for both improving underlying hormonal imbalances and management of weight for a large proportion of women with PCOS.

Medication are also the main method for the treatment of PCOS patients with metabolic disorders. The use of oral contraceptives has been shown effective in reducing acne and hirsutism and regulates the menstrual cycle. Various drugs that improve insulin sensitivity have been proposed and metformin is certainly the most widely used. Evidence indicated that metformin is effective overall and /or in specified subgroups, in improving weight, BMI, WHR ratio, testosterone and TG in women with PCOS. In addition, anti-obesity pharmacological agents, anti-androgen pharmacological agents, and lipid-lowering drugs need to be applied individually according to the needs of patients and their physical conditions.