Introduction
PCOS is a common and varied condition that affects women of reproductive age. Although the underlying cause of PCOS is due to abnormal leutenising and follicle stimulating hormone levels, insulin resistance is also involved in progression of symptoms.
Diagnosis of PCOS
Diagnosis of PCOS is according to the Rotterdam criteria: at least two out of three of hyperandrogenism, ovulatory dysfunction or polycystic ovaries.
PCOS types A & B together are often referred to as Classic PCOS and make up 45% of disease in the general population. Women with Classic PCOS appear to be more hirsute and obese, have worse menstrual irregularity and are more likely to be insulin resistant. Insulin resistance means a higher risk of future metabolic syndrome and a reduced chance of achieving a live birth.
A Vicious Cycle
It is important to remember that insulin resistance is tissue selective in PCOS women. Although muscle, fat and liver lose their sensitivity to insulin, the adrenals and ovaries remain sensitive. So, in order to overcome the resistance found in most of the body, the pancreas produces large amounts of insulin which means the still sensitive ovaries receive a relatively high dose.
These high insulin levels increase androgen production by the ovaries and in turn high androgen levels exacerbate insulin resistance by reducing the number of insulin receptors found on cells.
Thus, a vicious cycle occurs between androgens and insulin. Unfortunately, high androgen levels also have the effect of increasing fat deposition in the truncal zone. As excess fat accumulates in this area so does overall degree of insulin resistance which exacerbates the cycle.
A weight loss of 5-10% reduces circulating androgens and thus improves menstrual regularity and fertility however this can be difficult to sustain in the long term.
Weight Loss Management
- Metformin increases insulin sensitivity while inhibiting ovarian androgen production.
- In 2019, The Cochrane Collaboration reported that metformin use in women with PCOS has insulin lowering effects, a potential benefit in live birth rate but no conclusive effect on BMI.
- Meta-analyses of drugs such as Saxenda & Ozempic (GLP-1 agonists) show they appear to be more beneficial for weight loss and insulin resistance compared to metformin however data quality is low.
- A recent meta-analysis compared metformin to bariatric surgery in women with PCOS and obesity, 10 studies with 587 patients were included (Chang et al, J Gastrointest Surg, 2021).
- The analysis found that metformin increased the likelihood of pregnancy compared to placebo however bariatric surgery improved fertility more than metformin therapy alone.
- Those who underwent bariatric surgery were more than twice as likely to become pregnant than those treated with metformin 34.9% vs 17.1% (p = 0.026).
- Contraceptive counselling always occurs prior to surgery as fast resolution of ovulatory dysfunction leads to a high risk of unplanned pregnancy during the rapid weight loss phase.
