Signs of Insulin Resistance in PCOS

Signs of insulin resistance in PCOS are often subtle and can overlap with other features of the condition, making them easy to miss without proper clinical assessment. Polycystic ovary syndrome (PCOS) is one of the most common hormonal conditions affecting women of reproductive age in the UK, and insulin resistance is thought to affect a significant proportion of those diagnosed, including women of a healthy weight. Recognising the signs early matters because untreated insulin resistance raises the long-term risk of type 2 diabetes, cardiovascular disease and liver conditions. This article explains what to look for, how diagnosis works and what treatments are available.

What is insulin resistance and why is it common in PCOS?

Insulin resistance occurs when cells respond less effectively to insulin, prompting excess insulin production that stimulates ovarian androgen output. It is common in PCOS due to defects in insulin signalling pathways, independent of body weight.

Insulin resistance is a condition in which the body's cells respond less effectively to insulin, causing the pancreas to produce progressively more of the hormone to maintain normal blood glucose levels. Insulin is a hormone made by the pancreas that allows glucose from food to enter cells and be used for energy. When cells become resistant to its effects, glucose can accumulate in the bloodstream, raising the risk of type 2 diabetes and other metabolic complications over time.

Polycystic ovary syndrome (PCOS) is one of the most common hormonal conditions affecting women of reproductive age in the UK. Insulin resistance is thought to be present in a significant proportion of those affected, including women of a healthy weight, so it is not simply a consequence of being overweight.^[3][10] The precise mechanism is not fully understood, but research suggests that defects in insulin signalling pathways within muscle and fat cells may play a central role, independent of body weight.

Excess insulin in the bloodstream stimulates the ovaries to produce higher levels of androgens (male-type hormones such as testosterone).^[16][17] This hormonal imbalance is believed to contribute to many of the hallmark features of PCOS, including irregular periods, excess hair growth and difficulties with ovulation. Understanding this link is important because addressing insulin resistance can improve both metabolic and reproductive outcomes in women with PCOS. Further information is available from the NHS PCOS page and NICE Clinical Knowledge Summary (CKS) on polycystic ovary syndrome.

What are the signs of insulin resistance in PCOS?

Key signs include abdominal weight gain, acanthosis nigricans, fatigue after carbohydrate-rich meals, sugar cravings, irregular periods, acne, hirsutism and difficulty conceiving. Symptoms are non-specific and require clinical assessment for diagnosis.

The signs of insulin resistance in PCOS can be subtle and overlap considerably with other features of the condition itself, making them easy to overlook without clinical assessment. Recognising these signs early is important because untreated insulin resistance increases the long-term risk of type 2 diabetes, cardiovascular disease and metabolic-associated steatotic liver disease (MASLD, previously called non-alcoholic fatty liver disease).^[3][10]

Common signs and symptoms to be aware of include:

• Weight gain or difficulty losing weight, particularly around the abdomen, even with a balanced diet and regular exercise

• Acanthosis nigricans, a darkening and thickening of the skin in body folds such as the neck, armpits and groin, which is a recognised physical marker of elevated insulin levels

• Persistent fatigue or low energy, especially after meals containing refined carbohydrates or sugar

• Increased hunger or sugar cravings, which can occur when cells are not efficiently absorbing glucose

• Irregular or absent menstrual periods, driven in part by the effect of excess insulin on ovarian androgen production

• Acne and excess facial or body hair (hirsutism), resulting from elevated androgen levels stimulated by high circulating insulin

• Difficulty conceiving, linked to disrupted ovulation

It is important to note that symptoms such as fatigue and sugar cravings are non-specific and are not diagnostic of insulin resistance on their own. They warrant clinical assessment rather than self-diagnosis. Not all women with insulin resistance in PCOS will experience every symptom, and some may have no obvious signs at all.

Women who notice several of these features together, particularly alongside a known or suspected diagnosis of PCOS, should discuss them with their GP. Seek urgent medical attention (call 999 or go to your nearest emergency department) if you experience symptoms that may suggest severe hyperglycaemia or another acute metabolic problem, such as marked thirst and passing large amounts of urine, unexplained vomiting or abdominal pain, confusion or drowsiness, or rapid or difficult breathing. These symptoms require prompt assessment and are not typical of insulin resistance alone.

How do doctors diagnose insulin resistance in women with PCOS?

Diagnosis relies on a combination of fasting glucose, HbA1c, oral glucose tolerance test, lipid profile and physical examination, as no single UK-standard test exists. HOMA-IR and fasting insulin are used mainly in research rather than routine NHS primary care.

There is currently no single universally agreed test for diagnosing insulin resistance in clinical practice in the UK. NICE CKS guidance on polycystic ovary syndrome does not mandate a specific diagnostic test for insulin resistance as a routine step.^[3] Instead, clinicians use a combination of clinical assessment, blood tests and sometimes specialist investigations to build a picture of a woman's metabolic health.

Blood tests that may be used or considered include:

• Fasting glucose and HbA1c, to assess blood sugar regulation and screen for prediabetes or type 2 diabetes

• Oral glucose tolerance test (OGTT), which may be considered in women with PCOS who are at higher risk of impaired glucose tolerance, as it can detect abnormalities that fasting glucose or HbA1c alone may miss^[12][13]

• Fasting insulin levels, which, when interpreted alongside fasting glucose, can give an indication of insulin resistance using calculations such as the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR); however, fasting insulin measurement and HOMA-IR are not routinely recommended in NHS primary care and are used mainly in research settings^[3]

• Lipid profile, as insulin resistance is often associated with raised triglycerides and low HDL cholesterol

• Liver function tests, given the association between insulin resistance and MASLD

A physical examination noting features such as acanthosis nigricans, central adiposity and blood pressure measurement also forms part of the assessment. Women with PCOS are advised to have their cardiovascular risk factors and glucose tolerance reviewed regularly, even in the absence of symptoms. If a GP suspects significant metabolic risk, referral to an endocrinologist or specialist PCOS clinic may be appropriate. Women seeking an initial assessment through an online consultation can access clinician review through services such as Bolt Pharmacy, a GPhC-registered UK online pharmacy, where a prescriber can advise on appropriate next steps.

What treatments and lifestyle changes can help manage insulin resistance in PCOS?

NICE recommends lifestyle modification as first-line treatment, including reduced refined carbohydrates and regular exercise. Metformin is the most commonly used medication when lifestyle changes are insufficient, with renal function and B12 levels monitored during treatment.

Lifestyle modification remains the first-line approach recommended by NICE CKS for managing insulin resistance in PCOS, with evidence supporting meaningful improvements in insulin sensitivity, menstrual regularity and androgen levels through sustained changes to diet and physical activity.^[3][14] In women with PCOS who are overweight, even a modest reduction in body weight has been associated with improvements in hormonal and metabolic markers, though women of a healthy weight can also have insulin resistance and benefit from lifestyle support.^[3][14]

Dietary approaches that may help include:

• Reducing intake of refined carbohydrates and added sugars

• Choosing lower glycaemic index (GI) foods to moderate blood glucose fluctuations

• Increasing dietary fibre through vegetables, legumes and wholegrains

• Eating regular, balanced meals to avoid large glucose spikes

Physical activity is particularly effective at improving insulin sensitivity. Both aerobic exercise (such as brisk walking, cycling or swimming) and resistance training have demonstrated benefit. UK Chief Medical Officers' guidelines recommend at least 150 minutes of moderate-intensity activity per week for adults, alongside muscle-strengthening activities on at least two days per week.^[7][8]

Where lifestyle measures alone are insufficient, metformin is the most commonly used medication in the UK for insulin resistance in PCOS. Although it is not licensed specifically for PCOS, NICE CKS acknowledges its use in this context, particularly for women with impaired glucose tolerance or those who have not responded adequately to lifestyle changes. Metformin works by reducing hepatic glucose production and improving cellular insulin sensitivity.^[4]

Important safety and monitoring points for metformin include:

• Renal function should be checked before starting and monitored regularly during treatment, as metformin is not suitable if kidney function is significantly impaired

• Gastrointestinal side effects (nausea, diarrhoea, abdominal discomfort) are common, particularly when starting treatment; taking metformin with food and starting at a low dose with gradual titration can help reduce these effects

• Long-term use of metformin may reduce vitamin B12 absorption; periodic monitoring of B12 levels is advisable

• Metformin should be temporarily stopped during acute illness with dehydration, vomiting or diarrhoea, and before procedures involving iodinated contrast media, in line with BNF guidance

• Women who are pregnant, planning a pregnancy or breastfeeding should discuss the use of metformin with their GP or specialist, as individual clinical assessment is needed

Seek urgent medical attention (call 999 or go to your nearest emergency department) if you experience symptoms that may suggest a serious metabolic problem while taking metformin or managing PCOS, such as severe vomiting, abdominal pain, confusion, drowsiness, rapid breathing, or symptoms of severe hyperglycaemia (marked thirst, passing large amounts of urine, unexplained weight loss). Call NHS 111 if you are unsure whether your symptoms need urgent assessment.

In some cases, where PCOS is associated with significant weight-related metabolic risk, a clinician may discuss other options as part of a broader weight management plan. Women should speak to their GP in the first instance. Any suspected adverse drug reactions should be reported via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk.

Scientific References

1. Polycystic ovary syndrome: metformin in women not planning pregnancy (ESUOM6) — key points.
2. Polycystic ovary syndrome: metformin in women not planning pregnancy (ESUOM6) — PDF.
3. Polycystic ovary syndrome — Treatment summaries. BNF.
4. Metformin hydrochloride — Drugs. BNF.
5. Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk.
6. Vitamin B12 deficiency in over 16s: diagnosis and management (NG239).
7. Physical activity guidelines: UK Chief Medical Officers' report.
8. UK Chief Medical Officers' physical activity guidelines.
9. Physical activity guidelines for adults aged 19 to 64.
10. Role of insulin and insulin resistance in androgen excess disorders.
11. Dermatologic manifestations of polycystic ovary syndrome.
12. Assessment of insulin resistance and impaired glucose tolerance in women with polycystic ovary syndrome.
13. Comparison of diabetes mellitus and insulin resistance screening methods for women with polycystic ovary syndrome.
14. The role of lifestyle interventions in PCOS management.
15. Unlicensed use of metformin in children and adolescents.
16. Ovarian insulin signaling is intact despite systemic insulin resistance in a mouse model of polycystic ovary syndrome.
17. Polycystic ovary syndrome-associated acne: the interplay of hyperandrogenism, insulin resistance, and therapeutic strategies.
18. Hormone responses to buserelin in polycystic ovary syndrome and in eumenorrheic women with hyperandrogenism/hyperandrogenemia, and the relationship of these responses with insulin resistance.
19. Metabolic stress testing reveals persistent lipid-handling dysfunction in women with polycystic ovary syndrome despite exercise training.
20. The effect of high intensity interval training on free androgen index in patients with polycystic ovary syndrome.
21. Effect of exercise therapy on non-obese women with polycystic ovary syndrome: a protocol for a randomized controlled trial.
22. What ultimately underlies vitamin B12 and folate deficiency in subjects treated with biguanides?.

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