Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in people with ovaries of reproductive age, arising from a heterogeneous combination of hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology (PCOM). It is diagnosed using the Rotterdam criteria — 2 of these 3 features, after excluding conditions that mimic PCOS — and the specific combination present defines 4 distinct phenotypes with different reproductive and metabolic risk. Insulin resistance with compensatory hyperinsulinemia is the central pathophysiologic driver linking PCOS's reproductive features (excess insulin amplifies ovarian androgen production and disrupts normal follicle maturation) to its long-term metabolic consequences (type 2 diabetes, dyslipidemia, cardiovascular risk) — this single mechanism is why lifestyle intervention and insulin-sensitizing therapy are foundational across every phenotype, not only the ones with obesity.^[1]

This chapter is authored from the 2023 International Evidence-based Guideline for the Assessment and Management of PCOS — 254 recommendations co-produced by the American Society for Reproductive Medicine, the European Society of Human Reproduction and Embryology, the Endocrine Society, and the European Society of Endocrinology — and cross-checked against the Society of Obstetricians and Gynaecologists of Canada (SOGC) Clinical Gynaecology Committee's February 2025 position statement, which explicitly adapts the international guideline's recommendations to Canadian practice.^[2] It covers diagnosis, first-line combined hormonal contraceptives, metformin for the metabolic phenotype, spironolactone for hirsutism/acne, letrozole as the current first-line ovulation-induction agent (a genuine shift away from clomiphene supported by higher live-birth rates^[3]), foundational lifestyle intervention, long-term risk screening, and mental-health screening.

PCOS is diagnosed when 2 of these 3 features are present, once mimicking conditions have been excluded (see Assessment & Diagnosis). Which 2 (or all 3) are present defines 4 phenotypes:

Other commonly seen features

• Central/abdominal obesity, or in normal-weight patients, increased visceral adiposity ("lean PCOS") — insulin resistance can be present without an elevated BMI.
• Acanthosis nigricans (velvety hyperpigmented skin, typically at the neck or axillae) — a clinical marker of insulin resistance.
• Infertility from chronic anovulation.
• Higher rates of anxiety, depression, disordered eating, and body-image concerns than the general population.
• Symptoms of obstructive sleep apnea (snoring, witnessed apnea, daytime fatigue) — more common in PCOS independent of BMI and frequently under-recognized.

• Family history of PCOS, or of type 2 diabetes in a first-degree relative.
• Premature adrenarche.
• Low birth weight or rapid postnatal weight gain.
• Obesity/excess adiposity, which worsens both the hyperandrogenic and metabolic phenotype — though PCOS also occurs at a normal body weight.
• In-utero exposure to excess androgens.
• Valproate/valproic acid therapy — associated with a PCOS-like phenotype (menstrual irregularity, hyperandrogenism, polycystic-appearing ovaries) in some patients, particularly with use during adolescence.
• Higher reported prevalence in some populations, including South Asian ancestry, where the metabolic phenotype also tends to be more severe at a given BMI.

Step 1 — exclude conditions that mimic PCOS

Before applying the Rotterdam criteria, rule out other causes of the same clinical picture:

• Thyroid dysfunction — TSH.
• Hyperprolactinemia — serum prolactin.
• Non-classic congenital adrenal hyperplasia — an early-morning (follicular-phase) 17-hydroxyprogesterone, particularly with a suggestive family history/ancestry or rapid-onset hyperandrogenism.
• Consider Cushing syndrome or an androgen-secreting tumour only when a red flag from the section above is present — these are not routine screening tests in a typical presentation.

Step 2 — apply the Rotterdam criteria (adults)

Diagnose PCOS when at least 2 of the following 3 are present, once mimics above are excluded: ovulatory dysfunction; clinical or biochemical hyperandrogenism; and polycystic ovarian morphology, or an elevated AMH as a substitute for ultrasound in adults.^[1]

Biochemical hyperandrogenism testing

Measure total testosterone plus sex hormone-binding globulin to calculate a free androgen index, or free testosterone directly by equilibrium dialysis or LC-MS/MS where available — routine direct free-testosterone immunoassays are unreliable in this population. Draw a fasting, morning sample. A patient already taking combined hormonal contraception will have suppressed androgen levels, so a low result on therapy does not rule out PCOS; where feasible without compromising the patient's contraceptive needs, testing after a washout is more accurate.

Diagnosis in adolescents

Apply stricter criteria in adolescents, given how common physiologic multi-follicular ovaries and cycle irregularity are in the first few years post-menarche: require both hyperandrogenism (clinical or biochemical) and irregular menstrual cycles meeting adolescent-specific duration criteria based on time since menarche. Do not use PCOM on ultrasound to diagnose PCOS in adolescents — it is not specific enough at this age.^[1] An adolescent who does not fully meet these criteria but has risk features should be labelled "at increased risk" and reassessed at the transition to adult criteria, rather than definitively diagnosed or definitively excluded.

Metabolic screening at diagnosis

Insulin resistance with compensatory hyperinsulinemia is the pathophysiologic driver of PCOS, but routine fasting insulin or HOMA-IR testing is not recommended for either diagnosis or monitoring — clinically available insulin assays are not standardized and have limited clinical validity in this context.^[1] Screen instead for the downstream metabolic consequences directly:

• A 75 g oral glucose tolerance test is preferred over HbA1c or fasting glucose alone — it is more sensitive for detecting glucose intolerance in PCOS specifically. Repeat every 1-3 years, or sooner with additional risk factors (obesity, a family history of type 2 diabetes, or a personal history of gestational diabetes).
• Fasting lipid profile at diagnosis.
• Blood pressure at every visit.
• Weight, BMI, and waist circumference.

Endometrial and psychological screening at diagnosis

Assess the menstrual pattern to identify chronic anovulation with unopposed estrogen exposure (see Special Populations for endometrial-protection management), and screen every patient for anxiety and depressive symptoms with a regionally validated tool, plus body-image and disordered-eating concerns — screen at diagnosis and repeat based on clinical judgement, risk factors, and life events, including the perinatal period.^[1]

• Restore regular ovulatory cycles and prevent unopposed-estrogen-driven endometrial hyperplasia.
• Control hyperandrogenic symptoms — hirsutism, acne, and androgenic alopecia — to the patient's own goals.
• Achieve ovulation and pregnancy when fertility is desired.
• Improve insulin sensitivity and metabolic parameters to reduce long-term type 2 diabetes and cardiovascular risk.
• Support mental health — screen for and treat anxiety, depression, and disordered eating.
• Achieve realistic, health-focused weight/lifestyle goals, recognizing that even a modest (5-10%) weight loss meaningfully improves ovulation, metabolic parameters, and quality of life without requiring a specific target BMI.

• Structured lifestyle intervention (a reduced-calorie diet plus regular physical activity, ideally with behavioural support) is foundational therapy for every phenotype — even a 5-10% weight loss meaningfully improves ovulation rates, insulin sensitivity, and psychological well-being, and the benefit does not require reaching a specific target BMI.^[1]
• Regular physical activity (at least 150 minutes/week of moderate intensity, per general population guidance) supports both the metabolic and mental-health goals of treatment.
• Psychological therapy (cognitive behavioural therapy or similar) — offer as first-line treatment for a patient who screens positive for anxiety, depression, disordered eating, or significant body-image distress, alongside or instead of pharmacotherapy for these symptoms.^[1]
• Cosmetic hair-removal methods (laser epilation, electrolysis, or topical eflornithine cream for facial hair specifically) are useful adjuncts to, not substitutes for, systemic anti-androgen therapy for hirsutism — combining a cosmetic method with systemic treatment gives a faster, more complete response than either alone.
• Sleep evaluation and, where indicated, referral for sleep-apnea assessment.
• Smoking-cessation support, given the added cardiovascular risk on top of PCOS's own metabolic phenotype.
• Natural health products: myo-inositol (commonly dosed 4 g/day, often split into two 2 g doses, sometimes combined with D-chiro-inositol in a 40:1 ratio) is used by some patients for cycle regulation and metabolic symptoms; current Canadian guidance concludes the evidence for a meaningful effect on ovulation, clinical pregnancy, or live-birth rates remains limited, with insufficient evidence to recommend a specific product or dose — present it as an option with uncertain benefit rather than an evidence-based alternative to metformin or letrozole.^[2]

Pregnancy

Stop spironolactone (and any anti-androgen) as soon as pregnancy is confirmed or suspected — it carries a teratogenic risk of feminizing a male fetus. Letrozole and clomiphene are both contraindicated once pregnancy is confirmed; confirm a negative pregnancy test before starting each treatment cycle. Whether to continue metformin once pregnancy is confirmed after ovulation-induction therapy is individualized and typically specialist-directed — evidence for a benefit from continuing metformin specifically to prevent pregnancy complications, beyond its role in glycemic management, is not conclusive. Screen early for gestational diabetes, given the baseline glucose-intolerance risk in PCOS.

Breastfeeding

Metformin is compatible with breastfeeding, with minimal transfer into breast milk. Spironolactone has limited breastfeeding safety data and is generally avoided when a non-hormonal or topical alternative (e.g., eflornithine, cosmetic hair removal) can control symptoms instead. Follow standard postpartum contraceptive-selection guidance (not specific to PCOS) for COC timing while breastfeeding.

Adolescents

A combined hormonal contraceptive remains 1st line for menstrual regulation and hyperandrogenism in an adolescent who meets diagnostic criteria; consider metformin for an adolescent with overweight/obesity and confirmed metabolic risk. Avoid over-medicalizing an adolescent who does not fully meet the stricter adolescent diagnostic criteria (see Assessment & Diagnosis) — label as "at increased risk" and reassess at the transition to adult criteria rather than committing to a definitive, lifelong PCOS diagnosis prematurely.

Renal impairment

Metformin is contraindicated at an eGFR under 30 mL/min/1.73m2, and requires dose reduction and caution between 30-45; hold before an iodinated-contrast procedure per standard practice. Use spironolactone with caution, or avoid, in significant renal impairment given the added hyperkalemia risk.

Reassess menstrual regularity and hyperandrogenic symptoms only after an adequate trial of the chosen therapy — allow at least 6 months before judging a COC or spironolactone trial for hirsutism/acne inadequate, since the visible hair-growth response is slow. Repeat the 75 g OGTT every 1-3 years based on individual risk factors, and recheck blood pressure and lipids at routine follow-up visits. Reassess weight, BMI, and waist circumference, and revisit lifestyle-intervention goals, at each visit rather than only at diagnosis. Rescreen for anxiety, depression, and disordered eating periodically — at minimum with any significant life event, including the perinatal period, and whenever new symptoms are reported, not only at the initial visit.^[1] In a patient with chronic anovulation who is not on a COC or cyclic progestin, ask specifically about the bleeding pattern at every visit and manage per the endometrial-protection options above rather than allowing prolonged unopposed-estrogen exposure to go unaddressed. For a patient undergoing ovulation induction, reassess after each cycle (dose escalation for letrozole/clomiphene per the Drug Tables schedule) and refer for specialist reproductive-endocrinology input if pregnancy has not occurred after an adequate multi-cycle trial (commonly around 5-6 cycles).

1. Confirm adherence and correct timing before concluding any agent has failed — COC/spironolactone benefit for hirsutism takes at least 6 months to assess, and letrozole/clomiphene must be started on the correct cycle days.
2. If a standard-progestin COC alone has not adequately controlled hirsutism or acne after 6 months, add spironolactone (with contraception already reliable) rather than repeatedly switching COC formulations.
3. If hirsutism remains inadequately controlled despite a COC plus spironolactone at an adequate dose and duration, consider switching to a more potent anti-androgenic COC (cyproterone acetate/ethinyl estradiol) with explicit VTE counselling, or add a cosmetic hair-removal method (laser epilation, electrolysis, or topical eflornithine) as an adjunct.
4. If letrozole alone across an adequate trial (typically up to 5-6 cycles, with dose escalation per the Drug Tables schedule) has not produced ovulation or pregnancy, add metformin (particularly with a BMI ≥30 kg/m2) or switch to clomiphene plus metformin.
5. If ovulation-induction pharmacotherapy has failed despite an adequate trial, refer for specialist-directed gonadotrophin therapy or laparoscopic ovarian drilling, and consider IVF referral if infertility persists.
6. If metabolic parameters (glucose tolerance, lipids, blood pressure) remain abnormal despite lifestyle intervention and metformin, reassess anti-obesity pharmacotherapy eligibility per the dedicated Obesity guideline rather than escalating metformin indefinitely beyond its usual maximum dose.
7. If mental-health symptoms persist despite first-line psychological therapy, refer for pharmacologic treatment of the underlying anxiety/depression per standard psychiatric guidance — PCOS-specific hormonal treatment does not substitute for direct mental-health treatment.

• Ordering a fasting insulin level or calculating HOMA-IR to diagnose or monitor insulin resistance in PCOS — these assays are not standardized and are not recommended for routine clinical use.
• Diagnosing PCOS in an adolescent using PCOM on ultrasound alone — normal physiologic multi-follicular ovaries are common at this age, and PCOM is not a valid diagnostic criterion in adolescents.
• Assuming hirsutism and irregular cycles are routine PCOS without checking for a red flag (rapid-onset/severe virilization, markedly elevated testosterone, Cushingoid features) that should trigger a tumour or Cushing syndrome work-up instead.
• Starting spironolactone, or any anti-androgen, without first confirming effective contraception is in place.
• Defaulting to clomiphene as the first ovulation-induction agent out of habit — letrozole is now the preferred first-line option given its higher live-birth rate.
• Treating cyproterone acetate/ethinyl estradiol as an interchangeable, risk-free COC choice rather than a specific option with an elevated VTE signal that should be reserved and counselled on explicitly.
• Ordering fasting glucose or HbA1c alone for metabolic screening — a 75 g OGTT detects glucose intolerance in PCOS that these tests can miss.
• Skipping anxiety/depression/disordered-eating screening because the visit is focused on cycles, hirsutism, or fertility — mental-health comorbidity in PCOS is common and frequently under-recognized.
• Leaving chronic anovulation with unopposed estrogen exposure unaddressed for months at a time without a plan for endometrial protection.
• Judging a COC, spironolactone, or letrozole trial a failure before an adequate duration or cycle count has actually elapsed.

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Every anti-androgen row assumes effective contraception is already in place — see Choose Initial Treatment. Select any drug name to open its complete Pharmasist Drug Database page.

Combined hormonal contraceptives

1st line for menstrual regulation and hyperandrogenism. No single progestin has been shown clearly superior for hirsutism; anti-androgenic progestins are commonly selected specifically when hirsutism is the dominant complaint.

Evidence note: the elevated VTE signal specific to cyproterone acetate/ethinyl estradiol is confirmed by a Health Canada summary safety review.^[6]

Insulin sensitizer

Consider in every adult with PCOS and a BMI ≥25 kg/m2 for metabolic benefit; also an alternative for cycle regulation when a COC is not used, and an adjunct to ovulation induction.

Anti-androgens

For hirsutism/acne inadequately controlled by a COC alone after an adequate 6-month trial. Always combine with effective contraception given teratogenic risk.

Evidence note: the recommendation against routine potassium monitoring in an otherwise healthy young patient on spironolactone follows the current Endocrine Society hirsutism clinical practice guideline.^[4]

Ovulation induction

1st line for anovulatory infertility with no other infertility factor identified. Confirm a negative pregnancy test before starting each cycle — both agents are contraindicated once pregnancy is confirmed.

Natural health product

Evidence for a meaningful effect on ovulation, clinical pregnancy, or live-birth rates remains limited; present as an option with uncertain benefit rather than an evidence-based alternative to metformin or letrozole.

Evidence note: the current SOGC position statement concludes there is insufficient evidence to recommend a specific inositol product or dose.^[2]

Note: anti-obesity pharmacotherapy (GLP-1/GIP receptor agonists, orlistat, and related agents) is not repeated here — see the dedicated Obesity clinical guideline for full pharmacotherapy selection, dosing, and monitoring.