Polycystic Ovary Syndrome (PCOS)

Meet the patient

A 24-year-old receptionist comes with periods every 40 to 60 days since her teens, coarse hair on her chin and chest she lasers monthly, jawline acne, and an 8 kilogram weight gain over the last year. Her mother has type 2 diabetes. Today her HbA1c is 42 mmol/mol — prediabetic — and she has velvety darkening in her neck folds: acanthosis nigricans, the bedside flag for insulin resistance.[1][11]

Two exam questions are now live and you must answer both. Is this PCOS (and if so, which axis — reproductive or metabolic — is driving it)? And what will protect her endometrium and her fertility over the next decade? Everything below exists to answer those two questions at consultant depth.[1]

The one-line diagnosis — Rotterdam is 2 of 3, after you exclude the mimics

Diagnose PCOS when any 2 of 3 are present, and only after you have excluded the mimics. That trailing clause is the half candidates forget, and it is the half examiners test. The number rule to carry into the viva: 2 of 3, after you exclude the mimics.[4][1]

The three Rotterdam features, with the thresholds you must reproduce verbatim:[1]

• Oligo or anovulation — cycles over 35 days, or fewer than 8 per year, or chronic amenorrhoea; reflects chronic anovulation with unopposed oestrogen.
• Hyperandrogenism — clinical (modified Ferriman-Gallwey score of 4 or above, persistent jawline acne, androgenic alopecia) or biochemical (raised total or free testosterone, or a raised free androgen index).
• Polycystic ovarian morphology (PCOM) on ultrasound — 20 or more antral follicles per ovary of 2 to 9 mm and/or ovarian volume over 10 mL on modern transducers (AE-PCOS 2014 threshold, retained in the 2018 and 2023 guidelines).[1][8]

The classic trap: PCOM alone is not diagnostic. Over 20 percent of normal ovulatory women of reproductive age meet the modern PCOM threshold, so an ultrasound full of follicles in a woman with regular cycles and no hyperandrogenism is an ovary, not a diagnosis.[1]

The three diagnostic frameworks disagree only on which feature is mandatory — and examiners love the distinction:[1]

[1]

Four phenotypes — and which one bites metabolically

The two classic phenotypes carry the metabolic load; the mildest one barely does. Rotterdam does not give you one disease, it gives you four, sorted by severity.[9]

• Phenotype A (classic, full) — hyperandrogenism plus ovulatory dysfunction plus PCOM. The most severe, the most insulin-resistant, the highest cardiometabolic risk.
• Phenotype B (classic, non-PCOM) — hyperandrogenism plus ovulatory dysfunction without PCOM. Metabolic risk similar to A.
• Phenotype C (ovulatory PCOS) — hyperandrogenism plus PCOM with regular cycles. Moderate; fertility usually preserved.
• Phenotype D (non-hyperandrogenic) — ovulatory dysfunction plus PCOM, no hyperandrogenism. The mildest; some experts argue it is not PCOS at all.[1][9]

Everyone forgets: the practical point is not the letter, it is the metabolic risk. Phenotypes A and B warrant aggressive diabetes and cardiovascular screening; phenotype D does not. A modern clustering analysis (Dapas and Dunaif, 2020) formalises this intuition into a reproductive subtype (higher LH and SHBG, lower BMI and insulin — letrozole-responsive) and a metabolic subtype (higher BMI, glucose, insulin — metformin-responsive), a step toward precision endocrinology.[5]

How common, who, and why it is missed

PCOS affects around 8 to 13 percent of reproductive-age women — and up to 70 percent of them are never told they have it. That single sentence is why this disorder does so much preventable harm: the diagnosis is delayed by 2 to 4 years on average, and the metabolic consequences accumulate silently while the label is missing.[1][9]

Risk factors cluster around the two axes: family history (heritability around 70 percent in twin studies), obesity (present in 50 to 80 percent in some populations, though a lean-PCOS phenotype exists), premature adrenarche, and a first-degree relative with type 2 diabetes. High-risk ethnicities — South Asian, Indigenous, Hispanic, Middle Eastern — express the metabolic phenotype at a lower BMI and develop type 2 diabetes 5 to 10 years earlier, which is why you drop to Asian BMI cut-offs (23 to 27.5) for overweight and obesity screening in these groups.[3][5]

Why she has two diseases at once — the reproductive-metabolic cycle

Insulin resistance and hyperandrogenism feed each other in a vicious cycle, and that cycle is the whole disease. Every PCOS answer, every mechanism question, and every management decision hangs on those two linked ideas. Break either half and the syndrome improves — which is exactly why lifestyle works.[1][6]

1. The HPO axis runs too fast. The hypothalamic GnRH pulse generator accelerates — pulses fire every 60 to 90 minutes instead of the normal 90 to 120 — driving the pituitary to release more LH and less FSH. High LH stimulates ovarian theca-cell hyperplasia and over-expression of CYP17, the rate-limiting enzyme in androgen biosynthesis, so testosterone and androstenedione pour out. An LH-to-FSH ratio over 2 is supportive but no longer diagnostic — do not lean on it.[6]

2. Insulin resistance amplifies the androgen excess three ways. Insulin resistance is near-universal (around 70 percent of lean and 95 percent of obese PCOS) and centres on a post-receptor serine-phosphorylation defect. The resulting hyperinsulinaemia drives androgens by augmenting LH action on theca cells, by suppressing hepatic SHBG (which raises the free testosterone fraction even when total is normal), and by directly stimulating ovarian and adrenal steroidogenesis.[11]

3. Follicular arrest gives you the pearl necklace. With FSH relatively low, no single follicle is selected as dominant, so small antral follicles pile up in the subcapsular ovary — the string-of-pearls on ultrasound. These arrested follicles secrete anti-Mullerian hormone at 2 to 4 times the level of age-matched controls, and AMH itself further inhibits FSH-driven aromatase, locking the cycle; AMH also acts on hypothalamic GnRH neurons to keep the pulse frequency high.[12]

4. Anovulation leaves the endometrium drowning in unopposed oestrogen. No dominant follicle means no ovulation, no corpus luteum, no luteal progesterone. Meanwhile adipose-tissue aromatase converts the excess androgens to oestrone. The endometrium sits under chronic unopposed oestrogen — the mechanism behind the 2- to 3-fold increased risk of endometrial hyperplasia and cancer.[13]

5. Chronic low-grade inflammation is the third arm. PCOS is a state of elevated TNF-alpha, IL-6 and CRP driven by visceral adipocyte hypertrophy, with high leptin and low adiponectin. These mediators further impair insulin signalling and stimulate ovarian androgen production through NF-kB pathways.[15]

Read the patient like a consultant — the phenotype shifts with age

In her teens and twenties she presents with reproductive complaints; in her thirties and forties the metabolic features take over. The same disease wears a different face by decade, and a consultant reads both at once.[1][5]

The reproductive face she arrives with:[1]

• Menstrual — oligomenorrhoea (over 35 days or fewer than 8 per year) is the cardinal symptom; amenorrhoea for 3 or more months also occurs. Anovulatory cycles produce irregular, sometimes heavy bleeding, and anovulatory infertility accounts for around 80 percent of all anovulatory infertility.
• Clinical hyperandrogenism — hirsutism is the visible marker: male-pattern terminal hair on the upper lip, chin, chest, back, abdomen and inner thigh, scored on the modified Ferriman-Gallwey (9 sites, 0 to 4 each, cut-off 4 or above). Persistent jawline acne and androgenic alopecia complete the picture.
• Biochemical hyperandrogenism — total testosterone is mildly raised in 60 to 80 percent, but the free testosterone and free androgen index are more sensitive because SHBG is suppressed. DHEA-S is an adrenal androgen; a markedly raised level points away from PCOS.[1]

The metabolic face that follows her for life:[1]

• Central (android) obesity — waist over 88 cm in non-Asian or over 80 cm in Asian women.
• Acanthosis nigricans — velvety hyperpigmentation over neck, axillae, groin and knuckles; the single-glance clue to insulin resistance, present in 30 to 50 percent.
• Dyslipidaemia — high triglycerides, low HDL, increased small-dense LDL: atherogenic.
• Hypertension, glucose intolerance, obstructive sleep apnoea — the long-term burden.[1]

Lean PCOS is the trap that hides the metabolic risk. Around 20 percent of PCOS sits at a normal BMI yet is still insulin resistant by HOMA-IR or euglycaemic clamp. A normal weight does not licence you to skip the HbA1c — screen her anyway. Anxiety, depression and body-image distress run 2 to 4 times more common in PCOS and track the hirsutism and weight, so screen actively with PHQ-9 and GAD-7; they are treatable and they wreck adherence when missed.[1]

[1]

Exclude the mimics before you label her

Never write PCOS until you have excluded thyroid disease, hyperprolactinaemia, non-classic CAH, Cushing, and an androgen-secreting tumour. This exclusion is not a footnote — it is an examinable dimension in its own right, and the table below is the cornerstone of the hirsutism short-answer question.[1]

[1]

The discriminator line: rapid onset, severe virilisation, and a testosterone over 5 to 6 nmol/L is never PCOS — it is a tumour until proven otherwise. PCOS is slow, mild, and chronic; clitoromegaly, voice deepening and frontal balding shift you to urgent pelvic and adrenal imaging, not reassurance.[1]

The thresholds that decide an answer

Five numbers win or lose a PCOS stem — own them before you walk in. The modified Ferriman-Gallwey cut-off, the PCOM follicle threshold, the tumour-flag testosterone, the adolescent waiting period, and the ovarian volume ceiling.[1]

[1]

A few thresholds deserve their own sentence. The PCOM cutoff rose from 12 to 20 follicles because modern transducers over-call the old number — examiners may still quote 12 from older Indian texts, but 20 is the current standard. The modified Ferriman-Gallwey cut-off is 4 or above in most populations, with region-specific adjustments the 2023 guideline endorses. And testosterone over 5 to 6 nmol/L is the line that moves you from PCOS to tumour workup.[7]

The bedside round — look for the signs that change management

Examination in suspected PCOS rarely makes the diagnosis, but it changes the workup. Run it in this order: weight, waist and blood pressure first; then the modified Ferriman-Gallwey score across nine sites; then the skin for acanthosis, acne, alopecia and skin tags; then an active hunt for virilisation.[1]

• Anthropometrics — BMI (over 25, or over 23 in Asian populations, flags cardiometabolic risk) and waist circumference at the iliac crest.
• Modified Ferriman-Gallwey — 9 sites, graded 0 to 4; 4 or above is hirsutism in most populations.
• Skin — acanthosis nigricans and skin tags (insulin resistance), jawline acne, androgenic alopecia.
• Look hard for virilisation — clitoromegaly (clitoral index over 35 mm squared), voice deepening, frontal balding, breast atrophy. Any of these triggers urgent imaging, not a PCOS label.
• Thyroid and breasts — goitre, nodules; expressible galactorrhoea (prolactinoma); Cushing screen if the face and striae fit.
• Pelvic exam is not routine in a young nulliparous woman without symptoms.[1]

The history high-yields on five questions: menstrual pattern (cycle length, frequency, last period), fertility intent, onset and tempo of hirsutism (sudden and severe is the red flag), weight change (especially around menarche or stopping the OCP), and family history of PCOS, type 2 diabetes and early cardiovascular disease. Ask about valproate, antipsychotics and exogenous androgens, which can manufacture a PCOS-like picture.[1]

Investigations — three jobs, done in stages

Diagnosis is clinical (Rotterdam); investigation does three jobs — confirm hyperandrogenism, exclude the mimics, and stage the metabolic risk. There is no single diagnostic test, and the workup is staged, drawn in the early follicular phase (days 2 to 5 of a spontaneous or induced bleed) where timing matters.[1][7]

Stage 1 — exclude the mimics. Every woman with suspected PCOS has this panel at presentation:[1]

[1]

Stage 2 — confirm PCOM and assess the ovary. Transvaginal ultrasound is preferred (transabdominal if the patient is virginal): 20 or more antral follicles per ovary of 2 to 9 mm and/or ovarian volume over 10 mL on modern transducers; either ovary meeting threshold counts. Ultrasound is not required if the other two criteria are met, and is not recommended within 8 years of menarche because multifollicular ovaries are normal then. AMH, 2 to 4 times elevated, is an emerging serum surrogate for antral follicle count where ultrasound is unavailable — not yet a formal criterion because of inter-assay variability.[8][12]

Stage 3 — metabolic surveillance is part of the diagnosis. PCOS is a cardiometabolic disorder, so stage it like one:[1]

• Fasting glucose and HbA1c in all at diagnosis; add a 2-hour 75 g oral glucose tolerance test if BMI is 25 or above (23 Asian), high-risk ethnicity, prior gestational diabetes, or family history of type 2 diabetes — HbA1c alone misses up to a third of impaired glucose tolerance in PCOS.
• Fasting lipid profile at diagnosis and every 2 to 3 years.
• Liver function tests to screen for NAFLD, present in 30 to 50 percent.
• Sleep study (STOP-BANG or Berlin, then polysomnography) if she snores or has witnessed apnoeas — obstructive sleep apnoea reaches 30 to 50 percent in obese PCOS.
• Repeat the OGTT every 1 to 3 years when baseline is normal but risk persists.[1]

Supportive but not diagnostic: an LH-to-FSH ratio over 2 (sanity check only; often normal in obese PCOS), a raised AMH, and a normal or mildly raised oestradiol. In the pre-conception workup, add partner semen analysis (mandatory first), tubal patency (hysterosalpingogram or HyCoSy), mid-luteal progesterone (day 21 to 23) to confirm ovulation once cycles are regular, and rubella and varicella serology.[1]

[1]

The management mantra — and the ladder it dictates

Management is symptom-driven and lifestyle-first, organised around one mantra: lifestyle first, protect the endometrium, letrozole for fertility. Hold that line and the whole ladder slots into place; it is the single most repeatable sentence in the topic.[1][2]

PCOS is not a time-critical emergency, but three situations demand prompt action: sudden severe virilisation (investigate tumour, do not reassure), prolonged amenorrhoea with abnormal bleeding (sample the endometrium and start protection), and metabolic decompensation (new type 2 diabetes, manage per guidelines). The commonest resuscitation intervention is endometrial protection — induce a regular withdrawal bleed.[1]

The ladder, rung by rung:[1][2]

• 1. Lifestyle — first-line for every patient, every phenotype. A 5 to 10 percent weight loss through diet, 150 minutes a week of moderate aerobic exercise plus resistance training, and behaviour change restores ovulation in many; it is the single most effective intervention because it breaks the insulin-resistance half of the cycle at its root.
• 2. Menstrual irregularity without fertility desire — combined oral contraceptive pill. Ethinylestradiol 30 to 35 microgram with a progestin gives cycle control, endometrial protection, and raises SHBG to lower free testosterone. Use cyclical medroxyprogesterone 5 to 10 mg for 10 to 14 days every 1 to 3 months when the OCP is contraindicated (smoker over 35, migraine with aura, VTE risk).
• 3. Metabolic features — metformin. Start 500 mg once daily with the evening meal, titrate by 500 mg every 1 to 2 weeks to 500 mg twice daily then three times daily, usual target 1.5 to 2 g per day (maximum 2.55 g). Extended-release 1 to 2 g once daily is better tolerated. Counsel on GI side-effects and B12 with chronic use; stop 48 hours before contrast; contraindicated if eGFR under 30.
• 4. Hirsutism and acne — combined OCP first-line, plus cosmetic measures (laser, electrolysis, eflornithine cream). After six months add an anti-androgen — spironolactone 50 to 200 mg per day — only with reliable contraception, because anti-androgens are teratogenic and feminise a male fetus.
• 5. Infertility — letrozole first-line (2.5 to 5 mg days 2 to 6, titrate to 7.5 mg); clomiphene is second-line; gonadotrophins and laparoscopic ovarian drilling third-line; IVF reserved for failure of induction or additional factors.[2]

The insulin-resistance arm gets its own ladder: lifestyle always, then metformin, then GLP-1 receptor agonists for obesity when lifestyle and metformin are insufficient (significant weight loss, stop 2 months before conception), then bariatric or metabolic surgery for BMI over 35 to 40 with comorbidity (defer pregnancy 12 to 18 months). Treat comorbidities to target: HbA1c under 6.5 percent, blood pressure under 130/80, LDL under 2.6 mmol/L (under 1.8 in high cardiovascular risk).[1][11]

[1] [1]

Protect the endometrium — the preventable cancer

Chronic anovulation leaves the endometrium under unopposed oestrogen, and that is the most preventable cause of morbidity and death in PCOS. The risk of endometrial cancer is 2 to 3 times background overall, and up to 4 times in obese PCOS, typically diagnosed before 50, usually low-grade and oestrogen-receptor-positive. Protection with the OCP or cyclical progestogen reduces it dramatically.[13]

The named trap: the woman with prolonged amenorrhoea and no withdrawal bleeds is the one who silently accrues hyperplasia. Induce a regular withdrawal bleed — cyclical medroxyprogesterone or a combined OCP — and any woman with over 3 months of amenorrhoea plus abnormal bleeding gets an endometrial biopsy before reassurance. The 2023 guideline does not recommend routine ultrasound screening of asymptomatic PCOS; protection is preferred over surveillance.[7]

Fertility — letrozole changed everything (PPCOS II)

Letrozole is first-line ovulation induction in PCOS, and the PPCOS II trial is the reason. An aromatase inhibitor, it lowers oestrogen and releases FSH without the anti-oestrogenic endometrial and cervical-mucus effects of clomiphene. In 750 women with PCOS-related infertility, letrozole achieved a live birth of around 28 percent versus 19 percent with clomiphene, with a lower multiple-pregnancy rate — the single trial that shifted first-line induction from clomiphene to letrozole.[2]

A woman fails to conceive after 12 months of regular unprotected intercourse (6 months if over 35) enters a structured workup. Before induction, confirm ovulation with mid-luteal serum progesterone over 10 nmol/L (over 3 ng/mL), check partner semen analysis (mandatory first) and tubal patency, and optimise pre-conception: folic acid 400 to 800 microgram daily (5 mg if previous neural-tube defect or BMI over 35), weight and glucose to target, and stop teratogens — spironolactone, retinoids, GLP-1 agonists.[2]

The induction ladder, with the doses examiners expect:[2]

• Step 1 — Letrozole (first-line) — 2.5 mg orally on days 2 to 6, titrate to 5 mg then 7.5 mg if no ovulation (mid-luteal progesterone under 10 nmol/L) or no pregnancy after 3 ovulatory cycles.
• Step 2 — Clomiphene citrate (second-line) — 50 mg on days 2 to 6, titrate to 100 mg; its anti-oestrogenic endometrial thinning is the mechanism by which letrozole outperforms it.
• Step 3 — Gonadotrophins (third-line) — low-dose FSH starting 37.5 to 75 IU/day, step-up under cycle monitoring; cancel if over 3 mature follicles or oestradiol over 3000 pg/mL to avoid ovarian hyperstimulation.
• Step 3 alternative — Laparoscopic ovarian drilling — 4 to 6 punctures per ovary; restores ovulation in 50 to 70 percent of clomiphene-resistant PCOS, with surgical and adhesion risks.
• Step 4 — IVF — for failure of induction or additional tubal or male factor; use a GnRH antagonist protocol with a GnRH-agonist trigger because PCOS is the most OHSS-prone phenotype.[2][14]

Monitor with mid-luteal progesterone on day 21 to 23 and transvaginal ultrasound from day 10 (dominant follicle 18 to 24 mm). Maintain BMI under 30 where possible — each 5 percent weight loss roughly doubles the pregnancy rate. Failure to ovulate on maximum-dose letrozole, or any need for gonadotrophins, is the trigger to refer to reproductive endocrinology.[2][14]

Do not over-diagnose the teenager

In an adolescent, PCOS requires both hyperandrogenism and persistent ovulatory dysfunction — and you do not use PCOM at all. The HPO axis takes 2 to 3 years after menarche to mature, irregular cycles are normal in that window, and over 50 percent of normal teenagers have multifollicular ovaries. Over-diagnosis is the dominant harm in this age group.[10]

[1]

Manage symptoms while avoiding a premature label: cycle control with a low-androgenic OCP or cyclical progestin, weight and lifestyle, eflornithine for hirsutism, and active screening for depression and anxiety. Reassess at 18 to 20 — about 20 to 30 percent of adolescent PCOS labels are no longer present in early adulthood, because the axis has matured. The label in a teenager should be provisional.[10]

How PCOS patients come to harm — the preventable list

PCOS is a multi-system disorder; most of the harm is preventable, and naming the mechanism is what scores. The complications track the two axes across the lifespan.[1][5]

Reproductive: anovulatory infertility (letrozole restores ovulation in 70 to 80 percent), recurrent early pregnancy loss (around 1.5 to 2 times), gestational diabetes (2 to 3 times — early OGTT before 24 weeks in the 2023 guideline), pre-eclampsia (1.5 to 2 times), preterm delivery and large-for-gestational-age babies.[1][7]

Metabolic: type 2 diabetes (3 to 4 times BMI-matched controls; cumulative incidence 10 to 20 percent by age 40), impaired glucose tolerance in 30 to 40 percent of obese PCOS at diagnosis, dyslipidaemia in up to 70 percent, hypertension, metabolic syndrome in 30 to 50 percent, NAFLD or NASH in 30 to 50 percent, and obstructive sleep apnoea in 30 to 50 percent of obese PCOS — independent of BMI, and a driver of insulin resistance.[1]

Cardiovascular and endometrial: subclinical atherosclerosis from early adulthood (raised carotid intima-media thickness, coronary calcium); likely increased hard events (relative risk around 1.3 to 1.7 for coronary disease, though outcome data mature); modestly raised VTE, amplified by OCP in obese PCOS. Endometrial cancer 2 to 3 times, up to 4 times in obesity — the most direct consequence of unopposed oestrogen and the most preventable.[1][13]

The recurring pitfalls every candidate must name:[1]

• Diagnosing PCOS without excluding mimics — every woman needs TSH, prolactin, 17-OHP, androgens, and a Cushing screen.
• Omitting endometrial protection in prolonged amenorrhoea — endometrial cancer is the most preventable complication.
• Prescribing spironolactone without contraception — teratogenic; feminises a male fetus.
• Over-diagnosing adolescents — multifollicular ovaries and anovulatory cycles are normal for 2 to 3 years post-menarche.
• Treating hirsutism for under six months and calling failure — hair cycles are 6 to 12 months; reassess at six.
• Assuming a normal BMI excludes metabolic risk — lean PCOS is insulin resistant; screen anyway.
• Using clomiphene as first-line when letrozole is available — letrozole has higher live birth and lower multiple pregnancy (PPCOS II).[2]

The trials and guidelines that set the standard

The framework is anchored by four documents an examiner expects you to name:[1]

• Rotterdam 2003 consensus (ESHRE/ASRM-sponsored workshop) — defined PCOS as 2 of 3 features after excluding mimics and identified the four phenotypes; the international standard that harmonised research.[4]
• PPCOS II trial (Legro and colleagues, NEJM 2014) — letrozole 28 percent live birth versus clomiphene 19 percent in 750 women; shifted first-line ovulation induction to letrozole.[2]
• 2018 International Evidence-based PCOS Guideline (Teede and colleagues) — unified the care algorithm, raised the PCOM follicle threshold to 20 on modern transducers, and warned against over-diagnosing adolescents.[8]
• 2023 International Evidence-based PCOS Guideline update (Teede and colleagues) — 254 recommendations and practice points; opened the door to renaming the syndrome "metabolic reproductive syndrome"; added emphasis on inositol, GLP-1 agonists, lifestyle, and AMH as a possible surrogate for antral follicle count.[7]

The 2023 guideline is the most important modern document on the topic — quote it for the PCOM threshold, the metabolic-surveillance emphasis, and the rename debate. Regional deltas the viva probes: the mFG cut-off is region-specific (4 in most populations, lower in East Asian, higher in Mediterranean or South Asian backgrounds); metformin is globally first-line for metabolic features but retains a more central reproductive role in some South Asian protocols; clomiphene remains acceptable in European settings where letrozole is unlicensed for induction.[7]

The mantra, and the pearls that decide a viva

The mantra: lifestyle first, protect the endometrium, letrozole for fertility. Say it once, mean all three, and the management question answers itself.[1][2]

Prognosis, disposition, and the lifespan view

PCOS is lifelong, and its phenotype evolves across the lifespan — reproductive in youth, metabolic thereafter. Hyperandrogenic features often improve after menopause as ovarian androgen output falls, but the metabolic and cardiovascular risk persists or worsens, so surveillance continues. Fertility is achievable in 70 to 80 percent with letrozole plus or minus gonadotrophins plus or minus IVF, and the strongest single prognostic intervention is weight management.[1][5]

Disposition is outpatient and multidisciplinary: endocrinology, gynaecology or reproductive medicine, dietetics, psychology, and sleep medicine for OSA. Review annually — weight, blood pressure, a metabolic screen, mental health, and endometrial protection where relevant. In pregnancy, heighten surveillance for gestational diabetes and pre-eclampsia, give aspirin 75 to 150 mg daily from 12 weeks for pre-eclampsia prophylaxis in high-risk women, and offer an early OGTT.[7]

Ward-round test — four stems, thirty seconds each

Stem 1 — the woman from the top of the topic (answer)

The 24-year-old with 40-to-60-day cycles, chin hair, acne, an 8 kg weight gain, acanthosis nigricans, and an HbA1c of 42 mmol/mol. What is the diagnosis framework, and what do you do first?[1]

Model: She meets Rotterdam on reproductive and hyperandrogenic grounds, but before labelling PCOS you must exclude the mimics (TSH, prolactin, 17-OHP, testosterone and SHBG, DHEA-S, and a clinical Cushing screen). Then stage the metabolic axis — her acanthosis and prediabetic HbA1c warrant a 75 g OGTT, a fasting lipid profile and LFTs, and a sleep screen. First management step is lifestyle plus endometrial protection: a combined OCP gives cycle control and protects the endometrium from unopposed oestrogen while she loses 5 to 10 percent of body weight.[1][11]

Stem 2 — the woman whose voice is deepening (answer)

A 32-year-old known to have PCOS returns with voice deepening, clitoromegaly and frontal balding over four months. Total testosterone is 8 nmol/L. What do you do?[1]

Model: This is not PCOS. Rapid onset, severe virilisation, and a testosterone over 5 to 6 nmol/L is an androgen-secreting tumour until proven otherwise. Order an urgent pelvic ultrasound then adrenal CT or MRI, and involve endocrinology now. Do not reassure, do not increase the spironolactone, and do not attribute it to her PCOS label — the classic, dangerous trap.[1]

Stem 3 — six months of amenorrhoea and no fertility desire (answer)

A 29-year-old with PCOS has had no period for seven months and is not trying to conceive. She is reassured that the break is welcome. What is wrong with that plan?[13]

Model: The silence is the danger. Chronic anovulation leaves the endometrium under unopposed oestrogen, and her risk of endometrial hyperplasia and cancer is 2 to 3 times background. Induce a regular withdrawal bleed with a cyclical progestogen (medroxyprogesterone 5 to 10 mg for 10 to 14 days every 1 to 3 months) or a combined OCP, and any abnormal bleeding mandates an endometrial biopsy. Protecting the endometrium is the preventable-cancer half of the mantra.[13]

Stem 4 — the teenager with irregular cycles and a polycystic-looking ovary (answer)

A 15-year-old, two years post-menarche, has cycles every 40 days and mild acne. An ultrasound reports 22 follicles per ovary. Her GP labels her PCOS. What is the error?[10]

Model: Two errors. First, PCOM must not be used as a criterion within 8 years of menarche — multifollicular ovaries are normal in this age group, and over 50 percent of normal adolescents have them. Second, the adolescent diagnosis requires both hyperandrogenism and persistent ovulatory dysfunction for at least 2 years post-menarche; mild acne and 40-day cycles two years in do not meet that bar. Manage symptoms and reassess at 18 to 20 — the label should be provisional.[10]

References

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2. [2]Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome N Engl J Med, 2014.PMID 25006718
3. [3]Zehravi M, Maqbool M, Ara I. Polycystic ovary syndrome and reproductive health of women: a curious association Int J Adolesc Med Health, 2021.PMID 33878255
4. [4]Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS) Hum Reprod, 2004.PMID 14688154
5. [5]Joham AE, Norman RJ, Stener-Victorin E, et al. Polycystic ovary syndrome Lancet Diabetes Endocrinol, 2022.PMID 35934017
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7. [7]Teede HJ, Tay CT, Laven J, et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome Eur J Endocrinol, 2023.PMID 37580861
8. [8]Teede HJ, Misso ML, Costello MF, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome Fertil Steril, 2018.PMID 30033227
9. [9]Lizneva D, Suturina L, Walker W, et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome Fertil Steril, 2016.PMID 27233760
10. [10]Witchel SF, Oberfield SE, Peña AS Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls J Endocr Soc, 2019.PMID 31384717
11. [11]Zhao H, Zhang J, Cheng X, et al. Insulin resistance in polycystic ovary syndrome across various tissues: an updated review of pathogenesis, evaluation, and treatment J Ovarian Res, 2023.PMID 36631836
12. [12]Garg D, Tal R. The role of AMH in the pathophysiology of polycystic ovarian syndrome Reprod Biomed Online, 2016.PMID 27174394
13. [13]Palomba S, Piltonen TT, Giudice LC. Endometrial function in women with polycystic ovary syndrome: a comprehensive review Hum Reprod Update, 2021.PMID 33302299
14. [14]Kotlyar AM, Seifer DB. Women with PCOS who undergo IVF: a comprehensive review of therapeutic strategies for successful outcomes Reprod Biol Endocrinol, 2023.PMID 37528417
15. [15]Rudnicka E, Suchta K, Grymowicz M, et al. Chronic Low Grade Inflammation in Pathogenesis of PCOS Int J Mol Sci, 2021.PMID 33917519