In one line
PMOS (previously PCOS) is a lifelong metabolic-reproductive syndrome diagnosed on the Rotterdam criteria after exclusion of mimics; beyond making the diagnosis, the task is to stratify the woman's metabolic, cardiovascular and endometrial-cancer risk and match therapy to her stated goal — cycle control, hyperandrogenism, fertility or long-term cardiometabolic protection. The chronic anovulation that defines most phenotypes means unopposed oestrogen, which is why endometrial protection is a core, lifelong limb of management, not an afterthought.
Assessment
The Intermediate groundwork — what PMOS is, the basic Rotterdam triad, the hormonal axis, and the everyday contraceptive choices used to control cycles — is assumed; the work here is getting the diagnosis secure, the phenotype named, and the risk profile complete.
Diagnosis (2023 international guideline, Rotterdam framework). In an adult, two of three: (i) clinical and/or biochemical hyperandrogenism; (ii) ovulatory dysfunction; (iii) polycystic ovarian morphology (PCOM) on ultrasound or a raised AMH — provided you have excluded other causes.
- Biochemical hyperandrogenism — measure total and free testosterone; estimate free testosterone via the calculated free androgen index (good-quality assays, with SHBG). If total testosterone is markedly raised (a common viva cut-off is >5 nmol/L) or onset is rapid/virilising, you are obliged to exclude an androgen-secreting tumour and non-classic congenital adrenal hyperplasia (17-OHP), and Cushing's where the phenotype fits. DHEAS and androstenedione are second-line.
- Ovulatory dysfunction — cycles outside ~21–35 days, or persistent oligo/amenorrhoea. Always check TSH, prolactin and FSH to exclude thyroid disease, hyperprolactinaemia and primary ovarian insufficiency before settling on PMOS.
- PCOM — on transvaginal scan the threshold is now follicle number per ovary ≥20 (2–9 mm) in at least one ovary (or ovarian volume ≥10 mL); serum AMH may be used as an alternative to ultrasound in adults. The guideline deliberately gives no single universal AMH cut-off — laboratories must use population- and assay-specific thresholds, so quote AMH as supportive, never as a hard number in the exam. The "cysts" are a misnomer: these are arrested antral follicles, not pathological cysts — a "necklace" of small follicles stalled short of dominance, not the fluid-filled cysts the old name implied (Piltonen, JAMA Intern Med 2026). This is the conceptual core of the PCOS→PMOS rename; a genuine ovarian cyst is a different entity and does not make the diagnosis.
- Adolescents — require both hyperandrogenism and ovulatory dysfunction; ultrasound and AMH must not be used to diagnose PCOM within 8 years of menarche (low specificity). Label "at risk" and reassess at full reproductive maturity.
Name the phenotype
Rotterdam's "two of three" generates four phenotypes, and the phenotype, not the label "PMOS", predicts her metabolic trajectory and shapes counselling. The mechanism that links them is that the hyperandrogenic, anovulatory axis carries the insulin-resistance load — so phenotype severity tracks the presence of hyperandrogenism plus anovulation, not the ovarian appearance.
| Phenotype | Criteria present | Distinguishing mechanism | Metabolic/clinical consequence |
|---|---|---|---|
| A — "classic / complete" | Hyperandrogenism + anovulation + PCOM | Full insulin-resistant, hyperandrogenic axis; highest AMH and antral count | Highest insulin resistance, metabolic-syndrome and endometrial-cancer burden; most often anovulatory-infertile |
| B — "non-PCOM classic" | Hyperandrogenism + anovulation | Same hyperandrogenic-anovulatory drive without the morphology; easy to under-call because the scan is "normal" | Metabolic risk close to A — do not down-stage her because the ovaries look normal |
| C — "ovulatory" | Hyperandrogenism + PCOM | Androgen excess with preserved ovulation; presents for hirsutism/acne, not subfertility | Intermediate metabolic risk; the endometrial-protection argument is weaker because she ovulates |
| D — "non-hyperandrogenic" | Anovulation + PCOM | The only phenotype without androgen excess; the mildest insulin-resistance signal | Mildest metabolic disturbance, prognosis closest to unaffected women; still needs endometrial protection because she is anovulatory |
The clinical corollaries: A and B carry the heaviest cardiometabolic and endometrial burden and warrant the most aggressive metabolic surveillance; phenotype B is the trap — a "normal scan" tempts the junior to reassure, but she is metabolically a classic patient; phenotype D is the one to reassure proportionately on metabolic risk while still protecting the endometrium because she is anovulatory; phenotype C shifts the management centre of gravity from endometrial protection toward androgen control. Name the phenotype explicitly — "this is Rotterdam phenotype A" — and the rest of the plan follows from it.
The two drivers — how PMOS is actually driven
Beyond the Rotterdam label, the consultant-level model is two interacting mechanisms driving one disease (Barbieri 2026; Stener-Victorin, Nat Rev Dis Primers 2024). These describe how the syndrome is generated and how its features vary between women; they do not sort women into separate treatment types.
- The neuroendocrine (LH-clock) driver. A fast hypothalamic KNDy-neuron clock (kisspeptin / neurokinin-B / dynorphin in the arcuate nucleus) accelerates GnRH pulses, so the pituitary favours LH over FSH. LH drives the theca cell to make androgen (cholesterol → pregnenolone → … → testosterone), while the relative FSH deficit leaves antral follicles arrested. This tends to accompany the lean woman with a high LH:FSH ratio and high AMH.
- The insulin-resistance driver. Hyperinsulinaemia acts as a co-gonadotropin, amplifying LH-driven theca androgen output, and suppresses hepatic SHBG. Because only free testosterone is bioactive, low SHBG is a free-testosterone multiplier: it worsens hyperandrogenism at any given total testosterone. This tends to accompany the higher-BMI woman with acanthosis nigricans, low SHBG and MASLD (metabolic dysfunction–associated steatotic liver disease) risk.
Both mechanisms coexist in most women rather than sorting them into types, so a single driver rarely acts alone. Crucially, therapy is not chosen from an LH:FSH ratio or an AMH value but from the woman's goals and comorbidity (developed in Management): a combined hormonal contraceptive for cycle control and hirsutism, metformin for metabolic outcomes, an anti-androgen with contraception, and a GLP-1 agonist under obesity guidance. This model also explains why insulin resistance is mechanistically central yet not a diagnostic criterion: you target its consequences, not a HOMA number (below). The same biology frames the future drug target: NK3R (neurokinin-3-receptor) antagonists dim the KNDy/GnRH pulse generator and lower LH and testosterone — proof-of-concept in PCOS/PMOS only (George, JCEM 2016; Skorupskaite, Hum Reprod 2020), with no NK3R drug yet licensed for the condition, though the class is already approved for menopausal vasomotor symptoms (Fraser, JCEM 2021).
Why "metabolic" is in the name — and where the screen misleads
Having made the diagnosis, screen every woman regardless of BMI — the lean, normal-weight PMOS woman is the one most often missed, because insulin resistance in PMOS is partly intrinsic (independent of adiposity), so a normal BMI does not exonerate her.
- A 75 g OGTT is the most accurate glycaemic test: HbA1c and fasting glucose both systematically miss impaired glucose tolerance in PMOS, where the lesion is post-prandial. It is the most commonly omitted test. Repeat every 1–3 years by risk; bring it forward preconception and in pregnancy.
- Fasting lipid profile at diagnosis, annual blood pressure, weight/waist, and validated screening for depression and anxiety (the psychological morbidity is part of the syndrome, not incidental). Ask about snoring/daytime somnolence and screen for obstructive sleep apnoea where symptomatic.
- Do not order HOMA-IR or fasting insulin to "confirm" insulin resistance. Insulin resistance is not a diagnostic criterion, and the surrogate indices (HOMA-IR, fasting insulin, Belfiore) are assay-dependent and discordant — clinical measurement of insulin resistance is explicitly not recommended. You manage the downstream metabolic consequences (glucose, lipids, BP, weight), not a HOMA number. Sending a HOMA-IR is over-investigation.