Clinical overview
Hyperandrogenism is a state of androgen excess in a woman, expressed clinically (hirsutism, acne, androgenic alopecia, and at the severe end virilisation) and/or biochemically (raised serum androgens). It is one of the most common reproductive-endocrine presentations to gynaecology, and the overwhelming majority of cases — around 70–80% — are accounted for by PMOS (polyendocrine metabolic ovarian syndrome — the condition renamed in 2026 from polycystic ovary syndrome, PCOS). The clinician's job is twofold: first, to recognise the small but critical minority in whom androgen excess signals something dangerous — an androgen-secreting ovarian or adrenal tumour, Cushing's syndrome, or non-classical congenital adrenal hyperplasia — and second, to manage the common, benign causes well, because they carry real consequences for fertility, metabolic health, endometrial protection, and quality of life.
A note on naming. Throughout this chapter the condition is called PMOS, with (formerly PCOS) flagged at first use in each major section. The two terms mean the same disease. FCOG(SA) and MRCOG examinations still use "PCOS" during the transition period (see the dedicated section below), so you must recognise and answer to both.
The single most useful discriminator at the bedside is the tempo. Hirsutism that has crept on slowly over years, around puberty, with menstrual irregularity is the picture of PMOS. Hirsutism that appears suddenly and progresses rapidly, especially with frank virilisation (clitoromegaly, voice deepening, male-pattern temporal balding, increased muscle bulk), is a tumour until proven otherwise and demands urgent investigation. This chapter explains the androgen physiology and the pathophysiology of the major causes, then sets out a safe assessment and management approach. It connects to contraceptive-modalities (the mainstay of medical treatment), climacteric-and-menopause (postmenopausal hyperandrogenism), and heavy-menstrual-bleeding-pathology (anovulatory bleeding and endometrial risk).
From PCOS to PMOS — the 2026 rename
Figure B2.1 — The 2026 rename of PCOS to PMOS (polyendocrine metabolic ovarian syndrome): the same condition, why the name changed, and the global consensus process behind it.
In May 2026 the condition long known as polycystic ovary syndrome (PCOS) was formally renamed polyendocrine metabolic ovarian syndrome (PMOS) through a global consensus published in The Lancet (Teede et al.). The process was deliberately broad — a modified Delphi with nominal-group workshops gathering 14,360 patient and clinician voices across 56 organisations in 195 countries. It is essential to understand that this is the same condition — no diagnostic criteria changed at the rename; only the name did. Three problems with the old name drove the change:
- The "cysts" were always a misnomer. The ovaries in this condition do not contain pathological cysts. What ultrasound shows is a ring of arrested early-antral follicles (the "string of pearls"), 2–9 mm, whose development has stalled — not fluid-filled cysts. The burden of true ovarian cysts is not increased in the condition (Piltonen et al., JAMA Internal Medicine 2026). Naming a disease after a lesion it does not have bred confusion for patients and clinicians alike.
- It is not an ovary-only disease. PMOS is a multisystem polyendocrine and metabolic disorder: insulin resistance affects roughly 85% of patients (and ~75% even of lean patients), with raised lifetime risks of type 2 diabetes, MASLD (metabolic dysfunction–associated steatotic liver disease), dyslipidaemia and cardiovascular disease, alongside the neuroendocrine and psychological burden (depression, anxiety). The new prefixes name what the disease actually is — polyendocrine (neuroendocrine, androgen, insulin and AMH dysregulation), metabolic, and ovarian (retained, deliberately preserving acronym continuity).
- The old name drove stigma and delay. Around 70% of affected women remain undiagnosed and the average delay from first symptom to diagnosis is about 8 years; an ovary-centric, cyst-implying label contributed to both, and sat awkwardly with ICD and research nomenclature.
Transition and the exam. A 3-year transition is under way; the ICD codes and the International Guideline update land in 2028. Until then — and this is the practical point for candidates — FCOG(SA) and MRCOG questions, and most current textbooks and guidelines, still say "PCOS." Lead with PMOS, state "formerly PCOS" on first mention, and treat any exam stem that says "PCOS" as identical to PMOS.
Core knowledge
Androgen physiology in women
Figure B2.2 — Androgen sources, SHBG binding, free testosterone, and DHT-driven pilosebaceous effects.
Women make androgens from the ovary, the adrenal cortex, and by peripheral conversion. The relevant hormones, in rising order of potency:
- Dehydroepiandrosterone sulphate (DHEAS) — almost exclusively adrenal; a useful marker of an adrenal source of androgen.
- DHEA and androstenedione — pro-hormones from both ovary and adrenal (androstenedione roughly 50:50).
- Testosterone — about half from peripheral conversion of androstenedione, with the ovary and adrenal contributing the rest; the principal circulating androgen measured.
- Dihydrotestosterone (DHT) — the most potent androgen at the target tissue, generated locally from testosterone by 5α-reductase in the pilosebaceous unit.
Most circulating testosterone is bound to sex hormone-binding globulin (SHBG); only the free fraction is bioactive. SHBG is therefore pivotal: insulin and androgens both suppress hepatic SHBG, so in insulin-resistant states (PMOS, obesity) SHBG falls and the free, active androgen rises even when total testosterone looks unremarkable. This is quantified by the free androgen index (FAI = total testosterone ÷ SHBG × 100).
How androgens produce the clinical signs
Androgens act on the pilosebaceous unit, driving the transformation of fine, unpigmented vellus hair into coarse, pigmented terminal hair in androgen-dependent areas (upper lip, chin, chest, back, lower abdomen, inner thighs), and stimulating sebum production (acne). Local 5α-reductase activity and end-organ androgen-receptor sensitivity vary between individuals and ethnic groups — which is why idiopathic hirsutism exists (normal circulating androgens, regular ovulation, but increased skin sensitivity), and why the relationship between serum androgen level and clinical severity is loose.
Causes of hyperandrogenism
Ovarian
- PMOS (formerly PCOS) — by far the commonest cause (see below).
- Ovarian hyperthecosis — nests of luteinised theca cells producing testosterone; typically more marked, often postmenopausal, with higher testosterone levels and sometimes virilisation.
- Androgen-secreting ovarian tumours — Sertoli-Leydig cell tumours, hilus cell tumours, and others; usually cause rapid virilisation with markedly raised testosterone.
Adrenal
- Non-classical (late-onset) congenital adrenal hyperplasia — most often 21-hydroxylase deficiency, with a build-up of 17-hydroxyprogesterone; mimics PMOS and must be excluded biochemically.
- Cushing's syndrome — cortisol and adrenal-androgen excess.
- Adrenal tumours — adenoma or carcinoma; carcinoma classically produces very high DHEAS and testosterone with rapid virilisation.
Other
- Idiopathic hirsutism — normal androgens, regular cycles, increased skin sensitivity.
- Drug-induced — anabolic/androgenic steroids, danazol, valproate, some progestogens.
- Hyperprolactinaemia and acromegaly — through associated metabolic and adrenal effects.
- Severe insulin resistance (HAIR-AN syndrome — hyperandrogenism, insulin resistance, acanthosis nigricans).
- Pregnancy-related — luteoma of pregnancy, theca-lutein cysts (usually self-limiting).
PMOS (formerly PCOS) — the dominant cause, and its pathophysiology
Figure B2.3 — PMOS pathophysiology: a fast hypothalamic KNDy clock drives LH over FSH, and hyperinsulinaemia amplifies theca-cell androgen output (two-cell theory).
PMOS is a syndrome of androgen excess and ovulatory dysfunction, diagnosed by the Rotterdam criteria: at least two of three —
- oligo- or anovulation,
- clinical and/or biochemical hyperandrogenism,
- polycystic ovarian morphology on ultrasound or a raised anti-Müllerian hormone (AMH) —
after excluding the mimics above (thyroid disease, hyperprolactinaemia, non-classical CAH, Cushing's, tumours). The 2023 International Evidence-based Guideline (Teede et al., still published under the Polycystic Ovary Syndrome title that predates the rename) refined this: in adults, AMH may be used as an alternative to ultrasound for the morphology criterion; ultrasound thresholds were raised to reflect modern high-resolution transducers (a follicle number per ovary ≥20, or ovarian volume ≥10 mL); and ultrasound/AMH should not be used to diagnose PMOS within 8 years of menarche because multifollicular ovaries are normal in adolescence (adolescents require both hyperandrogenism and irregular cycles).
The pathophysiology is a self-reinforcing loop operating at three levels of the hypothalamic–pituitary–ovarian axis:
- Hypothalamus — a fast KNDy clock. The KNDy neurons of the arcuate nucleus (kisspeptin / neurokinin B / dynorphin) set an accelerated GnRH pulse frequency, which favours LH over FSH secretion and raises the LH:FSH ratio. (Proof of mechanism: the NK-3-receptor antagonist fezolinetant modestly lowers LH and testosterone in this condition — see climacteric-and-menopause for its menopause use.)
- Ovary — the two-cell theory. LH drives the theca cell to make androgens (cholesterol → … → testosterone). The neighbouring granulosa cell uses FSH-dependent aromatase to convert that testosterone to oestradiol — but with FSH relatively low, aromatase is under-driven, so testosterone accumulates instead of being converted.
- The metabolic "second hit" — insulin. Insulin resistance with compensatory hyperinsulinaemia acts as a co-gonadotropin, amplifying LH's effect on the theca cell, and suppresses hepatic SHBG synthesis. Lower SHBG is a multiplier, not an addition: the same total testosterone yields much higher free (bioactive) testosterone. This double hit (theca amplification + SHBG suppression) is what distinguishes the metabolically driven patient.
- Follicular arrest and its consequences. Relative FSH insufficiency arrests antral follicle development — the "string of pearls" of small follicles — producing anovulation, oligomenorrhoea and, through unopposed oestrogen, a raised risk of endometrial hyperplasia and carcinoma over time.
A useful clinical model is to think of two engines: a neuroendocrine "LH-clock" engine (typically the leaner, adolescent-onset patient with high LH:FSH and high AMH) and a hyperinsulinaemic metabolic engine (typically higher BMI, acanthosis, very low SHBG). Most women run both, and the dominant engine guides which treatment helps most.
Assessment
Figure B2.4 — Tempo-led hyperandrogenism triage, red-flag investigation thresholds, and common benign management steps.
History
- Onset and tempo — slow and peripubertal (PMOS/idiopathic) versus rapid and progressive (tumour).
- Menstrual and fertility history — oligo/amenorrhoea, subfertility.
- Virilising symptoms — voice change, clitoral enlargement, balding, increased muscularity.
- Drugs — anabolic steroids, danazol, valproate.
- Family/ethnic history — CAH, PMOS (formerly PCOS), type 2 diabetes; ethnicity influences normal hair patterns.
- Metabolic symptoms and weight history.
Examination
- Modified Ferriman–Gallwey score to quantify hirsutism across nine androgen-sensitive areas.
- Acne, androgenic alopecia pattern, and any signs of virilisation (clitoromegaly is a key red flag).
- Acanthosis nigricans (a marker of insulin resistance), BMI, waist circumference.
- Cushingoid features (striae, central obesity, proximal myopathy, plethora).
- Abdominal and pelvic examination for an ovarian or adrenal mass.
Investigations
- Total testosterone — the pivotal test (LC-MS/MS preferred in the low female range). A level more than twice the upper limit of normal (roughly >5 nmol/L) mandates urgent imaging for an androgen-secreting tumour.
- SHBG and free testosterone / FAI — to capture bioactive androgen when total testosterone is borderline.
- DHEAS — a markedly raised level points to an adrenal source (tumour).
- Early-morning, early-follicular 17-hydroxyprogesterone — screens for non-classical CAH; if raised, proceed to a short ACTH (Synacthen) stimulation test.
- LH, FSH (supportive of PMOS, no longer required for diagnosis), prolactin, TSH.
- Overnight dexamethasone suppression test or 24-hour urinary free cortisol if Cushing's is suspected.
- AMH and pelvic (transvaginal) ultrasound for ovarian morphology and to exclude an ovarian mass.
- Metabolic screen in PMOS — HbA1c (or oral glucose tolerance test), fasting lipids, and blood pressure, reflecting the metabolic core of the disease.
- Cross-sectional imaging (adrenal CT/MRI; dedicated ovarian imaging) when a tumour is suspected on biochemistry or tempo.
Management
The first principle is to treat the underlying cause: androgen-secreting tumours are surgically removed, non-classical CAH is managed with glucocorticoid replacement, Cushing's is treated on its own pathway, and offending drugs are stopped. For PMOS and idiopathic hirsutism the approach is medical and cosmetic, and the patient must be told at the outset that hair responses take 6–12 months because of the hair growth cycle.
- Lifestyle and weight reduction — the foundation in PMOS; even modest weight loss improves insulin sensitivity, raises SHBG, and can restore ovulation.
- Combined hormonal contraception — the mainstay of medical treatment for hyperandrogenism not seeking fertility: it suppresses ovarian androgen production, raises SHBG, and provides cycle control and endometrial protection. Preparations with anti-androgenic progestogens (cyproterone acetate, drospirenone) are favoured; drospirenone raises SHBG, levonorgestrel lowers it. See contraceptive-modalities.
- Anti-androgens — spironolactone (50–200 mg/day) is the most widely used; cyproterone acetate and finasteride are alternatives (flutamide is effective but hepatotoxic and rarely used). All anti-androgens are teratogenic (risk of under-virilisation of a male fetus) and must be combined with reliable contraception.
- Metformin — for the metabolic phenotype and as an adjunct for ovulatory and glycaemic benefit; an anti-obesity GLP-1 agonist (e.g. semaglutide) is increasingly used where weight and insulin resistance dominate. Together with COC and spironolactone these form the cheap, safe, synergistic "treat-both-engines" combination.
- Topical eflornithine slows facial hair growth; laser and electrolysis give durable cosmetic results.
- Endometrial protection — anovulatory women need cyclical progestogen or a combined/LNG-IUS approach to prevent hyperplasia from unopposed oestrogen.
- Fertility — for those wanting pregnancy, ovulation induction with letrozole (first-line, having replaced clomiphene) is pursued separately from androgen suppression.
Red flags / pitfalls
- Rapid-onset hirsutism or virilisation, very high testosterone (>5 nmol/L), or very high DHEAS — androgen-secreting tumour until excluded; investigate urgently.
- New hyperandrogenism after the menopause — think ovarian hyperthecosis or tumour, not PMOS.
- Diagnosing PMOS without excluding the mimics — non-classical CAH, Cushing's, hyperprolactinaemia, thyroid disease, and tumours must be ruled out.
- Forgetting 17-hydroxyprogesterone — non-classical CAH is a common PMOS impostor.
- Prescribing an anti-androgen without contraception — teratogenicity.
- Using ultrasound or AMH to diagnose PMOS in adolescents within 8 years of menarche — multifollicular ovaries are normal then; adolescents need both hyperandrogenism and irregular cycles.
- Treating the hair and ignoring the metabolism — PMOS carries diabetes, MASLD, dyslipidaemia, and cardiovascular risk; this is the whole point of the "metabolic" in the new name.
- Neglecting endometrial protection in chronic anovulation — unopposed oestrogen risks hyperplasia and carcinoma (endometrial-carcinoma).
- Treating the "cyst" — there is no cyst to treat; the ovarian appearance is arrested follicles, not pathology requiring surgery.
- Promising rapid cosmetic results — counsel that hair response takes 6–12 months.
Evidence anchors
- Teede HJ et al. — The Lancet (2026) — global consensus renaming PCOS to PMOS (polyendocrine metabolic ovarian syndrome); same condition, 3-year transition, ICD/guideline update 2028.
- International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome (2023) — Teede et al., Fertil Steril; Monash-led, endorsed by ESHRE/ASRM; Rotterdam criteria, AMH as an alternative to ultrasound in adults, metabolic screening, treatment hierarchy (letrozole first-line for fertility).
- Piltonen TT et al. — JAMA Internal Medicine (2026) — pathological cysts are not increased; the ovarian appearance is arrested antral follicles, underpinning the rename rationale.
- Stener-Victorin E et al. — Nat Rev Dis Primers (2024) and Joham AE et al. — Lancet Diabetes & Endocrinology (2022) — multisystem (neuroendocrine/metabolic/reproductive) pathophysiology; insulin as co-gonadotropin and the SHBG "double hit".
- Endocrine Society Clinical Practice Guideline — Evaluation and Treatment of Hirsutism in Premenopausal Women (testosterone-led work-up; anti-androgen + combined-contraceptive treatment).
- South African EML / NDoH Standard Treatment Guidelines — availability of combined hormonal contraception, spironolactone, metformin.