Female Hormone Abnormalities — Assessment & Management

Safety

Red Flags — Pituitary Emergency, Adrenal Crisis & Malignancy

Done

Sudden severe headache + visual loss, ophthalmoplegia, altered consciousness, vomiting or features of acute pituitary dysfunction Possible pituitary apoplexy. → Call 999/send to hospital urgently. Do not arrange outpatient MRI or ophthalmology review. In hospital, urgent endocrine bloods are taken if this does not delay treatment, and hydrocortisone is given when there is haemodynamic instability, altered consciousness, reduced visual acuity or severe visual-field loss (Society for Endocrinology). Gradual visual-field loss with a raised prolactin suggests a macroadenoma — urgent endocrinology referral.

Persistent bloating, early satiety, pelvic/abdominal pain, urinary urgency/frequency, unexplained weight loss, fatigue or bowel change; or ascites / unexplained pelvic or abdominal mass Possible ovarian cancer — raised FSH/LH are expected after menopause and are not tumour markers. → Ascites or an unexplained pelvic/abdominal mass: suspected-cancer referral. Persistent symptoms: follow the current NICE NG12 age- and CA-125-dependent pathway (CA-125 at 40 and over, ultrasound according to age and result); do not use CA-125 in isolation or as a screening test for a hormone abnormality.

Rapidly progressive virilisation (deepening voice, clitoromegaly, rapidly progressive severe hirsutism, marked muscle-mass change) over weeks–months, or markedly raised testosterone Possible androgen-secreting ovarian or adrenal tumour. → Urgent endocrinology/gynaecology assessment (not an NG12 route). Refer to endocrinology if total testosterone is >4 nmol/L. Refer urgently if about 6–7 nmol/L or higher, or if there is virilisation or rapid progression of androgenic features (CKS). About 5 nmol/L or higher warrants prompt confirmation and investigation, including considering ovarian/adrenal imaging (Society for Endocrinology 2025), especially if the result is unexpected or from an immunoassay. Interpret against the assay, laboratory reference range, SHBG, medication and clinical findings. Repeat a carefully collected early-morning testosterone and SHBG if clinically safe, but do not delay referral with convincing virilisation; measure DHEAS when an adrenal source is suspected. Imaging is arranged by the receiving specialist or the local urgent pathway — a stable patient with isolated biochemical elevation needs urgent specialist assessment, not emergency admission or same-day CT.

Severe illness, hypotension or shock, vomiting, abdominal pain, confusion, hypoglycaemia, hyponatraemia or unexplained deterioration — particularly with known or possible adrenal insufficiency Suspected adrenal crisis (any patient, not only those with amenorrhoea). ACTH is usually raised in primary adrenal insufficiency but low or inappropriately normal in secondary; hyperkalaemia is not expected in isolated secondary adrenal insufficiency. → Call 999. Give hydrocortisone 100 mg IV or IM immediately and IV 0.9% sodium chloride according to the emergency protocol; do not delay treatment for blood results (NICE NG243).

Young woman + primary amenorrhoea + absent secondary sexual characteristics + short stature + widely spaced nipples Turner syndrome (45,XO) — or other sex chromosome abnormality. → Genetics + paediatric endocrinology. Karyotype urgently. Cardiac screening (bicuspid aortic valve, coarctation). Bone density.

Cyclical severe pelvic pain + amenorrhoea + imperforate hymen or haematocolpos + abdominal mass in adolescent Haematocolpos (outflow tract obstruction). → Same-day gynaecology. USS pelvis. Surgical correction of obstructed outflow.

Pituitary apoplexy is a neurosurgical emergency — sudden haemorrhage or infarction into a pituitary adenoma causes rapid expansion within the bony sella, compressing the optic chiasm (bitemporal hemianopia), cranial nerves III, IV, VI (sudden ocular palsies — diplopia, ptosis), and potentially the hypothalamus. The clinical presentation: sudden severe headache ('thunderclap'), visual loss or diplopia, meningism, confusion. The endocrine emergency: acute panhypopituitarism from destruction of the remaining pituitary — ACTH deficiency → adrenal insufficiency → hypotension and collapse. Management is an emergency hospital pathway: 999; in hospital, urgent endocrine bloods if this does not delay treatment, hydrocortisone when there is haemodynamic instability, altered consciousness, reduced visual acuity or severe visual-field loss, urgent MRI and neurosurgical/endocrine input — primary care should not arrange outpatient MRI or ophthalmology separately. Trans-sphenoidal decompression is performed if visual loss is progressive. GPs must know that any woman with known pituitary adenoma who presents with sudden severe headache requires emergency assessment.

Diagnose

Female Hormone Axes — Framework

Done

The hypothalamic-pituitary-ovarian (HPO) axis

GnRH (hypothalamus, pulsatile) → FSH + LH (anterior pituitary) → Ovarian follicle development + oestrogen production. Oestrogen feeds back negatively (suppresses FSH/LH at low levels) and positively (triggers LH surge at peak mid-cycle → ovulation). Progesterone (corpus luteum, post-ovulation) → feeds back negatively. After menopause: ovarian failure → oestrogen falls → FSH + LH rise (negative feedback removed — hypergonadotrophic hypogonadism). Hypothalamic suppression (stress, weight loss, excess exercise) → low GnRH → low FSH/LH → low oestrogen → amenorrhoea (hypogonadotrophic hypogonadism).

Key hormones and their interpretation

FSH (follicle-stimulating hormone): high = ovarian failure or menopause; low/normal with amenorrhoea = hypothalamic or pituitary cause. LH (luteinising hormone): LH and FSH may assist in the differential diagnosis of amenorrhoea, but the LH:FSH ratio is not a diagnostic criterion for PCOS. Oestradiol (E2): low = menopause, hypothalamic amenorrhoea, ovarian failure; elevated = follicular phase normal, or oestrogen-secreting tumour. Progesterone (approximately 7 days before the expected next period — day 21 only in a regular 28-day cycle): a value above the laboratory's ovulatory threshold supports recent ovulation; interpret according to assay and timing. Prolactin: elevated = lactation, prolactinoma, hypothyroid, drugs; suppresses GnRH if chronically elevated. Testosterone + SHBG + free androgen index (FAI): elevated in PCOS, adrenal pathology, androgen-secreting tumour; interpret the calculated FAI against the reporting laboratory's reference range (no universal threshold). A normal testosterone does not exclude clinical hyperandrogenism. DHEA-S: adrenal androgen — elevated in CAH, adrenal tumour.

Thyroid and adrenal hormones in reproductive health

Hypothyroidism: disrupts menstrual cycle — menorrhagia, irregular cycles, anovulation. TRH elevates prolactin (direct stimulation of lactotrophs) → hyperprolactinaemia. Check TSH when clinically indicated or when menstrual disturbance is unexplained; free T4 is not routinely required if TSH is normal and there are no other indications. Adrenal causes: Cushing syndrome (excess cortisol → menstrual disruption, hirsutism, weight gain) — 24h urine cortisol or overnight dexamethasone suppression test. CAH (congenital adrenal hyperplasia — 21-hydroxylase deficiency): elevated 17-OHP, elevated androgens, menstrual disruption, clitoromegaly.

The LH:FSH ratio is not a diagnostic criterion for PCOS and should not be used to make or support the diagnosis — LH is pulsatile and varies with cycle phase and BMI. Under the 2023 International Evidence-based PCOS Guideline, adult PCOS requires two of: ovulatory dysfunction; clinical or biochemical hyperandrogenism; polycystic ovarian morphology on ultrasound or elevated AMH — after excluding other causes. LH and FSH remain useful in the differential diagnosis of amenorrhoea: a raised FSH suggests ovarian insufficiency, while low or inappropriately normal gonadotrophins suggest a hypothalamic or pituitary cause.

Diagnose

Assessment — History, Examination & Investigations

Done

Targeted hormone history

Menstrual pattern: regular (21-35 day cycle = ovulatory), oligomenorrhoea (>35 days), amenorrhoea (primary = never menstruated; secondary = no periods for >3-6 months after previous normal cycles). Cycle length, duration, flow. Intermenstrual or postcoital bleeding (cervical, endometrial pathology). Contraceptive history (pill-related amenorrhoea). Pregnancy symptoms (exclude pregnancy first in any woman of reproductive age with amenorrhoea). Fertility concerns. Menopausal symptoms (hot flushes, vaginal dryness, mood, sleep disruption — in perimenopausal or surgical menopause). Hyperandrogenism: hirsutism (Ferriman-Gallwey score — facial + body hair distribution), acne, alopecia. Weight change: rapid weight loss/gain, BMI. Exercise: elite athletes, eating disorder. Galactorrhoea (prolactin). Visual changes (pituitary macro). Stress, systemic illness.

Examination

BMI + weight trend. Thyroid (goitre). Secondary sexual characteristics development (Turner — absent or delayed). Hyperandrogenism features: hirsutism (modified Ferriman-Gallwey score ≥4–6, depending on ethnicity — International PCOS guideline 2023), acne severity, androgenic alopecia (bitemporal recession), clitoromegaly (suggests significant androgen excess, possible tumour). Acanthosis nigricans (insulin resistance — axillae, nape of neck). Cushing features (centripetal obesity, striae, thin skin, proximal myopathy, bruising). Galactorrhoea (bilateral expression). Pelvic examination if clinically indicated. Visual fields if there are visual or neurological symptoms, a very high or rising prolactin, or other evidence of pituitary disease.

Investigations — select by phenotype (no universal panel)

For amenorrhoea or oligomenorrhoea: Pregnancy test (urine hCG) (first in anyone of reproductive age with amenorrhoea) · medication and contraception review · TSH (if clinically indicated or menstrual disturbance is unexplained; free T4 not routine if TSH normal) · Prolactin (amenorrhoea, galactorrhoea or symptoms of hyperprolactinaemia; fasting is not essential — stress, recent breast stimulation, exercise, sleep and some medicines raise it; if mildly raised, repeat when rested and check macroprolactin per local laboratory practice) · FSH/LH ± oestradiol (when POI, hypothalamic/pituitary disease or ovarian failure is suspected; no particular cycle day is needed if amenorrhoeic; not needed to diagnose menopause at 45 or over) · Total testosterone + SHBG ± DHEAS (clinical hyperandrogenism or virilisation; interpret the calculated FAI against the reporting laboratory's reference range and use a reliable assay; 17-OHP where clinically indicated) · Progesterone (only for a specific fertility question — approximately 7 days before the expected next period; not routinely in clearly regular cycles) · Pelvic USS (pelvic pathology, abnormal bleeding, suspected ovarian pathology or diagnostic uncertainty; use current ultrasound reporting criteria). AMH is not routinely used to diagnose POI.

Mid-luteal progesterone timing is a critical point that is frequently got wrong in clinical practice — the test is designed to detect the progesterone peak from the corpus luteum following ovulation, which occurs approximately 7 days after ovulation. In a 28-day cycle (ovulation at day 14), this peak is at day 21. However, for women with longer cycles: the progesterone should be taken 7 days before the expected next period, not on a fixed day 21. A woman with a 35-day cycle ovulates at approximately day 21, meaning her progesterone peak is at day 28 — taking the blood on day 21 of this cycle will give a falsely low result (she hasn't ovulated yet). The instruction to patients: 'If your cycle is regular, take this test one week before your next period is due.' If the cycle is irregular and unpredictable, serial progesterone measurements or a different approach (tracking with LH kits) is needed. Do not routinely order progesterone in someone with clearly regular cycles unless there is a specific fertility question; interpret the result against the laboratory's ovulatory threshold.

Diagnose

PCOS, Hypothalamic Amenorrhoea & POI

Done

PCOS — 2023 International Guideline criteria (adults: 2 of 3)

(1) Ovulatory dysfunction: irregular cycles or amenorrhoea. (2) Clinical or biochemical hyperandrogenism: hirsutism, acne, alopecia — or raised testosterone/FAI against the laboratory reference range. (3) Polycystic ovarian morphology on ultrasound or elevated AMH (adults only): use the current ultrasound laboratory/reporting criteria (follicle thresholds depend on modern transvaginal equipment). Where irregular cycles and hyperandrogenism are both present, ultrasound or AMH is not required. Adolescents: both ovulatory dysfunction and hyperandrogenism are required; ultrasound and AMH should not be used (poor specificity). PCOS is a diagnosis of exclusion — consider pregnancy, thyroid disease, hyperprolactinaemia, non-classical congenital adrenal hyperplasia (17-OHP), hypothalamic amenorrhoea, POI, Cushing syndrome and androgen-secreting tumours where clinically appropriate. Do not diagnose PCOS from 'polycystic ovaries' alone. PCOS is the most common female endocrine disorder. Associated: insulin resistance, metabolic syndrome, T2DM and cardiovascular risk, endometrial hyperplasia risk with prolonged anovulation (unopposed oestrogen).

Premature ovarian insufficiency (POI)

POI (previously premature menopause): loss of ovarian function before age 40. Suspect POI in someone under 40 with amenorrhoea or infrequent periods and symptoms of oestrogen deficiency. Exclude pregnancy and measure FSH; confirm with a second FSH approximately 4–6 weeks later (NICE NG23: raised FSH on two samples 4–6 weeks apart; ESHRE 2024 uses FSH >25 IU/L with at least 4 months of disordered cycles). Do not diagnose POI from a single FSH result; no particular cycle day is needed if amenorrhoeic; do not routinely use AMH to diagnose POI. Aetiology — investigate selectively through appropriate specialist pathways: karyotype (e.g. mosaic Turner syndrome 45,X/46,XX), FMR1 premutation, autoimmune testing; iatrogenic causes — chemotherapy (alkylating agents), pelvic radiotherapy, bilateral oophorectomy. Consequences: oestrogen deficiency from young age → osteoporosis, cardiovascular risk, urogenital atrophy, cognitive effects, sexual dysfunction. HRT or a combined hormonal contraceptive should usually continue until at least the average age of natural menopause unless contraindicated — not optional. HRT is not contraceptive.

Hypothalamic amenorrhoea (functional)

Functional hypothalamic amenorrhoea is a diagnosis of exclusion — suppression of GnRH pulsatility from energy deficit (low body weight, eating disorder), excessive exercise (relative energy deficiency in sport — RED-S), psychological stress or chronic illness. Assess pregnancy, weight change, nutritional intake, exercise load, psychological stress, eating-disorder symptoms, medication and systemic disease. Initial tests usually include pregnancy testing, FSH/LH, oestradiol, prolactin and TSH as clinically indicated (typically low or low-normal FSH/LH and low oestradiol; IGF-1 is not a routine test). Management: restore adequate energy availability, reduce excessive exercise, treat eating disorders, psychological support, specialist input if fertility is desired, and bone-health assessment when amenorrhoea is prolonged, nutritional deficiency is significant or fracture risk is increased.

Premature ovarian insufficiency (POI) HRT is not elective — it is a medical necessity. The oestrogen deficiency that begins before age 40 in women with POI causes accelerated bone loss (POI carries approximately 3-fold increased hip fracture risk), premature cardiovascular disease (oestrogen-deprived women under 40 lose the normal female cardiovascular protection advantage), urogenital atrophy, sexual dysfunction, and significant quality-of-life impairment including cognitive effects and depression. HRT in POI is replacement of a physiologically absent hormone (analogous to thyroxine in hypothyroidism) — it does not carry the same risk profile as HRT started post-naturally-menopausal age in older women. The NICE NG23 menopause guidance explicitly states: 'Women with POI should be offered HRT and advised to continue it until at least the age of natural menopause.' HRT or a combined hormonal contraceptive should usually continue until at least the average age of natural menopause (about 51) unless contraindicated; HRT is not contraceptive. GPs who see women with POI on no HRT should initiate a conversation about HRT at every appointment until the decision is made — non-treatment is the greater clinical risk.

Refer

Referral Pathways

Done

999 / Same-day

999: pituitary apoplexy (sudden severe headache with visual loss, ophthalmoplegia/diplopia or altered consciousness) · adrenal crisis (any of shock or hypotension, vomiting, abdominal pain, confusion, hypoglycaemia or unexplained deterioration, especially with known or possible adrenal insufficiency — do not wait for blood results) · haemodynamic instability, severe hypoglycaemia or acute neurological/visual symptoms. Same-day emergency gynaecology: severe acute pelvic pain with suspected torsion or obstructed outflow

Endocrinology (urgent)

Rapidly progressive virilisation or markedly raised testosterone/DHEAS (urgent endocrinology/gynaecology; do not delay for repeat tests if virilisation is convincing) · Confirmed or suspected pituitary tumour (very high or rising prolactin, visual or neurological symptoms, or MRI abnormality) · Suspected Cushing syndrome · Primary amenorrhoea with abnormal pubertal development · CAH (elevated 17-OHP) · Primary adrenal insufficiency · Elevated DHEA-S suggestive of adrenal pathology

Reproductive medicine / gynaecology (urgent)

Confirmed or probable POI (under 40, raised FSH on two samples 4–6 weeks apart), especially with complex comorbidity — HRT/CHC, fertility counselling, baseline DXA · Anovulatory infertility including PCOS — ovulation induction (e.g. letrozole, off-label) via the fertility service

Gynaecology

PCOS with abnormal, heavy, prolonged or persistent bleeding or suspected endometrial pathology · Hypothalamic amenorrhoea + fertility treatment required · Ovarian pathology on USS

Suspected cancer pathway

Unexplained pelvic/abdominal mass or ascites · Persistent symptoms suggestive of ovarian cancer with abnormal investigations (CA-125/ultrasound per NICE NG12) · Unexplained postmenopausal bleeding aged 55 or over, not attributable to HRT (consider under 55; NICE NG12) · Suspicious adnexal lesion

GP management

PCOS: person-centred lifestyle support; combined hormonal contraceptive for cycle control and hyperandrogenism where suitable; endometrial-protection review; metformin mainly for metabolic indications in selected patients. Hypothalamic amenorrhoea: restore energy availability, eating-disorder treatment, psychological support; specialist advice if sex-steroid replacement is needed. Perimenopause and menopause: NICE NG23 — clinical diagnosis at 45 or over; HRT counselling and prescribing.

Prolonged anovulation in PCOS exposes the endometrium to unopposed oestrogen, which over years can cause endometrial hyperplasia and, rarely, carcinoma. Discuss endometrial protection with people with prolonged amenorrhoea or very infrequent bleeding: options include a combined hormonal contraceptive, a levonorgestrel IUS or intermittent progestogen (e.g. medroxyprogesterone acetate 10 mg OD for 10–14 days) according to individual circumstances. A withdrawal bleed is not necessary when a suitable continuous progestogen regimen or LNG-IUS already provides protection. Routine ultrasound monitoring of endometrial thickness in asymptomatic PCOS is not recommended, and the 4 mm postmenopausal-bleeding threshold does not apply to premenopausal PCOS. Investigate abnormal, heavy, prolonged or persistent bleeding, and refer for assessment where endometrial pathology is suspected.

Treat

PCOS Management — Metabolic, Reproductive & Menstrual

Done

PCOS — weight and lifestyle (cornerstone)

Person-centred advice: there is no single superior diet or exercise programme for PCOS. Support healthy eating, regular physical activity and prevention of weight gain; where weight loss is the person's goal, modest loss may improve cycles and metabolic features. Avoid weight stigma. Address metabolic health, sleep (consider obstructive sleep apnoea if symptomatic), eating disorders and psychological wellbeing.

PCOS — cycle regulation and endometrial protection

Combined hormonal contraceptive: first-line for menstrual irregularity and hyperandrogenism in those not seeking pregnancy; choose the lowest-risk suitable preparation after assessing VTE risk. Co-cyprindiol (cyproterone acetate 2 mg + ethinylestradiol 35 mcg): not first-line for all PCOS — use only when clinically appropriate after assessing VTE risk (higher than levonorgestrel-containing COCs), reassess benefit, and follow current MHRA advice and product information (stop 3–4 cycles after the acne or hirsutism has resolved); do not prescribe it merely because PCOS is present. Endometrial protection: discuss with people with prolonged amenorrhoea or very infrequent bleeding — a combined hormonal contraceptive, a levonorgestrel IUS or intermittent progestogen (e.g. medroxyprogesterone acetate 10 mg OD for 10–14 days) according to individual circumstances; a withdrawal bleed is not needed when a continuous progestogen regimen or LNG-IUS provides protection. Metformin: not routine for all PCOS — mainly for metabolic indications, and may be considered for cycle or fertility outcomes in selected patients; counsel on gastrointestinal adverse effects, check renal function, consider vitamin B12 deficiency, review at preconception/pregnancy and follow the local formulary.

PCOS — hyperandrogenism (hirsutism)

Cosmetic: laser hair removal (most effective long-term), electrolysis, eflornithine cream 11.5% (Vaniqa — reduces facial hair growth by inhibiting ornithine decarboxylase — apply BD; results in 4-8 weeks; prescription only). Pharmacological: co-cyprindiol — only when appropriate after VTE-risk assessment (see above). Spironolactone 50–100 mg OD (off-label for hirsutism; dosing per local formulary and specialist advice; androgen receptor antagonist; use with reliable contraception — may affect a male fetus; check potassium and renal function per local protocol). Finasteride is off-label and specialist-led in women and contraindicated in pregnancy — refer rather than initiate. Both are off-label for hirsutism in the UK: exclude pregnancy where appropriate, ensure reliable contraception, counsel about adverse effects and monitor according to the medicine and local protocol. Refer if there is virilisation, markedly abnormal androgens or diagnostic uncertainty.

The eflornithine cream (Vaniqa) is a specifically licensed topical treatment for facial hirsutism that is frequently unknown to GPs and patients — it works by irreversibly inhibiting ornithine decarboxylase, an enzyme required for hair follicle cell division and hair growth. It reduces the rate of facial hair growth rather than removing existing hair, so it must be combined with a hair removal method (shaving, waxing, laser) for full effectiveness. Application: thin film to affected facial areas BD, at least 8 hours between applications, wash hands after. Onset of effect: 4-8 weeks. If discontinued, hair growth returns to baseline within 8 weeks. Licensed indication: face and under-chin in women. It is available on NHS prescription. Combination with COCP or spironolactone produces additive antiandrogen + growth-suppression effect for maximum hirsutism control.

Treat

Menopause, POI & Hypothalamic Amenorrhoea Treatment

Done

Perimenopause and menopause — HRT prescribing

Diagnosis (NICE NG23): in otherwise healthy people aged 45 or over, diagnose perimenopause clinically from symptoms and cycle change, and menopause after 12 months without menstruation when not using hormonal contraception — FSH, oestradiol, AMH and ovarian ultrasound are not routinely required. Consider FSH at 40–45 with symptoms and cycle change, or under 40 when POI is suspected. Indications: vasomotor symptoms, genitourinary syndrome of menopause (GSM), sleep disturbance, mood disruption, musculoskeletal symptoms, bone protection (particularly in POI and early surgical menopause). Oestrogen-only HRT is appropriate only after total hysterectomy; anyone with a uterus needs adequate progestogen protection. Route: consider transdermal rather than oral HRT in people at increased VTE risk, including BMI over 30 kg/m²; otherwise the choice is individualised. Progestogen: micronised progesterone or a synthetic progestogen (norethisterone, medroxyprogesterone acetate, LNG-IUS) — it is not proven that micronised progesterone carries a lower breast-cancer risk than all synthetic progestogens; discuss the uncertainty using current BMS/NICE guidance. Sequential HRT is generally used in perimenopause or early postmenopause; continuous combined HRT generally after menopause when amenorrhoea is desired. Unscheduled bleeding needs safety-netting and investigation if persistent or outside expected initiation/change windows. Review 3 months after starting or changing treatment, then at least annually. Duration: continue while benefit outweighs risk — there is no fixed time limit.

POI — HRT requirements

Offer HRT or a combined hormonal contraceptive after diagnosis unless contraindicated, continuing until at least the average age of natural menopause. Younger people often need higher oestrogen doses than standard postmenopausal regimens (e.g. transdermal oestradiol 100 mcg patch or oestradiol gel 2 pumps daily, titrated to symptoms), with adequate progestogen if they have a uterus (e.g. micronised progesterone 200 mg for 12–14 days per month, sequential). Review clinically at 3 months, then at least annually — symptoms, adverse effects, bleeding pattern, adherence, blood pressure and cardiovascular risk, bone health, contraception and fertility wishes; routine FSH/oestradiol measurement is not used to assess HRT adequacy. DXA at diagnosis, with the repeat interval based on the baseline result, adherence and risk (ESHRE 2024). Fertility: spontaneous pregnancy is possible — contraception needed if pregnancy is undesired (HRT is not a contraceptive).

Hypothalamic amenorrhoea — management

Primary treatment: restore adequate energy availability, reduce excessive exercise, treat eating disorders (CAMHS/adult eating-disorder service; BEAT for support) and provide psychological support. Exercise-related (RED-S): sports medicine input and reduced training load. Bone health: assess (e.g. DXA) when amenorrhoea is prolonged, nutritional deficiency is significant or fracture risk is increased; ensure adequate dietary calcium and vitamin D sufficiency. If sex-steroid replacement is required for prolonged hypo-oestrogenism, seek specialist advice — a COCP should not be presented as the preferred bone treatment. Fertility: specialist input (e.g. pulsatile GnRH or gonadotrophin ovulation induction).

Next steps: see PCOS · Menopause and HRT · Hirsutism · Contraception · Infertility

The transdermal oestrogen preference for HRT in women at higher cardiovascular or VTE risk is based on the first-pass hepatic effect — oral oestrogen is absorbed via the portal circulation and undergoes first-pass metabolism in the liver, stimulating hepatic production of clotting factors (particularly factors VII and X) and C-reactive protein, modestly increasing VTE risk (approximately 2-fold increase vs baseline). Transdermal oestrogen (patches or gel) bypasses hepatic first-pass metabolism entirely, delivering oestrogen directly into the systemic circulation. Multiple observational studies (the E3N cohort, the UK General Practice Research Database studies) show that transdermal oestrogen does not increase VTE risk above baseline. This difference is clinically important for: women with a personal history of VTE (on anticoagulation or off), women with factor V Leiden or other thrombophilias, obese women (BMI >30 — already at elevated VTE risk), women with migraines with aura. NICE NG23 advises considering transdermal rather than oral HRT in people at increased VTE risk, including BMI over 30 kg/m²; transdermal oestrogen is not automatically required for every patient, and the choice remains individualised.

Lifestyle

Bone Health, Metabolic Health & Fertility Counselling

Done

Bone health in POI and hypothalamic amenorrhoea Both conditions cause oestrogen deficiency at an age when bone mass is still accruing. POI: DXA at diagnosis; if bone density is normal and adequate hormone therapy is used, a repeat within 5 years may have low value; if low bone density or osteoporosis, reassess about every 1–3 years based on risk (ESHRE 2024). Hormone replacement is the main bone protection in POI. Hypothalamic amenorrhoea: bone-health assessment when amenorrhoea is prolonged, nutritional deficiency is significant or fracture risk is increased; restoring energy availability is the priority and sex-steroid replacement is a specialist decision. Adequate dietary calcium and vitamin D sufficiency; weight-bearing and resistance exercise. Bisphosphonates in POI only with specialist advice when HRT is contraindicated — not as sole bone protection.

PCOS and metabolic health monitoring At diagnosis, assess BMI/weight trajectory, blood pressure, glycaemic status and lipids. Use HbA1c or fasting glucose where appropriate, but consider a 75-g OGTT (the most accurate test), particularly with higher BMI, family history, previous gestational diabetes, high-risk ethnicity, impaired results or pregnancy planning. Repeat testing every 1–3 years according to risk and previous results — routine annual testing for everyone is not required. Consider obstructive sleep apnoea if symptomatic. Person-centred lifestyle support; avoid weight stigma.

PCOS fertility counselling Most people with PCOS can achieve pregnancy. Optimise preconception health, but do not delay fertility treatment solely because of BMI while discussing risks. For anovulatory infertility due to PCOS with no other infertility factors, letrozole is recommended as first-line pharmacological ovulation induction in the 2023 International Evidence-based PCOS Guideline; it is off-label in the UK and should be initiated through an appropriate fertility service or clinician with relevant expertise — not as routine GP prescribing. NICE NG257 (Fertility problems, 2026) no longer contains PCOS ovulation-induction recommendations; a dedicated NICE PCOS guideline is in development. Clomifene, metformin as an adjunct, gonadotrophins and IVF are fertility-service decisions.

Menopause wellbeing and non-hormonal options If HRT is unsuitable or declined, discuss menopause-specific CBT and appropriate non-hormonal drug options. NICE NG23 advises not to routinely offer SSRIs, SNRIs or clonidine as first-line treatment for vasomotor symptoms alone. SSRIs, SNRIs, gabapentin, clonidine and fezolinetant require individual assessment of indication, interactions, adverse effects and local prescribing criteria; paroxetine and fluoxetine interact with tamoxifen. Fezolinetant (neurokinin 3 receptor antagonist; NICE TA1143, March 2026 — an option when HRT is unsuitable): MHRA warns of drug-induced liver injury — check liver function before starting, follow the current SPC/MHRA schedule for repeat monitoring, and stop and investigate if symptoms of liver injury or clinically significant transaminase abnormalities occur. Confirm local formulary status before prescribing.

Sexual health in hormonal disorders Genitourinary syndrome of menopause (GSM): vaginal dryness + dyspareunia + urgency in oestrogen-deficient states (menopause, POI, hypothalamic amenorrhoea). Local vaginal oestrogen (Vagifem, Ovestin) is effective with minimal systemic absorption; it can be continued for as long as needed, routine endometrial-thickness monitoring is not required, and unscheduled bleeding should be reported. With a history of breast cancer, especially on aromatase inhibitors, discuss with the breast-cancer/menopause specialist team. Non-hormonal: lubricants (YES WB), moisturisers (Replens), ospemifene (oral SERM). Low sexual desire disorder: testosterone therapy (testosterone gel off-label at female physiological dose — approximately one-tenth of the male dose — evidence-based for HSDD in postmenopausal women; NICE NG23: consider testosterone for low sexual desire if HRT alone is not effective).

Psychological impact of hormonal disorders PCOS: significantly elevated rates of depression (prevalence approximately 30-35%), anxiety (approximately 40%), body image distress, eating disorder behaviour. Screen with PHQ-9 + GAD-7 at every PCOS review. NHS Talking Therapies referral if scoring. POI: profound psychological impact — grief reaction, loss of fertility (often the most distressing aspect), premature ageing identity, partner and relationship effects. Specialist psychological support through Daisy Network (daisynetwork.org.uk — UK POI support charity). Menopause: anxiety, depression, cognitive symptoms, identity changes — acknowledge explicitly at every menopause consultation.

Contraception in hormonal disorders PCOS: despite irregular cycles, ovulation can occur unpredictably — contraception required if pregnancy not desired. COCP is both contraceptive and therapeutic (regulates cycles, reduces androgens). Progesterone-only pill (POP): less effective against hyperandrogenism but useful if COCP contraindicated. Mirena IUS: endometrial protection + contraception — excellent choice in PCOS. POI: HRT is NOT a contraceptive — approximately 5% spontaneous pregnancy rate despite POI diagnosis. Contraception required if pregnancy undesired. COCP can be used (provides oestrogen + progestogen + contraception).

Preconception care in hormonal disorders Folic acid: start before conception and continue through the first 12 weeks; use 5 mg only where indicated by national criteria, such as previous or family history of neural tube defect, diabetes or certain medicines — BMI alone is not an indication (NICE NG247). In coeliac disease, use 400 micrograms, assess and treat folate deficiency and ensure adherence to a gluten-free diet; 5 mg only where another recognised indication is present. Metformin in pregnancy: an individualised decision following obstetric/diabetes guidance — not routine solely to prevent gestational diabetes. BMI: discuss risks and optimise preconception health, but a BMI target is not an absolute prerequisite. Hypothalamic amenorrhoea: address energy deficit before fertility treatment, with specialist input if fertility is desired. POI: comprehensive fertility counselling via specialist reproductive medicine (e.g. oocyte donation; NHS funding criteria vary).

The testosterone therapy for hypoactive sexual desire disorder (HSDD) in postmenopausal women has finally received authoritative support from NICE NG23 (updated April 2026) — the guideline states that testosterone should be considered for women with HSDD whose other menopause symptoms are adequately controlled by HRT but who have persistent loss of sexual desire causing personal distress. The evidence base: multiple RCTs demonstrate that transdermal testosterone at physiological female doses (approximately one-tenth of the male dose) increases sexual desire, arousal, and satisfaction in postmenopausal women. Prescribing is off-label in women and should follow local specialist or menopause-service arrangements (preparations such as Testogel or AndroFeme 1 per local arrangements). Check baseline testosterone/SHBG where appropriate, keep levels within the female range, review clinical response and androgenic adverse effects (acne, hair growth), and stop if there is no meaningful benefit after an adequate trial. Long-term safety data are limited.

Safety

Follow-Up, Monitoring & Shared Care

Done

PCOS monitoring protocol

At diagnosis: BMI/weight trajectory, blood pressure, glycaemic status and lipids; repeat glycaemic testing every 1–3 years according to risk and previous results (consider a 75-g OGTT if higher risk or planning pregnancy). Symptom review: menstrual pattern, hirsutism, acne, mood. Endometrial-protection review if prolonged amenorrhoea or very infrequent bleeding (CHC, LNG-IUS or intermittent progestogen). Investigate abnormal, heavy, prolonged or persistent bleeding and refer where endometrial pathology is suspected — no routine endometrial-thickness surveillance.

POI monitoring

Clinical review 3 months after starting or changing HRT, then at least annually: symptoms (vasomotor, sexual, urogenital, mood), adverse effects, bleeding pattern, adherence, blood pressure and cardiovascular risk factors, contraception and fertility wishes — routine FSH/oestradiol is not used to assess HRT adequacy. Baseline DXA where available/appropriate; repeat DXA based on the baseline result, adherence and risk (not annually for all). Thyroid function if clinically indicated (autoimmune POI is associated with autoimmune thyroiditis). Aetiology tests (karyotype, FMR1, autoimmune) selectively through specialist pathways — antibodies are not used for longitudinal monitoring.

Menopause HRT monitoring

Review at 3 months after starting or changing treatment, then at least annually: benefit-risk reassessment, symptom control, side effects (breast tenderness, bloating, spotting), blood pressure, BMI. Mammography: continue NHS screening every 3 years. Combined HRT + breast cancer risk: discuss quantified risk (e-risk tool or NICE NG23 guidance) honestly. Duration: no fixed limit — continue if benefits outweigh risks. Stop if: new diagnosis of breast cancer, unexplained vaginal bleeding (investigate first), suspected VTE (stop HRT and arrange same-day assessment; seek specialist advice before any restart — transdermal may then be considered).

999 / Same-day

999: pituitary apoplexy · adrenal crisis · haemodynamic instability, severe hypoglycaemia or acute neurological/visual symptoms. Same-day emergency gynaecology: severe acute pelvic pain with suspected torsion or obstructed outflow

Urgent

Rapid virilisation or markedly raised testosterone/DHEAS → urgent endocrinology/gynaecology · Suspected pituitary tumour or Cushing syndrome → endocrinology · Confirmed or probable POI with complex comorbidity → reproductive medicine/endocrinology · Primary amenorrhoea with abnormal pubertal development · Suspected cancer pathway: unexplained pelvic/abdominal mass or ascites, unexplained postmenopausal bleeding aged 55 or over, not attributable to HRT (consider under 55), suspicious adnexal lesion

Do not routinely

LH:FSH ratio for PCOS · progesterone on day 21 regardless of cycle length · FSH/oestradiol to assess HRT dose · endometrial-thickness surveillance in PCOS · CA-125 as an ovarian-cancer screening test · annual DXA in every patient with POI · IGF-1 in functional hypothalamic amenorrhoea · anti-ovarian-antibody monitoring

Endometrial protection in PCOS should be individualised rather than delivered as a fixed withdrawal-bleed protocol. People with prolonged amenorrhoea or very infrequent bleeding who are not using a combined hormonal contraceptive or LNG-IUS should be offered a discussion of protection: a combined hormonal contraceptive, a levonorgestrel IUS or intermittent progestogen (e.g. medroxyprogesterone acetate 10 mg OD for 10–14 days) according to individual circumstances. A withdrawal bleed is not necessary when a suitable continuous progestogen regimen or LNG-IUS provides protection. If no bleed follows a progestogen course, do a pregnancy test where relevant. Routine endometrial-thickness ultrasound is not recommended in asymptomatic PCOS; investigate abnormal, heavy, prolonged or persistent bleeding and refer where endometrial pathology is suspected (2023 International Evidence-based PCOS Guideline). Coding the PCOS diagnosis and agreed endometrial-protection plan supports recall.