💉 Bleeding with HRT — Assessment & Management

RCGP SCA Algorithm — UK Primary Care

RCGP SCA10-min consult
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Bleeding with HRT — Assessment & ManagementBMS Nov 2024 pathway · risk-stratify (major/minor) · USCP if 1 major / 3 minor · TVS ET ≤4mm ccHRT / ≤7mm sHRT (fully seen) · adjust 6 months · 52mg LNG-IUD
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⚡ Snapshot. The whole pathway on one page: act now, triage, classify, treat today and safety-net. The Steps tab holds the detail.

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1
Safety

Red Flags — Endometrial Cancer, Ovarian Cancer & Cervical Disease

This guide is an educational primary-care aid and does not replace local referral pathways, the current BMS guideline, NICE guidance, product information or specialist advice. The BMS HRT bleeding pathway is partly consensus-based (expert opinion — NICE found insufficient evidence to define exactly when unscheduled bleeding on HRT should trigger a suspected-cancer referral) and should be applied with clinical judgement.

Immediate triage — 999 or same-day emergency assessment
999: haemodynamic instability, or very heavy bleeding with collapse, syncope or cardiovascular compromise. Same-day: symptomatic severe anaemia · acute severe pelvic pain · positive pregnancy test with pain or significant bleeding · fever, pelvic pain, offensive discharge or suspected pelvic sepsis · suspected ovarian torsion or acute abdomen.
Check
Observations · pregnancy test if pregnancy is possible · FBC if heavy/prolonged bleeding or symptoms of anaemia · medication and anticoagulant history.
Unexplained postmenopausal bleeding (not attributable to HRT timing or an identified benign cause) Requires assessment to exclude endometrial, cervical, vaginal and vulval pathology. Do not attribute bleeding to HRT, atrophy or a cervical lesion without appropriate examination and investigation. → Aged 55 and over: suspected cancer pathway referral (NICE NG12 (updated April 2026)); under 55: consider one. Transvaginal USS urgently (endometrial thickness: >4 mm in postmenopausal woman off HRT = significant). Do not reassure without investigation.
Bleeding first occurring >6 months after starting HRT, or >3 months after a change in dose or preparation Requires an urgent TVUS, usually within 6 weeks. Refer via the suspected-cancer pathway when BMS risk thresholds are met (1 major or 3 minor risk factors, irrespective of timing), the endometrium is above the relevant threshold, or clinical concern is high. Biopsy and/or hysteroscopy when indicated by ultrasound, risk profile or persistent bleeding — not automatically for every woman (BMS 2024). Endometrial cancer risk not excluded by HRT use.
Pelvic/abdominal mass or ascites; persistent ovarian-type symptoms Ascites or a pelvic/abdominal mass not obviously due to fibroids warrants suspected-cancer referral without waiting for CA-125 (NICE NG12 (updated April 2026)). Symptoms: persistent abdominal distension/bloating, early satiety or loss of appetite, pelvic or abdominal pain, urinary urgency or frequency, new IBS-type symptoms (particularly age ≥50). Age-specific CA-125 thresholds (aged 40+ with persistent or frequent symptoms) guide urgent abdominal/pelvic ultrasound — 35 IU/mL (40–49), 31 (50–59), 24 (60–69), 25 (70–79), 31 (80 and over); they are not diagnostic and a CA-125 below threshold does not exclude ovarian cancer.
Post-coital bleeding or irregular vaginal bleeding on HRT Cervical pathology — carcinoma, CIN, ectropion. → Speculum examination. Suspicious cervix → urgent suspected-cancer referral; do not delay for cervical cytology. Normal cervix but persistent or unexplained post-coital bleeding → local symptomatic gynaecology/cervical pathway (colposcopy may be arranged by the specialist service). Do not use a screening smear as a diagnostic test or reason to delay referral.
Bleeding on HRT with pelvic pain, fever or offensive discharge — especially after recent IUS insertion or uterine instrumentation Pelvic inflammatory disease / endometritis / intrauterine device complication. → Same-day gynaecology (999 if septic or haemodynamically unstable). Endocervical swabs + high vaginal swabs. IV antibiotics if unwell.
Perimenopausal bleeding or pelvic pain where pregnancy is possible HRT is not contraception — perform a pregnancy test. Positive test with significant pain, bleeding, syncope, shoulder-tip pain, haemodynamic instability or peritoneal signs → same-day emergency assessment via local early-pregnancy/ectopic pathway; call 999 if clinically unstable.
Breakthrough bleeding on continuous combined HRT (ccHRT) in the first 6 months (or within 3 months of a change) is common — this is the 'endometrial settling' period during which the combined oestrogen-progestogen suppresses the endometrium from its pre-HRT proliferative state. However, any bleeding beyond 6 months on ccHRT, or heavy/worsening bleeding at any time, is not normal and requires investigation. The critical principle: endometrial cancer can develop in women on HRT, and HRT use does not protect against endometrial cancer (combined HRT reduces but does not eliminate risk; oestrogen-only HRT significantly increases endometrial cancer risk — oestrogen-only HRT should never be prescribed to women with a uterus without concurrent progestogen). A GP who attributes prolonged or recurrent bleeding on ccHRT to 'the HRT' without arranging assessment per the BMS pathway (urgent TVUS, with endometrial assessment where indicated) risks missing endometrial cancer.
2
Diagnose

Understanding Normal and Abnormal Bleeding on HRT

Normal bleeding patterns on HRT
Sequential HRT: predictable withdrawal bleeding, usually at the end of the progestogen phase and generally lasting up to 7 days. Continuous combined HRT: spotting or irregular bleeding is common during the first 6 months, or within 3 months of changing treatment. Tibolone: irregular bleeding can occur early, but the patient should be postmenopausal before starting.
Abnormal bleeding on HRT — investigation required
Bleeding on continuous combined HRT after the expected settling period · bleeding in addition to or outside the expected sequential withdrawal bleed · prolonged bleeding >7 days · heavy bleeding, flooding or clots · persistent bleeding most days for 4 weeks or more · recurrent bleeding after a period of amenorrhoea · bleeding after stopping HRT that does not settle · any bleeding in a person taking tamoxifen · any unexplained postmenopausal bleeding not attributable to HRT timing · post-coital bleeding.
BMS endometrial risk factors — major
BMI ≥40 kg/m² · Lynch or Cowden syndrome · oestrogen-only systemic HRT >6 months in a person with a uterus · three-monthly/tricycling HRT >12 months · sequential HRT >5 years when started at age ≥45 · inadequate sequential progestogen exposure for ≥12 months (norethisterone or MPA <10 days/month, or micronised progesterone <12 days/month).
BMS endometrial risk factors — minor
BMI 30–39 kg/m² · oestrogen-only HRT 3–6 months with a uterus · tricycling HRT 6–12 months · inadequate sequential progestogen exposure 6–12 months · progestogen dose not proportionate to oestrogen dose >12 months · expired 52 mg LNG-IUS used for endometrial protection · PCOS/anovulatory cycles · diabetes.
BMS escalation
One major or three minor factors → suspected-cancer pathway referral (irrespective of timing). Two minor factors → urgent TVUS. Heavy, prolonged or persistent bleeding → urgent TVUS regardless of duration of HRT use. These are BMS recommendations, not NICE-derived diagnostic thresholds.
Confirming postmenopausal status before starting HRT
Natural menopause: last menstrual period >12 months ago (in women over 45). Under 40: premature ovarian insufficiency. 40-45: early menopause. FSH: not needed over 45 with typical symptoms; consider at 40–45 with symptoms and a change in cycle; under 40, suspected POI needs two raised FSH results 4–6 weeks apart (not interpretable on combined hormonal contraception or high-dose progestogen — NICE NG23). Note: FSH unreliable in perimenopause (fluctuates). Clinical diagnosis of menopause is acceptable in women over 45 with typical symptoms.
The distinction between sequential and continuous combined HRT is fundamental to interpreting bleeding patterns — sequential HRT is designed to produce a regular monthly withdrawal bleed (mimicking the menstrual cycle) by giving oestrogen continuously and progestogen cyclically for 12-14 days per month. The bleed occurs during or after the progestogen phase as the progestogen-primed endometrium sheds. This is expected and does not require investigation unless it is heavy, irregular, or occurs at unexpected times. Continuous combined HRT suppresses the endometrium completely — the woman should become amenorrhoeic within 3-6 months. The rationale for using ccHRT: women who are clearly postmenopausal (confirmed >12 months since last period) do not need or want a regular bleed. Using sequential HRT in a clearly postmenopausal woman unnecessarily maintains a monthly bleed. Standard practice is: sequential HRT for women who are perimenopausal (still having some periods) or recently postmenopausal (within 12 months of LMP); continuous combined HRT for women who are clearly postmenopausal (>12 months since LMP).
3
Diagnose

Assessment — History, Examination & Investigations

History
Age and whether peri- or postmenopausal · date of last spontaneous menstrual period · hysterectomy, subtotal hysterectomy, endometrial ablation or bilateral oophorectomy · adherence and missed doses · timing of bleeding in relation to the progestogen phase · duration, frequency, heaviness, clots, flooding or bleeding most days · pain, discharge or fever · tamoxifen or aromatase-inhibitor use · previous hyperplasia, polyp or endometrial cancer · Lynch/Cowden syndrome or relevant family history. Current HRT: type (sequential or continuous combined), formulation (oral, transdermal patch, gel, vaginal), oestrogen type and dose, progestogen type and dose, duration of use, date of any recent change. Bleeding pattern: timing relative to HRT phase, volume, duration, post-coital. Last cervical screening test + result. Menopausal symptoms (control level). Previous endometrial pathology (hyperplasia, polyp). PMH: diabetes (endometrial cancer risk factor), obesity (endometrial cancer risk), tamoxifen use (endometrial cancer risk), Lynch syndrome, PCOS (anovulatory cycles + endometrial hyperplasia). Last pregnancy. Contraception (perimenopausal women — HRT is not contraception).
Examination
BMI (obesity: endometrial cancer risk factor). BP (hypertension association). Abdominal examination (mass, ascites). Vulval inspection. Speculum examination where appropriate: cervix (ectropion, polyp, suspicious lesion, discharge), vaginal walls (atrophy — pale, dry mucosa on low-dose oestrogen). Bimanual examination: uterine size + tenderness + adnexal mass. Cervical screening only if due and clinically appropriate — never delay urgent referral for suspected cancer.
Investigations
Transvaginal USS (TVUSS) — endometrial thickness (ET) with unscheduled bleeding: ccHRT ≤4 mm / sHRT ≤7 mm reassuring only if fully visualised and uniform; >4 mm ccHRT / >7 mm sHRT, or incomplete view → urgent endometrial assessment; assess for polyps, fibroids, uterine abnormality. Endometrial assessment — indicated according to HRT regimen, ET, completeness of visualisation, bleeding pattern and risk factors. Hysteroscopy preferable to blind pipelle when a polyp, focal lesion, distorted cavity or inadequate pipelle is suspected. Full blood count (anaemia from chronic blood loss). Cervical screening if overdue. CA-125 if aged 40+ with persistent or frequent ovarian-cancer symptoms (age-specific thresholds guide urgent ultrasound; below threshold does not exclude cancer).
Urgent TVUS (usually within 6 weeks)
First bleeding >6 months after starting HRT · bleeding begins >3 months after a change in dose/preparation · heavy, prolonged or persistent bleeding · two minor BMS risk factors · pattern changes after previously regular withdrawal bleeds · bleeding after a period of amenorrhoea on ccHRT.
Ultrasound interpretation (unscheduled bleeding)
ccHRT ≤4 mm or sHRT ≤7 mm, fully seen and uniform → low risk; optimise HRT and review. Above the relevant threshold, or incomplete visualisation (even if the visible portion is below threshold) → urgent endometrial assessment. Focal lesion or polyp → gynaecology/hysteroscopy pathway. Persistent or recurrent bleeding despite normal TVUS → gynaecological assessment, often hysteroscopy and biopsy.
Endometrial sampling (pipelle) is used when indicated by TVUS findings, risk profile or persistent bleeding — it is a 3-5 minute outpatient procedure performed in community gynaecology or GP specialist clinics using a thin flexible plastic cannula (3mm diameter) inserted through the cervical os into the uterine cavity, which then samples the endometrium by aspiration. Sensitivity is lower for focal lesions — hysteroscopy + directed biopsy is more sensitive for focal pathology. A blind pipelle is not automatically the best first investigation for a focal lesion or recurrent bleeding — hysteroscopy is preferable when a polyp, focal lesion, distorted cavity or inadequate sample is suspected. A normal or insufficient pipelle does not reliably exclude a focal lesion; persistent or recurrent bleeding after a normal biopsy should prompt gynaecological review, usually with hysteroscopy. GPs with a special interest in gynaecology can be trained to perform pipelle biopsy in the practice (CoSRH or RCOG-accredited training). For GPs without this skill, referral to community gynaecology or colposcopy clinic is appropriate. The NHS suspected cancer pathway for abnormal bleeding should be used where endometrial cancer cannot be excluded on clinical and USS grounds.
4
Diagnose

HRT Formulations & Endometrial Risk

Oestrogen-only HRT (EO-HRT)
For women WITHOUT a uterus (post-hysterectomy) only. Associated with significantly increased endometrial cancer risk if given to women with a uterus. Never prescribe oestrogen-only HRT to a woman with an intact uterus (except for atrophic vaginitis — topical vaginal oestrogen only, which has minimal systemic absorption at low doses and does not require progestogen protection).
Progestogen protection adequacy
Sequential HRT: progestogen must be given for at least 10 days per cycle (norethisterone or medroxyprogesterone) or 12 days (micronised progesterone) to provide adequate endometrial protection (BMS 2024). Continuous combined HRT: progestogen given daily — provides continuous endometrial protection. 52 mg LNG-IUS: can provide the progestogen component of HRT for up to 5 years (CoSRH/BMS-supported practice). Mirena is licensed for endometrial protection with oestrogen replacement for 4 years; use beyond this is outside the product licence. Change the device at 5 years when used for HRT endometrial protection, irrespective of age at insertion. Different 52 mg LNG-IUS brands have different licensed indications and durations — prescribe by brand (MHRA). Contraceptive duration differs from duration for endometrial protection.
Progestogen-intolerant patients
Progestogen side effects (bloating, mood change, breast tenderness): the leading cause of HRT discontinuation. Management: try alternative progestogens (micronised progesterone — Utrogestan — may be better tolerated by some, and observational studies suggest a potentially lower breast-cancer risk than some synthetic progestogens, but comparative breast-cancer safety is not established — NICE considers the evidence insufficient; norethisterone; medroxyprogesterone acetate; levonorgestrel). Utrogestan 200 mg at night (12-14 days/month for sequential; 100 mg daily for ccHRT) — best tolerated option. LNG-IUS: localised progestogen effect, minimal systemic side effects.
Tibolone
Synthetic steroid with weak oestrogenic, progestogenic, and androgenic activity. Amenorrhoea in majority. Used for: postmenopausal women who have not had a bleed for at least 12 months, particularly those with libido concerns (androgenic component). Do not use in perimenopause simply to avoid sequential bleeding. Unexpected bleeding requires assessment. Increased stroke risk in older women, particularly over about 60. Contraindicated in current or past breast cancer (product information) — MHRA advises careful assessment of stroke, breast and endometrial risks. Breast cancer: the LIFT trial (NEJM 2008, older women with osteoporosis) found fewer invasive breast cancers, but LIBERATE (Lancet Oncol 2009) found more recurrences in women with previous breast cancer, and the Million Women Study found an increased risk — so tibolone is not a breast-safe alternative.
Micronised progesterone (Utrogestan) has an increasingly important role in HRT prescribing — multiple observational studies and the E3N cohort study suggest that Utrogestan (oral micronised progesterone, a bioidentical hormone identical to endogenous progesterone) may have a potentially lower breast cancer risk than some synthetic progestogens (medroxyprogesterone acetate, norethisterone, levonorgestrel) when used as the progestogen component of HRT. This evidence is observational (E3N cohort) rather than from randomised trials, and NICE NG23 considers the evidence insufficient to establish whether breast-cancer risk differs — comparative safety is not established. Utrogestan may be better tolerated by some individuals. The practical implication: for women with progestogen intolerance, switching to Utrogestan is a reasonable option, with balanced discussion of the uncertain breast-cancer evidence. Utrogestan is taken orally (100 mg daily for ccHRT; 200 mg daily for 12-14 days/month for sequential HRT) and should be taken at night (its sedative side effect is then beneficial).
5
Refer

Referral Pathways

Persistent, recurrent or unexplained bleeding on HRT (local route)
For persistent, recurrent or unexplained bleeding on HRT, assess for postmenopausal bleeding and follow the local gynaecology pathway. Refer on the suspected cancer pathway where NG12 criteria are met (aged 55 and over with unexplained postmenopausal bleeding); otherwise use the local urgent gynaecology/ultrasound pathway. Do not delay referral if bleeding is heavy, recurrent or clinically concerning.
Suspected-cancer pathway
One major or three minor BMS endometrial risk factors · endometrium above the relevant threshold (>4 mm ccHRT / >7 mm sHRT) in a woman with unscheduled bleeding · unexplained postmenopausal bleeding aged ≥55 (consider under 55 — NG12) · suspicious cervix · pelvic/abdominal mass or ascites not obviously due to fibroids · ultrasound suggesting ovarian malignancy · any vaginal bleeding on tamoxifen
Gynaecology (urgent, within 2 weeks)
Abnormal bleeding on HRT + TVUSS showing polyp or focal lesion → hysteroscopy + directed biopsy · Heavy breakthrough bleeding on sequential HRT despite dose optimisation · Post-coital bleeding persisting or unexplained with a normal cervix → local symptomatic gynaecology/cervical pathway (colposcopy may be arranged by the specialist service)
Community gynaecology / menopause clinic
Abnormal bleeding on HRT — endometrial biopsy (pipelle) in community setting. HRT formulation review + dose optimisation. Progestogen intolerance — switch to Utrogestan. Perimenopause + contraception + HRT needs.
Colposcopy
Cervical screening result showing HPV-positive with abnormal cytology (dyskaryosis). A cervix suspicious of cancer on speculum examination → suspected-cancer pathway, not routine colposcopy; do not delay referral for cytology.
GP management (first line)
Early bleeding (within 6 months of starting or 3 months of a change, no major and no more than one minor BMS risk factor, and not heavy, prolonged or persistent): optimise HRT and review at 3 months — do not reassure indefinitely. If bleeding continues after 6 months in total of adjustments, discuss an urgent TVS (within 6 weeks) versus weaning off HRT with non-hormonal alternatives (BMS 2024). If a suspected-cancer pathway referral is recommended but investigation is declined, recommend weaning off HRT, offer non-hormonal alternatives and review at 4 weeks — refer via the suspected-cancer pathway if bleeding continues after stopping. Irregular breakthrough on sequential HRT in first 3 months: may need dose adjustment. Atrophic vaginitis: topical oestrogen (Vagifem 10 mcg pessary or Ovestin cream) — does not require additional progestogen for endometrial protection. New unexplained bleeding while using vaginal oestrogen still requires assessment.
The suspected cancer pathway referral for endometrial cancer is defined in NICE NG12 (updated April 2026) — the endometrial criterion is postmenopausal bleeding in women aged 55 and over that is not attributable to HRT (suspected cancer pathway; consider it under 55). Unscheduled bleeding in women taking HRT is therefore not an NG12 criterion in itself: it is assessed using the BMS/RCOG/BGCS/BSGE/CoSRH/RCGP joint guideline on unscheduled bleeding on HRT (November 2024), which sets out when a woman on HRT needs ultrasound or urgent gynaecology assessment rather than expectant management. The practical definition of 'expected pattern' is: regular withdrawal bleed on sequential HRT during/after the progestogen phase; amenorrhoea after 6 months on ccHRT. Any deviation from this expected pattern warrants assessment per the BMS pathway. Much of the BMS risk-stratification is expert opinion, and NICE found insufficient evidence to determine exactly when unscheduled bleeding on HRT should trigger a suspected-cancer referral — apply with clinical judgement and use the confirmed local referral route.
6
Treat

Managing Breakthrough Bleeding — HRT Adjustments

Early breakthrough bleeding on ccHRT (<6 months)
Within 6 months of starting HRT or 3 months of a dose/preparation change, with no major and no more than one minor BMS risk factor, and not heavy, prolonged or persistent: (1) check adherence and correct administration; (2) check progestogen dose and duration are adequate; (3) consider reducing oestrogen dose if clinically appropriate; (4) consider an alternative progestogen or regimen; (5) consider a 52 mg LNG-IUS if suitable; (6) treat vaginal atrophy if present; (7) review at 3 months and safety-net clearly. Do not reassure indefinitely — urgent TVUS if bleeding becomes heavy, prolonged or persistent.
Persistent breakthrough bleeding on ccHRT (>6 months)
Requires urgent TVUS (usually within 6 weeks); endometrial assessment if above threshold, incomplete view, high risk or persistent bleeding. If no pathology found: adjust HRT; persistent or recurrent bleeding after normal assessment → gynaecological review, usually hysteroscopy. Options: (1) increase progestogen dose (e.g., switch to Utrogestan 200 mg OD from 100 mg OD); (2) switch progestogen type; (3) consider LNG-IUS (Mirena) for endometrial protection + local progestogen; (4) switch to sequential HRT (planned monthly bleed); (5) add norethisterone 5 mg OD for 7-10 days to induce a withdrawal bleed and reset the endometrium.
Irregular bleeding on sequential HRT
If additional to the expected withdrawal bleed: urgent TVUS (reassuring only if ≤7 mm, fully seen and uniform); endometrial assessment if above threshold or incomplete view. If withdrawal bleed is heavy: progestogen dose optimisation (at least 10 days/month of norethisterone or MPA, or 12 days/month of micronised progesterone — BMS 2024). Switching to Utrogestan 200 mg for 14 days/month if tolerability issues. If unacceptable bleeding pattern persists after dose optimisation: consider Mirena LNG-IUS + systemic oestrogen-only.
Atrophic vaginitis causing vaginal bleeding
Low-dose topical vaginal oestrogen: Vagifem (estradiol 10 mcg vaginal tablet) daily x 2 weeks then twice weekly; Ovestin (estriol 0.1% cream) nightly x 2 weeks then twice weekly; Imvaggis (estriol 0.03 mg pessary); Intrarosa (prasterone pessary). Systemic absorption is minimal at these doses — does not require systemic progestogen. Can be used in addition to systemic HRT. Low-dose vaginal oestrogen can be offered to most people with genitourinary menopause symptoms, including those using systemic HRT. History of breast cancer (NICE NG23): non-hormonal moisturisers or lubricants first line; if symptoms persist, vaginal oestrogen may be considered with shared decision-making; involve the breast-cancer team for people receiving an aromatase inhibitor. Explain that systemic absorption is minimal but the effect on recurrence remains uncertain, particularly in oestrogen-receptor-positive disease. Any new unexplained bleeding while using vaginal oestrogen still requires assessment — do not use it to explain away postmenopausal bleeding. NICE NG101 (2018, updated April 2025) advises not routinely offering systemic HRT after breast cancer.
The Mirena LNG-IUS for endometrial protection with systemic oestrogen is an evidence-based and increasingly used combination — the levonorgestrel IUS provides highly effective local endometrial progestogen suppression with minimal systemic absorption. The Mirena LNG-IUS is licensed (SPC) as an option for endometrial protection in women using any route of systemic oestrogen (oral, transdermal, gel, implant). The clinical advantages: (1) progestogen is delivered locally to the uterus — systemic progestogen side effects (mood, bloating, breast tenderness) are largely avoided; (2) the IUS gives endometrial protection — Mirena is licensed for 4 years; CoSRH/BMS-supported practice extends use to 5 years (outside licence), with the device changed at 5 years irrespective of age at insertion — eliminates daily medication compliance issues; (3) it also provides highly effective contraception (important for perimenopausal women who may still have ovarian activity); (4) it treats heavy menstrual bleeding concurrently; and (5) Mirena is licensed for HRT endometrial protection — brands differ in licensed indications and durations, so prescribe by brand (MHRA). GPs who fit coils should consider the Mirena LNG-IUS as a highly appropriate option for perimenopausal women wanting HRT who struggle with oral progestogen.
7
Treat

Endometrial Pathology Found on Investigation

Endometrial polyp
Common cause of breakthrough bleeding on HRT and abnormal uterine bleeding. Detected on TVUSS (intracavitary hyperechoic lesion — may appear with fluid around it on saline-instilled sonography). Treatment: hysteroscopic polypectomy — removes the lesion + provides histological diagnosis. Benign polyps: no specific HRT change required after removal; optimise progestogen adequacy. Risk of malignancy in postmenopausal polyps is higher with postmenopausal bleeding, large polyp or endometrial-cancer risk factors.
Endometrial hyperplasia
Hyperplasia without atypia: gynaecology-led management — a 52 mg LNG-IUS is generally the preferred medical treatment where appropriate; systemic progestogen if an IUS is unsuitable; repeat biopsy and treatment duration per specialist guidance. Atypical hyperplasia/EIN: urgent specialist management, usually hysterectomy if appropriate; fertility-sparing or conservative treatment only under specialist supervision. Do not increase Utrogestan or insert an LNG-IUS as standalone GP treatment for a histological diagnosis without specialist input.
Endometrial cancer diagnosed
Stage IA well-differentiated (type I — endometrioid): hysterectomy + bilateral salpingo-oophorectomy. Radiotherapy for high-risk features. Prognosis: 5-year survival >90% for stage I. Stage III-IV: multimodal treatment (surgery + radiotherapy + chemotherapy). GP role post-treatment: follow-up is led by the gynae-oncology team (often patient-initiated follow-up — BGCS uterine cancer guidelines, 2021); after total hysterectomy she has no cervix, so she is ceased from the NHS Cervical Screening Programme and routine vault cytology is not needed unless the specialist team directs it (e.g. CIN in the hysterectomy specimen); new vaginal bleeding or discharge needs prompt specialist review, DEXA (if oophorectomy + no HRT permissible), menopausal symptom management (vaginal oestrogen usually safe after early endometrial cancer — discuss with oncologist).
Cervical pathology on screening/colposcopy
CIN (cervical intraepithelial neoplasia): colposcopy + large loop excision of transformation zone (LLETZ). Post-LLETZ: test of cure (HPV test) about 6 months after treatment — HPV-negative → recall in 3 years; HPV-positive → back to colposcopy (NHS Cervical Screening Programme: programme and colposcopy management). Cervical cancer: gynaecological oncology referral. HRT does not cause or exacerbate CIN or cervical cancer — HPV is the cause. HRT can continue during and after CIN treatment.

Next steps: see Menopause and HRT · Breast cancer

Atypical endometrial hyperplasia/EIN is the highest-risk premalignant endometrial lesion and may coexist with endometrial cancer. The RCOG/BSGE Green-top Guideline No. 67 (2016) recommends total hysterectomy as the definitive treatment for most women with atypical hyperplasia who do not wish to preserve fertility. Fertility-sparing or conservative treatment (usually LNG-IUS with biopsy surveillance) is specialist-supervised only. All HRT should be stopped or significantly revised (minimum required progestogen at absolute minimum dose) in women with atypical hyperplasia. After hysterectomy for atypical hyperplasia (with bilateral oophorectomy): oestrogen-only HRT can be started immediately — there is no contraindication (the uterus is removed, progestogen is no longer needed).
8
Lifestyle

Bone Protection, Cardiovascular Health & Menopausal Wellbeing on HRT

Bone protection during HRT HRT prevents bone loss while it is taken, but is not universally indicated solely for osteoporosis prevention. Assess fracture risk using an accepted tool (FRAX or QFracture) and follow NOGG/local osteoporosis guidance. Consider HRT for bone protection in appropriate symptomatic individuals, particularly under 60, after discussing alternatives and contraindications. Calcium and vitamin D advice should be individualised according to dietary intake, deficiency risk and local guidance. DEXA is not routine at menopause or solely because HRT is stopped. Exercise: weight-bearing + resistance training. Smoking cessation + alcohol moderation.
Breast cancer risk communication Combined HRT (oestrogen + progestogen): a small increase in breast cancer risk that rises with duration of use (MHRA Drug Safety Update, August 2019; the NICE NG23 (2024) visual summaries give absolute figures — use them). Oestrogen-only HRT (for women post-hysterectomy): a smaller increase than combined HRT (MHRA 2019); WHI found no increase at about 7 years. Micronised progesterone (Utrogestan): observational studies suggest a potentially lower breast-cancer risk than some synthetic progestogens, but comparative safety is not established (NICE: evidence insufficient). GPs should communicate risk in absolute rather than relative terms. Use the NICE NG23 (2024) visual summaries of HRT risks and benefits.
Cardiovascular risk and HRT timing In people who start HRT before age 60 or within 10 years of menopause, the overall benefit–risk balance is generally more favourable; HRT should not be started solely for primary prevention of cardiovascular disease (NICE NG23). Oral oestrogen increases VTE risk; standard-dose transdermal oestrogen does not appear to increase VTE risk above baseline. Established coronary heart disease or stroke: specialist menopause expertise. For women with cardiovascular risk factors or personal VTE history: transdermal HRT is preferred (NICE NG23).
Weight management and HRT HRT does not cause weight gain — the weight gain of the menopause transition is attributable to age, reduced physical activity, and metabolic change, not HRT. HRT may improve body composition (reduces central adiposity + preserves lean muscle mass). Obesity (BMI >30): increases endometrial cancer risk, VTE risk, and metabolic syndrome. GLP-1 agonists (semaglutide) for obesity + menopause + metabolic syndrome: growing evidence base.
Sexual health and vaginal health on HRT Genitourinary syndrome of menopause (GSM — atrophic vaginitis, dyspareunia, urgency, recurrent UTIs): very common, significantly affects quality of life. Systemic HRT improves GSM partially. Local vaginal oestrogen (Vagifem, Ovestin, Imvaggis) is highly effective for GSM and can be added to systemic HRT. GSM is not cosmetic — it is a significant quality-of-life condition that responds well to treatment. Ospemifene (SERM — oral) licensed for dyspareunia from GSM as alternative to local oestrogen.
Sleep and cognitive effects of HRT HRT may improve sleep disturbed by night sweats; evidence for a specific benefit of particular regimens is limited. Effects on dementia risk are uncertain (observational data only; WHIMS showed adverse cognitive effects for HRT started after 65) — HRT should not be offered to reduce dementia risk.
Exercise prescription during menopause and HRT 150 min/week aerobic exercise (reduces vasomotor symptoms, improves mood, protects bone, reduces CVD risk). Resistance training 2x/week (maintains muscle mass lost at menopause — particularly important after 50). Pelvic floor exercises (reduces urinary symptoms of GSM). Exercise is not a substitute for HRT in symptomatic women but significantly augments treatment outcomes.
Duration of HRT — shared decision-making No mandatory maximum duration for HRT. NICE NG23: HRT should be continued as long as the woman wishes and the benefits outweigh the risks. Annual review: reassess symptoms, dose requirements, risk:benefit (new diagnoses, family history changes). Stopping HRT: offer a choice of gradual reduction or immediate cessation (NICE NG23). Gradual reduction may reduce short-term symptom recurrence, but there is no important long-term difference.
The cardiovascular timing hypothesis is one of the most important advances in understanding menopausal HRT in the last decade — the Women's Health Initiative (WHI) trial (2002) initially raised concerns about cardiovascular risk from HRT, but subsequent reanalysis showed that the adverse cardiovascular outcomes in WHI occurred predominantly in women who started HRT more than 10 years after menopause (average age 63 in WHI vs the typical HRT-starting age of 50-52). When HRT is started before age 60 or within 10 years of menopause, the overall benefit–risk balance is generally more favourable. NICE NG23 supports starting HRT in symptomatic perimenopausal and early postmenopausal women without contraindications, but HRT should not be started solely for primary prevention of cardiovascular disease; oral oestrogen increases VTE risk, whereas standard-dose transdermal oestrogen does not appear to. The proven benefits are symptom relief and prevention of bone loss while it is taken.
9
Safety

Follow-Up, Annual Review & Safety-Netting

Annual HRT review
Indication still present? Symptoms: controlled at current dose or dose adjustment needed? Bleeding pattern: expected for HRT type? Any new contraindications (breast cancer, unexplained bleeding, VTE, active liver disease)? Adverse effects. BP and relevant cardiovascular risk. Weight, BMI and lifestyle. Contraception where relevant. Cervical and breast screening status per the NHS screening programmes (not annual screening; breast screening 50-71 years, 3-yearly). Fracture risk assessment if concern. Discuss duration, risks, benefits. Signed review documented.
Switching from sequential to continuous combined HRT
Switch when woman is clearly postmenopausal (>12 months from LMP); if sequential HRT was started after 45, consider switching after 5 years or by age 54, whichever comes first (BMS). When switching: warn the patient that breakthrough bleeding may occur again in the first 3-6 months (endometrial re-settling). If bleeding first occurs >3 months after the switch, or becomes heavy, prolonged or persistent: urgent TVUS (BMS 2024).
Stopping HRT — monitoring
Expect return of menopausal symptoms on stopping. Bone loss resumes after stopping. Review at 3 months after stopping: symptom assessment, BP, consider restarting; assess fracture risk (FRAX/QFracture, NOGG) — no routine DEXA solely because HRT is stopped. No uterine surveillance required after stopping HRT unless abnormal bleeding develops.
Women on tamoxifen
Tamoxifen is a selective oestrogen receptor modulator — it stimulates the endometrium (agonist at uterine ER) and INCREASES endometrial cancer risk. Any vaginal bleeding in a woman on tamoxifen → suspected-cancer pathway referral (hysteroscopy and biopsy are often needed; TVUSS is less reliable on tamoxifen). Cannot use standard HRT alongside tamoxifen. Vaginal oestrogen: controversial — discuss with oncologist. Non-hormonal menopause symptom management: venlafaxine, clonidine, CBT.
Same-day / 999
999: haemodynamic instability, or very heavy bleeding with collapse, syncope or cardiovascular compromise. Same-day: symptomatic severe anaemia · acute severe pelvic pain · positive pregnancy test with pain or significant bleeding (999 if unstable) · fever, pelvic pain, offensive discharge or suspected pelvic sepsis · suspected ovarian torsion or acute abdomen. Pelvic mass or ascites → suspected-cancer referral (NG12); same-day if unwell.
Suspected-cancer pathway
Unexplained postmenopausal bleeding aged 55+ (consider under 55) · 1 major or 3 minor BMS risk factors · ET above threshold (>4 mm ccHRT / >7 mm sHRT) or incomplete view with unscheduled bleeding · suspicious cervix · mass/ascites or USS suggesting ovarian malignancy · any vaginal bleeding on tamoxifen · atypical endometrial hyperplasia confirmed (urgent specialist)
The HRT review (at 3 months, then at least annually) is recommended by NICE NG23 and is a medicolegal expectation — GPs who prescribe HRT without annual review (particularly combined HRT) are exposed to medicolegal risk if a woman later develops breast cancer or endometrial cancer and the review would have identified the need for dose adjustment or investigation. The annual review should be documented explicitly in the clinical record with: indication (symptoms still present), formulation and dose, bleeding pattern (expected or investigated), BP, new contraindications checked, cervical screening status, breast screening status, benefits and risks discussed, patient's informed decision to continue. A brief consultation note stating 'HRT review — continue' without documenting the above does not meet the standard. Many GP practices use a structured HRT review template in their clinical system — this is best practice. The Menopause Specialist Society (BMS — British Menopause Society) provides GP HRT review templates and the e-learning HRT prescribing course which is recommended for all GPs prescribing HRT.
Educational use only. Does not replace local referral pathways, the current BMS guideline, NICE guidance, product information or specialist advice. References: (1) BMS/BGCS/BSGE/CoSRH/RCOG/GIRFT/RCGP — Management of unscheduled bleeding on HRT (2024; current online update); (2) NICE NG23 Menopause: identification and management (updated 2024); (3) NICE NG12 Suspected cancer: recognition and referral (updated endometrial and ovarian recommendations); (4) MHRA Drug Safety Update — HRT: further information on the known increased risk of breast cancer; (5) MHRA Drug Safety Update — Tibolone: benefit–risk balance; (6) CoSRH Contraception for women aged over 40 years (current amended version); (7) MHRA Drug Safety Update — Levonorgestrel-releasing intrauterine systems: prescribe by brand name; RCOG/BSGE Green-top 67 (endometrial hyperplasia, 2016); NOGG. Drug dosing, contraindications and adverse effects: current individual SPCs and the your local formulary / APC website. Review at least annually, and sooner when the BMS pathway, NICE NG12/NG23 or the local referral pathway changes.