Intermenstrual And Irregular Bleeding
Intermenstrual and irregular bleeding refers to uterine bleeding that occurs between expected menstrual periods or deviates from the normal cyclical pattern in timing, frequency, or duration, potentially indicating hormonal imbalance, structural lesions, or systemic pathology.
Intermenstrual and Irregular Bleeding
Intermenstrual bleeding (IMB): bleeding that occurs between well-defined cyclical regular menses [1]. This is distinct from heavy menstrual bleeding (HMB), which occurs during the expected menses. The key here is that the patient's periods are recognisably regular, but she bleeds in between them.
Irregular bleeding: bleeding associated with a disturbance in normal menses [1]. Here the cycle itself is disrupted — the patient cannot identify a clear pattern. This may be due to anovulation, early pregnancy complications, or use of hormonal drugs [1].
Why does this distinction matter? Because they have different differential diagnoses [2]. IMB (bleeding between otherwise regular cycles) is commonly associated with surface lesions of the genital tract [1] — something is physically there (polyp, ectropion, carcinoma) that bleeds when irritated. Irregular bleeding, on the other hand, points more towards systemic/hormonal causes (anovulation, exogenous hormones, pregnancy) where the endometrium itself is unstable.
Let's break the terminology down:
- Inter- (Latin: "between") + menstrual (Latin menstrualis, from mensis = month) = bleeding between monthly periods
- Irregular = lacking the predictable cyclical pattern
Important Distinction
Always clarify with the patient: "Are your periods themselves regular, and you bleed in between?" (→ IMB, think structural/surface lesions) vs "Are your periods themselves irregular/unpredictable?" (→ irregular bleeding, think hormonal/anovulatory/pregnancy). This single question narrows your differential dramatically.
2. Epidemiology and Risk Factors
- IMB is extremely common — up to 10–15% of gynaecology referrals relate to abnormal uterine bleeding (AUB), of which IMB forms a significant proportion.
- Irregular/anovulatory bleeding is most common at the extremes of reproductive age [1] — adolescence (immature HPO axis) and perimenopause (declining ovarian reserve).
- PCOS occurs in ~5–10% of reproductive-aged women and is the most common endocrinopathy in reproductive-age women, accounting for ~75% of all anovulatory disorders causing infertility and ~90% of women with oligomenorrhoea [3].
- Cervical cancer (a cause of IMB) is a significant concern in Hong Kong. The age-standardised incidence rate is approximately 5–7 per 100,000 women. The Hong Kong Cervical Screening Programme recommends screening from age 25 for sexually active women.
- Endometrial cancer incidence in Hong Kong has been rising, now the most common gynaecological malignancy, linked to obesity and metabolic syndrome.
| Category | Risk Factors |
|---|---|
| Endometrial carcinoma | PCOS, tamoxifen use, unopposed oestrogen therapy, obesity [1], nulliparity, late menopause, diabetes mellitus, Lynch syndrome |
| Endometrial hyperplasia | Chronic anovulation (any cause), unopposed oestrogen, obesity |
| Cervical carcinoma | HPV infection (types 16, 18), early coitarche, multiple sexual partners, smoking, immunosuppression (HIV), non-attendance at screening |
| Endometrial/cervical polyps | Age > 40, obesity, hypertension, tamoxifen |
| Ectopic pregnancy | Previous ectopic, PID, tubal surgery, IVF, IUCD in situ, smoking |
| PCOS | Obesity, insulin resistance, T1/T2/GDM, history of premature adrenarche, 1st-degree family history of PCOS, use of AEDs especially valproic acid [3] |
| PID | Multiple sexual partners, young age, lack of barrier contraception, IUCD insertion |
| Breakthrough bleeding (hormonal) | Combined or progestogen-only contraceptives, poor compliance, drug interactions (e.g. enzyme-inducing drugs) |
3. Anatomy and Function (Relevant Review)
The uterus is a hollow muscular organ composed of three layers:
- Perimetrium (serosa) — outermost
- Myometrium — thick smooth muscle layer; relevant for fibroids (leiomyomas) and adenomyosis
- Endometrium — the inner mucosal lining, further divided into:
- Functionalis (superficial 2/3): the layer that proliferates, secretes, and sheds during menstruation. This is the dynamic, hormone-responsive layer.
- Basalis (deep 1/3): the regenerative layer that remains after menstruation and regenerates the functionalis. It is supplied by straight arteries (not hormone-responsive).
The functionalis is supplied by spiral arteries, which are exquisitely sensitive to progesterone. When progesterone is withdrawn (at the end of the luteal phase), these spiral arteries undergo rhythmic vasoconstriction → ischaemia → necrosis → shedding = menstruation.
Why does this matter for IMB/irregular bleeding?
- If there is no ovulation, there is no corpus luteum, therefore no progesterone. The endometrium is exposed to unopposed oestrogen only → it proliferates but never undergoes secretory transformation → it becomes thick, fragile, and vascular → it outgrows its blood supply → random, unpredictable shedding = irregular bleeding (anovulatory or "breakthrough" bleeding).
- If a structural lesion (polyp, fibroid, carcinoma) distorts the endometrial surface, it can erode, ulcerate, or have abnormal vasculature → bleeding between otherwise normal cycles = IMB.
The cervix has two types of epithelium:
- Ectocervix: stratified squamous epithelium (tough, multi-layered)
- Endocervix: columnar epithelium (single-layered, fragile, mucus-secreting)
- Squamocolumnar junction (SCJ): where these two meet; this is the transformation zone — the site where metaplasia occurs and where cervical carcinoma and CIN arise.
Ectropion (previously called "erosion") occurs when the columnar epithelium extends onto the ectocervix — it appears red and bleeds easily on contact. This is common with oestrogen exposure (pregnancy, COC use). It is benign but causes contact/post-coital bleeding and must be distinguished from cervical carcinoma.
Understanding the normal menstrual cycle is essential:
Key points:
- Follicular phase (Day 1–14): FSH drives follicular growth → rising oestrogen → endometrial proliferation
- Ovulation (Day 14): LH surge
- Luteal phase (Day 14–28): Corpus luteum produces progesterone → endometrial secretory transformation → stable, compact endometrium
- Menstruation: Corpus luteum regresses → progesterone withdrawal → spiral artery vasoconstriction → endometrial shedding
Physiological mid-cycle bleeding may be related to rapid decrease in oestrogen after LH surge with low progesterone level shortly after ovulation [1]. This is a brief, self-limited spotting around Day 14 — the endometrium momentarily loses oestrogen support before progesterone takes over.
Relevant for ectopic pregnancy — the most common site is the ampulla (70%), followed by isthmus (12%), fimbria (11%), and cornua (2%). The narrow lumen means a growing gestational sac quickly outgrows its blood supply or erodes into tubal vasculature → bleeding (both vaginal and intra-abdominal).
4. Aetiology and Pathophysiology
The FIGO PALM-COEIN classification system is the standard framework for abnormal uterine bleeding. It divides causes into Structural (PALM: Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia) and Non-structural (COEIN: Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified).
For IMB and irregular bleeding specifically, the key aetiologies from the lecture slides [1] are:
4.1 Structural Causes
Endometrial polyps, fibroid polyps, hyperplasia, and carcinoma [1]
Endometrial Polyps
- Localised overgrowths of endometrial glands and stroma projecting into the uterine cavity
- Usually pedunculated (on a stalk), ranging from a few mm to several cm
- Contain thick-walled blood vessels that are abnormal and fragile
- Why do they cause IMB? The polyp surface is exposed and prone to erosion and microtrauma. Its abnormal vasculature lacks the normal spiral artery architecture and does not respond normally to progesterone withdrawal → irregular, unpredictable bleeding independent of the menstrual cycle
- Risk factors: age > 40, obesity, hypertension, tamoxifen use
- Malignant transformation risk: ~1–3% (higher with advancing age, postmenopausal status)
Fibroid Polyps (Submucosal Leiomyomas)
- Fibroids (leiomyomas) are benign smooth muscle tumours of the myometrium
- Usually due to submucosal (or intramural) leiomyomas [2] — these are the ones that distort the endometrial cavity
- Submucosal fibroids can become pedunculated and protrude into the cavity like a polyp ("fibroid polyp")
- Why do they cause bleeding? They increase the endometrial surface area, distort the vasculature overlying the fibroid (vessels are stretched and compressed), and may cause venous ectasia and ulceration of the overlying endometrium. They also interfere with local haemostatic mechanisms (reduced endothelin, increased prostaglandins/tPA)
- May be associated with pressure symptoms [2] (urinary frequency from bladder compression, constipation from rectal compression, ureteric obstruction)
Endometrial Hyperplasia
- Abnormal proliferation of endometrial glands with an increased gland-to-stroma ratio
- Caused by prolonged unopposed oestrogen exposure (no progesterone to oppose proliferation)
- Classified (WHO 2014/2020) into:
- Hyperplasia without atypia: low malignant potential (~1–3%)
- Atypical hyperplasia (endometrial intraepithelial neoplasia, EIN): significant malignant potential (~30–40% progression to carcinoma)
- Why does unopposed oestrogen cause this? Oestrogen drives endometrial proliferation (mitosis). Progesterone normally counteracts this by inducing secretory differentiation and apoptosis. Without progesterone (anovulation, PCOS, exogenous oestrogen-only HRT), the endometrium just keeps proliferating → hyperplasia → atypia → carcinoma (the "hyperplasia-carcinoma sequence")
Endometrial Carcinoma
- Most common gynaecological malignancy in Hong Kong (rising incidence due to obesity epidemic)
- Predominantly Type 1 (endometrioid adenocarcinoma, ~80%) — oestrogen-driven, arises from hyperplasia
- Type 2 (serous, clear cell) — not oestrogen-driven, arises from atrophic endometrium, more aggressive, older patients
- Risk factors for endometrial carcinoma: PCOS, tamoxifen, unopposed oestrogen therapy, obesity [1]
- Why does obesity increase risk? Adipose tissue contains aromatase, which converts adrenal androgens (androstenedione) to oestrone (E1) via peripheral aromatisation → chronic unopposed oestrogen exposure
- Why does tamoxifen increase risk? Tamoxifen is a selective oestrogen receptor modulator (SERM) — it is an oestrogen antagonist in breast tissue (used for breast cancer) but an oestrogen agonist in the endometrium → stimulates endometrial proliferation
High Yield
The endometrial hyperplasia → carcinoma sequence is driven by unopposed oestrogen. Any condition causing anovulation (PCOS, obesity, perimenopause) removes progesterone's protective effect on the endometrium. This is why PCOS patients with oligomenorrhoea need cyclical progestogen to protect the endometrium — even if they don't want contraception.
PID: associated with pelvic pain, fever, vaginal discharge [1]
- Ascending infection from the lower genital tract (cervix) to the upper genital tract (endometrium → salpinges → peritoneum)
- Causative organisms: Chlamydia trachomatis (most common), Neisseria gonorrhoeae, anaerobes, Mycoplasma genitalium
- Why does PID cause IMB/irregular bleeding? Endometritis (infection of the endometrium) disrupts the normal endometrial architecture and vasculature → friable, inflamed endometrium that bleeds irregularly. The inflammatory mediators (prostaglandins, cytokines) also interfere with normal haemostasis and endometrial stability
- Can present acutely (pain, fever, discharge) or chronically (low-grade bleeding, dyspareunia)
- Complications: tubo-ovarian abscess, infertility, ectopic pregnancy, Fitz-Hugh-Curtis syndrome (perihepatitis)
Early pregnancy complications [1]:
Ectopic pregnancy: associated with pain, classically occurs 7–8 weeks from LMP [1]
- "Ecto-" (Greek: "outside") + "topos" (Greek: "place") = pregnancy outside the normal place (uterine cavity)
- Most commonly in the fallopian tube (95%)
- Why bleeding at 7–8 weeks? The gestational sac grows in the narrow tube → erodes into tubal vasculature. The trophoblast also produces hCG which initially supports the corpus luteum → but as the ectopic fails, hCG falls → corpus luteum regresses → progesterone drops → decidualised endometrium in the uterus sheds → vaginal bleeding. The pain is from tubal distension/rupture.
- Why does it classically present at 7–8 weeks? Because this is when the embryo has grown large enough to cause tubal distension. Earlier than 6 weeks, it may be asymptomatic.
Miscarriages: threatened, inevitable, complete, incomplete [1]
| Type | Os | Bleeding | Products | Uterine Size |
|---|---|---|---|---|
| Threatened | Closed | Usually mild | None passed | = dates |
| Inevitable | Open | Heavy | None yet passed | = dates |
| Incomplete | Open | Heavy, ongoing | Some passed | < dates |
| Complete | Closed (closing) | Settling | All passed | < dates |
| Missed | Closed | Minimal/none | Retained, non-viable | < dates |
- Why does miscarriage cause bleeding? When the pregnancy fails, the gestational tissue separates from the decidualised endometrium → the spiral arteries that supplied the implantation site are exposed → bleeding. If products remain (incomplete), the uterus cannot contract fully → the bleeding continues (the uterus needs to contract to compress the vessels, like after a full-term delivery).
Others: molar pregnancy, physiological/implantation bleeding [1]
- Molar pregnancy (hydatidiform mole): abnormal trophoblastic proliferation with hydropic degeneration of chorionic villi. Complete mole (46,XX, all paternal) or partial mole (69,XXX/XXY, triploid). Causes vaginal bleeding, markedly elevated hCG, "snowstorm" appearance on USS. Risk of gestational trophoblastic neoplasia (GTN).
- Implantation bleeding: occurs ~6–12 days after ovulation when the blastocyst implants into the endometrium. The trophoblast erodes into endometrial capillaries → light spotting. Brief, self-limited, often mistaken for a light period.
Cervical polyps, ectropion, carcinoma (classically post-coital) [1]
Cervical Polyps
- Benign proliferations of endocervical columnar epithelium, usually pedunculated
- Protrude through the external os → exposed to mechanical trauma (intercourse, speculum)
- Why post-coital bleeding? Direct contact causes surface trauma to the fragile columnar epithelium → bleeding
Cervical Ectropion
- Eversion of columnar epithelium onto the ectocervix
- Common in: pregnancy, COC use, adolescence (all high-oestrogen states — oestrogen causes the SCJ to move outward)
- Columnar epithelium is single-layered and fragile (unlike the tough stratified squamous epithelium of the ectocervix) → bleeds easily with contact
- Benign but must always be distinguished from cervical carcinoma on speculum examination
Cervical Carcinoma
- Classically post-coital [1] — the tumour is friable and vascular; intercourse causes mechanical disruption → bleeding
- HPV-related (types 16, 18 account for ~70%)
- Squamous cell carcinoma (most common, ~70%) or adenocarcinoma (~25%)
- In Hong Kong, cervical screening (Pap smear/liquid-based cytology ± HPV co-testing) is recommended every 3 years for women aged 25–64 who have ever been sexually active (after 2 consecutive normal annual smears)
Red Flag
Any postmenopausal bleeding (PMB) must be assumed to be endometrial carcinoma until proven otherwise. Similarly, persistent IMB or post-coital bleeding (PCB) in a sexually active woman warrants cervical examination and biopsy to exclude cervical carcinoma. Never dismiss these symptoms as "hormonal" without adequate investigation.
Vaginitis and STDs: look for associating vaginal symptoms [1]
- Cervicitis/vaginitis from Chlamydia, Gonorrhoea, Trichomonas, bacterial vaginosis, or candidiasis can cause intermenstrual spotting
- Why bleeding? Inflamed, friable cervical/vaginal mucosa bleeds on contact or spontaneously
- Associated symptoms: abnormal vaginal discharge (colour, odour), pruritus, dysuria, dyspareunia
- In Hong Kong, chlamydia and gonorrhoea testing is standard for any young woman presenting with IMB
4.2 Non-Structural Causes
Ovulatory dysfunction (AUB-O) [1]:
Signs and symptoms: prolonged oligomenorrhoea followed by heavy bleeding or spotting [1]
Causes: extremes of reproductive age, PCOS, intense exercise, eating disorder, severe stress, hyper- or hypothyroidism [1]
Why does anovulation cause irregular bleeding?
In a normal cycle, ovulation is the pivotal event. After ovulation, the corpus luteum produces progesterone, which:
- Converts the proliferative endometrium to a secretory endometrium (compact, stable)
- Stabilises the spiral arteries
- When withdrawn (at the end of the luteal phase), triggers organised, predictable shedding = menstruation
Without ovulation, there is no corpus luteum → no progesterone. The endometrium is exposed to unopposed oestrogen only:
- Oestrogen continues to drive proliferation → the endometrium becomes thick, fragile, and disorganised
- Without progesterone-mediated spiral artery stabilisation, the vasculature is unstable
- The endometrium eventually outgrows its blood supply → random focal necrosis → unpredictable, irregular shedding
- This shedding is often incomplete → some areas bleed while others continue to proliferate → prolonged oligomenorrhoea followed by heavy bleeding or spotting [1]
PCOS as the paradigm of anovulatory bleeding:
PCOS pathogenesis [3]:
- Altered FSH and LH action: increased serum LH, increased ovarian expression of LH receptors [3]
- Increased LH-to-FSH ratio → hypersecretion of androgens in theca cells in ovarian follicles [3], leading to:
- Decreased FSH action: due to insufficient FSH stimulation, local inhibition of FSH action → impaired follicular development [3]
- Insulin resistance: compensatory hyperinsulinaemia → increased androgen secretion by stimulating theca cell secretion of androgens AND inhibiting hepatic sex hormone binding globulin (SHBG) production [3] → more free androgens
Impaired folliculogenesis results in appearance of multiple small follicles that fail to develop into dominant follicles → anovulation [3]
Prolonged oligo-/anovulation → oligo-/amenorrhoea with prolonged unopposed oestrogen [3]
PCOS ovulatory dysfunction: [3]
- Usually presents with normal or slightly delayed menarche with normal cycles → followed by irregular cycles [3]
- Oligomenorrhoea developed after 30 years is unlikely to be PCOS-related [3]
- Some may have intermittent breakthrough bleeding and HMB instead [3]
- Excess risk of endometrial hyperplasia/carcinoma: due to chronic unopposed oestrogen exposure [3]
Other causes of anovulation:
- Extremes of reproductive age: In adolescence, the HPO axis is immature → GnRH pulsatility is not yet established → inconsistent LH surges → anovulation. In perimenopause, the declining follicular pool leads to erratic folliculogenesis → intermittent ovulation/anovulation.
- Hypothalamic amenorrhoea (intense exercise, eating disorders, severe stress): Energy deficit/stress → increased CRH and cortisol → suppression of GnRH pulsatility → anovulation. Also decreased leptin (from low body fat) → reduced GnRH drive.
- Thyroid disorders: Hypothyroidism → increased TRH → increased prolactin → inhibits GnRH pulsatility. Also decreased SHBG (hypothyroidism) → altered oestrogen/androgen dynamics. Hyperthyroidism → increased SHBG → altered oestrogen metabolism.
Unscheduled/breakthrough bleeding in combined or progestogen-type contraceptives [1]
- Combined oral contraceptives (COCs): Breakthrough bleeding is common in the first 3 months of use. The exogenous oestrogen/progestogen suppresses the HPO axis and maintains a thin, atrophic endometrium. If the endometrium becomes too thin, it becomes fragile → random spotting.
- Progestogen-only methods (POP, implant, Depo-Provera, LNG-IUS): Progestogen-only methods cause endometrial atrophy and decidualisation with abnormal vascular patterns → unpredictable bleeding. The endometrium is thin but fragile, with abnormal superficial vessels that bleed irregularly.
- Why does poor compliance cause bleeding? Missing pills → temporary drop in exogenous hormone levels → partial endometrial shedding → spotting. This is essentially a mini-withdrawal bleed.
- Drug interactions: Enzyme-inducing drugs (rifampicin, carbamazepine, phenytoin, some antiretrovirals) accelerate hepatic metabolism of steroid hormones → lower circulating hormone levels → breakthrough bleeding.
Physiological mid-cycle bleeding: possibly related to rapid decrease in oestrogen after LH surge with low progesterone level shortly after ovulation [1]
- Occurs around Day 14 of a 28-day cycle
- Brief (1–2 days), light spotting
- Why? Just before ovulation, oestrogen peaks. After the LH surge triggers ovulation, the pre-ovulatory follicle transforms into the corpus luteum. During this transition, there is a transient dip in oestrogen (the follicle has ruptured and is reorganising) before progesterone rises. This brief oestrogen withdrawal can cause a small amount of endometrial shedding.
- Self-limited, benign — diagnosis of exclusion
Coagulopathy [1]
- Bleeding disorders can present as menorrhagia and/or IMB
- Von Willebrand disease is the most common inherited bleeding disorder (prevalence ~1% of population) and should be considered especially if HMB since menarche [2]
- Other: platelet disorders, clotting factor deficiencies, anticoagulant therapy (warfarin, DOACs, heparin)
- Why does coagulopathy cause abnormal bleeding? Normal endometrial haemostasis during menstruation relies on platelet plugs, fibrin clot formation, and vasoconstriction. If any of these are impaired, bleeding is excessive or prolonged. Coagulopathy can also unmask bleeding from otherwise trivial endometrial or cervical lesions.
5. Classification
The PALM-COEIN system (FIGO 2011, updated 2018) classifies causes of AUB in non-pregnant reproductive-age women:
| Category | Structural (PALM) | Non-Structural (COEIN) |
|---|---|---|
| P | Polyp | C – Coagulopathy |
| A | Adenomyosis | O – Ovulatory dysfunction |
| L | Leiomyoma | E – Endometrial (local haemostatic factors) |
| M | Malignancy & hyperplasia | I – Iatrogenic |
| N – Not yet classified |
PALM-COEIN Mnemonic
PALM = things you can see/image (structural) → Polyp, Adenomyosis, Leiomyoma, Malignancy. COEIN = things you can't see (non-structural) → Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not classified. A patient can have more than one cause — the system allows multiple categories to be ticked.
From the lecture slides [1], a practical clinical classification:
Structural causes:
- Endometrial: polyps, fibroid polyps, hyperplasia, carcinoma
- Cervical: polyps, ectropion, carcinoma
- Infection: PID, vaginitis/STDs
- Pregnancy-related: ectopic, miscarriage, molar, implantation
Non-structural causes:
- Ovulatory dysfunction (AUB-O)
- Iatrogenic (hormonal contraceptives, breakthrough bleeding)
- Physiological mid-cycle bleeding
- Coagulopathy
6. Clinical Features
6.1 History Taking
The history is the most important tool. The lecture slides [1] outline a structured approach:
Documentation of menstrual irregularity [1]:
-
Amount, pattern, duration [1]
- Quantify the bleeding: How many pads/tampons per day? How soaked? Clots (size)? Flooding?
- Pattern: Is it spotting? Is it as heavy as a period? Continuous or intermittent?
- Duration: How many days does it last? Is it getting worse?
-
Timing: intermenstrual bleeding, post-coital bleeding [1]
- IMB: "Do you bleed between your periods?" → Think surface lesions (polyps, ectropion, carcinoma), endometrial pathology
- Post-coital bleeding (PCB): "Do you bleed after sex?" → Think cervical pathology (ectropion, polyp, carcinoma), cervicitis/STD, vaginal pathology
- Post-menopausal bleeding (PMB): "Have you gone through menopause and now have bleeding?" → Think endometrial carcinoma (until proven otherwise)
-
Previous menstrual history: LMP + 2 previous periods [1]
- LMP: essential to exclude pregnancy, date the cycle
- 2 previous periods: establishes the patient's baseline — were cycles previously regular? What has changed?
- Menarche age, previous cycle regularity, any prior episodes of abnormal bleeding
Anaemic symptoms: headache, palpitation, SOB, dizziness, fatigue, pica [1]
- These indicate significant chronic blood loss
- Pica (craving non-food substances like ice, starch) is a specific feature of iron deficiency anaemia — the mechanism is unclear but may relate to altered dopamine signalling from iron deficiency in the CNS
Medication use: hormonal and herbal medicine, drug compliance [1]
- COCs, POPs, implants, Depo-Provera, LNG-IUS — any hormonal method can cause breakthrough bleeding
- Compliance: missed pills are a very common cause of breakthrough bleeding
- Herbal medicines: some (e.g. dong quai, ginseng) have phytoestrogenic properties
- Anticoagulants (warfarin, DOACs): can unmask or worsen bleeding
Risk factors for endometrial carcinoma: e.g. PCOS, tamoxifen, unopposed oestrogen therapy, obesity [1]
- Must be actively screened for in any woman with abnormal bleeding, especially > 40 years or with risk factors
Sexual and contraceptive history [1]
- Current contraception method (type, compliance)
- Risk of pregnancy (last intercourse, contraceptive use/failure)
- Risk of STDs (number of partners, barrier use, previous STDs)
- Cervical screening history (last Pap smear and result)
- Pain:
- Pelvic pain + fever + discharge → PID
- Unilateral pain + bleeding at 7–8 weeks → ectopic pregnancy
- Cramping pain + bleeding → miscarriage
- Dysmenorrhoea + HMB → adenomyosis / endometriosis
- Vaginal discharge: character (colour, odour, consistency) → infection
- Pressure symptoms: urinary frequency, constipation → large fibroid
- Systemic symptoms: weight changes, heat/cold intolerance → thyroid disease
- Bleeding from other sites: gums, nosebleeds, easy bruising, family history → coagulopathy
- Psychosocial impact: effect on daily life, work, relationships, sexual function
Structured History Framework
A useful mnemonic for AUB history: "PALM-COEIN + PQRST"
- P: Pattern (regular vs irregular)
- Q: Quantity (pads, clots, flooding)
- R: Related symptoms (pain, discharge, systemic)
- S: Sexual/contraceptive history
- T: Timing (IMB, PCB, PMB) + Timeline (onset, progression, LMP)
| Symptom | Pathophysiological Basis | Think... |
|---|---|---|
| Bleeding between regular periods (IMB) | Surface lesion eroding/exposing abnormal vessels; endometrial polyp with fragile vessels | Polyp, ectropion, cervical carcinoma, endometrial pathology |
| Post-coital bleeding | Mechanical trauma to fragile cervical/vaginal lesion → bleeding | Cervical ectropion, polyp, carcinoma, cervicitis |
| Irregular, unpredictable bleeding | Anovulation → unopposed oestrogen → unstable, thick endometrium → random shedding | PCOS, perimenopause, hypothalamic amenorrhoea |
| Prolonged oligomenorrhoea followed by heavy bleeding | Anovulation → prolonged proliferative phase → endometrium outgrows blood supply → massive irregular shedding | AUB-O (anovulatory dysfunction) [1] |
| Mid-cycle spotting (Day 14) | Transient oestrogen dip after LH surge before progesterone rises | Physiological — diagnosis of exclusion |
| Bleeding on hormonal contraception | Atrophic endometrium too thin/fragile, or missed pills → partial withdrawal bleed | Breakthrough bleeding — reassure if < 3 months, check compliance |
| Bleeding + pelvic pain + fever | Ascending infection → endometritis → inflamed, friable endometrium | PID |
| Bleeding + unilateral pain (7–8 weeks) | Ectopic trophoblast eroding tubal vessels; hCG fall → endometrial shedding | Ectopic pregnancy |
| Bleeding + cramping + open os | Failed pregnancy → placental separation → exposed spiral arteries | Miscarriage (inevitable/incomplete) |
| Bleeding + abnormal discharge | Cervicitis/vaginitis → inflamed, friable mucosa | STD, vaginal infection |
| Heavy periods since menarche | Inherited deficiency in clotting factors/platelets → impaired endometrial haemostasis | Von Willebrand disease, other coagulopathy |
Physical examination should include general examination, abdominal examination, and pelvic examination (speculum + bimanual).
| Sign | Finding | Pathophysiological Basis |
|---|---|---|
| General | Pallor (conjunctival, palmar crease) | Chronic blood loss → iron deficiency anaemia |
| Tachycardia | Compensatory response to anaemia (increased cardiac output to maintain O₂ delivery) | |
| Hirsutism, acne, acanthosis nigricans | Hyperandrogenism + insulin resistance → PCOS | |
| BMI > 30 (obesity) | Peripheral aromatisation of androgens → oestrone → unopposed oestrogen → endometrial pathology | |
| Thyroid signs (goitre, tremor, bradycardia) | Thyroid dysfunction → anovulation | |
| Bruising, petechiae | Coagulopathy → impaired haemostasis | |
| Abdominal | Pelvic mass (suprapubic) | Large uterine fibroid extending above pubic symphysis |
| Tenderness (lower abdominal) | PID (bilateral), ectopic (unilateral), miscarriage | |
| Peritonism (guarding, rebound) | Ruptured ectopic → haemoperitoneum | |
| Speculum | Cervical polyp (smooth, red, pedunculated) | Proliferation of endocervical epithelium → protrudes through os |
| Cervical ectropion (red, granular area around os) | Columnar epithelium everted onto ectocervix (oestrogen effect) | |
| Cervical mass (friable, irregular, bleeds on touch) | Cervical carcinoma → neovascularisation, tumour friability | |
| Products of conception at os | Incomplete/inevitable miscarriage → partially expelled tissue | |
| Abnormal vaginal discharge | Infection → inflammatory exudate | |
| Atrophic vagina | Postmenopausal oestrogen deficiency → thin, dry epithelium | |
| Bimanual | Bulky, irregularly enlarged uterus | Fibroids (multiple, different sizes) |
| Bulky, uniformly enlarged, tender uterus | Adenomyosis (diffuse myometrial thickening) | |
| Enlarged, soft uterus (larger than expected for dates) | Molar pregnancy (excessive trophoblastic proliferation → uterine distension) | |
| Cervical excitation tenderness (chandelier sign) | PID → inflammation of adnexa → pain on cervical motion | |
| Adnexal mass/tenderness | Ectopic pregnancy (tubal mass), tubo-ovarian abscess, ovarian pathology | |
| Small, anteverted, mobile, non-tender uterus | Normal finding — suggests non-structural cause (AUB-O, iatrogenic) |
The first question is always: Is she pregnant? A urine pregnancy test (urine hCG) must be performed in any reproductive-age woman with abnormal vaginal bleeding. This is non-negotiable — missing an ectopic pregnancy can be fatal.
The second question: Is this IMB (bleeding between regular periods) or irregular bleeding (the cycle itself is disrupted)? This guides your differential.
High Yield Summary
Key Concepts:
-
IMB = bleeding between well-defined regular menses → think surface/structural lesions (cervical polyp, ectropion, carcinoma, endometrial polyp/hyperplasia/carcinoma). Irregular bleeding = disturbance of the cycle itself → think anovulation, hormonal causes, pregnancy.
-
Always exclude pregnancy first (urine β-hCG) in any reproductive-age woman with abnormal bleeding. Ectopic pregnancy is life-threatening.
-
Anovulatory bleeding (AUB-O) occurs because no ovulation → no corpus luteum → no progesterone → unopposed oestrogen → thick, unstable endometrium → irregular, unpredictable shedding. Presents as prolonged oligomenorrhoea followed by heavy bleeding or spotting.
-
PCOS is the most common cause of anovulatory bleeding. Pathogenesis involves increased LH:FSH ratio → theca cell androgen excess → impaired folliculogenesis; insulin resistance → hyperinsulinaemia → more androgens, less SHBG.
-
Unopposed oestrogen drives the endometrial hyperplasia → carcinoma sequence. Risk factors: PCOS, tamoxifen, unopposed oestrogen HRT, obesity.
-
Post-coital bleeding should prompt examination to exclude cervical carcinoma (and ectropion/polyps). Postmenopausal bleeding = endometrial carcinoma until proven otherwise.
-
Breakthrough bleeding on hormonal contraceptives is common in the first 3 months and with poor compliance. Always check compliance before investigating further.
-
History framework: Amount/pattern/duration, timing (IMB/PCB), LMP + 2 previous periods, anaemic symptoms, medications, risk factors for endometrial CA, sexual/contraceptive history.
Active Recall - Intermenstrual and Irregular Bleeding
Differential Diagnosis of Intermenstrual and Irregular Bleeding
The differential diagnosis is best approached by first answering three critical triage questions, then systematically working through structural and non-structural causes. The lecture slides [1][4] provide a clear framework that we will elaborate on.
Before diving into the differential, you must answer these questions at the bedside:
- Is she pregnant? → Urine β-hCG. This is non-negotiable. A ruptured ectopic pregnancy kills.
- Is the bleeding from the genital tract? → Any urinary/bowel symptoms? Only seen upon wiping/when going to toilet? [4] — Rule out haematuria (UTI, renal calculus) and rectal bleeding (haemorrhoids, colorectal pathology) misidentified as vaginal bleeding.
- What is the pattern of bleeding? → This is the key discriminator:
Approach to Source of Bleeding
Volume: heavy bleeding usually from uterus; staining, spotting, light bleeding may be from any genital tract site [4].
Colour: brown implies old blood from light bleeding/spotting from anywhere from upper vagina to uterus; red can be from any genital tract source [4].
Course: consistently post-coital → usually cervical pathology; intermenstrual → usually due to surface lesions of genital tract [4].
Comprehensive Differential Diagnosis Table
The following table organises differentials by the lecture framework [1][4], expanded with clinical distinguishing features.
| Cause | Key Distinguishing Features | Pathophysiological Basis |
|---|---|---|
| Endometrial polyp [1] | IMB, often light spotting; may cause HMB if large. Post-reproductive age, tamoxifen use | Pedunculated overgrowth of endometrial glands/stroma with abnormal, fragile thick-walled vessels → bleeds independently of cycle |
| Fibroid polyp (submucosal leiomyoma) [1] | IMB or HMB; irregular bleeding in submucosal fibroids if associated with overlying endometritis, surface of fibroid becomes necrotic or ulcerated [5]; profuse bleeding if fibroid polyp protrudes through cervix [5]; may have pressure symptoms | Increased endometrial surface area over fibroid → increased bleeding; submucosal position distorts overlying vasculature; pedunculated fibroid polyp exposed to trauma |
| Endometrial hyperplasia [1] | Irregular bleeding, often prolonged/heavy episodes interspersed with amenorrhoea. Risk factors: PCOS, tamoxifen, unopposed oestrogen Tx, obesity [1] | Unopposed oestrogen → continuous endometrial proliferation → increased gland:stroma ratio → thick, fragile endometrium → irregular shedding |
| Endometrial carcinoma [1] | Post-menopausal bleeding (PMB) is the classic presentation; in pre-menopausal women → persistent IMB/irregular bleeding unresponsive to medical therapy. Constitutional symptoms late. | Malignant glandular proliferation → neovascularisation with abnormal, friable vessels → bleeds spontaneously; tumour necrosis → bleeding |
| PID [1] | Associated with pelvic pain, fever, vaginal discharge [1]. IMB or irregular bleeding; sexually active, young woman | Ascending infection → endometritis → inflamed endometrium with disrupted vasculature and increased prostaglandin/cytokine release → friable surface bleeds irregularly |
| Ectopic pregnancy [1] | Associated with pain, classically occurs 7–8 weeks from LMP [1]. Positive β-hCG. Unilateral adnexal tenderness ± mass. Can present with haemodynamic collapse if ruptured. | Trophoblast implanted in tube erodes into tubal vasculature → tubal bleeding (± intraperitoneal). Failing ectopic → declining hCG → corpus luteum regression → progesterone withdrawal → decidualised endometrial shedding → vaginal bleeding |
| Miscarriage [1] | Threatened, inevitable, complete, incomplete [1]. Positive β-hCG, uterine-pattern cramping, products may be seen/passed | Placental separation from decidualised endometrium → exposed spiral arteries → bleeding. Incomplete evacuation → uterus cannot contract → ongoing bleeding |
| Molar pregnancy [1] | Markedly elevated β-hCG (disproportionate to dates), "snowstorm" USS, uterus large for dates, possible hyperemesis, thyrotoxicosis features | Abnormal trophoblastic proliferation → massively elevated hCG → excessive uterine distension; hydropic villi have no functioning fetal vasculature → degeneration → bleeding |
| Cervical polyp [1] | PCB, IMB spotting; visible on speculum exam — smooth, red, pedunculated mass at os | Endocervical columnar epithelium proliferates → protrudes through os → single-layered fragile epithelium exposed to mechanical trauma |
| Cervical ectropion [1] | PCB; red, granular area around os on speculum. Common with COC use, pregnancy. | Oestrogen drives SCJ outward → columnar epithelium (single-layered, fragile) exposed on ectocervix → bleeds easily with contact |
| Cervical carcinoma [1] | Classically post-coital [1]; may cause IMB, foul-smelling discharge. Irregular, friable mass on speculum. Advanced: pelvic pain, haematuria, leg oedema | Malignant squamous/glandular cells form friable, vascular tumour → contact or spontaneous bleeding. HPV-driven oncogenesis (E6 degrades p53, E7 inactivates Rb) |
| Vaginitis and STDs [1] | Look for associating vaginal symptoms [1]: discharge (colour, odour), pruritus, dysuria, dyspareunia. IMB or PCB. | Cervicitis/vaginitis → inflamed mucosa with vasodilation, increased capillary permeability → friable surface bleeds on contact |
| Atrophic vaginitis [4] | Atrophic vaginitis in older women [4]. PMB, vaginal dryness, dyspareunia | Post-menopausal oestrogen deficiency → vaginal epithelium thins (loss of glycogen, lactobacilli) → fragile, easily traumatised → contact bleeding |
| Vaginal lacerations [4] | Lacerations in younger, sexually active women [4]. Acute onset, history of trauma/intercourse | Physical disruption of vaginal mucosa → torn vessels |
| Vulval lesions [4] | Vulval skin tags, sebaceous cysts, condylomata [4]. Localised to vulva, visible on inspection | Surface lesion irritation/trauma → bleeding |
| Cause | Key Distinguishing Features | Pathophysiological Basis |
|---|---|---|
| Ovulatory dysfunction (AUB-O) [1] | Prolonged oligomenorrhoea followed by heavy bleeding or spotting [1]. Causes: extremes of reproductive age, PCOS, intense exercise, eating disorder, severe stress, hyper- or hypothyroidism [1] | No ovulation → no corpus luteum → no progesterone → unopposed oestrogen → unstable proliferative endometrium → random, unpredictable shedding |
| Breakthrough bleeding (iatrogenic) [1] | Unscheduled/breakthrough bleeding in combined or progestogen-type contraceptives [1]. Temporal relationship with starting/changing hormonal method or missed pills | Exogenous hormones suppress HPO axis → thin atrophic endometrium → fragile → spotting. Missed pills → transient hormone withdrawal → partial shedding |
| Physiological mid-cycle bleeding [1] | Related to rapid decrease in oestrogen after LH surge with low progesterone level shortly after ovulation [1]. Day 14 of cycle, 1–2 days, light spotting. Diagnosis of exclusion. | Transient oestrogen dip between follicular rupture and corpus luteum maturation → brief endometrial instability → minor shedding |
| Coagulopathy [1] | HMB ± IMB; especially if HMB since menarche [2]; bleeding from other sites (gums, nose, bruising); family history | Impaired platelet plug formation, fibrin clot formation, or vasoconstriction → defective endometrial haemostasis → prolonged/irregular bleeding |
| Thyroid disease [4] | Thyroid disease [4]; weight changes, heat/cold intolerance, tremor/bradycardia. Most commonly associated with oligo-amenorrhoea [2] but can cause IMB | Hypothyroidism: ↑TRH → ↑prolactin → suppressed GnRH → anovulation. Altered SHBG → oestrogen metabolism changes. Hyperthyroidism: ↑SHBG, altered feedback |
| Hyperprolactinaemia [4] | Hyperprolactinaemia [4]; galactorrhoea, oligo-/amenorrhoea, headache/visual field defects if prolactinoma | Prolactin directly inhibits GnRH pulsatility → suppressed FSH/LH → anovulation → irregular/absent bleeding. Can cause breakthrough bleeding before full amenorrhoea |
| Copper IUCD [2] | HMB > IMB; temporal relationship with IUCD insertion | Foreign body reaction → chronic endometrial inflammation → increased prostaglandin release → vasodilation + increased fibrinolysis → heavier, sometimes irregular bleeding |
| C/S scar defect (isthmocele) [4] | C/S scar defect [4]; IMB, especially prolonged brownish spotting after menses; history of prior caesarean section | Niche/defect in lower uterine segment myometrium → menstrual blood pools in the defect during menses → slowly leaks out afterwards → prolonged post-menstrual brownish spotting (old blood) |
| Uterine AVM [4] | Rare; can present with sudden heavy bleeding, often after uterine surgery/pregnancy | Abnormal arteriovenous connections in myometrium/endometrium → high-flow vascular malformation → bleeding when endometrium sheds or when AVM is disrupted |
| Idiopathic (DUB) [4] | Dysfunctional uterine bleeding: absence of identifiable cause [4]. Diagnosis of exclusion | Anovulatory DUB: disruption in HPO axis → chronic endometrial lining stimulation by oestrogen, more common at extremes of reproductive age. Ovulatory DUB: hormonal axis is normal but there is haemostatic and vasoconstrictive dysfunction in the endometrial lining. [4] |
This is a practical "pattern recognition" approach — the bleeding pattern steers you toward the right diagnosis.
The priority of differentials shifts with age, because the underlying physiology changes:
| Age Group | Most Likely Causes | Why? |
|---|---|---|
| Adolescence (< 20) | Anovulatory bleeding (AUB-O) [1] — immature HPO axis; coagulopathy (esp. VWD); pregnancy | HPO axis not yet fully mature → inconsistent GnRH pulsatility → anovulation. Coagulopathy often unmasked at menarche |
| Early reproductive (20–35) | Pregnancy complications; PID/STDs; cervical ectropion; hormonal contraceptive breakthrough bleeding; PCOS | Sexually active, peak fertility → pregnancy must be excluded. STD exposure. COC/hormonal use common |
| Late reproductive (35–45) | Fibroids; endometrial polyps; adenomyosis; anovulatory bleeding (early perimenopause); endometrial hyperplasia | Fibroids most common in 30s–40s. Perimenopausal HPO axis becomes erratic → mixed ovulatory/anovulatory cycles |
| Perimenopausal (45–55) | Anovulatory bleeding; endometrial hyperplasia/carcinoma; polyps; fibroids | Declining ovarian reserve → irregular anovulation → unopposed oestrogen → hyperplasia risk rises significantly |
| Postmenopausal (> 55) | Endometrial carcinoma (must exclude first); atrophic vaginitis; endometrial polyp; cervical carcinoma; HRT-related | No endogenous cycles → any bleeding is abnormal. Atrophic endometrium is the most common cause, but carcinoma must be ruled out first |
Key Differential Pairs to Distinguish
These are commonly confused pairs in clinical practice and exams:
| Feature | Endometrial Polyp | Endometrial Carcinoma |
|---|---|---|
| Bleeding pattern | IMB, often light/spotting | Persistent IMB, PMB, progressive |
| Pain | Usually painless | Late: pelvic pain |
| USS | Focal echogenic lesion, often pedunculated | Thickened, irregular endometrium |
| Definitive Dx | Hysteroscopy + polypectomy + histology | Endometrial biopsy (Pipelle) or hysteroscopy + biopsy |
| Key point | Low malignant potential (~1–3%) but must be sent for histology | Must be excluded in any woman > 40 with AUB or any woman with risk factors |
| Feature | Cervical Ectropion | Cervical Carcinoma |
|---|---|---|
| Appearance | Smooth, uniform, red area around os | Irregular, friable, ulcerated, bleeds on touch |
| Age | Young women, COC users, pregnant | Usually > 30; HPV-related |
| Bleeding | PCB, light | PCB, may be heavier; foul-smelling discharge |
| Action | Benign — reassure (treat if symptomatic) | Urgent colposcopy + biopsy |
| Feature | Anovulatory Bleeding (AUB-O) | Endometrial Polyp/Hyperplasia |
|---|---|---|
| Pattern | Prolonged oligomenorrhoea followed by heavy bleeding or spotting [1] | IMB between otherwise regular cycles (polyp); irregular heavy bleeding (hyperplasia) |
| Examination | Often normal pelvis | May have thickened endometrium on USS |
| Age | Extremes of reproductive age [1] | Any age (polyp); risk increases with age, obesity |
| Response to progestogen | Usually responds well (cyclical progestogen restores order) | Polyp: does not resolve with hormones (needs removal). Hyperplasia: may respond to progestogen but needs biopsy first |
Critical Distinction
Anovulatory bleeding and endometrial pathology can coexist — chronic anovulation (e.g. PCOS) causes unopposed oestrogen which can lead to endometrial hyperplasia and carcinoma. Do not assume irregular bleeding in a young woman with PCOS is "just anovulatory" without adequate investigation — excess risk of endometrial hyperplasia/carcinoma due to chronic unopposed oestrogen exposure [3].
When a patient presents with oligomenorrhoea, hyperandrogenism, and polycystic ovarian morphology, you must also consider mimics of PCOS [3]:
| Condition | How to Differentiate |
|---|---|
| Non-classic congenital adrenal hyperplasia (NCCAH / late-onset CAH) [3] | Differentiated by high morning value of 17-hydroxyprogesterone serum level in early follicular phase; exaggerated response to high-dose ACTH stimulation test [3]. More common in Mediterranean, Hispanic, Ashkenazi Jewish women |
| Androgen-secreting tumour / ovarian hyperthecosis [3] | Usually associated with severe virilisation (more severe than usual PCOS) [3]. Rapid onset. Very high testosterone (often > 150–200 ng/dL). Imaging for adrenal/ovarian mass |
| Cushing's syndrome | Excluded by normal dexamethasone suppression test. Look for striae, proximal myopathy, moon facies, buffalo hump |
| Thyroid disorders | TFTs — exclude hypo-/hyperthyroidism |
| Hyperprolactinaemia | Serum prolactin level. May cause galactorrhoea. If very elevated → MRI pituitary for prolactinoma |
A useful way to ensure you don't miss anything is to think anatomically from outside in, then add non-structural causes:
| Anatomical Level | Differentials |
|---|---|
| Vulva [4] | Skin tags, sebaceous cysts, condylomata, carcinoma |
| Vagina [4] | Atrophic vaginitis, lacerations, vaginitis/ulcers, carcinoma |
| Cervix [1] | Ectropion, polyp, cervicitis, carcinoma |
| Uterus — Endometrium [1] | Polyp, hyperplasia, carcinoma, endometritis (PID) |
| Uterus — Myometrium [4] | Fibroid (submucosal), adenomyosis, AVM, C/S scar defect |
| Fallopian tube / Adnexa | Ectopic pregnancy, tubo-ovarian abscess |
| Ovary [4] | Anovulation (PCOS, functional) |
| Systemic / Non-structural [1][4] | Coagulopathy, thyroid, hyperprolactinaemia, iatrogenic (hormonal), physiological mid-cycle |
| Pregnancy-related [1] | Ectopic, miscarriage (all types), molar, implantation |
High Yield Summary — Differential Diagnosis
-
Always exclude pregnancy first (β-hCG) — ectopic pregnancy is life-threatening.
-
Pattern guides the differential: HMB → fibroids, adenomyosis, coagulopathy, DUB; IMB → surface pathologies (polyps, hyperplasia, CA, vaginitis, STDs); PCB → cervical pathologies [4].
-
IMB is commonly associated with surface lesions of the genital tract [1]; irregular bleeding may be due to anovulation, early pregnancy complications, or use of hormonal drugs [1].
-
Age matters: Anovulatory bleeding dominates at extremes of reproductive life; fibroids/polyps in mid-reproductive years; endometrial carcinoma must be excluded in peri-/postmenopausal women and in younger women with risk factors.
-
PCOS mimics must be excluded: late-onset CAH (17-OHP), androgen-secreting tumour (severe virilisation, very high testosterone), Cushing's, thyroid disorders, hyperprolactinaemia [3].
-
DUB (dysfunctional uterine bleeding) is a diagnosis of exclusion — anovulatory DUB (HPO axis disruption, more common at extremes of age) vs ovulatory DUB (normal hormones but endometrial haemostatic/vasoconstrictive dysfunction) [4].
-
Think anatomically (vulva → vagina → cervix → endometrium → myometrium → adnexa → systemic) to avoid missing rare but important causes (AVM, C/S scar defect, vulval malignancy).
Active Recall - Differential Diagnosis of IMB and Irregular Bleeding
References
[1] Lecture slides: Adrian Lui Gynecology Notes.pdf (p19 — Intermenstrual and Irregular Bleeding) [2] Lecture slides: Adrian Lui Gynecology Notes.pdf (p13 — Heavy Menstrual Bleeding) [3] Lecture slides: Adrian Lui Gynecology Notes.pdf (p41 — PCOS investigations and differentials) [4] Lecture slides: Adrian Lui Gynecology Notes.pdf (p11 — Differential diagnoses and approach to AUB) [5] Lecture slides: Adrian Lui Gynecology Notes.pdf (p90 — Uterine fibroids clinical features)
Diagnostic Criteria, Algorithm, and Investigation Modalities
Unlike conditions such as PCOS (Rotterdam criteria) or PID (CDC criteria), intermenstrual and irregular bleeding is a symptom, not a diagnosis. There are no formal "diagnostic criteria" for the symptom itself. Instead, the diagnostic process aims to identify the underlying cause of the bleeding. What we do have are:
- Indications/thresholds for investigation — who needs endometrial sampling, imaging, etc.
- Diagnostic criteria for specific underlying conditions (e.g. Rotterdam for PCOS, histological criteria for hyperplasia/carcinoma)
- A structured diagnostic algorithm — a stepwise approach to reach the diagnosis
Let's work through all three systematically.
1. Indications and Thresholds for Investigation
These are the critical "trigger points" from the lecture slides that tell you when to move beyond history and examination to formal investigation. Understanding the why behind each threshold is essential.
Endometrial aspirate (EA): a simple outpatient procedure [6]
Indications — mainly when suspicious for endometrial pathologies: [6]
| Indication | Threshold | Why This Threshold? |
|---|---|---|
| Presence of risk factors for endometrial pathology [6][7] | e.g. obesity, PCOS, on tamoxifen, failed treatment [6][7] | These patients have chronic unopposed oestrogen → increased risk of hyperplasia/carcinoma regardless of age |
| Age ≥ 40 with persistent IMB or irregular bleeding [6][7] | Age ≥ 40 | Endometrial carcinoma incidence rises after 40. At this age, the pre-test probability of endometrial pathology is high enough to justify sampling |
| Age ≥ 45 with regular heavy period [6][7] | Age ≥ 45 | Even in HMB with regular cycles (where fibroids/DUB are more likely), the risk of underlying endometrial pathology is significant enough by age 45 to warrant sampling |
| Any AUB if age ≥ 45 [8] | Age ≥ 45 | Broader threshold — any pattern of abnormal bleeding at this age should prompt endometrial assessment |
| Abnormal Pap smear showing AGC-endometrial [8] | Any age | Atypical glandular cells of endometrial origin on cytology raise concern for endometrial pathology → direct endometrial sampling needed |
| Monitoring previous endometrial pathology or surveillance in high-risk (e.g. Lynch syndrome/HNPCC) [8] | As per protocol | These patients have ongoing elevated risk and require periodic endometrial surveillance |
Process: to be done during speculum exam → insertion of endometrial suction curette (e.g. Pipelle) to aspirate endometrial tissue → send for histopathology [6]
Must Know
Pregnancy test must be done (or document no unprotected sex) before EA [6]. Performing endometrial aspiration on a pregnant uterus can disrupt a viable pregnancy or miss an ectopic.
Why is EA so useful? It is a blind sampling technique — quick, cheap, can be done in clinic without anaesthesia. The Pipelle device has a sensitivity of ~90–99% for endometrial carcinoma (high detection rate for diffuse disease) but is less reliable for focal lesions like polyps (may miss them because it samples randomly). This is why hysteroscopy is superior for focal pathology.
Hysteroscopy ± endometrial biopsy: diagnostic and therapeutic [6]
Indication: superior to EA but limited availability [6]
| Indication | Why? |
|---|---|
| Suspected endometrial polyp or submucosal fibroids [6][7] | EA (blind sampling) often misses focal lesions. Hysteroscopy allows direct visualisation → targeted biopsy → and can simultaneously remove polyps/fibroids ("see and treat") |
| Irregular bleeding while on hormonal therapy for > 3 months [6][7] | Breakthrough bleeding on hormonal Tx usually settles within 3 months. If it persists, structural pathology must be excluded — hysteroscopy is the gold standard |
| Endometrial aspirate failed or inconclusive [6][7] | Insufficient tissue, inadequate sample, or uncertain histology → need direct visualisation and targeted biopsy |
| PMB on tamoxifen [9] | Tamoxifen causes a pseudo-thickened endometrium on USS (subendometrial cystic changes give a falsely thick measurement) → USS is unreliable in this setting → hysteroscopy is preferred for direct assessment |
| PMB with endometrial thickness > 4mm [9] | Thickened endometrium in a postmenopausal woman raises concern for hyperplasia/carcinoma → hysteroscopy allows visualisation + biopsy |
Setting: under GA or LA (outpatient procedure) [6] Process: insertion of a 3mm endoscope through cervix into uterus → ± targeted biopsy at suspicious endometrial sites → ± removal of lesion, e.g. polyp [6]
Pelvic US when suspect structural pathology [6][7]
| Indication | Why? |
|---|---|
| Suspicious of fibroids: uterus palpable abdominally, Hx/PE suggestive of pelvic mass, examination inconclusive or difficult [6][7] | Fibroids are best characterised by USS — number, size, location (submucosal vs intramural vs subserosal), which guides management |
| Suspicious of adenomyosis: TVUS for significant dysmenorrhoea, bulky tender uterus on PE [7] | TVUS can show characteristic features of adenomyosis (heterogeneous myometrium, myometrial cysts, asymmetric wall thickening) |
| PMB: TVUS to measure endometrial thickness [9] | Should be ≤ 4mm in postmenopausal women (NPV 99.4–100%) [9] — a normal TVUS is very reassuring. If > 4mm → further investigation (hysteroscopy/biopsy) |
| Suspected ectopic pregnancy | USS (usually TVUS) to look for intrauterine gestational sac; if absent with positive β-hCG → pregnancy of unknown location (PUL) → ectopic until proven otherwise |
The following algorithm integrates the lecture material [1][6][7][8][9] into a stepwise approach:
The Key Principle
The algorithm follows a "exclude the dangerous, then characterise the cause" logic:
- Exclude pregnancy (ectopic can kill)
- Examine the cervix (don't miss cervical carcinoma — it's visible)
- Assess for anaemia and systemic causes (bloods)
- Sample the endometrium if indicated (exclude endometrial carcinoma/hyperplasia)
- Image if structural pathology suspected (characterise fibroids/polyps/adenomyosis)
- Hysteroscopy if focal lesion suspected or EA inadequate (gold standard for endometrial cavity assessment)
3. Investigation Modalities — Detailed Breakdown
| Investigation | What You're Looking For | Key Findings/Interpretation |
|---|---|---|
| Urine pregnancy test (β-hCG) | Pregnancy (any type) | Positive → pregnancy-related cause. Must be done before EA. Negative → proceed with non-pregnancy workup |
| Speculum examination | Cervical/vaginal pathology | Note any current uterine bleeding from cervical os [6]; note any lower genital tract abnormalities: e.g. mass, laceration, discharge [6]; note any cervical pathology [6]; cervical ectropion (smooth red area), polyp (pedunculated), suspicious mass (friable, irregular), discharge |
| Cervical smear [6] | Cervical dysplasia/malignancy | Perform if (1) due for screening (2) looks suspicious but no obvious lesion [6]. Liquid-based cytology ± HPV co-testing. Report: NILM, ASC-US, LSIL, HSIL, AGC, squamous cell carcinoma |
| Bimanual examination | Uterine size/contour, adnexal masses | Adenomyosis: symmetrical enlargement of uterus; uterine fibroid: asymmetrical enlargement of uterus [6][7]; note any adnexal mass [6][7] |
| Test | Indication | Key Findings/Interpretation |
|---|---|---|
| CBC: Hb, platelets [6][7] | All patients with AUB | Low Hb → iron deficiency anaemia from chronic blood loss. Low MCV → microcytic (iron deficiency). Thrombocytopenia → consider coagulopathy/ITP. High platelets → reactive thrombocytosis from chronic bleeding |
| Pregnancy test [6][7] | All reproductive-age women with AUB | See above — non-negotiable |
| ± Clotting profile [6][7] | If HMB since menarche, or FHx positive [6][7] | Prolonged PT/APTT → coagulation factor deficiency. Low VWF antigen/activity → von Willebrand disease (most common inherited bleeding disorder). Order VWF panel specifically if suspicious |
| ± Iron profile [6][7] | For iron deficiency anaemia [6][7] | Low ferritin (most specific early marker), low serum iron, high TIBC, low transferrin saturation → iron deficiency. Ferritin < 30 μg/L is diagnostic in context of AUB |
| ± TFT [6][7] | Only when clinically symptomatic (uncommon) [6][7] | Elevated TSH + low fT4 → hypothyroidism → anovulation. Suppressed TSH + high fT4 → hyperthyroidism. Note: thyroid disease most commonly associated with oligo-amenorrhoea [2] rather than IMB |
| ± Hormonal profile: LH, FSH, E2 [7] | Further workup on anovulation [7]; suspected PCOS, premature ovarian insufficiency, hypothalamic amenorrhoea | Normal or slightly elevated LH, normal FSH, normal E2 → normogonadotrophic anovulation (PCOS pattern). Increased LH:FSH ratio [3] (≥ 2–3:1 suggestive but not diagnostic [3]). Low FSH/LH/E2 → hypogonadotrophic hypogonadism (hypothalamic cause). High FSH, low E2 → hypergonadotrophic hypogonadism (ovarian failure) |
| ± Prolactin [7] | Endocrine profile [7]; galactorrhoea, oligo-/amenorrhoea | Elevated prolactin → hyperprolactinaemia (drug-induced, prolactinoma, hypothyroidism). If very elevated (> 200 μg/L → macro-prolactinoma likely → MRI pituitary) |
| ± Testosterone [7] | PCOS [7]; hirsutism, acne, virilisation | Mildly elevated total testosterone (PCOS seldom exceeds 150 ng/dL) [3]. If markedly elevated (> 150–200 ng/dL) → consider androgen-secreting tumour [3]. Also check DHEAS (adrenal source), 17-OH-progesterone (late-onset CAH) |
| ± 17-OH-progesterone | Suspected late-onset CAH (NCCAH) | High morning value in early follicular phase [3] → suggestive. Confirm with high-dose ACTH stimulation test [3] |
| ± OGTT | PCOS [7]; metabolic risk assessment | ~10% of PCOS patients have T2DM, 30% have impaired glucose tolerance [3]. 75g OGTT recommended for all PCOS patients (fasting glucose alone misses ~50% of IGT) |
When to Order What — A Practical Guide
- Every patient: CBC, pregnancy test
- Suspected anaemia: Iron profile
- HMB since menarche / bleeding tendency: Clotting profile, VWF panel
- Suspected anovulation / PCOS: LH, FSH, E2, prolactin, testosterone, TFT, OGTT
- Virilisation / severe hyperandrogenism: Testosterone, DHEAS, 17-OHP, dexamethasone suppression test, adrenal/ovarian imaging
- Thyroid symptoms: TFT
- Galactorrhoea: Prolactin → if elevated, MRI pituitary
Endometrial aspirate/sampling (EA): a simple outpatient procedure [6]
How it works:
- A thin, flexible plastic catheter (Pipelle de Cornier) is inserted through the cervical os into the uterine cavity
- The inner plunger is withdrawn, creating negative suction pressure → aspirates a strip of endometrial tissue
- The tissue is placed in formalin → sent to histopathology
- Takes ~1–2 minutes; usually performed without anaesthesia (some cramping is expected)
- Can be completed in 5 minutes without anaesthesia [8]
What it tells you:
| Histology Result | Interpretation | Next Step |
|---|---|---|
| Proliferative endometrium | Normal follicular phase pattern; if seen in the luteal phase (Day 21) → anovulation (no progesterone effect) | If anovulation confirmed → treat with cyclical progestogen |
| Secretory endometrium | Normal luteal phase pattern → confirms ovulation | Reassuring — ovulatory cycle. Consider other causes |
| Hyperplasia without atypia | Increased gland:stroma ratio, no cytological atypia. Low malignant potential (~1–3%) | Medical management with progestogen (oral or LNG-IUS). Re-sample in 3–6 months |
| Atypical hyperplasia (EIN) | Cytological atypia present. High malignant potential (~30–40% → carcinoma) | Hysterectomy recommended if family complete. If fertility desired → high-dose progestogen + close surveillance |
| Endometrial carcinoma | Malignant glandular cells | Refer Gynae-Oncology. Staging investigations |
| Insufficient/inadequate tissue | Not enough tissue obtained for diagnosis | EA failed or inconclusive → hysteroscopy ± biopsy [6][7] |
| Normal in postmenopausal women | Atrophic/inactive endometrium | Reassuring — if PMB, most likely atrophic vaginitis |
Limitations:
- Blind technique → can miss focal lesions (polyps, small submucosal fibroids)
- Sensitivity for endometrial carcinoma: ~90–99% (very good for diffuse disease)
- Sensitivity for polyps: only ~10–30% (poor — polyps are focal and the catheter may miss them)
- Cannot be done if cervical stenosis (common in postmenopausal women)
- Should not be done if pregnant (pregnancy test first!)
The gold standard for endometrial cavity assessment.
How it works:
- A thin rigid or flexible endoscope (typically 3–5mm diameter) is inserted through the cervix into the uterine cavity
- The cavity is distended with saline or CO₂ to allow visualisation
- Direct visualisation of the entire endometrial surface → can identify polyps, submucosal fibroids, hyperplasia, carcinoma, adhesions, septa
- Targeted biopsy can be taken from suspicious areas (unlike EA which is blind)
- Therapeutic: polyps can be removed, submucosal fibroids resected, adhesions lysed — "see and treat" approach
Advantages over EA:
- Directly visualises focal lesions (polyps, fibroids) that EA may miss
- Allows targeted biopsy → higher diagnostic accuracy for focal pathology
- Can treat at the same time (polypectomy, myomectomy)
Disadvantages:
- More invasive, requires trained operator
- Limited availability (not available in every clinic)
- May require GA (though outpatient/office hysteroscopy under LA is increasingly common)
- Risk (rare): uterine perforation (~0.1%), infection, fluid overload (if excessive distension media)
Pelvic US when suspect structural pathology [6][7]
Two approaches:
- Transabdominal US (TAUS): requires full bladder as acoustic window. Good for large fibroids, general pelvic survey. Less resolution for endometrium.
- Transvaginal US (TVUS): probe placed in vagina → closer to uterus → higher resolution. Preferred for endometrial assessment, adenomyosis, early pregnancy, adnexal masses.
Key USS Findings and Their Interpretation:
| Finding | Interpretation | Clinical Significance |
|---|---|---|
| Endometrial thickness | Should be ≤ 4mm in postmenopausal women (NPV 99.4–100%) [9]; in premenopausal women, varies with cycle (proliferative: 4–8mm; secretory: 8–14mm) | In PMB: ≤ 4mm → very reassuring (carcinoma essentially excluded). > 4mm → needs further investigation (EA or hysteroscopy). At 4mm, sensitivity 96%, specificity 53% [8] |
| Thickened, irregular endometrium | Possible hyperplasia or carcinoma | Needs tissue sampling (EA or hysteroscopy + biopsy) |
| Focal echogenic lesion in cavity | Endometrial polyp (often with feeding vessel on Doppler) | Hysteroscopy for removal + histology. EA may miss it |
| Submucosal fibroid | Hypoechoic mass distorting endometrial cavity | Suspected endometrial polyp or submucosal fibroids → hysteroscopy [6][7] |
| Intramural/subserosal fibroids | Hypoechoic masses within myometrium / outer surface | USS characterises number, size, location. Guides management decisions |
| Heterogeneous myometrium, myometrial cysts, asymmetric wall thickening | Adenomyosis | MRI if USS inconclusive. TVUS for significant dysmenorrhoea, bulky tender uterus on PE [7] |
| Empty uterus with positive β-hCG | Pregnancy of unknown location (PUL) → ectopic until proven otherwise | Serial β-hCG (48-hourly) + repeat TVUS. If β-hCG > discriminatory zone (~1500–2000 IU/L) and no IUP → likely ectopic |
| Adnexal mass ± free fluid | Ectopic pregnancy (if β-hCG positive); ovarian pathology; tubo-ovarian abscess | Correlate with clinical picture and β-hCG |
| "Snowstorm" pattern / multiple cystic spaces in uterus | Molar pregnancy (hydatidiform mole) | Check β-hCG (markedly elevated). Evacuate mole + histology + hCG surveillance |
| Polycystic ovarian morphology: ≥ 20 follicles measuring 2–9mm and/or ovarian volume > 10mL [3] | PCOS (one of the Rotterdam criteria) | Found in ~25% of all women, so US feature alone cannot form diagnosis [3]. Must correlate with clinical/biochemical features |
| C/S scar niche | Isthmocele — fluid-filled defect in lower uterine segment | Explains post-menstrual brownish spotting. Sonohysterography or MRI for better characterisation |
Saline Infusion Sonography (SIS) / Sonohysterography:
- Saline is infused into the uterine cavity during TVUS → distends the cavity → better delineation of intracavitary lesions (polyps, submucosal fibroids)
- Acts as a "poor man's hysteroscopy" — less invasive than hysteroscopy but better than plain TVUS for focal lesions
- Sensitivity for polyps: ~90% (much better than plain TVUS)
| Investigation | Indication | Key Points |
|---|---|---|
| Cervical cytology (Pap smear / LBC) | If (1) due for screening (2) looks suspicious but no obvious lesion [6] | Screens for cervical dysplasia (CIN). Abnormal results (ASC-US, LSIL, HSIL, AGC) → colposcopy. Not a diagnostic test for carcinoma — it is a screening test |
| HPV testing | Co-testing with cytology in women ≥ 30; primary HPV screening (some programmes) | High-risk HPV types (16, 18) are causative for cervical carcinoma. HPV-negative + normal cytology → very low risk → can extend screening interval |
| Colposcopy ± biopsy | Abnormal cervical cytology; suspicious cervical lesion on speculum | Magnified examination of cervix with acetic acid/Lugol's iodine → identifies transformation zone abnormalities → targeted punch biopsy. Diagnostic for CIN grade and carcinoma |
| STD swabs | Suspected cervicitis, vaginitis, PID | Endocervical swab for Chlamydia (NAAT — most sensitive), Gonorrhoea (NAAT + culture for sensitivity), high vaginal swab for Trichomonas, bacterial vaginosis, Candida |
| Investigation | Indication | What It Shows |
|---|---|---|
| MRI pelvis | Inconclusive USS for adenomyosis; staging of endometrial/cervical carcinoma; characterising complex fibroids | Superior soft-tissue resolution. Adenomyosis: junctional zone > 12mm. Endometrial carcinoma: depth of myometrial invasion. Cervical carcinoma: parametrial invasion, lymph node involvement |
| CT abdomen/pelvis | Staging of gynaecological malignancy (lymph nodes, distant metastases) | Not first-line for AUB workup |
| Serum β-hCG (quantitative) | Pregnancy of unknown location, ectopic pregnancy monitoring, molar pregnancy | Serial β-hCG: normal early pregnancy doubles every 48h. Abnormal rise (< 66% in 48h) → non-viable/ectopic. Very high β-hCG (> 100,000 IU/L) → molar pregnancy |
| Diagnostic laparoscopy | Suspected ectopic pregnancy when USS inconclusive and patient haemodynamically stable | Direct visualisation of tubal ectopic. Can treat at same time (salpingectomy/salpingotomy) |
4. Diagnostic Criteria for Key Underlying Conditions
Rotterdam criteria: ≥ 2 of the following met [3]:
- Oligo- or anovulation [3]
- Hyperandrogenism: biochemical or clinical [3]
- PCOS features in US defined as ≥ 1 ovary meeting criteria of ≥ 20 follicles measuring 2–9mm and/or increased ovarian volume > 10mL (by 0.5 × length × width × thickness) [3]
AND exclusion of other aetiologies with similar features, e.g. thyroid disorders, hyperprolactinaemia, CAH, Cushing's syndrome, adrenal tumours [3]
PCOS Diagnosis Pitfall
Polycystic ovarian morphology on USS is found in ~25% of all women [3], so US feature alone cannot form diagnosis [3]. You need at least ONE other criterion (anovulation OR hyperandrogenism) PLUS exclusion of mimics. Many students make the mistake of diagnosing PCOS based on ultrasound alone.
Similarly, many clinicians use LH:FSH ratio ≥ 2–3:1 as diagnostic criteria but this is NOT DIAGNOSTIC [3]. It is supportive but not required.
| Category | Histological Features | Malignant Potential | Management |
|---|---|---|---|
| Hyperplasia without atypia | Increased gland:stroma ratio, irregular gland architecture, no cytological atypia | Low (~1–3%) | Cyclical progestogen or LNG-IUS. Re-biopsy in 3–6 months |
| Atypical hyperplasia / EIN (Endometrial Intraepithelial Neoplasia) | Cytological atypia (nuclear enlargement, irregular nuclei, prominent nucleoli), crowded glands | High (~30–40%) | Hysterectomy if family complete. High-dose progestogen + surveillance if fertility desired |
Diagnosed histologically (EA or hysteroscopy biopsy → confirmed at hysterectomy).
Key staging relevant to diagnosis:
- Stage I: Confined to uterine corpus
- IA: < 50% myometrial invasion
- IB: ≥ 50% myometrial invasion
- Stage II: Cervical stromal invasion
- Stage III: Local/regional spread (serosa, adnexa, vagina, lymph nodes)
- Stage IV: Distant metastases (bladder/bowel mucosa, distant organs)
Staging requires surgical pathology (total hysterectomy + bilateral salpingo-oophorectomy + lymph node assessment).
TVUS endometrial thickness: should be ≤ 4mm in postmenopausal women (NPV 99.4–100%) [9]
Performance: [8]
Why 4mm? The goal is to rule out endometrial carcinoma with high confidence. A thin endometrium (≤ 4mm) has a very high NPV — essentially no cancer is lurking behind a thin endometrial stripe. The trade-off is low specificity (many false positives — benign thickened endometrium still needs biopsy), but this is acceptable because missing a cancer is far worse than doing an unnecessary biopsy.
Note: NOT routinely performed in asymptomatic patients with incidental finding of thickened endometrium unless > 11mm and associated with other US findings or risk factors [9]. This is important — don't over-investigate incidental findings in asymptomatic women.
5. Special Scenarios
Breakthrough bleeding in combined regimens: [10]
- Those occurring in the first 6 months of treatment require no immediate intervention [10]
- For combined cyclical regimen: if bleeding is not around time of progestogen withdrawal / persistently irregular → endometrial biopsy [10]
- For continuous combined regimen: if bleeding occurs after achievement of amenorrhoea → endometrial biopsy [10]
Why? The first 6 months of HRT allow the endometrium to "settle" into the new hormonal environment. Breakthrough bleeding during this period is usually benign (endometrial adjustment). However:
- In cyclical regimens, bleeding should occur predictably during the progestogen-free/withdrawal period. If it occurs at other times → suspicion of endometrial pathology
- In continuous combined regimens, the goal is endometrial atrophy → amenorrhoea. If bleeding recurs after amenorrhoea was established → something has changed (new pathology?) → investigate
A special algorithm because it is a time-critical, potentially fatal diagnosis:
| Step | Test | Key Decision Point |
|---|---|---|
| 1 | β-hCG positive | Is she pregnant? Yes → |
| 2 | TVUS | IUP visible? If yes → likely intrauterine pregnancy (ectopic coexistence = heterotopic, very rare ~1:30,000 naturally). If no → PUL (pregnancy of unknown location) |
| 3 | Quantitative β-hCG | Discriminatory zone: if β-hCG > 1500–2000 IU/L and no IUP on TVUS → likely ectopic. If < discriminatory zone → too early to see on USS → serial β-hCG |
| 4 | Serial β-hCG (48-hourly) | Normal rise: > 66% in 48h → likely viable IUP (repeat USS when β-hCG reaches discriminatory zone). Abnormal rise (< 66%) or plateau/fall → non-viable pregnancy (ectopic or failing IUP). Fall > 50% → likely complete miscarriage |
| 5 | If ectopic confirmed/suspected | Haemodynamically stable: medical (methotrexate) or surgical (laparoscopy). Haemodynamically unstable: emergency laparotomy/laparoscopy |
High Yield Summary — Diagnosis
-
Pregnancy test is mandatory in all reproductive-age women with AUB — before any endometrial sampling.
-
Endometrial aspirate indications: age ≥ 40 with persistent IMB/irregular bleeding; age ≥ 45 with HMB; risk factors for endometrial CA (obesity, PCOS, tamoxifen, failed treatment). It is a blind office procedure — good for diffuse disease, poor for focal lesions.
-
Hysteroscopy is superior to EA for focal lesions (polyps, submucosal fibroids), failed/inconclusive EA, and persistent bleeding on hormonal therapy > 3 months. It allows "see and treat."
-
TVUS endometrial thickness ≤ 4mm in postmenopausal women has NPV 99.4–100% — essentially excludes carcinoma. > 4mm → needs tissue sampling.
-
PCOS diagnosis = Rotterdam criteria (≥ 2 of 3: anovulation, hyperandrogenism, polycystic morphology on USS) PLUS exclusion of mimics. USS features alone are not diagnostic (25% of normal women have them). LH:FSH ratio is supportive but not diagnostic.
-
Bleeding on HRT: first 6 months → observe. After 6 months, unscheduled bleeding → endometrial biopsy. Bleeding after established amenorrhoea on continuous combined HRT → investigate.
-
Algorithm: Pregnancy test → Speculum exam → Bloods (CBC, ± clotting, ± iron, ± hormones, ± TFT) → EA if indicated → USS if structural pathology suspected → Hysteroscopy if focal lesion or EA inadequate.
Active Recall - Diagnosis of IMB and Irregular Bleeding
References
[1] Lecture slides: Adrian Lui Gynecology Notes.pdf (p19 — Intermenstrual and Irregular Bleeding) [2] Lecture slides: Adrian Lui Gynecology Notes.pdf (p13 — Heavy Menstrual Bleeding) [3] Lecture slides: Adrian Lui Gynecology Notes.pdf (p41 — PCOS investigations and differentials) [6] Lecture slides: Adrian Lui Gynecology Notes.pdf (p14 — Physical exam and Investigation for HMB) [7] Lecture slides: Adrian Lui Gynecology Notes.pdf (p20 — Investigation for IMB/Irregular Bleeding) [8] Lecture slides: Adrian Lui Gynecology Notes.pdf (p97 — Endometrial hyperplasia evaluation) [9] Lecture slides: Adrian Lui Gynecology Notes.pdf (p22 — Post-menopausal Bleeding evaluation) [10] Lecture slides: Adrian Lui Gynecology Notes.pdf (p36 — Algorithm for HRT Administration)
Management of Intermenstrual and Irregular Bleeding
The management of IMB and irregular bleeding follows one cardinal rule: treat the underlying cause. The symptom itself is not the disease — it is a signal. Once you have completed the diagnostic workup (pregnancy test → speculum → bloods → EA/USS/hysteroscopy as indicated), management is directed at whatever you find.
That said, there are important empirical/symptomatic treatments that can be started while awaiting investigations or when no structural cause is found (i.e. anovulatory/dysfunctional bleeding). The lecture slides [7] give a clear tiered approach.
2. Management of IMB / Irregular Bleeding When No Structural Cause Is Found (AUB-O / DUB)
This is the most common scenario in clinical practice — a young woman with irregular bleeding, negative pregnancy test, normal speculum, and no structural pathology on imaging. The cause is usually anovulatory dysfunction (AUB-O).
Management of underlying cause as appropriate [7]
Combined OC pills: 1st line treatment unless contraindicated [7]
How COCs work for irregular/anovulatory bleeding:
- COCs contain both oestrogen (ethinylestradiol, EE) and progestogen (e.g. levonorgestrel, desogestrel, drospirenone)
- The oestrogen component stabilises the endometrium (promotes growth and healing of the functionalis layer) and provides a predictable hormonal milieu
- The progestogen component opposes oestrogen-driven proliferation, induces secretory transformation, and stabilises the endometrial vasculature (spiral arteries)
- Together, they suppress the HPO axis (suppress GnRH → suppress FSH/LH → suppress folliculogenesis → suppress erratic ovarian hormone production)
- During the pill-free interval (or placebo pills), the withdrawal of both hormones triggers an organised, predictable withdrawal bleed
- Net effect: transforms chaotic, unpredictable anovulatory bleeding into regular, predictable, lighter withdrawal bleeds
Why COCs are first-line:
- Regulate the cycle
- Reduce bleeding volume
- Provide contraception (many of these patients are reproductively active)
- Protect the endometrium from unopposed oestrogen (the progestogen component prevents hyperplasia)
- Treat associated dysmenorrhoea
- In PCOS: also improve acne and hirsutism (especially with anti-androgenic progestogens like cyproterone acetate or drospirenone)
Contraindications to COCs (UKMEC Category 4 — absolute contraindications):
| Contraindication | Why? |
|---|---|
| Active or history of VTE (DVT/PE) | Oestrogen is prothrombotic (↑clotting factors II, VII, VIII, X, ↑fibrinogen, ↓antithrombin III) |
| Ischaemic heart disease / stroke | Oestrogen promotes thrombosis and atherogenesis |
| Migraine with aura | Oestrogen increases risk of ischaemic stroke in migraineurs with aura |
| Breast cancer (current) | Breast cancer is hormone-sensitive; oestrogen promotes tumour growth |
| Active liver disease / hepatic tumour | Oestrogen is hepatically metabolised; liver disease impairs clearance; hepatic adenoma risk |
| Uncontrolled hypertension (≥ 160/100) | Oestrogen → fluid retention, endothelial dysfunction → further ↑BP → ↑cardiovascular risk |
| Smoking ≥ 15 cigarettes/day AND age ≥ 35 | Synergistic cardiovascular risk with oestrogen |
| < 6 weeks postpartum (breastfeeding) | Oestrogen ↓breast milk production; ↑VTE risk in puerperium |
| Major surgery with prolonged immobilisation | ↑VTE risk |
Key Principle
The major concern with COCs is venous thromboembolism (VTE) and arterial cardiovascular events. The oestrogen component is the culprit. When COCs are contraindicated, you must use progestogen-only methods instead.
High-dose progestogen: when contraindicated to COC pills [7]
Regimens:
- Cyclical oral progestogens: e.g. Primolut N (norethisterone) 5mg TDS on day 5–26 of each cycle [11]
- Medroxyprogesterone acetate (MPA) 10mg daily for 10–14 days per cycle (luteal phase supplementation)
How cyclical progestogen works:
- In anovulatory cycles, the endometrium is exposed to oestrogen only (no progesterone because no ovulation). The progestogen mimics what the corpus luteum would normally do:
- Converts the proliferative endometrium to secretory (compact, stable)
- When the progestogen is stopped (e.g. after day 26), withdrawal triggers an organised, predictable bleed — essentially an "artificial period"
- Repeated cyclical use prevents the endometrium from becoming dangerously thick → protects against endometrial hyperplasia
- Why "day 5–26"? This covers most of the cycle, giving the endometrium a prolonged progestogen exposure (mimicking a long luteal phase) to ensure adequate secretory transformation before withdrawal
When to use:
- COC contraindicated (VTE risk, migraines with aura, etc.)
- Patient does not need/want contraception (cyclical progestogen at standard doses does NOT reliably inhibit ovulation — it is not a contraceptive unless used in specific POP formulations)
- PCOS patients who need endometrial protection but cannot take COCs
Side effects: bloating, mood changes, breast tenderness, acne (androgenic progestogens like norethisterone), weight gain
Levonorgestrel-releasing IUCD: alternative to COC pills [7]
How the LNG-IUS works:
- Releases 20μg/day of levonorgestrel (LNG) directly into the uterine cavity
- Local progestogenic effect on the endometrium:
- Profound decidualisation and atrophy of endometrial glands → very thin, inactive endometrium → dramatically reduced bleeding
- Thickens cervical mucus → barrier to ascending infection and sperm (provides contraception)
- Does NOT reliably suppress ovulation (unlike COCs) — ~50% of cycles are still ovulatory
- Why it's excellent for AUB: The local drug delivery means very high endometrial progestogen concentration with minimal systemic absorption → fewer systemic side effects than oral progestogens, yet powerful endometrial suppression
- Reduces menstrual blood loss by ~90% at 12 months
- Effective for 5 years (Mirena) or 8 years (updated data for contraception; 5 years for HMB indication)
- Also provides highly effective contraception (> 99%)
- Can be used if fibroids < 3cm with no cavity distortion [11]
Advantages:
- "Fit and forget" — excellent compliance (no daily pills to remember)
- Combined endometrial protection + contraception
- Fewer systemic side effects
- Can be used in women with contraindications to oestrogen
Disadvantages/Considerations:
- Irregular spotting/bleeding is common in the first 3–6 months (as the endometrium atrophies — counselling is essential)
- Not suitable if uterine cavity is distorted (large submucosal fibroids → may be expelled or malpositioned)
- Requires insertion procedure (minor)
- Small risk of expulsion (~5%), perforation (very rare, ~0.1%), infection (slightly increased risk in first 20 days)
Iron supplement: FeSO₄ 300mg BD × 12 weeks [7]
2nd line: Ferrum Hausmann chewable tablet BD or 3mL droplet QD × 12 weeks [7]
3rd line: IV iron [7]
Why iron?
- Chronic abnormal bleeding → iron deficiency anaemia. The body's iron stores (ferritin) are depleted faster than they can be replenished from diet alone
- Oral iron replaces depleted stores. Ferrous sulphate (FeSO₄) 300mg contains ~60mg elemental iron per tablet; BD provides ~120mg elemental iron/day. Only ~10% is absorbed, so ~12mg/day enters the bloodstream
- Why 12 weeks? It takes 2–3 months to replenish iron stores after correcting the Hb. Even after Hb normalises, continue iron to refill ferritin
Ferrous sulphate vs Ferrum Hausmann:
- FeSO₄ is a ferrous (Fe²⁺) salt — cheap, effective, but causes significant GI side effects (nausea, constipation, black stools, abdominal pain) because free Fe²⁺ is irritating to the GI mucosa
- Ferrum Hausmann (iron polymaltose complex) is a ferric (Fe³⁺) preparation — non-ionic iron complex that releases iron slowly → fewer GI side effects but slightly lower absorption. Used when FeSO₄ is not tolerated
- IV iron (e.g. ferric carboxymaltose / Ferinject, iron sucrose): bypasses GI absorption entirely. Used when: oral iron not tolerated, non-compliant, severe anaemia requiring rapid correction, malabsorption, or ongoing losses exceeding oral replacement capacity
3. Management by Specific Underlying Cause
Polyp can be observed (1/4 chance to spontaneously resolve if < 1cm) [7]
- Small, asymptomatic polyps (< 1cm): Observation is reasonable. ~25% resolve spontaneously (slough off)
- Symptomatic polyps or > 1cm: Hysteroscopic polypectomy — "see and treat." The polyp is visualised and excised under direct vision, then sent for histology (to exclude hyperplasia/malignancy within the polyp)
- Why histology is essential: ~1–3% of polyps harbour malignancy (higher in postmenopausal women, those on tamoxifen). You cannot tell benign from malignant by appearance alone
Medical treatment: [11]
Non-hormonal drugs:
-
Tranexamic acid: oral Transamin 1g TDS up to 4 days, max 4g daily [11]
- "Trans-" = across, "examic" from "examic acid" — an antifibrinolytic
- Mechanism: Competitively inhibits plasminogen activation → prevents plasmin from breaking down fibrin clots → stabilises clots in the endometrial vasculature → reduces blood loss
- Why for fibroids? Fibroids cause HMB partly through increased local fibrinolysis (↑tPA). Tranexamic acid directly counters this
- Contraindication: Active thromboembolic disease (because you're inhibiting fibrinolysis → theoretically ↑clot risk, though evidence for increased VTE is weak)
-
Iron supplement: oral ferrous sulphate 300mg TDS × 6 months if Hb < 10g/dL [11]
-
± Mefenamic acid: oral Ponstan 250–500mg TDS [11]
- An NSAID (fenamate class) — inhibits cyclooxygenase → reduces prostaglandin synthesis
- Note: does NOT appear to decrease blood loss in fibroids but can decrease painful menses [11]
- Why doesn't it reduce bleeding in fibroids? In AUB-E (dysfunctional bleeding without fibroids), excess prostaglandins (PGE₂, PGI₂) cause vasodilation and increased bleeding, so NSAIDs help. In fibroids, the bleeding is mechanical (increased surface area, distorted vasculature) — prostaglandin inhibition doesn't address this
Hormonal drugs:
-
GnRH agonists or antagonists: usually for pre-operative size reduction before hysteroscopic resection [11]
- GnRH agonists (e.g. leuprolide, goserelin): Initially stimulate GnRH receptors → "flare" effect → then continuous exposure desensitises and downregulates the receptors → pituitary becomes unresponsive → profound suppression of FSH/LH → very low oestrogen ("medical menopause")
- MoA: desensitisation → medically induce menopause → decrease size of fibroid, decrease menstrual-related symptoms [11]
- Problem: rapid relapse following discontinuation, significant climacteric symptoms with menopause-related side effects (e.g. bone density) → therefore NOT for long-term use [11]
- Why fibroids shrink: Fibroids are oestrogen-dependent — remove oestrogen and they shrink (by ~30–50% over 3 months). This makes surgery easier (smaller fibroid, less vascular)
- GnRH antagonists (e.g. relugolix, elagolix): Directly block GnRH receptors without the initial flare → faster onset of suppression. Newer agents (relugolix with add-back oestrogen/progestogen) allow longer-term use by mitigating menopausal side effects while maintaining fibroid suppression
-
Progesterone receptor modulators: e.g. ulipristal acetate, mifepristone [11]
-
Mirena IUCD if fibroids < 3cm with no cavity distortion [11]
Surgical treatment: [11]
Indications: NOT dependent on anatomical factor [11] — i.e., surgical indications are based on symptoms and clinical concern, not fibroid size alone.
- Symptomatic [11] (but warn patient that urinary frequency may not improve as it may be due to detrusor instability, not fibroid compression)
- Rapid growth or postmenopausal growth → worrisome of malignancy [11]
- Unexplained subfertility with significant submucosal component [11]
| Hysterectomy | Myomectomy |
|---|---|
| Definitive treatment | Uterus-conserving |
| Acute haemorrhage not responding to other therapies [11] | Desire to preserve fertility |
| Completed childbearing or no fertility wish [11] | Still in reproductive years |
| Increased risk for CA cervix, endometrium, ovaries (e.g. CIN, endometrial hyperplasia) [11] | May recur (15–30% recurrence rate) |
| Patient preference [11] | Types: laparoscopic, trans-abdominal, hysteroscopic (± endometrial ablation) [11] |
| Types: vaginal, abdominal, laparoscopic [11] |
Alternative treatments:
-
Uterine artery embolisation (UAE) [11][12]
- How it works: Interventional radiology procedure — catheter inserted via femoral artery → guided to uterine artery → embolisation particles (PVA particles, gelfoam) injected → block blood supply to fibroids → ischaemic necrosis → shrinkage
- Clinical indication: uterine fibroid embolisation [12]
- Reduces fibroid volume by ~40–60% and improves symptoms in ~80–90% of patients
- Not recommended if future fertility desired (may affect ovarian reserve and uterine blood supply)
- Risks: post-embolisation syndrome (pain, fever, malaise), infection, fibroid expulsion, rarely premature ovarian insufficiency
-
High-intensity focused ultrasound (HIFU) [11]
- Focused ultrasound waves generate heat at a focal point within the fibroid → thermal ablation → coagulative necrosis → fibroid shrinks
- Non-invasive (no incision, no anaesthesia needed)
- Limited to certain fibroid locations/sizes
Management [13]:
Medical treatment: generally similar to endometriosis (unlike fibroids, where hormonal treatments are generally ineffective) [13]
- Oral contraceptive pills: little data on efficacy but still commonly used [13]
- Progestogen-only treatment: e.g. Mirena, Depo-Provera [13] — Mirena is particularly effective because local progestogen induces decidualisation and atrophy of the ectopic endometrial tissue within the myometrium
- Others: GnRH agonists, aromatase inhibitors [13]
Hysterectomy: definitive treatment [13]
- Only way to excise as there is no surgical plane for simple enucleation (even in adenomyoma) [13] — unlike fibroids which have a pseudocapsule allowing shelling out, adenomyosis diffusely infiltrates the myometrium
- Extent: subtotal hysterectomy as cervix and ovaries are not affected [13]
- Route: vaginal, laparoscopic, open, robotic [13]
Uterus-conserving procedures: [13]
- Uterine artery embolisation (UAE): reserved for failure or contraindication to medical + surgical therapy [13]
- Effect: ~2/3 had long-term decreased symptom severity, but there is a high rate of additional intervention for persistent or recurrent symptoms [13]
- Ablative techniques: e.g. RFA, HIFU (investigational) [13]
Asymptomatic adenomyosis incidentally found does not require any treatment [13]
| Type | Management | Rationale |
|---|---|---|
| Hyperplasia without atypia | Cyclical progestogen (oral MPA 10–20mg/day for 14 days/cycle) or continuous progestogen (LNG-IUS preferred). Re-biopsy at 3–6 months | Low malignant potential (~1–3%). Progestogen induces secretory transformation and apoptosis → reverses the hyperplasia. LNG-IUS superior to oral progestogen for regression rates (~96% vs ~66%) |
| Atypical hyperplasia (EIN) | Family complete: Hysterectomy (+ BSO recommended as ~40% harbour concurrent carcinoma). Fertility desired: High-dose progestogen (MPA 400–600mg/day or LNG-IUS) with endometrial surveillance biopsy every 3 months | High malignant potential (~30–40%). Hysterectomy is definitive. Fertility-sparing management is possible but requires very close surveillance — recurrence is common |
- Refer to Gynae-Oncology
- Standard treatment: Total hysterectomy + bilateral salpingo-oophorectomy (TH-BSO) ± pelvic/para-aortic lymph node dissection ± adjuvant therapy (radiotherapy ± chemotherapy depending on stage, grade, histological type)
- Fertility-sparing treatment possible in highly selected cases (Grade 1 endometrioid, Stage IA, no myometrial invasion, strong fertility desire): high-dose progestogen + very close surveillance
| Pathology | Management |
|---|---|
| Cervical ectropion | Asymptomatic: reassure and observe. Symptomatic (persistent PCB, troublesome discharge): cautery (silver nitrate or electrocautery) or cryotherapy — destroys the exposed columnar epithelium → heals with squamous epithelium (squamous metaplasia) |
| Cervical polyp | Polypectomy (grasp and twist the stalk at its base in clinic) → send for histology. Simple, usually done during speculum examination |
| Cervicitis / STD | Empirical antibiotics: Chlamydia → doxycycline 100mg BD × 7 days (or azithromycin 1g single dose). Gonorrhoea → ceftriaxone 500mg IM single dose + azithromycin 1g PO. Contact tracing essential |
| Cervical carcinoma | Urgent referral to Gynae-Oncology. Staging (FIGO). Treatment depends on stage: early → radical hysterectomy (Wertheim's) or trachelectomy (fertility-sparing) + pelvic lymphadenectomy; advanced → concurrent chemoradiotherapy (cisplatin-based) |
- Empirical broad-spectrum antibiotics covering Chlamydia, Gonorrhoea, and anaerobes
- Outpatient regimen (mild–moderate): Ceftriaxone 500mg IM single dose + Doxycycline 100mg BD × 14 days + Metronidazole 400mg BD × 14 days
- Inpatient (severe / tubo-ovarian abscess): IV cefoxitin + PO doxycycline, or IV clindamycin + IV gentamicin
- Contact tracing and partner treatment mandatory
- IUCD removal if present and clinically appropriate
Miscarriage management [14]:
Threatened miscarriage:
- Expectant management: preferred for all cases [14]
- Bed rest: commonly recommended but NOT evidence-based (associated with risk of DVT) [14]
- Avoid sexual intercourse, physical exertion: commonly recommended but NOT evidence-based [14]
- Progestogen treatment: promising with early evidence [14]
Complete miscarriage:
- Ensure complete passage of products of gestation [14]
- Routine suction curettage: not recommended [14]
Incomplete and missed miscarriage — approach (NICE guideline): [14]
- Expectant management × 7–14 days: 1st line due to cost-effectiveness and decreased risk of intervening and accidentally terminating a viable pregnancy [14]
- Medical management: 2nd choice if expectant management not acceptable [14] — vaginal misoprostol 800μg single dose [14]
- Surgical management: 3rd choice [14] — suction evacuation under LA or GA [14]
Indications for immediate surgical management: [14]
- Evidence of infection: always indicates need for surgical management [14]
- Increased risk of haemorrhage, e.g. late 1st trimester [14]
- Coagulopathies, unable to have blood transfusion [14]
Anti-D immunoglobulin: for Rh(D)-negative patients [14]
Ectopic pregnancy:
- Haemodynamically unstable / ruptured: Emergency surgery (laparoscopy or laparotomy) → salpingectomy (removal of affected tube)
- Haemodynamically stable, unruptured:
- Surgical: Laparoscopic salpingectomy (preferred if no desire for future fertility or contralateral tube is healthy) or salpingotomy (if fertility desired and contralateral tube damaged)
- Medical: Methotrexate (MTX) — a folate antagonist that inhibits rapidly dividing trophoblastic cells. Single-dose IM. Criteria: haemodynamically stable, unruptured, β-hCG < 5000 IU/L (some guidelines < 3000), no fetal heartbeat, no significant haemoperitoneum, compliant patient for follow-up
- Expectant: If β-hCG is low and declining spontaneously → may resolve without intervention. Requires very close serial β-hCG monitoring
Molar pregnancy:
- Suction evacuation of the mole (NOT medical induction — risk of embolisation of trophoblastic tissue)
- Histological confirmation
- Serial β-hCG monitoring post-evacuation until undetectable (weekly then monthly for 6–12 months depending on complete vs partial mole)
- Contraception during surveillance (pregnancy would confound hCG monitoring)
- If hCG plateaus or rises → gestational trophoblastic neoplasia (GTN) → chemotherapy
Local oestrogen cream: for atrophic vaginitis/endometritis [9]
Regimen: Premarin cream 0.5g QD × 2 weeks then 3×/week for 6 months [9]
How it works: Topical oestrogen is applied directly to the vaginal mucosa → stimulates proliferation and maturation of vaginal epithelium → restores glycogen content → restores lactobacilli → normalises vaginal pH → mucosa becomes thicker, more resilient, better lubricated → resolves bleeding, dryness, and dyspareunia
Why local rather than systemic? Local application achieves therapeutic vaginal concentrations with minimal systemic absorption → avoids the risks associated with systemic HRT (VTE, breast cancer) while effectively treating the vaginal symptoms
Beyond the general COC/progestogen/LNG-IUS approach above, PCOS management includes:
- Endometrial protection is the priority in PCOS patients not trying to conceive — cyclical progestogen or COC to prevent unopposed oestrogen exposure and hyperplasia
- Weight loss (if overweight/obese): Even 5–10% weight loss can restore ovulatory cycles — reduces peripheral aromatisation of androgens, improves insulin sensitivity, reduces SHBG suppression
- Metformin (off-label): Improves insulin sensitivity → reduces hyperinsulinaemia → reduces androgen production → may restore ovulatory cycles. Not first-line for bleeding management but useful adjunct in metabolic phenotype
- Anti-androgens (if hirsutism/acne predominant): Cyproterone acetate (often combined with EE as co-cyprindiol / Diane-35), spironolactone
- If fertility desired: Ovulation induction — letrozole (first-line, aromatase inhibitor) or clomiphene citrate (SERM)
- First 3 months: Reassure — breakthrough bleeding is common as the endometrium adjusts. Check compliance.
- After 3 months:
- Check compliance (most common cause of persistent breakthrough bleeding)
- Check for drug interactions (enzyme-inducing drugs: rifampicin, carbamazepine, phenytoin reduce COC efficacy)
- Consider increasing oestrogen dose (if on low-dose COC) or switching preparation
- Exclude other pathology (STD screen, speculum exam, USS/EA if persistent > 3 months → irregular bleeding while on hormonal therapy for > 3 months → hysteroscopy ± endometrial biopsy [7])
Algorithm for managing bleeding on HRT: [10]
| Scenario | Action |
|---|---|
| Breakthrough bleeding in first 6 months of HRT | No immediate intervention required [10] |
| Combined cyclical regimen: bleeding not around time of progestogen withdrawal / persistently irregular | Endometrial biopsy [10] |
| Continuous combined regimen: bleeding after achievement of amenorrhoea | Endometrial biopsy [10] |
When a patient presents acutely with torrential irregular bleeding and is haemodynamically compromised, the priority is resuscitate first, investigate second:
- ABC + IV access (2 large-bore cannulae)
- Bloods: FBC, group & save ± crossmatch, coagulation screen, β-hCG
- Fluid resuscitation / blood transfusion if needed
- Medical haemostasis:
- High-dose oral progestogen: Norethisterone 5mg TDS (can increase to 5mg QDS acutely) — stabilises the endometrium rapidly
- IV conjugated oestrogen (if available): 25mg IV every 4–6 hours × 24 hours — rapidly promotes endometrial proliferation and healing (used in acute settings when progestogen alone is insufficient)
- Tranexamic acid: 1g IV or PO TDS — stabilises clots
- If medical therapy fails:
- Intrauterine balloon tamponade (Foley catheter with 30–60mL balloon in uterine cavity)
- Surgical: uterine curettage, hysteroscopy, or hysterectomy as last resort
| Treatment | Mechanism | Indication | Key Contraindication/Limitation |
|---|---|---|---|
| COC pills [7] | Suppress HPO axis; stabilise endometrium; regular withdrawal bleed | 1st line for IMB/irregular bleeding (AUB-O) | VTE history, migraine with aura, breast cancer, uncontrolled HTN, smoker ≥ 35 |
| High-dose progestogen [7] | Oppose oestrogen; induce secretory change; predictable withdrawal bleed | When COC contraindicated | Not reliable contraception at standard doses |
| LNG-IUS (Mirena) [7] | Local progestogen → endometrial atrophy | Alternative to COC | Distorted uterine cavity (large submucosal fibroids) |
| Iron (FeSO₄) [7] | Replenish iron stores | All patients with iron deficiency anaemia from AUB | GI intolerance → switch to ferrum hausmann → IV iron |
| Tranexamic acid | Antifibrinolytic → stabilise endometrial clots | HMB (especially fibroids) | Active thromboembolism |
| Mefenamic acid | NSAID → ↓prostaglandins → ↓dysmenorrhoea | Painful menses (does NOT reduce bleeding in fibroids [11]) | GI ulcer, renal impairment, aspirin-sensitive asthma |
| GnRH agonists | Downregulate HPO → medical menopause → fibroid shrinkage | Pre-operative fibroid size reduction [11] | NOT for long-term use (bone density loss) [11] |
| Hysteroscopic polypectomy | Remove focal endometrial lesion | Symptomatic polyp, polyp > 1cm, histology needed | — |
| Myomectomy | Remove fibroids preserving uterus | Symptomatic fibroids + fertility desire | Recurrence risk (15–30%) |
| Hysterectomy | Definitive removal of uterus | Completed family, failed medical Mx, malignancy concern | Irreversible; major surgery |
| UAE | Embolise uterine arteries → fibroid ischaemia | Symptomatic fibroids, not fit for surgery, no fertility desire | Future fertility concern; post-embolisation syndrome |
| Local oestrogen | Restore vaginal epithelium | Atrophic vaginitis | — |
High Yield Summary — Management
-
Management is directed at the underlying cause. The symptom (IMB/irregular bleeding) is a signal, not the disease.
-
For AUB-O / no structural cause: 1st line = COC pills (unless contraindicated) → 2nd line = high-dose progestogen → alternative = LNG-IUS (Mirena) [7].
-
Endometrial polyp < 1cm: can observe (1/4 chance of spontaneous resolution) [7]. Symptomatic or > 1cm → hysteroscopic polypectomy.
-
Fibroids: medical Mx (tranexamic acid, GnRH agonists for pre-op shrinkage, Mirena if < 3cm no cavity distortion) → surgical (myomectomy if fertility desired, hysterectomy if family complete) → alternatives (UAE, HIFU) [11].
-
Adenomyosis: medical Mx similar to endometriosis (COC, progestogen-only, GnRH agonists). Hysterectomy is definitive as no surgical plane for enucleation. Asymptomatic = no treatment [13].
-
Miscarriage: expectant (1st line) → medical (misoprostol 800μg vaginal, 2nd line) → surgical (suction evacuation, 3rd line). Infection always warrants surgical Mx [14].
-
Iron supplementation: FeSO₄ 300mg BD × 12 weeks → Ferrum Hausmann if intolerant → IV iron [7].
-
HRT bleeding: first 6 months = observe. After that, unscheduled bleeding → endometrial biopsy [10].
Active Recall - Management of IMB and Irregular Bleeding
References
[7] Lecture slides: Adrian Lui Gynecology Notes.pdf (p20 — Management of IMB/Irregular Bleeding) [9] Lecture slides: Adrian Lui Gynecology Notes.pdf (p22 — Post-menopausal Bleeding treatment) [10] Lecture slides: Adrian Lui Gynecology Notes.pdf (p36 — Algorithm for HRT Administration) [11] Lecture slides: Adrian Lui Gynecology Notes.pdf (p92 — Fibroid medical and surgical treatment) [12] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p85 — Transcatheter Embolization indications) [13] Lecture slides: Adrian Lui Gynecology Notes.pdf (p51 — Adenomyosis management) [14] Lecture slides: Adrian Lui Gynecology Notes.pdf (p172 — Miscarriage management)
Complications of Intermenstrual and Irregular Bleeding
Complications can arise from three sources: (A) the abnormal bleeding itself, (B) the underlying cause of the bleeding, and (C) the treatments used to manage the bleeding. We will systematically address all three, explaining the pathophysiology of each complication from first principles.
A. Complications of the Bleeding Itself
This is the single most common complication of chronic IMB/irregular bleeding.
Anaemic symptoms: headache, palpitation, SOB, dizziness, fatigue, pica [1]
Why does chronic uterine bleeding cause iron deficiency anaemia?
- Each mL of blood lost contains ~0.5mg of iron (bound to haemoglobin)
- Normal menstrual blood loss is 30–40mL/cycle (~15–20mg iron/cycle)
- With abnormal bleeding, losses may be 80–200mL+/cycle or continuous intermenstrual losses → iron losses far exceed dietary absorption (~1–2mg/day)
- The body's iron stores (ferritin in hepatocytes and macrophages) are progressively depleted
- Once stores are exhausted → iron supply to the bone marrow falls → inadequate haemoglobin synthesis → microcytic, hypochromic red blood cells → anaemia
Symptom pathophysiology:
| Symptom | Mechanism |
|---|---|
| Fatigue, weakness | Reduced O₂ delivery to tissues (less Hb to carry O₂); iron is also a cofactor in mitochondrial electron transport chain enzymes → cellular energy production is impaired even before frank anaemia |
| Palpitations, tachycardia | Compensatory ↑cardiac output to maintain tissue O₂ delivery despite reduced O₂-carrying capacity |
| Dyspnoea (SOB) | ↑respiratory rate/effort to maximise O₂ loading in lungs (compensating for reduced O₂ transport) |
| Dizziness | Reduced cerebral O₂ delivery |
| Headache | Cerebral vasodilation in response to hypoxia → stretching of pain-sensitive meningeal vessels |
| Pica [1] | Craving non-food substances (ice/pagophagia, starch, clay). Mechanism poorly understood — possibly related to altered dopamine receptors in CNS (iron is a cofactor for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis) |
| Pallor | Reduced haemoglobin → less red colouration of skin/mucous membranes (especially conjunctivae, palmar creases, nail beds) |
| Koilonychia | Spoon-shaped nails — iron deficiency impairs nail matrix keratinisation |
| Angular cheilitis, glossitis | Iron is required for epithelial cell turnover → deficiency → atrophy of rapidly dividing mucosal cells |
Severity: Can range from mild (compensated, asymptomatic with low ferritin) to severe (Hb < 7g/dL, symptomatic, requiring blood transfusion in acute-on-chronic decompensation). Severe anaemia can precipitate high-output cardiac failure in elderly patients or those with underlying cardiac disease.
Important Clinical Point
Iron deficiency anaemia from chronic AUB is insidious — the body compensates remarkably well over time (rightward shift of the O₂-Hb dissociation curve via ↑2,3-DPG, increased cardiac output, expanded plasma volume). A woman may present with an Hb of 5–6 g/dL and appear deceptively well. Always check the Hb in any woman with chronic abnormal bleeding, even if she "looks fine."
This occurs in acute, heavy bleeding — most commonly from:
- Ruptured ectopic pregnancy (haemoperitoneum)
- Incomplete miscarriage with retained products
- Acute heavy anovulatory bleeding (endometrium shedding massively after prolonged unopposed oestrogen)
- Profuse bleeding if fibroid polyp protrudes through cervix [5]
Why shock? Rapid blood loss exceeding ~15–20% of circulating blood volume (Class II haemorrhage) → inadequate venous return → reduced cardiac output → inadequate tissue perfusion → organ dysfunction. If uncorrected → Class III/IV haemorrhagic shock → multi-organ failure → death.
Signs: Tachycardia, hypotension, cold/clammy peripheries, prolonged capillary refill, oliguria, altered consciousness.
Why is ectopic pregnancy the most dangerous? Because bleeding is both external (vaginal) and internal (into the peritoneal cavity from the ruptured tube). The internal bleeding may not be immediately apparent. The patient can lose > 1L into the abdomen before haemodynamic compromise becomes clinically obvious.
Often underappreciated but very real:
- Anxiety: Unpredictable bleeding causes constant worry about soiling clothes, embarrassment, ability to participate in social/work activities
- Sexual dysfunction: Fear of bleeding during intercourse → avoidance → relationship strain
- Depression: Chronic symptoms, fatigue from anaemia, disruption of daily life
- Work/school absenteeism: Significant socioeconomic impact
- Fear of serious disease: Many women fear cancer when they experience abnormal bleeding — appropriate counselling is therapeutic
B. Complications of Underlying Causes
The complications here depend on which specific condition is causing the IMB/irregular bleeding. We will focus on the most important and exam-relevant ones.
Excess risk of endometrial hyperplasia / carcinoma: due to chronic unopposed oestrogen exposure [3]
This is the most feared long-term complication of chronic anovulation.
Why? No ovulation → no corpus luteum → no progesterone → endometrium exposed to unopposed oestrogen continuously:
- Oestrogen drives endometrial proliferation (mitosis in glandular epithelium)
- Progesterone normally induces secretory differentiation AND promotes apoptosis of proliferating cells
- Without this braking mechanism → continuous proliferation → hyperplasia → accumulation of genetic mutations → atypical hyperplasia (EIN) → endometrioid adenocarcinoma (Type 1)
- This is the "hyperplasia–carcinoma sequence" — a stepwise progression driven by unopposed oestrogen
Clinical implication: Any woman with chronic anovulation (PCOS, hypothalamic amenorrhoea, perimenopause) must have endometrial protection — either cyclical progestogen or COCs to induce regular withdrawal bleeds and prevent endometrial build-up. Failure to do this exposes her to a preventable cancer.
PCOS metabolic complications: [3]
- ~10% of PCOS patients have T2DM, 30% have impaired glucose tolerance [3]
- Metabolic syndrome: obesity, insulin resistance, NAFLD, dyslipidaemia, hypertension, sleep apnoea
- Cardiovascular disease: long-term increased risk due to metabolic syndrome constellation
- Why? The insulin resistance that drives PCOS also drives the metabolic syndrome — these are manifestations of the same pathophysiology
Fibroid-related complications: [5]
| Complication | Pathophysiological Mechanism |
|---|---|
| Anaemic symptoms in prolonged heavy bleeding [5] | Chronic blood loss → iron deficiency (see above) |
| Pressure symptoms [5] | Irregularly enlarged uterus (usually > 12-week size): abdominal distension and pelvic mass; urinary frequency (anterior fibroid); rarely acute urinary retention (classically a 12-week uterus with cervical fibroid or posterior fibroid pushing onto a retroverted uterus → kinking of urethra); hydronephrosis; tenesmus (posterior fibroid) [5] |
| Venous compression [5] | Very large uteri may compress vena cava → increased risk of VTE [5]. Mechanisms: direct compression of pelvic veins → venous stasis → Virchow's triad (stasis + endothelial injury + hypercoagulability) → DVT/PE |
| Pain (uncommon but important) [5] | Red degeneration: classically occurs in mid-2nd trimester of pregnancy [5] — fibroid outgrows its blood supply during rapid pregnancy-related growth → haemorrhagic infarction → acute pain + fever + uterine tenderness. Torsion of pedunculated fibroid → acute pain ± fever [5]. Fibroid polyp ± prolapse: due to uterine contractions attempting to expel the fibroid polyp [5] |
| Pregnancy-related complications [5] | Infertility: association is controversial but appears to be increased in those distorting the cavity [5]. Miscarriage and preterm labour: due to adverse effect of submucosal fibroids on implantation, placentation, and increase in uterine contractility [5]. Malpresentation and obstructed labour: distortion of birth canal [5]. PPH: increased risk by decreased force and coordination of uterine contractions → increased risk of atony [5]. Red degeneration during pregnancy [5]. Caesarean section may be difficult when located in lower uterine segment [5] |
| Malignant transformation | Leiomyosarcoma is extremely rare (< 0.1% of fibroids). Rapid growth or postmenopausal growth is worrisome of malignancy [11] — postmenopausal fibroids should be shrinking (loss of oestrogen stimulus); if they grow, suspect sarcomatous transformation |
PID: associated with pelvic pain, fever, vaginal discharge [1]
| Complication | Mechanism |
|---|---|
| Tubo-ovarian abscess | Extension of salpingitis → collection of pus in fallopian tube (pyosalpinx) and ovary → walled-off abscess. Risk of rupture → generalised peritonitis → sepsis |
| Infertility | Salpingitis → tubal inflammation → intraluminal adhesions and fibrosis → tubal occlusion. ~10% risk after single episode, ~20% after two, ~40% after three episodes |
| Ectopic pregnancy | Tubal damage from previous PID → impaired tubal transport of ovum/embryo → embryo implants in the damaged tube instead of reaching the uterine cavity |
| Chronic pelvic pain | Post-inflammatory pelvic adhesions → distortion of normal anatomy → visceral pain |
| Fitz-Hugh-Curtis syndrome | Perihepatitis — inflammation tracks to the liver capsule (especially with chlamydial/gonococcal infection) → perihepatic adhesions ("violin string" adhesions) → right upper quadrant pain mimicking biliary/hepatic pathology |
- Tubal rupture: The growing gestational sac erodes through the tubal wall → massive intraperitoneal haemorrhage → haemodynamic shock → death if not treated emergently
- Tubal damage: Even with treatment (salpingotomy), the affected tube may be permanently damaged → reduced fertility, increased risk of recurrent ectopic
- Rh sensitisation: Feto-maternal haemorrhage in ectopic pregnancy can sensitise Rh-negative mothers → future pregnancies at risk of haemolytic disease of the newborn. This is why Anti-D immunoglobulin is given to Rh(D)-negative patients [14]
- Progression of hyperplasia without atypia: Low risk (~1–3%) but possible if untreated → atypical hyperplasia → carcinoma
- Progression of atypical hyperplasia: High risk (~30–40%) → endometrial carcinoma. Up to 40% of patients with atypical hyperplasia on biopsy already harbour concurrent carcinoma on hysterectomy specimen
- Endometrial carcinoma: Local invasion (myometrium, cervix), lymphatic spread (pelvic/para-aortic lymph nodes), distant metastases (lung, liver, bone). Early stage has excellent prognosis (Stage I five-year survival > 90%); advanced stage much worse
- Local invasion: parametrium, bladder (→ haematuria, vesicovaginal fistula), rectum (→ rectovaginal fistula)
- Lymphatic spread: pelvic → para-aortic → distant lymph nodes
- Ureteric obstruction: parametrial tumour compresses ureters → hydronephrosis → renal failure (a common mode of death in advanced cervical carcinoma)
- Lower limb lymphoedema: pelvic lymph node involvement → lymphatic obstruction
- VTE: cancer-associated hypercoagulability + pelvic venous compression
- Haemorrhage: Incomplete miscarriage → retained products prevent uterine contraction → ongoing heavy bleeding → haemodynamic compromise
- Infection (septic miscarriage): Retained necrotic products → ascending infection → endometritis → myometritis → septicaemia. Evidence of infection always indicates need for surgical management [14]
- Asherman's syndrome: Overly aggressive curettage (especially in the setting of infection) damages the basalis layer of the endometrium → intrauterine adhesions (synechiae) → amenorrhoea, infertility, recurrent miscarriage
- Rh sensitisation: As above — anti-D required for Rh-negative patients
- Psychological: Grief, guilt, anxiety, depression, post-traumatic stress — often underappreciated. Adequate counselling and follow-up are essential
- Gestational trophoblastic neoplasia (GTN): After evacuation, persistent trophoblastic activity (hCG fails to decline or rises) → can progress to invasive mole, choriocarcinoma, or placental site trophoblastic tumour. Why hCG monitoring is mandatory: hCG is produced by trophoblast; persistent/rising hCG after evacuation = persistent trophoblastic disease. Complete mole has ~15–20% risk of GTN; partial mole ~1–5%.
- Thyrotoxicosis: Very high hCG levels → structural similarity between hCG and TSH → hCG cross-reacts with TSH receptors on thyroid → thyroid hormone hypersecretion → clinical hyperthyroidism (tremor, tachycardia, weight loss)
- Hyperemesis: Markedly elevated hCG stimulates the vomiting centre
- Pre-eclampsia: Can occur in the first trimester (which is otherwise very rare and should raise suspicion for molar pregnancy) — mechanism involves abnormal trophoblastic invasion
C. Complications of Treatment
| Treatment | Complications | Mechanism |
|---|---|---|
| COC pills | VTE (DVT/PE) — most important; headache, breast tenderness, nausea, mood changes, breakthrough bleeding, rare: stroke, MI | Oestrogen increases hepatic synthesis of clotting factors (II, VII, VIII, X, fibrinogen), decreases antithrombin III, increases platelet aggregability → prothrombotic state |
| Progestogens | Bloating, mood changes, breast tenderness, acne (androgenic progestogens), weight gain, breakthrough bleeding | Progestogenic and androgenic receptor activation → fluid retention, altered lipid profile, sebaceous gland stimulation |
| GnRH agonists | Significant climacteric symptoms with menopause-related side effects (e.g. bone density loss) → NOT for long-term use [11]; hot flushes, vaginal dryness, mood changes, irregular bleeding [11] | Profound oestrogen suppression → medical menopause → loss of oestrogen's protective effects on bone (↑osteoclast activity, ↓osteoblast activity → net bone resorption), vasomotor centre, urogenital epithelium |
| Tranexamic acid | Theoretical VTE risk (rarely reported); GI upset; visual disturbances (rare) | Inhibition of fibrinolysis theoretically promotes clot persistence; however, evidence for clinically significant VTE risk is very limited |
| Mefenamic acid | GI ulceration/bleeding, nephrotoxicity, bronchospasm in aspirin-sensitive patients | COX inhibition → ↓prostaglandin synthesis → ↓protective mucus and bicarbonate secretion in gastric mucosa → mucosal erosion; ↓renal prostaglandin → ↓renal blood flow |
LNG-IUS complications: [15]
| Complication | Mechanism / Detail |
|---|---|
| Infection: increased risk in first 20 days, but very low risk after 3 weeks → minimised by proper pre-insertion screening + aseptic technique [15] | Insertion procedure introduces cervical flora into the sterile uterine cavity. Risk is highest immediately post-insertion; after the cervical mucus plug re-forms, risk drops to baseline |
| Uterine perforation: peritonitis, intense pain, bleeding [15] | The insertion device can penetrate through the myometrium during insertion (risk: ~1 in 1000). If the IUCD migrates into the peritoneal cavity → peritonitis, injury to adjacent organs (bowel, bladder) |
| Expulsion, translocation: require regular follow-up [15] | IUCD may be partially or completely expelled from the uterine cavity (risk ~5%). More common with nulliparity, heavy menses, or distorted cavity. Translocation = movement of IUCD into abnormal position |
| Irregular bleeding/spotting | Common in first 3–6 months as the endometrium atrophies. Usually self-limiting → counselling essential to prevent premature removal |
| Oligo-/amenorrhoea | Long-term progestogenic effect → endometrial atrophy → reduced/absent shedding. This is actually a benefit for many patients (reduced blood loss) but can cause anxiety if not counselled |
Endometrial aspiration (Pipelle):
- Very safe; minor complications: cramping, vasovagal reaction, light bleeding, very rarely uterine perforation or infection
- Failed/inadequate sample: Not a complication per se, but a limitation — may necessitate hysteroscopy
Hysteroscopy:
- Uterine perforation (~0.1%) → may require laparoscopy to assess for intra-abdominal injury
- Infection (rare)
- Fluid overload (if excessive distension media absorbed) → hyponatraemia, pulmonary oedema (more relevant with monopolar resectoscope using glycine; less with bipolar using normal saline)
- Bleeding
Myomectomy:
- Haemorrhage (can be significant — myomectomy bed bleeds freely)
- Adhesion formation (especially after open myomectomy) → future infertility, bowel obstruction
- Uterine rupture in subsequent pregnancy (if full-thickness myometrial incision — must deliver by elective Caesarean section)
- Recurrence of fibroids (15–30%)
Hysterectomy:
Complications of hysterectomy (relevant to cervical carcinoma context but applicable generally): [16]
| Complication | Detail |
|---|---|
| Haemorrhage | Intraoperative or post-operative; uterine and vaginal cuff vessels |
| Surgical injury to surrounding tissues [16] | Bladder, ureter, bowel, vessels [16]. Ureter is at particular risk where it crosses under the uterine artery ("water under the bridge") |
| Bowel complications [16] | Constipation, ileus, adhesions, intestinal obstruction, fistula [16] |
| Wound complications | Infection, pain, bruises, delayed healing, keloid formation [16] |
| Infection | Wound infection, pelvic abscess, urinary tract infection (especially with prolonged catheterisation) |
| VTE | Pelvic surgery → venous stasis + tissue injury → Virchow's triad → DVT/PE. Prophylaxis essential (LMWH, compression stockings, early mobilisation) |
| Bladder dysfunction [16] | After radical hysterectomy: damage to bladder nerves → routine placement of urinary catheter × 10–14 days followed by bladder training [16]. This is unique to radical hysterectomy (Wertheim's) where the parametria (containing the pelvic autonomic nerves) are excised |
| Vaginal cuff dehiscence | Rare (~0.3%); more common after laparoscopic or vaginal hysterectomy. Can present with pelvic pain, vaginal bleeding, or evisceration |
| Early menopause | If bilateral oophorectomy performed (BSO) → immediate surgical menopause → vasomotor symptoms, osteoporosis risk, cardiovascular risk. If ovaries preserved, menopause may still occur 1–3 years earlier than expected (disrupted ovarian blood supply) |
| Psychosexual impact | Loss of uterus → grief, altered body image, loss of fertility → depression, relationship strain. Requires sensitive pre-operative counselling |
Uterine Artery Embolisation (UAE):
- Post-embolisation syndrome (pain, fever, malaise, nausea — in ~30–50%): inflammatory response to ischaemic necrosis of fibroid tissue
- Infection/abscess of necrotic fibroid (rare but serious)
- Fibroid expulsion (if submucosal — can cause heavy bleeding, infection)
- Premature ovarian insufficiency (non-target embolisation of ovarian arteries → follicular loss; risk increases with age > 40)
- Amenorrhoea (~5%)
High Yield Summary — Complications
-
Iron deficiency anaemia is the most common complication of chronic AUB. Symptoms include headache, palpitation, SOB, dizziness, fatigue, pica [1]. Can be severe enough to cause high-output cardiac failure.
-
Chronic anovulation → excess risk of endometrial hyperplasia / carcinoma due to unopposed oestrogen [3]. This is the most important long-term complication of untreated PCOS/anovulatory bleeding — and it is preventable with cyclical progestogen.
-
Fibroid complications: pressure symptoms (urinary, bowel, VTE from vena cava compression), pregnancy-related (miscarriage, preterm labour, malpresentation, PPH), red degeneration in pregnancy, torsion of pedunculated fibroid [5].
-
PID complications: tubo-ovarian abscess, infertility (~10% per episode), ectopic pregnancy, chronic pelvic pain, Fitz-Hugh-Curtis syndrome.
-
Ectopic pregnancy → tubal rupture → haemorrhagic shock → death. This is why pregnancy test is mandatory in any reproductive-age woman with AUB.
-
Incomplete miscarriage → haemorrhage (retained products prevent contraction) and sepsis (infection always indicates need for surgical management) [14]. Asherman's syndrome from over-zealous curettage.
-
Treatment complications: COCs → VTE (oestrogen-mediated prothrombotic state); GnRH agonists → bone density loss, NOT for long-term use [11]; LNG-IUS → perforation, expulsion, infection (highest in first 20 days) [15]; hysterectomy → ureteric/bladder injury, bladder dysfunction (especially radical hysterectomy), VTE [16].
Active Recall - Complications of IMB and Irregular Bleeding
References
[1] Lecture slides: Adrian Lui Gynecology Notes.pdf (p19 — Intermenstrual and Irregular Bleeding) [3] Lecture slides: Adrian Lui Gynecology Notes.pdf (p41 — PCOS) [5] Lecture slides: Adrian Lui Gynecology Notes.pdf (p90 — Uterine fibroids clinical features) [11] Lecture slides: Adrian Lui Gynecology Notes.pdf (p92 — Fibroid medical and surgical treatment) [14] Lecture slides: Adrian Lui Gynecology Notes.pdf (p172 — Miscarriage management) [15] Lecture slides: Adrian Lui Gynecology Notes.pdf (p151 — LNG-IUS / IUCD complications) [16] Lecture slides: Adrian Lui Gynecology Notes.pdf (p123 — Hysterectomy complications)
High Yield Summary
IMB = bleeding between well-defined regular menses → think surface/structural lesions (polyps, ectropion, cervical CA, endometrial pathology).
Irregular bleeding = disturbed cycle itself → think anovulation, pregnancy, hormonal drugs.
Always exclude pregnancy first (β-hCG) — ectopic is life-threatening.
Anovulation (AUB-O): No corpus luteum → no progesterone → unopposed oestrogen → thick, fragile endometrium → prolonged oligomenorrhoea then heavy bleeding/spotting. Extremes of reproductive age, PCOS (most common), stress, thyroid disease.
PCOS pathogenesis: ↑LH:FSH → androgen excess → impaired folliculogenesis; insulin resistance → hyperinsulinaemia → ↓SHBG → more free androgens.
Unopposed oestrogen drives hyperplasia → carcinoma sequence. RFs: PCOS, obesity, tamoxifen, unopposed oestrogen HRT.
Post-coital bleeding → cervical pathology (ectropion, polyp, cervical carcinoma). PMB → endometrial carcinoma until proven otherwise.
Breakthrough bleeding on hormonal contraceptives: common first 3 months; check compliance; investigate if persistent > 3 months.
Physiological mid-cycle spotting (Day 14): transient oestrogen dip — diagnosis of exclusion.
High Yield Summary — Differential Diagnosis
Three triage questions: (1) Pregnant? (2) Genital tract source? (3) What pattern?
| Pattern | Key DDx |
|---|---|
| IMB | Endometrial/cervical polyp, hyperplasia/CA, ectropion, cervicitis/STD, breakthrough bleeding, C/S scar defect |
| Irregular | AUB-O (PCOS, perimenopause), endometrial pathology, iatrogenic, coagulopathy |
| PCB | Cervical ectropion, polyp, cervical carcinoma, cervicitis |
| PMB | Endometrial carcinoma (must exclude) |
Anatomical sieve (bottom up): Vulva → vagina → cervix → endometrium → myometrium → adnexa → systemic.
Pregnancy-related: Ectopic (7–8 weeks, pain + bleeding), miscarriage, molar pregnancy — always β-hCG.
PCOS mimics: Late-onset CAH (17-OHP), androgen-secreting tumour (severe virilisation, testosterone > 150–200), Cushing's, thyroid, hyperprolactinaemia.
Anovulatory vs endometrial pathology can coexist — PCOS patients still need endometrial assessment.
DUB = diagnosis of exclusion (anovulatory: HPO disruption; ovulatory: endometrial haemostatic defect).
High Yield Summary — Diagnosis
IMB/irregular bleeding is a symptom — no formal diagnostic criteria; investigate to find the cause.
Mandatory for all reproductive-age women: β-hCG + CBC.
| Investigation | Indication |
|---|---|
| EA (Pipelle) | Age ≥ 40 persistent IMB/irregular; age ≥ 45 regular HMB; RFs (obesity, PCOS, tamoxifen); all PMB |
| Hysteroscopy | Suspected polyp/submucosal fibroid; EA failed; bleeding on hormonal Tx > 3 months |
| TVUS | Structural pathology; ET ≤ 4 mm postmenopausal = reassuring |
| Clotting + vWF | HMB since menarche, mucocutaneous bleeding |
| Hormonal profile | Irregular cycles: LH, FSH, E2, PRL, testosterone, TFT, OGTT (PCOS) |
| Colposcopy + biopsy | Abnormal smear or suspicious cervical lesion |
| STD swabs | Cervicitis suspected |
PCOS (Rotterdam): ≥ 2 of 3 — oligo/anovulation, hyperandrogenism, polycystic morphology on USS — plus exclude mimics. USS alone is NOT diagnostic (~25% of normal women). LH:FSH ratio is supportive only.
HRT bleeding: First 6 months → observe. Bleeding after amenorrhoea on continuous combined → endometrial biopsy.
Algorithm: Pregnancy test → speculum → bloods → EA if indicated → USS → hysteroscopy if focal lesion.
High Yield Summary — Management
Treat the underlying cause — symptom is a signal, not the diagnosis.
AUB-O / no structural cause:
| Line | Treatment |
|---|---|
| 1st line | COCP (unless C/I) — suppresses HPO axis, organises endometrium, protects against hyperplasia |
| 2nd line | High-dose cyclical progestogen (norethisterone 5 mg TDS days 5–26) |
| Alternative | LNG-IUS (Mirena) — local progestogen, ~90% ↓MBL; not reliable contraception at standard progestogen doses |
| Supportive | Iron supplementation (FeSO₄ 300 mg BD × 12 weeks) |
Cause-specific:
- Endometrial polyp: Hysteroscopic polypectomy if symptomatic or > 1 cm (always histology)
- Hyperplasia without atypia: Progestogen (Mirena preferred) + re-biopsy 3–6 months
- Atypical hyperplasia: Hysterectomy (or high-dose progestogen if fertility desired)
- Cervical ectropion: Reassure; cautery/cryotherapy if symptomatic
- Cervical polyp: Polypectomy + histology
- PID: Ceftriaxone + doxycycline + metronidazole
- PCOS: Endometrial protection (cyclical progestogen/COCP), weight loss, metformin adjunct
Miscarriage: Expectant (1st line) → misoprostol 800 μg vaginal (2nd) → suction evacuation (3rd); infection always needs surgery.
Acute torrential bleeding: Resuscitate → high-dose progestogen → IV TXA → balloon tamponade → surgery.
High Yield Summary — Complications
IDA from chronic blood loss — most common complication of the bleeding itself.
Chronic anovulation → endometrial hyperplasia → carcinoma — preventable with cyclical progestogen; most important long-term complication of untreated PCOS/anovulatory bleeding.
Fibroid complications: Pressure symptoms, pregnancy complications (red degeneration, miscarriage, PPH), VTE from large uterus.
PID complications: TOA, infertility (~10% per episode), ectopic pregnancy, chronic pelvic pain, Fitz-Hugh-Curtis syndrome.
Ectopic pregnancy: Tubal rupture → haemorrhagic shock → death. Rh-negative → anti-D.
Endometrial/cervical malignancy: Local invasion, lymphatic spread, ureteric obstruction.
Treatment complications: COCP → VTE; GnRH agonists → bone loss; Mirena → perforation (~0.1%), expulsion (~5%), infection (highest first 20 days); hysterectomy → ureteric/bladder injury, bladder dysfunction (radical), lymphoedema.
Psychological: Anxiety, depression, sexual dysfunction, work absenteeism — often underappreciated.
Heavy Menstrual Bleeding (hmb)
Heavy menstrual bleeding is excessive menstrual blood loss (>80 mL per cycle) that interferes with a woman's physical, social, emotional, or material quality of life.
Post-menopausal Bleeding (pmb)
Post-menopausal bleeding is any vaginal bleeding occurring 12 or more months after the last menstrual period, requiring investigation to exclude endometrial carcinoma.