Hypermenorrhoea (Heavy Menstrual Bleeding) - No Fibroids, OCP Declined

Clinical Clarification

CAUSES of Hypermenorrhoea (AUB Classification - PALM-COEIN)

Structural (PALM)

Non-structural (COEIN)

Key: Anovulatory bleeding (AUB-O) is the most common cause in reproductive-age women. Without progesterone to stabilize the endometrium, shedding is irregular, not limited in amount or duration, and not accompanied by spiral arteriolar vasoconstriction - Berek & Novak's Gynecology, p. 437.

• Hypothyroidism (TSH) - severe hypothyroidism causes HMB
• Hyperprolactinaemia
• Chronic PID
• Morbid obesity

NEXT STEP OF MANAGEMENT (OCP declined, wants future pregnancy)

Step 1 - Complete the workup (if not done)

• CBC (rule out anaemia, thrombocytopenia)
• TSH, prolactin
• Coagulation screen (PT, aPTT, bleeding time, von Willebrand studies) - especially if HMB since menarche
• Transvaginal ultrasound (adenomyosis, endometrial thickness, polyps)
• Endometrial biopsy if age >35 or risk factors for hyperplasia
• Day 21 progesterone (to confirm if ovulatory)

Step 2 - Medical Management Options (fertility-sparing, OCP declined)

• Up to 96% reduction in blood loss at 12 months
• ~50% of users become amenorrhoeic at 12 months
• Releases low-dose levonorgestrel locally into the uterine cavity - causes gland atrophy and decreases flow
• Does NOT impair future fertility (removed when pregnancy desired)
• Approved for contraception but highly effective for HMB
• First-line non-OCP option for menorrhagia - Swanson's Family Medicine Review, p. 411

• 1g TDS during menstruation (cycle days 1-5)
• Reduces blood loss by ~40-50%
• No hormonal effects, fertility preserved
• Good for women who want purely cycle-based treatment

• Taken during menstruation
• Reduce blood loss by 20-30%
• Also help if dysmenorrhoea is present

• Norethisterone 5mg TDS from day 5-26 of cycle
• Effective for anovulatory bleeding - addresses inadequate luteal phase
• Does not provide contraception (unlike OCP)
• Can be used if patient wants a hormonal option without combined pill

• Eventually induces amenorrhoea
• Provides contraception
• Note: Fertility return may be delayed after stopping

Step 3 - If Medical Management Fails (refractory cases)

Summary Algorithm for THIS Patient

Hypermenorrhoea + No fibroids on hysteroscopy + OCP declined + Wants future pregnancy
            ↓
Complete workup: CBC, TSH, coagulation screen, TVUS, Day 21 progesterone
            ↓
   ┌─────────────────────────────────────────┐
   │ FIRST-LINE: LNG-IUS (Mirena)            │
   │ - 96% reduce blood loss                 │
   │ - Reversible, fertility preserved       │
   └─────────────────────────────────────────┘
            OR (if IUS refused or not appropriate)
   ┌─────────────────────────────────────────┐
   │ Tranexamic acid + NSAID during periods  │
   │ ± Cyclic progestogen (day 5-26)         │
   └─────────────────────────────────────────┘
            If no response → Surgical evaluation

Sources: Swanson's Family Medicine Review, p. 410-411; Berek & Novak's Gynecology, p. 437; Rosen's Emergency Medicine.

Hypermenorrhoea - Full Detailed Explanation

1. Understanding the Clinical Scenario

• Heavy flow ("hypermenorrhoea")
• Cycles every 25 days (slightly frequent)
• Hysteroscopy (HSK) - no fibroids found (rules out submucosal leiomyoma)
• Doctor suggested OCPs but patient declined
• Wants future pregnancy (so fertility must be preserved)

2. CAUSES - Full Explanation Using PALM-COEIN

PALM = Structural Causes

• Endometrial polyps are fleshy overgrowths of the endometrial lining
• They cause heavy menstrual bleeding AND intermenstrual spotting
• Important: Hysteroscopy is actually the gold standard to diagnose polyps. If HSK was done and no polyps were reported, this is largely ruled out - BUT small polyps can be missed
• Associated with tamoxifen use and infertility
• Treatment: Hysteroscopic polypectomy (fertility-preserving)

• Endometrial glands and stroma embedded within the myometrium (uterine muscle)
• Causes the uterus to become bulky, boggy, and tender
• Classic presentation: Heavy, PAINFUL, regular cycles - "dysmenorrhoea + menorrhagia"
• NOT visible on hysteroscopy (hysteroscopy only sees the uterine cavity surface)
• Diagnosed on transvaginal ultrasound (heterogeneous myometrium, myometrial cysts) or MRI (most accurate)
• This is a commonly missed cause when hysteroscopy is done and called "normal"

• Endometrial hyperplasia from unopposed oestrogen can cause HMB
• Endometrial carcinoma - less likely in young women but must be considered if >35 years or risk factors (obesity, PCOS, nulliparity, diabetes)
• Diagnosed by endometrial biopsy

COEIN = Non-Structural Causes

• 5-20% of women with menorrhagia have an undiagnosed bleeding disorder
• Most common: Von Willebrand Disease (VWD) - a deficiency/dysfunction of VWF protein needed for platelet plug formation
• Suspect if:
  • Heavy bleeding since menarche (first period)
  • Easy bruising, epistaxis (nosebleeds)
  • Prolonged bleeding after dental work or surgery
  • Family history of bleeding disorders
  • Postpartum haemorrhage
• Also consider: Thrombocytopenia (low platelets), liver disease (reduced clotting factor production), anticoagulant drugs

In a normal ovulatory cycle, after ovulation the corpus luteum produces progesterone. Progesterone stabilises the endometrium by causing it to become secretory and structurally organised. When progesterone is withdrawn at the end of the cycle, the endometrium sheds in an orderly, synchronised way - with spiral arteriolar vasoconstriction that limits blood loss.

When there is no ovulation (anovulation), there is no progesterone. The endometrium is stimulated by oestrogen alone and keeps proliferating. When it eventually breaks down, it does so randomly, from different sites at different times, without vasoconstriction - so bleeding is heavy, irregular, and prolonged.

• Low oestrogen levels = irregular light/prolonged bleeding
• High sustained oestrogen = episodes of amenorrhoea followed by sudden heavy bleeding

• In ovulatory women, the endometrium itself can be the problem
• Imbalance between local vasoconstrictors (prostaglandin F2α, endothelin-1) and vasodilators (prostaglandin E2, prostacyclin I2)
• When vasodilators dominate, more blood loss occurs during menstruation
• This is why NSAIDs work - they block prostaglandin synthesis, shifting the balance toward vasoconstriction
• Chronic endometritis (e.g., from Chlamydia infection) can also cause menorrhagia

• Copper IUD causes heavier periods
• Anticoagulants (heparin, warfarin, NOACs)
• Steroids, tamoxifen
• Breakthrough bleeding with progestin-only pills / implants

• Arteriovenous malformations
• Myometrial hypertrophy
• Rare and poorly understood causes

3. Why the Doctor Suggested OCPs

1. Suppressing ovulation (no LH surge)
2. Providing cyclical progestogen that stabilises the endometrium
3. Thinning the endometrium (reduced blood loss)
4. Regularising cycles

4. NEXT STEP OF MANAGEMENT (OCP Declined, Fertility Desired)

Step 1 - Investigations That Should Be Done First

Step 2 - Medical Treatment Options (Fertility-Preserving, No OCP)

Option A: Levonorgestrel-IUS (LNG-IUS / Mirena) - BEST FIRST-LINE CHOICE

• A small T-shaped device placed inside the uterus
• Releases a tiny, steady dose of levonorgestrel (a progestogen) directly into the uterine cavity
• This causes: local endometrial gland atrophy → thins the endometrium → dramatically reduces menstrual flow
• Systemic absorption is minimal (avoids most hormonal side effects)

• Up to 96% reduction in blood loss at 12 months
• About 50% of women become completely amenorrhoeic (no periods) at 12 months
• As effective as surgical endometrial ablation

• No systemic hormonal effects
• Fertility fully restored when removed (woman can get pregnant shortly after removal)
• Lasts up to 5-7 years
• Does not interfere with the HPO axis in the same way OCPs do
• First-line non-pill option per ACOG and FIGO guidelines

• Irregular/unpredictable spotting in first 3-6 months (counsel the patient about this upfront)
• Cramping at insertion
• Small risk of expulsion or perforation

Option B: Tranexamic Acid (TXA)

• The endometrium normally breaks down fibrin clots through fibrinolysis (via plasminogen activators)
• In women with HMB, there is excess fibrinolytic activity in the endometrium
• Tranexamic acid is an antifibrinolytic - it blocks the conversion of plasminogen to plasmin, preventing clot breakdown
• This helps blood clots form and stay at the bleeding site, reducing blood loss

• No hormonal effects at all - does not affect fertility or ovulation
• Only taken during periods (not a daily medication)
• Can be combined with NSAIDs for additive effect

Option C: NSAIDs (e.g., Mefenamic Acid, Ibuprofen)

• Block COX enzymes → reduce prostaglandin synthesis
• Shift endometrial prostaglandin balance toward vasoconstrictors (PGF2α > PGE2)
• Reduce both blood loss AND dysmenorrhoea (pain)

Option D: Cyclic Oral Progestogens

• Artificially replaces the progesterone that is absent in anovulatory cycles
• Stabilises the endometrium so it sheds in an organised, controlled manner

• Norethisterone 5mg 3 times a day, days 5 to 26 of the cycle
• Medroxyprogesterone acetate (MPA) 10mg OD, days 12-26

• Works best for anovulatory AUB (AUB-O)
• Does NOT provide contraception (unlike OCPs)
• Fertility is preserved
• Side effects: Bloating, mood changes, breast tenderness

Option E: Depot Medroxyprogesterone Acetate (DMPA / Depo-Provera)

• IM injection every 3 months
• Eventually induces amenorrhoea in most women
• Downside: Fertility return may be delayed by 6-18 months after stopping - relevant for this patient who wants to conceive

Step 3 - If Medical Treatment Fails (Surgical Options)

5. The Big Picture - Putting It Together

Patient: Hypermenorrhoea, HSK = no fibroids, wants future pregnancy, OCP refused
         ↓
First: Investigate → TSH, CBC, Day 21 progesterone, TVUS, coag screen if indicated
         ↓
 Is there an identifiable cause?
 ├─ Hypothyroidism → Treat with levothyroxine
 ├─ PCOS → Metformin ± progestogens
 ├─ Adenomyosis on TVUS → LNG-IUS best option
 ├─ Polyp on TVUS → Hysteroscopic polypectomy
 ├─ VWD/Coagulopathy → TXA + DDAVP + haematology referral
 └─ No clear cause (AUB-E or AUB-O) → Proceed to treatment below
         ↓
Medical Treatment (OCP declined, fertility desired):
 FIRST CHOICE → LNG-IUS (Mirena) - 96% reduction, reversible
 ALTERNATIVE → Tranexamic acid + NSAID during periods
 IF ANOVULATORY → Add cyclic norethisterone day 5-26
         ↓
 No response after 3-6 months?
         ↓
Surgical review (ablation only if family complete; GnRH agonist as bridge)

Sources: Berek & Novak's Gynecology (PALM-COEIN, AUB-O mechanism, AUB-C); Swanson's Family Medicine Review (LNG-IUS 96% efficacy, management algorithm)

Updated Clinical Picture

What This Tells You Clinically

TRACK 1 - STOP THE BLEEDING (Immediate)

High-Dose Progestogen (Norethisterone) - Drug of Choice Here

• The endometrium has been continuously stimulated by oestrogen without progesterone (anovulatory)
• It has become thick, fragile, and unstable - shedding from random sites continuously
• High-dose progestogen rapidly stabilises and organises the endometrium, stopping the shedding
• Once stopped and dose reduced, a withdrawal bleed occurs (like a "reset"), after which normal cycles can resume

• Norethisterone 5 mg THREE times a day (every 8 hours) to stop active bleeding
• Once bleeding stops (usually within 24-48 hours), continue for another 7-10 days
• Then taper the dose and stop
• A withdrawal bleed will follow 2-3 days after stopping
• After this, start cyclic norethisterone (day 5-26) for ongoing cycle control

This is the standard approach in anovulatory prolonged bleeding without OCP - analogous to using progesterone to "lock down" a runaway endometrium.

If Extremely Heavy / Not Responding:

• IV conjugated oestrogen (Premarin 25mg IV) - rapidly promotes endometrial proliferation and re-epithelialisation to stop acute bleeding
• Then follow with progestogen to stabilise

Tranexamic Acid (Adjunct)

• 1g TDS during active bleeding
• Reduces ongoing blood loss by 40-50% by blocking fibrinolysis
• Can be used simultaneously with progestogen
• Safe, no fertility impact

NSAIDs (Adjunct)

• Mefenamic acid / Ibuprofen
• Reduces prostaglandin-driven vasodilation in endometrium
• Helps control flow + any pain

TRACK 2 - TREAT THE ANAEMIA

Iron Replacement (Mandatory)

• Ferrous sulphate 325 mg (contains ~65 mg elemental iron) - 2 to 3 tablets per day
• Total elemental iron needed: 200-300 mg/day
• Take on an empty stomach for best absorption (with vitamin C)
• Reticulocyte count rises in 4-7 days, peaks at 10 days
• Hb rises by ~1 g/dL per week with adequate iron
• Continue treatment for 3-6 months after Hb normalises to replenish iron stores (ferritin)

• If she has chest pain, breathlessness at rest, haemodynamic instability → transfuse 1-2 units packed RBCs
• If she is stable (just tired, pale) → IV iron (faster than oral, bypasses GI absorption issues) + oral iron ongoing
• IV iron options: Ferric carboxymaltose (single large dose), iron sucrose

TRACK 3 - LONG-TERM PREVENTION (Once Bleeding Controlled)

LNG-IUS (Mirena) - INSERT AFTER ANAEMIA IS CORRECTED

• Wait until Hb is >10 g/dL before insertion (reduces procedure risk)
• 96% reduction in blood loss at 12 months
• 50% achieve complete amenorrhoea
• Fully reversible - remove when she wants to conceive
• No systemic hormonal effects

• Cyclic norethisterone (day 5-26 each month)
• Tranexamic acid during each period

Complete Management Summary for This Patient

PROBLEM: Bleeding x 25 days + Hb 8 g/dL + No fibroids + OCP declined

STEP 1 → STOP BLEEDING (Immediately)
   Norethisterone 5mg TDS until bleeding stops, then taper
   + Tranexamic acid 1g TDS
   + NSAIDs (mefenamic acid 500mg TDS)

STEP 2 → TREAT ANAEMIA (Simultaneously)
   Hb 8, stable → IV Ferric Carboxymaltose OR Oral Ferrous Sulphate 325mg TDS
   Hb 8, symptomatic → 1-2 units packed RBCs + IV iron

STEP 3 → INVESTIGATE THE CAUSE
   TSH, Prolactin, Day 21 progesterone
   TVUS (adenomyosis? polyp?)
   Coagulation screen if HMB since menarche

STEP 4 → LONG-TERM CONTROL (Once stable, Hb > 10)
   Insert LNG-IUS (Mirena) ← FIRST CHOICE
   OR Cyclic norethisterone day 5-26

STEP 5 → CONTINUE IRON for 3-6 months to replenish stores

Histology Shows Endometrial Overgrowth = ENDOMETRIAL HYPERPLASIA

1. What Is Endometrial Hyperplasia?

• Glands keep multiplying and crowding
• The gland-to-stroma ratio increases abnormally
• The endometrium becomes architecturally and/or cytologically abnormal
• This is endometrial hyperplasia

"Endometrial hyperplasia is defined as an abnormal proliferation of the endometrial glands relative to the stroma, resulting in an increased gland-to-stroma ratio." - Robbins, Cotran & Kumar Pathologic Basis of Disease

2. WHO Classification (2014 - Current Binary System)

"Up to 40% of females with a diagnosis of atypical hyperplasia are found to have carcinoma when a hysterectomy is performed." - Robbins Pathology

3. Old Classification (Still Used in Exams)

4. Why Did This Patient Get Endometrial Hyperplasia?

• No ovulation → no corpus luteum → no progesterone
• Oestrogen continues to drive endometrial proliferation, month after month
• Eventually the endometrium does not shed normally; it overgrows
• Bleeding occurs when the overgrown endometrium outstrips its blood supply and breaks down chaotically

PTEN tumour suppressor gene is mutated in >20% of endometrial hyperplasias - this is also mutated in endometrial carcinoma, confirming hyperplasia is a precancerous continuum - Robbins Pathology

5. Management Based on Histology Result

A. Hyperplasia WITHOUT Atypia (Low Risk - 1-3% cancer)

• Delivers high local progesterone directly to the endometrium
• Causes gland atrophy and reverses hyperplasia
• Preferred especially in this patient - fertility preserving, no OCP needed
• Regression rates of hyperplasia without atypia with LNG-IUS: >80-90%

• Megestrol acetate 40-160 mg/day (continuous)
• OR Norethisterone day 5-26 cyclically
• Continue for at least 3-6 months
• Repeat endometrial biopsy to confirm regression

• Repeat biopsy after 3-6 months of treatment
• If regressed → continue prevention (LNG-IUS best), address underlying cause
• If not regressed → escalate (increase dose or reconsider diagnosis)

• PCOS → Metformin + weight loss
• Hypothyroidism → Levothyroxine
• Obesity → Weight loss alone can reverse hyperplasia

B. Atypical Hyperplasia / EIN (HIGH RISK - 29% cancer; 40% may already have hidden carcinoma)

• Recommended for all women who have completed their family
• Why: 25-43% of atypical hyperplasia cases harbour an undiagnosed endometrial carcinoma at hysterectomy
• Hysterectomy removes all risk

• Megestrol acetate 160 mg/day (continuous) - most reliable for reversal
• OR LNG-IUS + oral progestogen combined
• Response rate: ~76% (24% never respond)
• Median time to regression: 12 weeks
• Recurrence rate after regression: ~24% within 1 year

• Endometrial biopsy every 3 months
• MRI to assess myometrial invasion (rule out concurrent carcinoma)
• If no regression by 6-9 months → hysterectomy even in young patient
• After successful pregnancy → hysterectomy recommended (definitive)
• "Progestational therapy can successfully treat disease while preserving fertility... patients must be counselled that failure to identify recurrence may lead to delay in definitive surgery and a compromised prognosis." - Berek & Novak's Gynecology

6. Complete Management Algorithm for THIS Patient

Histology: Endometrial Hyperplasia
              ↓
    FIRST: Is atypia present or absent?
              ↓
 ┌────────────────────────────────────────────────┐
 │ WITHOUT ATYPIA (1-3% cancer risk)              │
 │                                                │
 │ • LNG-IUS (FIRST CHOICE - fertility sparing)   │
 │   OR Cyclic norethisterone day 5-26            │
 │ • Treat underlying cause (PCOS, obesity, TSH)  │
 │ • Repeat biopsy at 3-6 months                  │
 │ • Iron supplementation for Hb 8               │
 └────────────────────────────────────────────────┘
              OR
 ┌────────────────────────────────────────────────┐
 │ WITH ATYPIA / EIN (29% cancer risk)            │
 │                                                │
 │ Family complete → HYSTERECTOMY                 │
 │                                                │
 │ Wants pregnancy (as in this patient):          │
 │ • MRI first (rule out myometrial invasion)     │
 │ • Megestrol acetate 160mg/day                  │
 │ • Biopsy every 3 months                        │
 │ • If regressed → conceive ASAP (IVF/IUI)      │
 │ • After delivery → Hysterectomy recommended    │
 │ • No regression by 6-9 months → Hysterectomy  │
 └────────────────────────────────────────────────┘

SIMULTANEOUSLY IN BOTH CASES:
• Iron therapy (Hb 8) - ferrous sulphate 325mg TDS
• Stop bleeding: norethisterone high dose + tranexamic acid
• Investigate: TSH, fasting glucose, TVUS, BMI assessment

7. Why This Diagnosis Changes Everything

Sources: Robbins, Cotran & Kumar Pathologic Basis of Disease; Berek & Novak's Gynecology, p. 2145-2146

PubMed Evidence: Fertility-Sparing Progestin Therapy in Atypical Endometrial Hyperplasia

1. Does Progestin Therapy Work? (Complete Response Rates)

• Complete response (CR) rate for AEH: 87%
• Pregnancy rate after CR: 48%
• Live birth rate: 37%
• Recurrence rate: ~22%
• Patients treated with LNG-IUS alone had the highest CR rate (85% for endometrial cancer, even higher for AEH)

• Overall complete remission: 82.8%
• Pregnancy rates by regimen:
  • Megestrol/MPA alone: 56.3%
  • LNG-IUS alone: 63.1%
  • MPA + LNG-IUS combined: 59.8%
  • Megestrol + Metformin: 57.9%
• Live birth rates: 68-81% across regimens
• Women who had hysteroscopic evaluation alongside progestins had higher pregnancy rates (68.6% vs 60.5%) and better live birth rates (81.2% vs 67%)

2. Does Adding Metformin Help?

• Progestin + metformin vs progestin alone:
  • Lower relapse rate with combination (OR 0.46, 95% CI 0.24-0.91; p=0.03) ← statistically significant
  • Remission rates: similar (no significant difference)
  • Pregnancy and live birth rates: similar between groups
• Conclusion: Adding metformin reduces recurrence without harming fertility outcomes

• Metformin + progestin may slightly increase CR compared to progestin alone (RR 1.85, 95% CI 1.07-3.19; p=0.03) - low certainty evidence
• Effect on live birth rate: little to no difference (RR 1.80, 95% CI 0.88-3.68) - low certainty
• No fatal adverse events; weight gain more frequent in progestin-alone group
• Overall: evidence is LOW certainty - more RCTs needed
• Note: No evidence found yet for overall survival or progression-free survival comparisons

3. What If It Recurs? Can You Retreat?

• CR after re-treatment with progestins: 81.1%
• Cumulative CR rates: 22.8% at 3 months, 51.7% at 6 months, 82.6% at 9 months
• Progestin re-treatment had higher risk of recurrence vs hysterectomy (OR 6.78) - but 51 women (14%) still achieved pregnancy after recurrence
• 1 death (0.4%) from disease progression
• Conclusion: Repeat progestin therapy is viable for women who still desire fertility after recurrence, but hysterectomy is the safer oncological choice

4. Does Hysteroscopy + Progestin Beat Progestin Alone?

• Hysteroscopic surgery + progesterone:
  • CR rate: 100% (95% CI 97-100%) for AEH patients
  • Pregnancy rate: 47%, live birth rate: 44%
  • Recurrence rate: only 11% (lower than progestin alone ~22%)
• Conclusion: Hysteroscopic resection of lesions + progestin improves complete response and reduces recurrence vs progestin alone

5. Evidence Summary Table

Clinical Takeaways from the Evidence

1. Progestin therapy works - ~87% CR rate for AEH. This is a legitimate, evidence-based fertility-sparing option.
2. LNG-IUS performs as well as or better than oral progestins for CR and gives superior pregnancy rates (~63%). It is the preferred route of delivery.
3. Add metformin to progestin - it reduces recurrence (OR 0.46) without compromising fertility. Especially important in women with PCOS or insulin resistance.
4. Hysteroscopic resection of the lesion first, then progestin - achieves near 100% CR and reduces recurrence to ~11%. This is the most effective fertility-sparing approach.
5. Recurrence is ~22% - patients must be counselled and followed with biopsy every 3 months. Recurrence is re-treatable with progestins.
6. Conceive promptly after CR - recurrence rises over time. ART (IVF/IUI) should be offered early if natural conception is delayed.
7. The evidence is largely low-to-moderate certainty (the Cochrane 2025 review confirms this). Definitive RCT data on overall survival is still lacking. Patients must be fully counselled about the oncological risk.