• The uterus is a muscular, pear-shaped pelvic organ situated between the bladder (anterior) and rectum (posterior), supported by the pelvic floor and ligaments (broad, round, uterosacral, cardinal)

• Three layers of the uterine wall:

  1. Endometrium (inner mucosal lining) — undergoes cyclical proliferation and shedding; two zones:
     • Functional layer (stratum functionalis): shed during menstruation
     • Basal layer (stratum basalis): regenerates the functional layer
  2. Myometrium (middle muscular layer) — thick smooth muscle responsible for uterine contractions
     • Three indistinct sublayers: inner longitudinal, middle circular (thickest, contains most blood vessels — the "stratum vasculare"), outer longitudinal
     • The myometrium is the effector organ in dysmenorrhea — excessive/dysregulated contractions cause ischaemic pain
  3. Perimetrium/Serosa (outer peritoneal covering)

• Uterine blood supply: primarily from the uterine arteries (branches of the internal iliac arteries) with contributions from the ovarian arteries

  • The arcuate arteries run circumferentially within the myometrium → give off radial arteries → which become spiral arteries in the endometrium
  • Spiral arteries are unique: they are sensitive to hormonal changes and constrict/dilate with the menstrual cycle. During menstruation, they constrict → ischaemia → necrosis of the functional endometrium → shedding

• Uterine innervation:

  • Sympathetic and parasympathetic supply via the inferior hypogastric plexus (pelvic plexus) and uterovaginal plexus
  • Sensory (pain) fibres from the uterine body travel with sympathetic fibres via the hypogastric nerves to T10–L1 spinal segments → this is why dysmenorrhea pain is felt in the lower abdomen and can radiate to the back and thighs
  • The cervix and lower uterine segment send pain fibres via the pelvic splanchnic nerves (S2–S4)

1. Proliferative phase (follicular phase): Oestrogen from the developing follicle stimulates endometrial proliferation and growth of spiral arteries
2. Secretory phase (luteal phase): Post-ovulation, the corpus luteum produces progesterone → endometrial glands become secretory, stroma becomes oedematous, spiral arteries coil tightly
3. Menstruation: If no implantation → corpus luteum regresses → progesterone withdrawal → this is the critical event:
   • Progesterone withdrawal triggers the release of prostaglandins (PGF2α and PGE2) from the endometrial cells
   • Prostaglandins cause myometrial contractions and vasoconstriction of spiral arteries → ischaemia → pain ^[1]

Primary dysmenorrhea is caused by excessive prostaglandin production by the endometrium during menstruation, leading to abnormally strong and prolonged uterine contractions and ischaemia. ^[1]

Step-by-step pathophysiology:

1. Progesterone withdrawal at the end of the luteal phase (corpus luteum regression if no pregnancy)
2. This leads to destabilization of endometrial cell membranes → activation of phospholipase A2
3. Phospholipase A2 cleaves arachidonic acid from membrane phospholipids
4. Arachidonic acid is metabolized by:
   • Cyclooxygenase (COX-1 and COX-2) → Prostaglandins (PGF2α, PGE2) and Thromboxane A2
   • Lipoxygenase → Leukotrienes (also contribute to pain and inflammation)
5. PGF2α is the key mediator:
   • Potent stimulator of myometrial smooth muscle contraction → dysrhythmic, tonic contractions with elevated baseline uterine tone
   • Vasoconstriction of spiral arteries → endometrial ischaemia
   • The combination of high intrauterine pressure (sometimes exceeding arterial pressure, > 150–180 mmHg in severe cases) and vasoconstriction creates tissue ischaemia → pain
6. PGE2 contributes to:
   • Pain sensitization — lowers the threshold of nociceptors
   • Vasodilation in some vascular beds → contributes to associated symptoms like headache and flushing
7. Vasopressin may also play a role:
   • Levels are elevated in women with dysmenorrhea
   • Acts as an additional uterine muscle stimulant and vasoconstrictor
   • May contribute to the "ischaemic" component of pain

Why only ovulatory cycles?

• Anovulatory cycles do not produce a corpus luteum → no significant progesterone → no progesterone withdrawal → less organized secretory endometrium → less prostaglandin production
• This is why primary dysmenorrhea typically begins 1–2 years after menarche (when ovulatory cycles become established) and why the combined oral contraceptive pill (COCP) — which suppresses ovulation — is an effective treatment

Supporting evidence:

• Women with primary dysmenorrhea have been shown to have 2–7× higher endometrial prostaglandin levels compared to pain-free women
• Menstrual fluid prostaglandin levels correlate with pain severity
• NSAIDs (prostaglandin synthesis inhibitors) relieve dysmenorrhea in ~80% of women

Other contributing factors:

• Leukotrienes (via the lipoxygenase pathway) — also contribute to myometrial contraction and may explain why ~20% of women do not respond to NSAIDs alone
• Psychological/central factors: Central sensitization, catastrophising, and anxiety can amplify pain perception. There is overlap with other functional pain syndromes (e.g., IBS, fibromyalgia, chronic fatigue syndrome — note the association with dysmenorrhea mentioned in the IBS section) ^[3]
• Cervical stenosis — a narrower cervical os may impede menstrual outflow → higher intrauterine pressure needed to expel menstrual debris → more pain (this partly explains why pain often improves after vaginal delivery)

Secondary dysmenorrhea has a structural/pathological cause. The pathophysiology depends on the specific etiology:

• As discussed in the previous section, this is pain caused by excessive prostaglandin production in the absence of pelvic pathology
• It is placed first in the differential because it is the most common cause overall, but it remains a diagnosis of exclusion — you must rule out secondary causes, especially when there are red flags
• Key features that point towards primary: onset 1–2 years post-menarche, pain coinciding with menses onset (not preceding it by days), duration 48–72h, responds to NSAIDs/COCP, normal pelvic examination

• The most common cause of secondary dysmenorrhea ^[1]
• Ectopic endometrial-like tissue (most commonly on the ovaries, uterosacral ligaments, peritoneum of the pouch of Douglas, and rectovaginal septum) undergoes cyclical hormonal stimulation → local bleeding, inflammation, adhesion formation
• Why does it cause dysmenorrhea? The ectopic tissue produces prostaglandins locally + peritoneal inflammation irritates nociceptors + adhesions distort pelvic anatomy and tether organs, pulling with movement and uterine contraction
• Distinguishing features: pain typically starts before menstruation (often 1–2 days before flow) and may persist into the post-menstrual period; deep dyspareunia, dyschezia (painful defecation, especially during menses — suggesting rectovaginal involvement), dysuria during menses (bladder involvement), subfertility
• Examination: tender nodularity in the pouch of Douglas on rectovaginal examination; fixed retroverted uterus (adhesions)
• Endometriomas ("chocolate cysts") on the ovary may present as an ovarian/pelvic mass ^[1][2]

• Endometrial glands and stroma infiltrate the myometrium → the muscle hypertrophies around these foci → the uterus becomes globally enlarged and contracts abnormally
• Why does it cause dysmenorrhea? The ectopic endometrial tissue within the myometrium bleeds cyclically → local inflammation + disrupted myometrial architecture → abnormal, painful contractions; also ↑ local prostaglandin and cytokine production
• Distinguishing features: progressively worsening dysmenorrhea and menorrhagia in a multiparous woman, typically > 35 years; uterus is uniformly enlarged, globular, and tender ("boggy") on examination ^[2]
• Often coexists with endometriosis (up to 70% overlap in some series)

• Benign smooth muscle tumours of the myometrium; the most common pelvic tumour in women ^[2]
• Why do they cause dysmenorrhea? Depends on type:
  • Submucosal fibroids: distort the endometrial cavity → ↑ surface area for bleeding → menorrhagia; the uterus contracts forcefully to try to expel the fibroid (like expulsive labour contractions) → severe crampy pain
  • Intramural fibroids: compress surrounding myometrium and vasculature → ischaemia → pain; may also distort cavity
  • Pedunculated submucous fibroids may prolapse through the cervix → intense cramping as the uterus attempts expulsion
  • Red degeneration (haemorrhagic infarction, classically in pregnancy) causes acute pain
• Distinguishing features: menorrhagia (most common symptom), pressure symptoms (urinary frequency, constipation, abdominal distension), irregularly enlarged, firm, non-tender uterus with palpable discrete lumps on examination ^[2]
• Fibroids are oestrogen- and progesterone-dependent → grow during reproductive years, may shrink after menopause ^[2]
• Uterine fibroid, ovarian mass and cancer are important differential diagnoses of pelvic mass ^[2][5]

• Ascending infection from the lower genital tract (commonly Chlamydia trachomatis, Neisseria gonorrhoeae) → endometritis → salpingitis → ± tubo-ovarian abscess
• Why does it cause dysmenorrhea? Chronic endometritis causes ongoing endometrial inflammation → altered prostaglandin production and pain signalling; pelvic adhesions from prior acute PID can cause chronic pelvic pain that worsens with menses (because uterine contractions pull on adhesions)
• Distinguishing features: lower abdominal pain (usually bilateral and lower than appendicitis), exacerbated by coitus (dyspareunia), abnormal vaginal discharge, fever, cervical motion tenderness (chandelier sign), adnexal tenderness ^[4][6]
• Acute PID is more of an emergency presentation; chronic/subclinical PID contributes to chronic dysmenorrhea

• Ovarian cysts may present as pelvic mass ± pain ^[2]
• Functional cysts (follicular, corpus luteum) can cause cyclical pain if they:
  • Rupture: sudden onset lower abdominal pain, often with strenuous physical activity; may cause haemoperitoneum → peritoneal irritation ^[6]
  • Undergo torsion: acute onset pain, often with waves of nausea and vomiting ± fever (if necrosis) ^[6]
  • Bleed internally (haemorrhagic cyst): acute unilateral pain
• Endometriomas: cyclical pain due to hormonally responsive tissue within the cyst → strongly associated with endometriosis ^[2]
• Mature cystic teratomas (dermoid cysts): usually asymptomatic but can torse or rupture (chemical peritonitis if contents spill) ^[6]
• Key point: ovarian cyst complications (rupture, torsion, haemorrhage) tend to cause acute pelvic pain rather than cyclical dysmenorrhea, but should always be in the differential, especially in acute presentations ^[4]

• Localised hyperplasia of endometrial glands and stroma that protrude into the uterine cavity
• Why do they cause pain? The uterus may contract to try to expel the polyp (similar mechanism to submucous fibroids). They also cause irregular and heavy bleeding.
• Distinguishing features: intermenstrual bleeding, menorrhagia, postmenopausal bleeding; often incidental finding on ultrasound

• Narrowing of the cervical canal — congenital or acquired (post-cone biopsy, LLETZ, radiation, menopause-related atrophy)
• Why does it cause pain? Obstructed outflow of menstrual blood → ↑ intrauterine pressure → the uterus must contract more forcefully to expel menstrual debris → ischaemic pain. In severe cases → haematometra (blood accumulation in the uterus)
• Distinguishing features: scanty menstrual flow, severe cramping, history of cervical procedures

• Congenital malformations (e.g., unicornuate uterus with a non-communicating rudimentary horn, bicornuate uterus, septate uterus, obstructed hemivagina)
• Why does it cause pain? Obstructed outflow from one horn or compartment → blood accumulates → distension → severe pain. May present as "primary dysmenorrhea" in adolescents that doesn't respond to standard treatment
• Distinguishing features: severe dysmenorrhea from menarche, non-responsive to NSAIDs/COCP, ± pelvic mass (haematometra/haematocolpos), history of associated renal anomalies (Müllerian and renal development are linked embryologically)

• Why does it cause pain? Foreign body reaction in the endometrium → local inflammatory response → ↑ prostaglandin production → worsened uterine contractility and pain
• Distinguishing features: temporal relationship — dysmenorrhea (and often menorrhagia) begins or worsens after IUD insertion, typically most pronounced in the first 3–6 months
• Note: the levonorgestrel-releasing IUS (Mirena) actually reduces dysmenorrhea (by causing endometrial atrophy → ↓ prostaglandin production)

• Must always be considered in a woman of reproductive age presenting with pelvic pain ± vaginal bleeding ^[4][6]
• Why does it cause pain? An implanted embryo outside the uterine cavity (most commonly in the fallopian tube) grows → distends the tube → pain. If it ruptures → haemoperitoneum → acute abdomen, haemodynamic instability
• Distinguishing features: missed or late period, positive pregnancy test, unilateral adnexal pain, cervical excitation tenderness, ± vaginal spotting, ± shoulder tip pain (diaphragmatic irritation from haemoperitoneum)
• Always perform a pregnancy test in any woman of reproductive age with acute pelvic pain ^[4]

• Mid-cycle lower abdominal/pelvic pain occurring at ovulation (~day 14)
• Why does it cause pain? Follicular rupture during ovulation → release of follicular fluid (which may contain blood) onto the peritoneum → mild peritoneal irritation ^[6]
• Distinguishing features: occurs mid-cycle (not with menses), unilateral, mild and self-limiting (hours to 1–2 days), alternates sides month-to-month

There is no single diagnostic test for primary dysmenorrhea. The diagnosis is made when all of the following are present:

1. Cyclical, crampy lower abdominal/suprapubic pain temporally related to menstruation (begins within hours of onset of menstrual flow, or up to 1 day before; duration ≤ 72 hours)
2. Onset within 1–2 years of menarche (once ovulatory cycles are established)
3. No red flag features suggesting secondary cause (no progressive worsening, no menorrhagia beyond normal, no dyspareunia, no dyschezia, no subfertility, no abnormal discharge, no intermenstrual bleeding)
4. Normal pelvic examination — this is the single most important clinical finding. Normal-sized uterus, no adnexal masses, no cervical motion tenderness, no nodularity in the pouch of Douglas
5. Reasonable response to empirical therapy with NSAIDs and/or combined oral contraceptive pill (COCP) — approximately 80% of women with primary dysmenorrhea respond to first-line treatment

Secondary dysmenorrhea is suspected when the clinical picture does not fit primary dysmenorrhea, specifically when any of the following are present:

• Onset of dysmenorrhea after age 25 or new-onset in a woman who previously had pain-free periods
• If a lady has a baseline of no dysmenorrhea, and suddenly develops dysmenorrhea → considered secondary ^[1]
• Secondary dysmenorrhea: remember to ask for associated symptoms of menorrhagia / subfertility, associated pelvic mass → think adenomyosis ^[1]
• Progressive worsening of pain over time
• Pain beginning > 1–2 days before menstruation or persisting after menses ends
• Abnormal pelvic examination findings
• Failure to respond to NSAIDs and/or COCP
• If arising from the first ever period, then considered primary / early onset, normal for that lady → need to think of structural abnormalities (e.g., septate uterus, menstrual blood confined into a cavity) ^[1]

The specific diagnostic criteria for each secondary cause are those of the underlying condition (e.g., endometriosis staging criteria, fibroid classification). The investigation strategy below is designed to identify these causes.

These are not routinely required for dysmenorrhea but are indicated in specific scenarios:

Pelvic ultrasound is commonly performed ^[5] and is the first-line imaging investigation for suspected secondary dysmenorrhea.

Two approaches:

Key ultrasound findings and their interpretation:

These are often underestimated but have genuine physiological rationale. They should be offered to all women as first-line or adjunctive measures.

NSAIDs ("Non-Steroidal Anti-Inflammatory Drugs") are the cornerstone of primary dysmenorrhea treatment. The name tells you the mechanism: they reduce inflammation without being steroids.

Why do NSAIDs work in dysmenorrhea?

• NSAIDs inhibit cyclooxygenase (COX) enzymes → ↓ conversion of arachidonic acid to prostaglandins (PGF2α and PGE2)
• This directly addresses the core pathophysiology: ↓ prostaglandin production → ↓ myometrial contractility → ↓ uterine ischaemia → ↓ pain
• Also ↓ the systemic effects of prostaglandins (nausea, diarrhoea, headache)
• Effective in ~80% of women with primary dysmenorrhea

Practical prescribing tips:

• Start NSAIDs at onset of menses (or 1–2 days before if cycle is predictable) — prostaglandin production peaks in the first 48h of menstruation, so early dosing prevents the prostaglandin cascade from ramping up
• Continue for 2–3 days (duration of pain)
• Take with food to ↓ GI irritation
• If one NSAID doesn't work, try a different one — there is inter-individual variation in response (possibly due to varying contributions of leukotrienes vs. prostaglandins)
• If no improvement after trying 2–3 different NSAIDs over 3 menstrual cycles each, consider hormonal therapy

Contraindications to NSAIDs:

Management will depend on the age, symptom, condition and wish of the patient ^[2].

• If dysmenorrhea is clearly temporally related to Cu-IUD insertion and is intolerable:
  • Switch to LNG-IUS (Mirena) — provides contraception AND reduces dysmenorrhea/menorrhagia
  • Or remove and use alternative contraception

• School and work absenteeism: Dysmenorrhea is the single most common cause of recurrent short-term absenteeism in adolescent girls and young women. Studies in Hong Kong show that 10–15% of affected women miss school or work during every menstrual cycle
• Why? The pain from PGF2α-mediated uterine ischaemia can be genuinely debilitating (intrauterine pressures exceeding systolic BP → "uterine angina") ^[14]. When combined with systemic prostaglandin effects (nausea, vomiting, diarrhoea, headache, fatigue), the cumulative symptom burden renders normal function impossible during peak pain days
• Social and recreational limitation: Avoidance of exercise, social events, and activities during menses

• Anxiety and depression: Chronic recurrent pain creates a cycle of anticipatory anxiety before each menstrual period → heightened perception of pain (central sensitisation) → more anxiety. Over time, this can develop into a chronic pain syndrome
• Why does chronic pain cause depression? Persistent nociceptive input alters neurotransmitter balance (↓ serotonin, ↓ noradrenaline) in the descending pain modulatory pathways → simultaneously impairs mood regulation and pain inhibition. This is a bidirectional relationship: depression ↓ pain threshold, and chronic pain ↑ depression risk
• Sleep disturbance: Pain during the night disrupts sleep architecture → fatigue, poor concentration, irritability → further ↓ quality of life
• Body image and self-esteem: Adolescents in particular may feel embarrassed or "abnormal" due to the severity of their symptoms, especially if peers appear unaffected

Because women with primary dysmenorrhea use NSAIDs and hormonal therapies cyclically over many years, they are at risk of treatment-related adverse effects:

• In a subset of women, prolonged nociceptive input from recurrent severe primary dysmenorrhea can lead to central sensitisation — the spinal cord and brain become hyperexcitable, amplifying pain signals even in the absence of peripheral input
• Why does this happen? Repeated activation of C-fibre nociceptors → release of substance P and glutamate in the dorsal horn → NMDA receptor activation → "wind-up" phenomenon → pain persists between menstrual periods, expands beyond the original territory (e.g., generalised pelvic pain, back pain, pain with intercourse), and becomes disproportionate to any identifiable stimulus
• This can evolve into chronic pelvic pain (defined as menstrual or non-menstrual pain for ≥ 6 months occurring below the umbilicus ^[14]) — a condition that is much harder to treat and often overlaps with IBS, interstitial cystitis, and fibromyalgia

• A critically important "complication" of labelling dysmenorrhea as primary is the failure to recognise an underlying secondary cause
• If a clinician attributes worsening pain to "bad primary dysmenorrhea" without re-evaluating, conditions like endometriosis or adenomyosis may go undiagnosed for years (average diagnostic delay for endometriosis is 7–10 years globally)
• Consequences of delayed diagnosis: progressive disease, adhesion formation, organ damage, and irreversible subfertility

Fibroids classically do NOT cause dysmenorrhea ^[1] — a pure fibroid will seldom cause dysmenorrhea, so have to think of adenomyosis ^[1]. However, there are two exceptions ^[1]:

• Heavy bleeding related to the fibroid will cause clot formation in the uterus, and uterus will try to expel these clots, causing pain ^[1]
• Pedunculated fibroid in the uterine cavity — uterus will think foreign body and want to expel → hence dysmenorrhea sensation ^[1]

As UAE is used as a treatment for symptomatic fibroids in women with dysmenorrhea, its complications are worth noting:

• Pelvic pain (almost universal, usually resolves in 14–17 days) ^[14]
• Post-embolisation syndrome ( < 40%): fever, nausea, pain, malaise, leukocytosis ^[14]
• Vaginal expulsion of fibroid tissue (10%) ^[14]
• Amenorrhoea (2% if < 45y, 8% if > 45y): may be due to ovarian insufficiency or endometrial atrophy ^[14]
• Pelvic inflammatory disease ( < 2%) ^[14]
• Recurrence of symptoms requiring intervention: 25% if < 40y, 10% if 40–50y ^[14]