Disorders of Menstruation: Terminologies, Etiologies, and Evaluation

1. NORMAL MENSTRUAL CYCLE - Reference Values

2. KEY TERMINOLOGIES

A. Amenorrhea

• Primary amenorrhea: Absence of menarche (first menstrual period) - classically by age 16, but evaluation should begin at:
  • Age 15-16 in the presence of normal growth and secondary sexual characteristics
  • Age 13 if secondary sexual characteristics are absent or height <3rd percentile
  • Age 12-13 if breast development is present with cyclic pelvic pain
  • Within 2 years of breast development if menarche has not occurred
• Secondary amenorrhea: Cessation of menstrual periods for 3-6 months in a woman who previously had regular cycles; or 6 months in women with previously irregular cycles

B. Abnormal Uterine Bleeding (AUB)

C. Dysmenorrhea

D. Other Terms

• Menarche: First menstrual period
• Menopause: Diagnosed after 12 months with no menstrual period without hormonal contraception

3. ETIOLOGIES - THE PALM-COEIN CLASSIFICATION (FIGO 2011)

STRUCTURAL (PALM)

NON-STRUCTURAL (COEIN)

4. ETIOLOGIES BY CATEGORY OF AMENORRHEA

A. Disorders of the Uterus or Outflow Tract

• Asherman syndrome (uterine synechiae): Intrauterine adhesions, most often following curettage or endometritis; causes secondary amenorrhea despite normal hormonal drive
• Müllerian anomalies: Imperforate hymen, transverse vaginal septum, Müllerian aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) - causes primary amenorrhea with normal secondary sexual characteristics
• Cervical stenosis

B. Disorders of Ovulation (Hypothalamic-Pituitary-Gonadal axis)

Hypothalamic causes:

• Functional hypothalamic amenorrhea: weight loss, excessive exercise, psychological stress - GnRH pulse frequency is reduced
• Kallmann syndrome: GnRH deficiency with anosmia
• Craniopharyngioma, other space-occupying lesions

Pituitary causes:

• Hyperprolactinemia (prolactinoma most common): prolactin inhibits GnRH pulsatility
• Sheehan syndrome: postpartum pituitary necrosis
• Empty sella syndrome

Ovarian causes:

• Polycystic Ovary Syndrome (PCOS): Most common cause of anovulatory cycles; associated with oligomenorrhea or amenorrhea, androgen excess, polycystic ovaries
• Premature ovarian insufficiency (POI): FSH >40 IU/L before age 40; causes include Turner syndrome (45,X), autoimmune oophoritis, fragile X permutation, chemotherapy
• Turner syndrome (45,X): Most common chromosomal cause of primary amenorrhea; associated with streak gonads

Other endocrine causes:

• Thyroid disorders (both hypo- and hyperthyroidism)
• Congenital adrenal hyperplasia (CAH)
• Cushing syndrome

5. EVALUATION

Step 1: History

• Age of menarche; duration and frequency of cycles; recent changes
• Character of bleeding (volume, duration, clots, pain)
• Reproductive history: pregnancies, deliveries, prior uterine surgery
• Symptoms of androgen excess: hirsutism, acne, voice change
• Symptoms of thyroid disease, galactorrhea (prolactin excess)
• Exercise habits, body weight changes, dietary restrictions, stress
• Medications and hormonal contraception use
• Family history of bleeding disorders

Step 2: Physical Examination

• BMI and weight
• Signs of androgen excess: acne, hirsutism, clitoromegaly, temporal balding
• Thyroid enlargement
• Galactorrhea
• Pelvic examination: uterine size, cervical lesions, vaginal atrophy, structural abnormalities

Note: Recent guidelines no longer recommend routine pelvic examination in asymptomatic, average-risk women, but pelvic examination is an important part of evaluating amenorrhea, AUB, and pelvic pain. - Harrison's Principles of Internal Medicine 22E

Step 3: Laboratory Tests

Step 4: Imaging

• Pelvic ultrasound (2D/3D) or saline sonohysterography: First-line imaging; identifies fibroids, polyps, adenomyosis, ovarian pathology
  • Adenomyosis: anechoic myometrial tissue with acoustic shadowing (fan-shaped shadowing)
• Hysteroscopy with endometrial biopsy: Gold standard for intrauterine pathology; improves sensitivity and specificity over either alone

Step 5: Endometrial Biopsy Indications (Bailey & Love)

• Women with suspected endometrial pathology
• All women >45 years old in whom medical treatment was unsuccessful
• Women with persistent intermenstrual bleeding
• Endometrial thickness >4 mm in postmenopausal women; >7 mm in women with known PCOS
• Irregular bleeding on HRT after first 3 months
• Younger women with major risk factors: PCOS, obesity, unopposed estrogen therapy, family history of endometrial/colorectal cancer

Step 6: Additional Investigations (as needed)

• Karyotype: If primary amenorrhea with absent secondary sexual characteristics (Turner syndrome, etc.)
• MRI pituitary: If prolactin elevated or suspected sellar mass
• MRI pelvis: For Müllerian anomalies or adenomyosis characterization
• Colonoscopy: If rectal/colorectal bleeding cannot be excluded

6. DIAGNOSTIC FRAMEWORK - Summary

AUB/Amenorrhea
     |
     ├─ Exclude PREGNANCY (beta-hCG) first always
     |
     ├─ Uterus/Outflow Tract disorders?
     |    ├─ Ultrasound + hysteroscopy + biopsy
     |    └─ Causes: polyps, fibroids, Asherman's, Müllerian anomalies, malignancy
     |
     └─ Ovulatory disorders?
          ├─ FSH high → Ovarian failure (Turner, POI, autoimmune)
          ├─ FSH low/normal + LH:FSH ratio elevated → PCOS
          ├─ Prolactin elevated → Hyperprolactinemia (prolactinoma)
          ├─ TSH abnormal → Thyroid disease
          └─ Normal labs + history of weight loss/stress → Functional hypothalamic amenorrhea

• Harrison's Principles of Internal Medicine 22E (2025) - Chapter 405: Menstrual Disorders and Pelvic Pain, by Janet E. Hall & Anuja Dokras
• Bailey and Love's Short Practice of Surgery 28th Edition - Chapter 87: Abnormal Uterine Bleeding in the Non-Pregnant State
• Berek & Novak's Gynecology - Chapters 7 & 10