Menstrual Cycle Disorders - A Comprehensive Overview for Medical Students

1. Normal Menstrual Cycle - Quick Recap

• Cycle length: 21-35 days (average 28)
• Duration of flow: 2-7 days
• Blood loss: 20-80 mL per cycle
• Controlled by the hypothalamic-pituitary-ovarian (HPO) axis via GnRH → FSH/LH → estrogen/progesterone

2. Classification of Menstrual Disorders

Terminology You Must Know (Ganong's Physiology)

3. Amenorrhea

Primary Amenorrhea

• Imperforate hymen
• Vaginal aplasia / congenital vaginal atresia

• Congenital absence of the uterus
• Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser [MRKH] syndrome)

• Turner syndrome (45,X) - streak gonads, webbed neck, short stature
• XO gonadal dysgenesis and variants
• Polycystic ovary syndrome (PCOS)
• 17-hydroxylase deficiency

• Kallmann syndrome (hypogonadotropic hypogonadism + anosmia)
• Constitutional delay
• Nutritional disorders

Secondary Amenorrhea

• Polycystic ovary syndrome (PCOS)
• Primary ovarian insufficiency (POI) / premature ovarian failure (POF) - failure of ovarian estrogen production in a hypergonadotropic state before age 40
• Ovarian tumors
• Chemo/radiation toxicity

• Hyperprolactinemia (prolactinoma)
• Sheehan syndrome (postpartum pituitary necrosis)
• Acquired hypopituitarism

• Functional hypothalamic amenorrhea (excessive exercise, stress, low body weight) - GnRH pulse frequency is slowed due to excess opioid activity; notably responds to naltrexone
• Infiltrative/tumoral disease

• Asherman syndrome (intrauterine synechiae post-trauma/curettage)

• Thyroid disorders (hypo- or hyperthyroidism)
• Cushing syndrome, adrenal disorders
• Drugs: antipsychotics (haloperidol, phenothiazines), antidepressants, antihypertensives (methyldopa), oral contraceptives, drugs with ovarian toxicity (busulfan, cisplatin)

Hypergonadotropic Amenorrhea (Goldman-Cecil Medicine)

4. Abnormal Uterine Bleeding (AUB)

• ~20% is postmenarchal (adolescent) bleeding due to immaturity of the HPO axis
• ~50% is perimenopausal, related to incipient ovarian failure
• ~75% of cases have no demonstrable organic cause = anovulatory (dysfunctional) bleeding

• Endometrial polyps
• Submucosal leiomyomas (fibroids)
• Adenomyosis
• Endometrial hyperplasia/carcinoma

Menstrual Cycle Disorders - A Comprehensive Guide for Medical Students

1. Terminology You Must Know

2. Amenorrhea

Primary Amenorrhea

• Imperforate hymen
• Vaginal aplasia / congenital vaginal atresia

• Congenital absence of the uterus
• Mullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome)
• Androgen insensitivity syndrome (46,XY - phenotypic female, no uterus)

• Turner syndrome (45,X) - streak gonads, short stature, webbed neck
• XX/XY gonadal dysgenesis
• PCOS
• 17-hydroxylase deficiency (sexual infantilism + elevated gonadotropins)
• Autoimmune oophoritis, resistant ovary syndrome

• Kallmann syndrome - GnRH deficiency + hyposmia/anosmia
• Constitutional delay
• Nutritional disorders, excessive exercise

Secondary Amenorrhea

Rule #1: Always exclude pregnancy first. Ganong's states: "secondary amenorrhea should be considered to be due to pregnancy until proved otherwise."

Hypergonadotropic Amenorrhea (Primary Ovarian Insufficiency)

• Genetic: Turner syndrome (45,X - most common), pure gonadal dysgenesis (46,XX or 46,XY), Trisomy X, FMR1 premutation (>5% of women with XX spontaneous POI carry FMR1 mutations - important for genetic counseling about fragile X in offspring)
• Autoimmune oophoritis
• Iatrogenic: busulfan, cisplatin, cyclophosphamide, radiation

3. Abnormal Uterine Bleeding (AUB)

• ~20% is postmenarchal (adolescent) - due to HPO axis immaturity
• ~50% is perimenopausal - incipient ovarian failure
• ~75% of cases have no structural cause = anovulatory (dysfunctional) uterine bleeding

• Polyps, Adenomyosis, Leiomyoma, Malignancy
• Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not classified

• Hemodynamically stable: oral contraceptive pill (off-label) every 6 hours for 5-7 days; bleeding should stop within 24 hours
• Hormonal therapy (progestins, OCPs) long-term
• Surgical options (D&C, endometrial ablation, hysterectomy) for refractory cases

4. Dysmenorrhea and Endometriosis

Primary Dysmenorrhea

• No underlying pathology
• Usually occurs in ovulatory cycles
• Mechanism: Prostaglandins cause exaggerated uterine contractions and myometrial ischemia
• Associated symptoms: nausea, diarrhea, headache, emotional changes
• Treatment:
  • First-line: NSAIDs (e.g., ibuprofen, naproxen, mefenamic acid) - start at onset of bleeding/cramping, continue for up to 3 days
  • If NSAIDs fail: add oral contraceptives (inhibit ovulation → reduce prostaglandin release)
  • If still intractable: laparoscopy to rule out secondary causes

Secondary Dysmenorrhea

Endometriosis

• Affects ~10% of reproductive-age women
• Ectopic endometrial tissue (glands + stroma), most commonly within the peritoneal cavity
• Classic triad: dysmenorrhea + infertility + dyspareunia
• Can also appear in surgical scars, umbilicus, vulva

Sectioned ovary showing multiple large and small endometriotic cysts filled with degenerated blood ("chocolate cysts"). - Robbins & Kumar Basic Pathology

• Surgical: fulguration/excision of implants, lysis of adhesions at laparoscopy
• Medical (hormonal suppression):
  • Continuous oral contraceptives
  • Progestins (e.g., norethindrone 5 mg/day)
  • GnRH analogues (e.g., leuprorelin 3.75 mg SC monthly)
  • GnRH antagonists: elagolix (150 mg orally daily up to 24 months) or relugolix (40 mg orally daily)
  • Danazol (androgenic steroid - less commonly used now)
• After a course of treatment, maintain on OCP until fertility desired
• Surgery for severe pain, large endometriomas, or infertility work-up

5. Premenstrual Syndrome (PMS)

• Irritability, mood changes, depression
• Bloating, edema
• Headache, fatigue
• Decreased concentration, constipation

• SSRIs (fluoxetine) - effective (serotonin involvement)
• Alprazolam (benzodiazepine) - short-term relief
• GnRH agonists in doses that suppress the pituitary-ovarian axis
• Lifestyle measures: salt restriction, regular exercise

6. Quick Diagnostic Approach Summary

Menstrual Disorder
       |
   Amenorrhea?
   /          \
Primary      Secondary
(no period    (was having
 ever)         periods)
   |               |
Check:          βhCG first!
- Karyotype        |
- FSH/LH        Elevated FSH → POI
- Pelvic US     Low FSH → Hypothalamic/Pituitary
- MRI brain     Normal FSH + ↑Prolactin → Prolactinoma
                Uterine cause → Asherman's

Key Exam High-Yield Points

1. Primary amenorrhea most common cause with secondary sexual characteristics present = imperforate hymen / anatomic outflow obstruction
2. Most common cause of secondary amenorrhea = pregnancy
3. Turner syndrome = 45,X, elevated FSH/LH, streak gonads, amenorrhea
4. Asherman syndrome = post-D&C synechiae, secondary amenorrhea with normal FSH/LH/prolactin
5. Sheehan syndrome = postpartum hemorrhage → pituitary infarction → panhypopituitarism
6. Kallmann syndrome = GnRH deficiency + anosmia
7. Primary dysmenorrhea = prostaglandins → treat with NSAIDs
8. Endometriosis = "chocolate cysts," CA-125 may be elevated, diagnosed definitively by laparoscopy
9. FMR1 premutation (fragile X carrier) is found in >5% of XX spontaneous POI cases
10. Adolescent AUB - always screen for von Willebrand disease