Epidemiology
Etiology
- Age: Women < 40 yo.
- Idiopathic: Most common (~90% of cases).
- Genetic:
- Turner syndrome (45,X or mosaicism).
- FMR1 gene premutation (Fragile X syndrome carriers: 55–200 CGG repeats).
- Autoimmune:
- Autoimmune polyglandular syndrome (APS type 1 or 2).
- Concomitant Hashimoto thyroiditis or Addison disease (anti-21-hydroxylase Abs).
- Iatrogenic/Environmental:
- Pelvic radiation or chemotherapy (especially alkylating agents like cyclophosphamide).
- Bilateral oophorectomy or pelvic surgery.
- Metabolic/Infectious: Galactosemia, viral oophoritis (mumps).
Pathophysiology
Follicular dysfunction or depletion → ↓ estrogen levels → reduced feedback inhibition of estrogen on FSH and LH → ↑ FSH and LH (usually FSH > LH)
Clinical features
- Amenorrhea or abnormal uterine bleeding
- Climacteric symptoms such as vaginal dryness, vasomotor symptoms, dyspareunia, and irritability
- Infertility
Diagnostics
- Age is < 40 years
- There has been irregular menstruation for ≥ 3 consecutive months
- ↑ FSH levels (> 30–40 mIU/mL)
- ↓ Estradiol levels (< 50 pg/mL)
Differential Diagnostics
- Functional Hypothalamic Amenorrhea (FHA):
- Diff: ↓/Normal FSH & LH, low estradiol; associated with low BMI, excessive exercise, eating disorders, or extreme stress.
- Polycystic Ovary Syndrome (PCOS):
- Diff: Normal/↑ LH with normal FSH (↑ LH:FSH ratio), hyperandrogenism (hirsutism, acne), polycystic morphology on US, no elevated menopausal FSH.
- Hyperprolactinemia:
- Diff: ↑ Prolactin, low/normal gonadotropins, galactorrhea, pituitary adenoma on MRI.
- Asherman Syndrome (Intrauterine Adhesions):
- Diff: Normal FSH, LH, and Estradiol; negative withdrawal bleed after estrogen + progesterone challenge; hx of postpartum curettage or endometritis.
- Physiologic Menopause:
- Diff: Occurs at normal physiological age (≥ 40 yo, average 51 yo).