Document Structure

Page 1 - Overview of the HPG Axis

• Components: hypothalamus, anterior pituitary, ovaries
• GnRH - decapeptide, pulsatile secretion (60-90 min intervals required), half-life 2-4 min; continuous GnRH causes receptor downregulation (basis for agonist therapy)
• KNDy-Kisspeptin neurons - the GnRH pulse generator; maturation drives puberty; kisspeptin receptor mutations cause precocious puberty (activating) or Kallmann syndrome (inactivating)
• FSH vs. LH table - targets, actions, feedback regulation

Page 2 - The Menstrual Cycle

• Follicular phase: FSH drives follicle growth → rising estradiol → negative feedback early, then positive feedback (LH surge) when estradiol >200 pg/mL for >48 hours
• Ovulation: LH surge triggers oocyte release ~36 hours later
• Luteal phase: corpus luteum secretes progesterone → negative feedback; degeneration → withdrawal → menses
• Feedback summary table: estradiol, progesterone, inhibin A/B, activin - phase-specific roles
• Inhibins and activins - structure, selective FSH suppression vs. stimulation

Page 3 - Menarche

• Timing: average 12 years (range 10-14)
• Mechanism: release of CNS inhibition on GnRH neurons via KNDy maturation; nocturnal pulsatility is the earliest sign
• Sequence of pubertal events table: adrenarche → thelarche → pubarche → peak height velocity → menarche → regular cycles
• Factors influencing timing: leptin/body fat, genetics, nutrition, secular trend
• Abnormalities: precocious puberty (GnRH agonist treatment), primary amenorrhea, isolated premature menarche

Page 4 - Menopause

• Definition and perimenopause staging table (hormonal patterns at each stage)
• Pathophysiology: follicle pool depletion drives all changes; inhibin B falls first, then FSH rises, then estradiol falls
• Clinical features: vasomotor (hot flushes in 75%, mechanism tied to LH bursts), urogenital atrophy, osteoporosis, cardiovascular risk, neuropsychological effects

Page 5 - Management & Clinical Correlates

• HRT indications, types (estrogen-only vs. combined), routes, timing hypothesis (window of opportunity)
• Risks (WHI data) and benefits
• Diagnosis (FSH >40 IU/L x2; AMH as ovarian reserve marker)
• Menarche vs. Menopause comparison table (9 parameters side-by-side)
• Amenorrhea diagnostic flowchart (HPG axis level)
• Lifetime hormonal profile table: childhood through postmenopause