1. HYPOTHALAMO-PITUITARY-OVARIAN AXIS Roots to Obstetrics & Gynaecology Prof. Hemantha Dodampahala (MBBS, MD, FRCSE, FRCOG. FISUOG) Dept of Obstetrics & Gynaecology Faculty of Medicine, Colombo

2. Physiology Hypothalamo- Pituitary - Ovarian Axis (HPOA) GnRHH FSH / LH P OestrogenO Negative feedback Maintains homeostasis

3. Spectrum of events in both sexes Birth Puberty Menarche /adrenarche Reproduction / coitarche Climacteric Menopause /Andropause

4. Genotype and Phenotype  Genetic sex determines the gonad based on Y chromosome (SRY)  Testosterone/DHT Anti-Müllerian Hormone  LH FSH via GnRH (HPO axis) fetal, early infancy, childhood, late pre-puberty and puberty

5. Puberty Altered endocrine system occurs years earlier to physical, mental and social change Fetal – GnRh neurone activity at 12 week Male – T secreted from 7 weeks and peaks 15- 18 weeks Female – maintenance of oöcyte population depends on normal X chromosome complement

6. Puberty, Menarche and Primary Amenorrhoea Breast Development Pubic hair growth Axillary hair growth Growth – Increase in body contours, proteins, fat = weight gain Menarche ** Good practice is to check the items in order in case of primary amenorrhoea Mean age of puberty 12-14 Menarche before 16 years

7. HYPOTHALAMUS GnRH Pituitary FSH / LH Gonad ESTROGEN/TESTOSTERONE Negative feedback Positive feedback for LH ovulation

8. Functions of HPO axis in an adult female cyclicalMajor aspect of reproductive capacity is its cyclical activity dominant folliclesStrikingly reflected in the growth and development of dominant follicles. single ovulationNormally in human ovaries - a single dominant follicle that results in a single ovulation each menstrual cycle Relationships that underlie folliculogenesis, ovulation, and luteogenesis

9. Follicular growth is gonadotrophin dependent D1D14D28 Recruitment Dominant OvulationCorpus follicleluteum FSH LH Progesterone P E2

10. Anovular Subfertility and Male Hypogonadism

11. Recruitment at a constant rate in first three decades OR reaches a critical number of ~25,000 at 37.5 y Then rate of loss accelerates ~2-fold A decrease in fecundity accompanies this accelerated loss of OR Ovarian reserve Reflected in serum FSH concentration

12. Two Cell Theory

13. Follicle selection FSH  LH Inhibin Activin E 2  Progesterone  Follicular atresia

14. Climacteric Reproductive decline occurs after third decade Follicular atresia accelerates from 37.5 years Thus reproductive aging precedes the menopause by 10 - 15 years Increased FSH & low Inhibin B

15. Hormonal changes with established menopause Decline in E2 Less marked decline in E1 (peripheral aromatization)  E1 higher in obese women  In the menopuse E2 < E1

16. Summary Basis of the H-P-O axis In terms of the life cycle of females Diagnostic relevance

18. Menopause from Individual Point of View

19. Thank You!