Menopause Professor Susan Davis Women’s Health Program Department of Medicine Alfred Hospital, Monash University.

Menopause The last menstrual bleed in a woman with an intact uterus Permanent loss of ovarian follicular development Loss of cyclical production of estradiol, progesterone and testosterone.

Primordial follicles Fundamental reproductive units of the ovary pool of non-growing follicles from which all dominant preovulatory follicles are selected formed between 6-9 months of gestation Only 400 will complete development and undergo ovulation/corpus luteum formation → others die by atresia Continued decline in number - by menopause primordial follicles difficult to find

AFTER MENOPAUSE FEW/ NONE LEFT FOLLICULAR DEPLETION AND AGE 20 WEEK FETUS 7.5 MILLION BIRTH 300,000 Age of reaching critical threshold of 25,000 varies from late 20’s to 40’s → age alone has limited predictive value for determining ovarian reserve 37 YEARS 25,000 51 YEARS 1000 AFTER MENOPAUSE FEW/ NONE LEFT

Natural menopause is a consequence of follicular depletion Autopsy data, women 7-44yrs 100000 B B 10000 Women in menopausal transition J B B 1000 J with regular menses Primordial Follicles / Ovary F F B 100 F Perimenopausal women F F 10 F F Postmenopausal women 1 H H H H 10 20 30 40 50 60 Age in Years Richardson et al., J.C.E.M., 1987

Follicular health Every month ~ 500 ova develop activated by BMP15 and GDF9 Ova go through phase of growth, then atresia As oocyte numbers decline so does the oocyte quality. The ANTRAL follicle count in the follicular phase is a good predictor of IVF outcome AGE predicts fertility