The document discusses the physiology of menopause. It begins by defining menopause and perimenopause. It then describes the declining ovarian follicle pool starting in a woman's late 30s. This leads to compensated and decompensated ovarian failure as follicle numbers drop below 1000. During this transition, FSH and LH levels rise while estrogen levels drop. Other hormonal changes include reductions in androgens and progesterone. The consequences of menopause include short-term symptoms like hot flashes as well as long-term risks for osteoporosis and cardiovascular disease due to lowered estrogen levels.

1. PHYSIOLOGY OF MENOPAUSE www.freelivedoctor.com

2. MENOPAUSE MENOPAUSE comes from the greek word ' menos'( month) and 'pausis'(cessation). Diagnosis is made retrospectively after a minimum of one year amenorrhoea. PERIMENOPAUSAL TRANSITION-- The years prior to menopause that encompass the change from normal ovulatory cycles to cessation of menses. www.freelivedoctor.com

3. THE DECLINING OOCYTE POOL Accelerated follicular depletion begin at age 37-38, and menopause follows 13 years later. menopause occurs when the number of follicles falls below a critical threshold, about 1000 ,regardless of age. www.freelivedoctor.com

4. COMPENSATED FAILURE Initially ovarian failure is compensated by rising Gn levels, about the age of 30yrs inhibin production from granulosa cells fall leading to a reduced INHIBIN : FSH ratio. www.freelivedoctor.com

5. DECOMPENSATED FAILURE Critical decline in oocyte pool leads to further rise in FSH.(10-20 FOLD) LH rises only 3-fold due to its shorter half life. OESTROGEN levels drop due to reduction in follicle number and granulosa cell ageing. Permanent cessation of progesterone production. www.freelivedoctor.com

6. OTHER HORMONAL CHANGES Both adrenal and ovarian androgen levels fall.the drop in androgen levels is profound in premature ovarian failure. OESTROGEN therapy increase SHBG LEVELS ---further fall in free androgen levels. Main postmenopausal oestrogen is oestrone-produced mainly by adipose tissue and postmenopausal ovary by aromatization of adrenal androstenedione. insulin resistance and rise in central adiposity. www.freelivedoctor.com

7. PREDICTION OF OVARIAN RESERVE FSH level>30 is diagnostic of menopause. combination of FSH, INHIBIN WITH ANTI-MULLERIAN HORMONE. Measurement of ovarian volume. www.freelivedoctor.com

8. PREMATURE OVARIAN FAILURE Defined as cessation of menstruation before the age of 40 years. CAUSES : spontaneous or idiopathic turner syndrome fragile X syndrome FSH receptor polymorphism INCIDENCE IS RISING. www.freelivedoctor.com

9. CONSEQUENCES OF MENOPAUSE IMMEDIATE INTERMEDIATE LONG TERM www.freelivedoctor.com

10. IMMEDIATE HOT FLUSHES--- Thought to arise due to loss of oestrogenic induced opioid activity in the hypothalamus. NA and serotonin mediate this activity. Obese women are protected due to large amounts of oestrone and low SHBG. www.freelivedoctor.com

11. INSOMNIA, ANXIETY, IRRITABILITY POOR CONCENTRATION MOOD DISTURBANCES REDUCTION IN SEXUALITY AND LIBIDO MEMORY LOSS www.freelivedoctor.com

12. INTERMEDIATE CONSEQUENCES Oestrogen deficiency leads to rapid loss of collagen dyspareunia and vaginal bleeding urethral syndrome(dysuria, urgency and frequency) increased bruising generalized aches and pains www.freelivedoctor.com

13. Long term health problems Osteoporosis Disorder of bone matrix resulting in reduction in bone strength to the extent that there is increased risk of fractures. Women lose 50% of their skeleton by the age of 70 years, but men only lose 25% by the age of 90 years. Predisposing factors- genetic predisposition, use of corticosteroids, pre-menopausal amenorrhea, smoking, premature ovarian failure www.freelivedoctor.com

14. Cardiovascular Protective effect of oestrogen— increase in HDL decrease in LDL NO mediated vasodilatation antioxidant effect direct effect on aorta decreasing atheroma www.freelivedoctor.com

15. Risk factors include high BMI and a decrease in oestradiol levels. Women with day3FSH > 7 IU/ml compared to those with day3 FSH < 7 IU/ ml were found to have higher lipid levels. www.freelivedoctor.com

16. C N S Oestrogen has a direct effect on the vasculature of the CNS and promotes neuronal growth and neurotransmission. Also improves cerebral perfusion and cognition in women. Causes alzheimers disease, dementia. (intervenes at the level of amyloid precursor protein). www.freelivedoctor.com

17. Diagnosis Characteristic history of hot flushes and night sweats with prolonged periods of amenorrhoea. Measurement of plasma hormone level is not necessary. However in a young patient or in a woman after hysterectomy, where the diagnosis is more difficult, measurement of FSH is helpful. (> 15 iu/ml). www.freelivedoctor.com