1. Physiology of Menopause Dr Samaa Nazer Consultant - Assistant Professor King Abdulaziz University

2. Menopause  Menopause :- Perminent cessation of menstruation caused by failure of ovarian follicular development in the presence of adequate gonadotrophin stimulation.  Climacteric :- The physiologic period in a women's life during which there is regression of ovarian function.  Premature ovarian failure :- Cessation of menstruation due to depletion of ovarian follicles before the age of 40y.

3. Menopause Menopause Age Median - 51.4, range of 48-55 yrs Median for perimenopause - 47.5 years, median length of 4 years Premature menopause -caused by genetic abnormalities on the long and short arm of X chromosome Earlier menopause: –surgical causation (30%) –family history of early menopause –cigarette smoking, blindness –abnormal chromosome karyotype –precocious puberty –left-handedness Later age : –obesity –higher socioeconomic class

4. Menopause & Society In most societies in the western world, about 13 % to 14% of the population are older than 50 years. Average age of menopause in USA is 50-51 year

5.  Physiologic menopause  Iatrogenic menopause :- Surgical, radiation therapy,chemotherapy, infection and tumer Types of Menopause

6. physiology of the perimenpausae Shorten of menstrual cycle length or anovulatory cycle and prolong cycle Shorten of the follicular phase, ↓ no of follicles ↑ FSH ↓ inhibin hormone Estradiol level fluctuate but remain within the wide range Progesterone level fluctuate depending on the presence &adequacy of ovulation Androgen level steadily ↓ during the transitional period

7. Ovarian Dysfunction Women are born with about 1.5 million ova At menarche ↓ 400,000 ova Most women menstruate about 400 times between menarche & menopause With menopause, the ovary is no longer capable of responding to pituitary gonadotropins →↓ production of estrogen &progesterone

8. Physiology of menopause Ovarian dysfunction Few remaining follicular units present but those are no longer capable of normal response despite stimulation by marked ↑ of gonadotropins.

9. OVARIAN DYSFUNCTION Degeneration of granulosa & thica cells Failure to react to endogenous gonadotrophine ↓ Estrogen ↑ FSH & LH

10. Changes in hormones metabolism associated with menopause Androgens :- ↑ androgen level due to stromal cell stimulation by endogenous gonadotrophins ↓ Androstenedion (adrenal) ↑ Testosterone level This lead to defeminization hirsutism,virilism,

11. Con. Estrogen : In preimenpausal women,the main Estrogen is E2 In post menopause is E1(from the peripheral conversion of Androstenadione)

12. Clinical manifestation of menopause  Target organ response to ↓ Esterogen CVS Urogenital system Bone Skin &teeth Brain  Symptoms related to ↓ estrogen Vasomotor instability Altered menstrual function Vaginal atrophy Urinary tract symptom Osteoporosis

13. Cardiovascular system changes Leading cause of death - twice as many women die of cardiovascular disease than of cancer Incidence rates of coronary heart disease in both men and women were similar 6-10 years after the menopause Serum cholesterol increases significantly at 1-2 yrs or more after the menopause - marked by an increase in triglycerides, an increase in LDL, decrease in HDL - and are less cardio protective

14. Atrophy of vaginal epithelium -> atrophic vaginitis (itching, burning, discomfort, dyspareunia and vaginal bleeding) Urologic: 30% drop in urethral closure pressure at rest and during stress in postmenopausal women because of atrophy of the urethral mucosa, varying degrees of bladder and urethral prolapsed and loss of UV angle Atrophic urethritis -> urgency, frequency, dysuria, suprapubic pain, ø UTI Atrophic cystitis -> urge incontinence, frequency, dysuria, and nocturia Descent of uterus due to decreased collagen in uterosacral ligaments and cardinal ligament Genitourinary system changes

15. Menopause &Osteoporosis 25% of women have radiological evidence of osteoporosis by 60; by 80Y 1 in 4 have fractured a hip; after age 65 1 in 3 have a vertebral fracture 15% of women with hip fracture after age 80 will die of complications within 6 months Initial period of up to 4-5 years after the menopause there is accelerated loss of bone at rate of 1-2% per year; trabecular bone mainly Bone loss is mainly in the trabecular type while cortical type occur later. Three most common fractures in postmenopausal women - vertebrae, ultra distal radius and neck of femur

16. Menopause &osteoporosis Risk factors: –white or Asian –reduced weight for height –early spontaneous menopause or surgical menopause –family history of osteoporosis –low dietary calcium intake –low vitamin D intake –high caffeine intake –high alcohol intake –high protein intake –cigarette smoking –endocrine disorders - diabetes mellitus, hyperthyroidism, Cushing disease

17. Hot Flushes Cause of hot flushes: –the mechanism is not known, but data indicate that symptom result from a defect in central thermoregulatory function A pulse of LH is released with the onset of each hot flush, therefore a central hypothalamic mechanism Development of hot flushes more than1 year prior to the menopause is probably not due to estrogen deficiency but to other factors such as stress

18. Hot flushes &menopause Onset : 10% prior to menopause 50% after cessation of menses it has abrupt onset, last for 30 sec - 5min Flush preceded by increase in digital perfusion, followed by increases in skin temp, circulating norephinephrine levels and LH levels, heart rate

19. Skin and Teeth Significant decrease in epidermal thickness and collagen content postmenopausally, healing of skin is generally slower Postmenopausal estrogen maintains premenopausal levels of synthesis of collagen and prevents thinning of skin and retards wrinkling process Women ingesting estrogen postmenopausally are less likely to loose teeth

20. Other systemic symptom Anxiety,depression,irritability,fatigue headaches, tiredness, lethargy, nervousness, depression, sleep difficulties, inability to concentrate, hot flushes Sleep latency interval is increased and amount of REM is decreased The mechanism is not clear ?? Postmenopausal women have lower level of plasma β-endorphin

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