Physiology of Menopause

Dr Samaa Nazer Consultant - Assistant Professor

King Abdulaziz University

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.

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

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

Physiologic menopause

Iatrogenic menopause :-

Surgical, radiation therapy ,chemotherapy, infection and tumer

Types of Menopause

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

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

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.

OVARIAN DYSFUNCTION

Degeneration of granulosa & thica cells

Failure to react to endogenous gonadotrophine

↓ Estrogen

↑ FSH & LH

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,

Con.

• Estrogen : • In preimenpausal women ,the main

Estrogen is E2 • In post menopause is E1(from the

peripheral conversion of Androstenadione)

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

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

• 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

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

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

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

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

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

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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