Physiology of Menopause Staging System Hormone Level Changes

Not applied in Cigarette smokers BMI < 18, BMI > 30 Heavy aerobic exercise Chronic menstrual cycle irregularity Hysterectomy Abnormal uterine (fibroids), ovarian (endometrioma) anatomy Definition Menopause After 12 months of amenorrhoea FMP (retrospective diagnosis) Near complete but natural ovarian hormone secretion Perimenopause (Climacteric) Around the menopause Begin same time as MT (menopausal transition) (stage -2) Ends 12 months after FMP Age at Menopause 51 y/o (median age at natural menopause) Experience menopause Earlier Africans Caucasian African-Americans Japanese Malaysian Hispanics of Mexican

Later

Etiologic Factors for Early Menopause Race, ethnicity (Latin America > Japanese, Europe, North America) Parity (nulliparous > multiparous) No prior OCP use Socioeconomic status y Education, unemployed y Marital status single > married Familial, genetic factors Environmental toxins y Smoking y Chemotherapy y Irradiation y Galactose consumption BMI > 30, physical activity Depression, anxiety Surgical trauma to ovarian blood supply oophorectomy, hysterectomy Physiological Basis of Menopause Oocyte depletion in ovary Reproductive aging Steady loss of occytes atresia, ovulation Does not necessarily occur at constant rate Relatively wide age range 45-55 y/o Variation number of follicles at birth, rate of occyte loss

Hormonal Changes in Menopausal Transition (MT) Ovarian Inhibin Factor FSH E2 production (early stage of MT) E2 (several years of final menstrual period) Favour greater output of FSH (in absence of any changes in E2 production) Inhibin B (early MT) Inhibin A (luteal phase) Activin A (MT stage)

Symptoms of Menopausal Transition (MT) Irregular cycle Vasomotor symptoms Hot flashes Breast tenderness Insomnia Migraines Premenstrual dysphoria (sadness) Genital atrophic symptoms Sexual function problems Hot Flashes Frequent in stages -1 and +1 Transient periods of intense heat upper arms, face Flushing of skin, profuse sweating Accompanied with y Chills y Palpitations y Anxiety Causes Changes in core body temperature Changes in endogenous hormone levels Estrogen Downward shift of temperature set point occurs intermittently Misperception that body is warmer than it should be Body disperses heat Warm sensation Estrogen LH pulses Vasodilatory effects Consequences Sleep disturbances Fatigue Irritability Forgetfulness Acute physical discomfort -ve effects on work Atrophy of Estrogen Dependent Tissues Breast sags Vagina thin, atrophic Vulva thin, atrophic Trigone of bladder atrophies General skin atrophy Pelvic floor support Genital Changes Vaginal atrophy, dryness Vascularity Estrogen - glycogen of vaginal epithelial - lactobacilli - pH (overgrowth of coliforms, streptococci) Associated symptoms y Itching y Burning y Discomfort y Vaginal bleeding Uterine prolapse Cardinal, uterosacral ligaments lose tonicity (support the uterus) Cystocele, rectocele Elastic tissue around vagina Urethra support Lower Urinary Tract Changes Estrogen receptors located on urethra, bladder trigone After menopause, urethra become thinner (due to regression of squamous epithelial layer) Dysuria (thinned urethra) Frequency (atrophic trigonitis) Stress incontinence (less sphincter tone) Urge incontinence (atrophic trigonitis)

Psychological Changes Depression Tiredness Irritability Energy Memory Concentration Libido Anxiety Skin, Joint Symptoms Thin, dry skin Brittle nails Loss of hair Aches, pains Due to Loss of tissue collagen 30% of skin collagen is lost within 5 years Long Term Problems Osteoporosis Coronary heart disease Alzheimer disease Osteoporosis Bone mass - Fractures Fracture of spine, hip, wrist Osteoclast, osteoblast cells estrogen receptors (promote bone remodelling) Factors Bone Loss Nutrition alcohol, caffeine, Ca2+/ vitamin D Body weight thin Lifestyle inactivity, smoking, bed rest Genetic family history, female, race Sex hormone status premature menopause, postmenopausal Diseases Cushing s syndrome, Hyperthyroidism, Diabetes mellitus Drugs steroids, thyroxine Estrogen protection against osteoporosis Sensitivity of bone to PTH (without change amount of circulatory PTH) Calcitonin Ca2+ absorption in intestine Coronary Heart Disease Estrogen protection against cardiovascular disease y LDL y HDL Direct protective effect of estrogen upon arterial wall y atherosclerotic plaques y Direct vasodilatation effects Alzheimer Disease Estrogen Synapses, neuronal growth -amyloid in Alzheimer Action of Ca2+ Regulatory Hormones Bone Kidney PTH Bone resorption Ca2+, PO4(Ca2+, PO4-) reabsorption Vitamin D Bone resorption Ca2+, PO4(PTH presence) reabsorption Calcitonin Bone resorption Ca2+, PO4reabsorption

GIT No direct effect Ca2+, PO4reabsorption No direct effect