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 Later
Africans Caucasian
African-Americans Japanese
Hispanics of Mexican Malaysian

Etiologic Factors for Early Menopause

Race, ethnicity (Latin America > Japanese, Europe, North America)
Parity (nulliparous > multiparous)
No prior OCP use
Socioeconomic status
 ↓ Education, unemployed
 Marital status – single > married
Familial, genetic factors Hormonal Changes in Menopausal Transition (MT)
Environmental toxins ↑ Ovarian Inhibin Factor

↓
Smoking
↑ FSH
 Chemotherapy ↓
 Irradiation ↑ E2 production (early stage of MT)
 Galactose consumption ↓

BMI > 30, ↓ physical activity ↓ E2 (several years of final menstrual period)
Depression, anxiety Favour greater output of FSH (in absence of any changes in E2 production)
Surgical trauma to ovarian blood supply – oophorectomy, hysterectomy ↓ Inhibin B (early MT)
↓ Inhibin A (luteal phase)
Physiological Basis of Menopause ↑ Activin A (MT stage)
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
Symptoms of Menopausal Transition (MT) Psychological Changes
Irregular cycle Depression
Vasomotor symptoms – Hot flashes Tiredness
Breast tenderness Irritability
Insomnia ↓ Energy
Migraines ↓ Memory
Premenstrual dysphoria (sadness) ↓ Concentration
Genital atrophic symptoms ↓ Libido
Sexual function problems Anxiety

Hot Flashes Skin, Joint Symptoms

Frequent in stages -1 and +1 Thin, dry skin
Transient periods of intense heat – upper arms, face Brittle nails
Flushing of skin, profuse sweating Loss of hair
Accompanied with Aches, pains
 Chills Due to
 Palpitations Loss of tissue collagen
 Anxiety 30% of skin collagen is lost within 5 years
Causes
Changes in core body temperature Long Term Problems
Changes in endogenous hormone levels Osteoporosis
↓ Estrogen Coronary heart disease
↓
Alzheimer disease
Downward shift of temperature set point occurs intermittently
↓ Osteoporosis
Misperception that body is warmer than it should be ↓ Bone mass - ↑ Fractures
↓ Fracture of spine, hip, wrist
Body disperses heat Osteoclast, osteoblast cells – estrogen receptors (promote bone remodelling)
↓
Factors – ↑ Bone Loss
Warm sensation
Nutrition – alcohol, caffeine, ↓ Ca2+/ vitamin D
Body weight – thin
↓ Estrogen
↓ Lifestyle – inactivity, smoking, bed rest
↑ LH pulses Genetic – family history, female, race
↓ Sex hormone status – premature menopause, postmenopausal
Vasodilatory effects Diseases – Cushing’s syndrome, Hyperthyroidism, Diabetes mellitus
Consequences Drugs – steroids, thyroxine
Sleep disturbances Estrogen protection against osteoporosis
Fatigue ↓ Sensitivity of bone to PTH (without change amount of circulatory PTH)
Irritability ↑ Calcitonin
Forgetfulness ↑ Ca2+ absorption in intestine
Acute physical discomfort Coronary Heart Disease
-ve effects on work Estrogen protection against cardiovascular disease
 ↓ LDL
Atrophy of Estrogen Dependent Tissues  ↑ HDL
Breast sags Direct protective effect of estrogen upon arterial wall
Vagina thin, atrophic  ↓ atherosclerotic plaques
Vulva thin, atrophic  Direct vasodilatation effects
Trigone of bladder atrophies
Alzheimer Disease
General skin atrophy
Estrogen
↓ Pelvic floor support ↓
↑ Synapses, neuronal growth
↓
Genital Changes
Vaginal atrophy, dryness ↓ β-amyloid in Alzheimer
↓ Vascularity
↓ Estrogen - ↓ glycogen of vaginal epithelial - ↓ lactobacilli - ↑ pH Action of Ca2+ Regulatory Hormones
(overgrowth of coliforms, streptococci) Bone Kidney GIT
Associated symptoms PTH ↑ Bone resorption ↑ Ca2+, ↓ PO4- No direct effect
 Itching (Ca2+, PO4-) reabsorption
 Burning Vitamin D ↑ Bone resorption ↑ Ca2+, ↑ PO4- ↑ Ca2+, ↑ PO4-
 Discomfort (PTH presence) reabsorption reabsorption
 Vaginal bleeding Calcitonin ↓ Bone resorption ↓ Ca2+, ↓ PO4- No direct effect
Uterine prolapse reabsorption
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)