2: Lecture 4 Flashcards
How to decrease effects of aging
Caloric restriction, increase antioxidant uptake
Regular exercise
Decrease hormone fluctuations caused by decreased hormone production
How does hormones change with age
Estrogen
Men–>steady linear decrease
Women–> large drop with menopause
Testosterone
Men and Women–>steady decrease
What is menopause
Permanent cessation of menstruation resulting from loss of ovarian function
Hormone changes before and after menopause
Before
*high levels of estrone and estradiol
*low levels of LH and FSH (inhibited by estrogen)
After
*Drop in levels of estrone, estradiol, and progesterone
*high levels of LH and FSH (no inhibition by estrogen)
Sources of estrogen before menopause
Estradiol is secretes and synthesized in ovaries
Estrone is produces in adipose tissue (stimulated by secretion of androstenedione from ovaries)
Sources of estrogen after menopause
Estrone (produces in adipose tissue) is produced by androstenedione secreted from adrenal glands
Ovaries stop secreting estradiol
Type of estrogen receptors
1) Estrogen receptor alpha (ERalpha)
2) Estrogen receptor beta (ERbeta)
NOT isoforms
Where does estrogen act
Brain, heart, liver, bones, and uterus
Progesterone receptor ISOFORMS
Product of alternative splicing
Progesterone receptor A (PR-A)
progesterone receptor B (PR-B)
Targets of progesterone action
CNS: Thermoregulation, sleep, EEG patterns
Systemic effects: protein and glucose metabolism, water and electrolyte metabolism
Uterus: progesterone protects against endometrial cancer
Mammary glands
hypothalamus and anterior pituitary
Early symptoms of menopause
Hot flashes, insomnia, moodiness
Intermediate symptoms of menopause
Vaginal atresia, bladder dysfunction, skin atrophy
Late symptoms of menopause
Osteoporosis, cardiovascular disease
Risk of Estrogen therapy (ET)
Increased risk of endometrial cancer
Safe in patients without uterus
Use of Estrogen progestin therapy (EPT)
Decrease the chance of endometrial cancer in patients with a uterus
Benefits of hormone replacement therapy
Decrease in symptoms
Decrease in osteoporosis
Decrease in cardiovascular disease in women below 60 and within 10 years of menopause
Decrease in risk of colon cancer
Risks of hormone replacement therapy
Increased risk of venous thrombosis, stroke, breast cancer, gallstones, dementia
What is osteoporosis
Decrease in bone density that increase risk of bone fractures
Menopause accelerates the decrease in bone mass density
Estrogen has important role in regulation of bone remodeling
How does Estrogen regulate bone remodeling?
High estrogen decrease production of RANKL (produced by osteoblasts)–>lower RANKL decreases osteoclast activity (breaking down bone)–>this increases osteoprotegerin that increases bone formation
Non-pharmacologic treatments for osteoporosis prevention
Calcium and Vitamin D
Pharmacologic treatment for osteoporosis prevention
Bisphosphonates (antiresorptive drug)
Selective estrogen receptor modulators (SERMS)
Main action of Bisphosphonates
Inhibit osteoclast function and inhibit bone resorption
Mechanism of Bisphosphonates
Nitrogen-containing bisphosphonates inhibit an enzyme in cholesterol biosynthesis pathway–>disrupts protein prenylation in osteoclasts–>creates cytoskeletal abnormalities in osteoclasts–>osteoclasts apoptosis
May increase risk of thigh bone fractures
Where is ERalpha
Predominant estrogen receptor in female reproductive tract and breast
Where is ERbeta
Predominant estrogen receptor in endothelial cells, bones, and prostate
Main action of SERM (selective estrogen receptor modulator)
ex. bazedoxifene
Has antagonist action in breast and uterus AND agonist action in bone and lipid metabolism
SERMs can either activate or inhibit the receptors selectively
Overall increase bone density and decreases LDL
Actions of ideal SERM (selective estrogen receptor modulator)
Strengthen bones, decrease LDL levels and increase HDL cholesterol levels, relive hot flashes, reduce breast cancer risk, reduce uterine cancer risk
Major risk factors of cardiovascular disease
Hyperlipidemia (high lipid levels in the blood)
Atherosclerosis (cholesterol plaques in artery walls)
How does estrogen effect cholesterol levels
Estrogen increases HDL levels
Estrogen decreases LDL levels
Estrogen also increases vascular dilation and decreases coronary artery LDL uptake
What affects benefit/risk ratio of hormonal replacement therapy
The age when the patient starts treatment
Over 20 years after menopause–>HRT increase risk of cardiovascular disease
Less than 10 years after menopause–>no increase in risk of cardiovascular disease
