2: Lecture 4

Question 1

How to decrease effects of aging

Answer 1

Caloric restriction, increase antioxidant uptake
Regular exercise
Decrease hormone fluctuations caused by decreased hormone production

Question 2

How does hormones change with age

Answer 2

Estrogen
Men–>steady linear decrease
Women–> large drop with menopause
Testosterone
Men and Women–>steady decrease

Question 3

What is menopause

Answer 3

Permanent cessation of menstruation resulting from loss of ovarian function

Question 4

Hormone changes before and after menopause

Answer 4

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)

Question 5

Sources of estrogen before menopause

Answer 5

Estradiol is secretes and synthesized in ovaries
Estrone is produces in adipose tissue (stimulated by secretion of androstenedione from ovaries)

Question 6

Sources of estrogen after menopause

Answer 6

Estrone (produces in adipose tissue) is produced by androstenedione secreted from adrenal glands
Ovaries stop secreting estradiol

Question 7

Type of estrogen receptors

Answer 7

1) Estrogen receptor alpha (ERalpha)
2) Estrogen receptor beta (ERbeta)
NOT isoforms

Question 8

Where does estrogen act

Answer 8

Brain, heart, liver, bones, and uterus

Question 9

Progesterone receptor ISOFORMS

Answer 9

Product of alternative splicing
Progesterone receptor A (PR-A)
progesterone receptor B (PR-B)

Question 10

Targets of progesterone action

Answer 10

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

Question 11

Early symptoms of menopause

Answer 11

Hot flashes, insomnia, moodiness

Question 12

Intermediate symptoms of menopause

Answer 12

Vaginal atresia, bladder dysfunction, skin atrophy

Question 13

Late symptoms of menopause

Answer 13

Osteoporosis, cardiovascular disease

Question 14

Risk of Estrogen therapy (ET)

Answer 14

Increased risk of endometrial cancer
Safe in patients without uterus

Question 15

Use of Estrogen progestin therapy (EPT)

Answer 15

Decrease the chance of endometrial cancer in patients with a uterus

Question 16

Benefits of hormone replacement therapy

Answer 16

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

Question 17

Risks of hormone replacement therapy

Answer 17

Increased risk of venous thrombosis, stroke, breast cancer, gallstones, dementia

Question 18

What is osteoporosis

Answer 18

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

Question 19

How does Estrogen regulate bone remodeling?

Answer 19

High estrogen decrease production of RANKL (produced by osteoblasts)–>lower RANKL decreases osteoclast activity (breaking down bone)–>this increases osteoprotegerin that increases bone formation

Question 20

Non-pharmacologic treatments for osteoporosis prevention

Answer 20

Calcium and Vitamin D

Question 21

Pharmacologic treatment for osteoporosis prevention

Answer 21

Bisphosphonates (antiresorptive drug)
Selective estrogen receptor modulators (SERMS)

Question 22

Main action of Bisphosphonates

Answer 22

Inhibit osteoclast function and inhibit bone resorption

Question 23

Mechanism of Bisphosphonates

Answer 23

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

Question 24

Where is ERalpha

Answer 24

Predominant estrogen receptor in female reproductive tract and breast

Question 25

Where is ERbeta

Answer 25

Predominant estrogen receptor in endothelial cells, bones, and prostate

Question 26

Main action of SERM (selective estrogen receptor modulator)

Answer 26

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

Question 27

Actions of ideal SERM (selective estrogen receptor modulator)

Answer 27

Strengthen bones, decrease LDL levels and increase HDL cholesterol levels, relive hot flashes, reduce breast cancer risk, reduce uterine cancer risk

Question 28

Major risk factors of cardiovascular disease

Answer 28

Hyperlipidemia (high lipid levels in the blood)
Atherosclerosis (cholesterol plaques in artery walls)

Question 29

How does estrogen effect cholesterol levels

Answer 29

Estrogen increases HDL levels
Estrogen decreases LDL levels
Estrogen also increases vascular dilation and decreases coronary artery LDL uptake

Question 30

What affects benefit/risk ratio of hormonal replacement therapy

Answer 30

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