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PHAR 301 > Aging and Menopause > Flashcards

Aging and Menopause Flashcards

1
Q

what happens to estrogen with age, in men and women?

A

Men: no change with age

Women: sharp drop in estrogen at menopause

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2
Q

what happens to progesterone with age, in men and women?

A

no change in men or women

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3
Q

what is menopause?

A

permanent cessation of menstruation resulting from loss of ovarian function

stop producing oocytes, stop producing estrogen

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4
Q

how have years of active life after menopause changed over time?

A

increased

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5
Q

how do FSH, LH, estrone, and estradiol levels change after menopause?

A

FSH and LH: big increase
Estradiol: big decrease
Estrone: decrease

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6
Q

what is estrone?

A

estradiol metabolite

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7
Q

what is the source of estrogen before menopause?

A

ovary and granulosa cells make lots of estradiol

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8
Q

what is the source of estrogen after menopause?

A

adrenals make androstenedione which adipose uses to produce a bit of estrone

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9
Q

what 2 hormones are used in female hormone replacement therapy?

A
  1. estrogen
  2. progesterone
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10
Q

what is the mechanism of estrogen action?

A
  1. estrogen enters the nucleus
  2. estrogen acts on ER
  3. estrogen+ER interacts with response elements to change gene expression and affect cell behaviour
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11
Q

where are ERs located in the body? (6)

A

throughout the body
- brain
- heart
- breast
- liver
- uterus
- bone

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12
Q

what are 2 types of ER? how are they similar, how are they different?

A

ER alpha and ER beta

similar in ligand binding domain and DNA binding domain

different in hinge and activation domain

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13
Q

why does the type of ER matter?

A

can selectively cause drugs to activate one or the other

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14
Q

describe the 2 types of progesterone mechanisms

A

GENOMIC PATHWAY
- Progesterone enters nucleus and acts on PR to change gene expression
- slow

SECOND MESSENGER
- Progesterone binds PR on membrane and activates non-genomic secondary messengers
- fast

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15
Q

what are 5 targets of progesterone action (i.e. where are PR located)?

A
  1. CNS
  2. systemic effects
  3. endometrium, vagina, cervix
  4. mammary gland
  5. hypothalamus + anterior pituitary
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16
Q

what does progesterone affect in the CNS? (3)

A
  1. sleep
  2. EEG patterns
  3. thermoregulation
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17
Q

what systemic effects does progesterone affect? (3)

A
  1. glucose metabolism
  2. protein metabolism
  3. water and electrolyte metabolism
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18
Q

what are the 3 early menopause-related symptoms? how long do these effects last?

A
  1. hot flashes
  2. insomnia
  3. moodiness

weeks to months

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19
Q

what are the 3 intermediate menopause-related symptoms? how long do these effects last?

A
  1. vaginal atresia
  2. bladder dysfunction
  3. skin atrophy

months to years

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20
Q

what are the 2 late menopause-related symptoms? how long do these effects last?

A
  1. osteoporosis
  2. CVD

years to decades

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21
Q

why is progesterone added to estrogen?

A

P added to E in women with an intact uterus to reduce increased risk of endometrial cancer

^estrogen alone could lead to endometrial cancer

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22
Q

what hormones can people without a uterus take?

A

E alone or E+P

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23
Q

what are 4 benefits of using hormonal therapy for menopause?

A
  1. symptom control
  2. skeletal benefit
  3. decreased coronary heart disease
  4. breast cancer (E alone)
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24
Q

what are 3 EARLY menopause symptoms?

A
  1. hot flashes
  2. night sweats
  3. moodiness
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25
Q

what percent of postmenopausal women experience hot flashes, night sweats, and moodiness?

A

50-85%

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26
Q

what are the 3 ways to control menopausal symptoms? do they work?

A
  1. lifestyle modifications –> less practical
  2. hormone therapy –> works well
  3. non-hormonal approaches –> some may work
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27
Q

describe the crossover study showing that estrogen can reduce the incidence of hot flashes

A

1 group received ctrl, 1 group received estrogen then switched

group that received estrogen had lower hot flasehs

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28
Q

how can you use estrogen for vaginal dryness?

A

use low dose local estrogen creams (systemic estrogen not needed)

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29
Q

in what type of woman is hormone replacement therapy (HRT) recommended?

A

women <60 or within 10 years of menopause onset, no contraindications, willing take estrogen with/without progesterone

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30
Q

what is a possible alternative to HRT?

A

phytoestrogens

31
Q

what are phytoestrogens, where are they found?

A

plant estrogens in food, like soy

32
Q

are there benefits of phytoestrogens?

A

limited evidence of benefit, most have not been tested

33
Q

what is osteoporosis?

A

decrease in bone density

34
Q

what percent of the population does osteoporosis affect? what percent are women?

A

osteoporosis affects 55% of the population over 50

80% of these ppl are women

35
Q

what are 8 lifestyle risk factors for osteoporosis?

A
  1. low calcium diet
  2. lack of exercise
  3. very high-protein diet
  4. high alcohol use
  5. smoking
  6. lack of vit D from sun, diet, pills
  7. high salt diet
  8. high caffeine use
36
Q

what are 3 additional things you can look at to assess the fracture risk?

A
  1. age
  2. bone density
  3. prior fractures
37
Q

how does bone remodeling work?

A

OSTEOBLASTS
- precursor cells that build up bone

OSTEOCLASTS
- breaking down bone (bone resorption)
- uses RANKL

the ratio of osteoblasts and osteoclasts is important to maintain bone density!

38
Q

what happens to bone density with estrogen deficiency?

A

increased osteoclast activity –> increased breakdown/resorption

39
Q

does estrogen HRT help osteoporosis?

A

yes, bone density is maintained

40
Q

describe the Women’s Health Initiative HRT study

A

a randomized clinical trial to evaluate benefit and risk of treatments in post-menopausal women

41
Q

what were 2 issues with the Women’s Health Initiative study?

A
  1. many of the women started on HRT quite late post-menopause
  2. some of the women were obese which affects estrogen production because adipose can make estrogen
42
Q

what is the impact of HRT on the risk of osteoporosis/hip fracture?

A

less hip fracture than placebo (associated with age)

43
Q

how much calcium supplementation is required in post-menopausal women not taking estrogen?

A

1500 mg/day

44
Q

why is vit D supplementation good to help osteoporosis?

A

maintains Ca2+ balance to help with bone density

45
Q

does vit D and calcium administered together help to prevent fractures?

A

yes, vit D and calcium prevent fractures in elderly women

those who received placebo had a higher risk of fractures

46
Q

what do bisphosphonates do?

A

aka “anti-resorptives”

bind Ca2+ and accumulates in bone to inhibit osteoclast function –> inhibits bone breakdown

47
Q

what is the mechanism of action of bisphosphonates?

A

nitrogen-containing bisphosphonates inhibit an enzyme in the cholesterol biosynthesis pathway and disrupt protein prenylation

this creates cytoskeletal abnormalities in osteoclasts to kill osteoclasts –> reduced bone resorption

48
Q

how do bisphosphonates affect the number of fractures?

A

fewer fractures with bisphosphonates

49
Q

what are Selective Estrogen Receptor Modulators (SERMs)?

A

can selectively bind different ER to induce genetic change

50
Q

what would a perfect SERM cause? (5)

A
  1. strengthen bone
  2. lower LDL, raise HDL
  3. relieve hot flashes
  4. reduce risk of breast cancer
  5. reduce risk of uterine cancer
51
Q

describe the selectivity of different ER for raloxifene

A
  • Partial agonist for ER alpha
  • Pure antagonist for ER beta
  • agonist for GPER
52
Q

what is GPER?

A

GPCR version of ER on cell membrane that induces secondary messengers

53
Q

what are the effects of raloxifene in bone and lipids?

A

in bone and lipids, raloxifene is AGONIST for ER alpha –> help with osteoporosis

54
Q

what are the effects of raloxifene in breast and vagina?

A

in breast and vagina, raloxifene is ANTAGONIST for ER beta –> wouldn’t contribute to breast cancer

55
Q

what is HDL?

A

good cholesterol

moves cholesterol back to the liver for removal from the bloodstream

56
Q

what is LDL?

A

bad cholesterol

helps cholesterol stick to the artery walls

57
Q

what happens to lipids in menopause?

A

reduced estrogen causes decreased HDL and increased LDL

58
Q

how does estrogen affect HDL/LDL? what 2 things does this lead to?

A

increases HDL, decreases LDL

leads to increased vascular dilation, decreased coronary artery LDL uptake

59
Q

what is the impact of HRT on the risk of CVD?

A

higher risk of CVD > 20 years after menopause

60
Q

what is the recommendation for HRT preventing CVD?

A

HRT with estrogen may reduce CVD in women <60 within the first 10 years of menopause

61
Q

what happens to CVD if you start HRT after the first 10 years of menopause

A

may cause increased risk of CVD in the first 2 years of using HRT

62
Q

what is the impact of HRT on breast cancer?

A

HRT increases risk of breast cancer

63
Q

what are 2 risk factors that could cause HRT to increase the risk of breast cancer?

A
  1. age
  2. family history of breast cancer
64
Q

what is the impact of HRT on stroke and pulmonary embolism?

A

HRT causes a small increase in risk of stroke in a small population

65
Q

what is the impact of HRT on colorectal cancer?

A

risk of colorectal cancer decreases with HRT

66
Q

what are 5 benefits of HRT?

A
  1. menopausal symptoms
  2. osteoporosis
  3. CVD (within 10 years of menopause)
  4. breast cancer (E alone)
  5. colorectal cancer
67
Q

what are 4 risks of HRT?

A
  1. good for osteoporosis but other alternatives are available
  2. CVD >10 years after menopause
  3. stroke
  4. pulmonary embolism
68
Q

how do levels of testosterone change as men age?

A

no sharp drop, slowly decreases with age

69
Q

where are testosterone receptors? (6)

A
  1. systemic
  2. CNS
  3. hypothalamus + anterior pituitary
  4. penis
  5. striated muscle
  6. prostate, seminal vesicles
70
Q

why is there a lower incidence of osteoporosis in men?

A

they have higher bone density

71
Q

what is recommended to treat osteoporosis in men (3)? and what is not recommended (1)?

A

RECOMMENDED:
1. Vit D
2. Ca2+
3. Bisphosphantes

NOT RECOMMENDED:
Testosterone

72
Q

what is required before using testosterone as replacement therapy

A

must establish firm diagnostic criteria for testosterone deficiency before treatment

73
Q

is there a lot of evidence for using testosterone as replacement therapy?

A

no, there is limited data to support the true benefit

74
Q

what are 3 possible risks of testosterone as replacement therapy?

A
  1. prostate effects
  2. CVD
  3. pulmonary emoblism

PHAR 301 (11 decks)

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