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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
what percent of postmenopausal women experience hot flashes, night sweats, and moodiness?
50-85%
26
what are the 3 ways to control menopausal symptoms? do they work?
1. lifestyle modifications --> less practical 2. hormone therapy --> works well 3. non-hormonal approaches --> some may work
27
describe the crossover study showing that estrogen can reduce the incidence of hot flashes
1 group received ctrl, 1 group received estrogen then switched group that received estrogen had lower hot flasehs
28
how can you use estrogen for vaginal dryness?
use low dose local estrogen creams (systemic estrogen not needed)
29
in what type of woman is hormone replacement therapy (HRT) recommended?
women <60 or within 10 years of menopause onset, no contraindications, willing take estrogen with/without progesterone
30
what is a possible alternative to HRT?
phytoestrogens
31
what are phytoestrogens, where are they found?
plant estrogens in food, like soy
32
are there benefits of phytoestrogens?
limited evidence of benefit, most have not been tested
33
what is osteoporosis?
decrease in bone density
34
what percent of the population does osteoporosis affect? what percent are women?
osteoporosis affects 55% of the population over 50 80% of these ppl are women
35
what are 8 lifestyle risk factors for osteoporosis?
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
what are 3 additional things you can look at to assess the fracture risk?
1. age 2. bone density 3. prior fractures
37
how does bone remodeling work?
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
what happens to bone density with estrogen deficiency?
increased osteoclast activity --> increased breakdown/resorption
39
does estrogen HRT help osteoporosis?
yes, bone density is maintained
40
describe the Women's Health Initiative HRT study
a randomized clinical trial to evaluate benefit and risk of treatments in post-menopausal women
41
what were 2 issues with the Women's Health Initiative study?
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
what is the impact of HRT on the risk of osteoporosis/hip fracture?
less hip fracture than placebo (associated with age)
43
how much calcium supplementation is required in post-menopausal women not taking estrogen?
1500 mg/day
44
why is vit D supplementation good to help osteoporosis?
maintains Ca2+ balance to help with bone density
45
does vit D and calcium administered together help to prevent fractures?
yes, vit D and calcium prevent fractures in elderly women those who received placebo had a higher risk of fractures
46
what do bisphosphonates do?
aka "anti-resorptives" bind Ca2+ and accumulates in bone to inhibit osteoclast function --> inhibits bone breakdown
47
what is the mechanism of action of bisphosphonates?
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
how do bisphosphonates affect the number of fractures?
fewer fractures with bisphosphonates
49
what are Selective Estrogen Receptor Modulators (SERMs)?
can selectively bind different ER to induce genetic change
50
what would a perfect SERM cause? (5)
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
describe the selectivity of different ER for raloxifene
- Partial agonist for ER alpha - Pure antagonist for ER beta - agonist for GPER
52
what is GPER?
GPCR version of ER on cell membrane that induces secondary messengers
53
what are the effects of raloxifene in bone and lipids?
in bone and lipids, raloxifene is AGONIST for ER alpha --> help with osteoporosis
54
what are the effects of raloxifene in breast and vagina?
in breast and vagina, raloxifene is ANTAGONIST for ER beta --> wouldn't contribute to breast cancer
55
what is HDL?
good cholesterol moves cholesterol back to the liver for removal from the bloodstream
56
what is LDL?
bad cholesterol helps cholesterol stick to the artery walls
57
what happens to lipids in menopause?
reduced estrogen causes decreased HDL and increased LDL
58
how does estrogen affect HDL/LDL? what 2 things does this lead to?
increases HDL, decreases LDL leads to increased vascular dilation, decreased coronary artery LDL uptake
59
what is the impact of HRT on the risk of CVD?
higher risk of CVD > 20 years after menopause
60
what is the recommendation for HRT preventing CVD?
HRT with estrogen may reduce CVD in women <60 within the first 10 years of menopause
61
what happens to CVD if you start HRT after the first 10 years of menopause
may cause increased risk of CVD in the first 2 years of using HRT
62
what is the impact of HRT on breast cancer?
HRT increases risk of breast cancer
63
what are 2 risk factors that could cause HRT to increase the risk of breast cancer?
1. age 2. family history of breast cancer
64
what is the impact of HRT on stroke and pulmonary embolism?
HRT causes a small increase in risk of stroke in a small population
65
what is the impact of HRT on colorectal cancer?
risk of colorectal cancer decreases with HRT
66
what are 5 benefits of HRT?
1. menopausal symptoms 2. osteoporosis 3. CVD (within 10 years of menopause) 4. breast cancer (E alone) 5. colorectal cancer
67
what are 4 risks of HRT?
1. good for osteoporosis but other alternatives are available 2. CVD >10 years after menopause 3. stroke 4. pulmonary embolism
68
how do levels of testosterone change as men age?
no sharp drop, slowly decreases with age
69
where are testosterone receptors? (6)
1. systemic 2. CNS 3. hypothalamus + anterior pituitary 4. penis 5. striated muscle 6. prostate, seminal vesicles
70
why is there a lower incidence of osteoporosis in men?
they have higher bone density
71
what is recommended to treat osteoporosis in men (3)? and what is not recommended (1)?
RECOMMENDED: 1. Vit D 2. Ca2+ 3. Bisphosphantes NOT RECOMMENDED: Testosterone
72
what is required before using testosterone as replacement therapy
must establish firm diagnostic criteria for testosterone deficiency before treatment
73
is there a lot of evidence for using testosterone as replacement therapy?
no, there is limited data to support the true benefit
74
what are 3 possible risks of testosterone as replacement therapy?
1. prostate effects 2. CVD 3. pulmonary emoblism

PHAR 301 (11 decks)

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