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PMCOL 343 > estrogen > Flashcards

estrogen Flashcards

1
Q

where are GnRH neurons

A

in the hypothalamus

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2
Q

what is GnRH

A

gonadotrophin releasing hormone

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3
Q

when do GnRH neurons fire

A

at hourly intervals

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4
Q

where does the GnRH act

A

on anterior pituitary gland (gonadotropes)

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5
Q

where are gonadotropes

A

anterior pituitary gland

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6
Q

what do the gonadotropes release

A

gonadotrophins

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7
Q

what are the 2 gonadotrophins

A

luteinizing hormone (LH) and follicle-stimulating hormone (FSH)

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8
Q

where does LH and FSH act

A

on the ovary

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9
Q

what does the ovary release

A

estrogen and progesterone

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10
Q

when in the menstrual cycle does LH peak

A

right before ovulation

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11
Q

when in the menstrual cycle does FSH peak

A

right before ovulation

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12
Q

when in the menstrual cycle does estradiol peak

A

before ovulation, then a bit more later in the cycle

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13
Q

when in the menstrual cycle does progesterone peak

A

later in the cycle, day 21

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14
Q

what causes LH and FSH peak in the menstrual cycle

A

estrogen acting as a positive regulator on the gonadotrophins until the ovum is released

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15
Q

what does estrogen do to the gonadotropes usually

A

inhibit

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16
Q

what does progesterone do to the gonadotropes

A

inhibit

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17
Q

what does progesterone do to the hypothalamic GnRH neurons

A

inhibit

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18
Q

where does estrogen inhibit

A

anterior pituitary gonadotrope glands

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19
Q

where does progesterone inhibit

A

anterior pituitary gonadotrope glands and hypothalamic GnRH neurons

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20
Q

what is E2

A

estradiol

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21
Q

what is another name for estradiol (2)

A

E2 or estradiol-17β

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22
Q

what are the 3 types of estrogens

A

E1 - estrone
E2 - estradiol
E3 - estriol

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23
Q

which estrogen is the most potent

A

E2

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24
Q

which estrogen is the main endogenous estrogen

A

E2

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25
Q

where is E2 synthesized in females

A

in the ovary and placenta

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26
Q

where is E2 synthesized in males

A

testis and adrenal cortex

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27
Q

what is the name for E1

A

estrone

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28
Q

what is the name for E2

A

estradiol

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29
Q

what is the name for E3

A

estriol

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30
Q

how potent is E1

A

not, low binding affinity for estrogen receptors

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31
Q

how potent is E3

A

not, low binding affinity for estrogen receptors

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32
Q

where is E1 synthesized

A

in liver from estradiol

in peripheral tissues from androstenedione and other androgens

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33
Q

where is E3 synthesized

A

in liver from estradiol

in peripheral tissues from androstenedione and other androgens

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34
Q

which E is made in the ovaries

A

E2

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35
Q

which E is made in the liver

A

E1 and E3

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36
Q

where is estradiol metabolized

A

into the liver

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37
Q

what is estradiol metabolized into

A

estrone, estriol, conjugated metabolites

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38
Q

what is estradiols binding to albumin like

A

weak

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39
Q

how long is the half life for estradiol

A

short, only minutes

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40
Q

what is SHBG

A

sex hormone binding globulin

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41
Q

what is estradiols binding to SHBG like

A

stronger

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42
Q

where does estradiols bind weak

A

albumin

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43
Q

where does estradiols bind strong

A

SHBG (sex hormone binding globulin)

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44
Q

what increases sex hormone binding globulin

A

estrogen and thyroid hormone

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45
Q

what decreases sex hormone binding globulin

A

androgen and growth hormone

46
Q

where are estradiol conjugated metabolites excreted

A

in bile then GI tract

47
Q

what happens with estradiol conjugated metabolites in the GI tract

A

they may be hydrolyzed to active estrogen in GI tract and reabsorbed (via bacteria)

48
Q

what can antibiotics do to birth control efficacy and why

A

decrease cause less estrogen can be made in GI from the estradiol conjugated metabolites

49
Q

how do non genomic actions of estrogen work

A

rapid effects via plasma membrane estrogen receptors

50
Q

what does estrogen do to acute blood vessel diameter

A

acute vasodilation

51
Q

how do genomic actions of estrogen work

A

intracellular estrogen receptors, ERα and ERβ

52
Q

where are ERα and ERβ

A

in female reproductive tract, breast, pit, hypo, bone, liver, etc

53
Q

what does ERα and ERβ receptor activation cause

A

changes in gene transcription

54
Q

how are synthetic estrogens made (what are 2 types)

A
  • chemical alternations to the estrogen molecule

- non-steroidal compounds with estrogenic activity

55
Q

why do we make synthetic estrogens from chemical alternations to the estrogen molecule

A

to increase the effectiveness of oral administration

56
Q

what are non-steroidal compounds with estrogenic activity structurally like

A

presence of phenolic A ring which is important for binding to ER

57
Q

what does estrogen do to growth spurt

A

helps with the long bones and epiphyseal closure

58
Q

what does estrogen do to female maturation

A
  • growth of vagina uterus fallopian tubes

- secondary sex characteristics

59
Q

what are 3 female secondary sex characteristics

A
  • enlargement of breasts
  • changes in distribution of body fat
  • growth of axillary and pubic hair
60
Q

what does estrogen do to endometrium

A

increase in thickness and vascularity of endometrium

61
Q

what does estrogen do to regulation of menstrual cycle

A

brief positive feedback on the pituitary to stimulate pre-ovulatory LH and FSH surge mid cycle

62
Q

what does estrogen do to progesterone receptors + where

A

increases progesterone receptor synthesis in uterus vagina pituitary and hypothalamus

63
Q

what does estrogen do to blood + how

A

increase coagulation - decrease in anticoagulation factors

64
Q

what does estrogen do to bone

A

decrease in resorption by increase osteoclast apoptosis and decreasing the maturation of osteoclasts

65
Q

what does estrogen do to osteoclast

A

increase apoptosis and decrease maturation

66
Q

what does estrogen do to binding proteins

A

increase levels of corticosteroid-binding globulin, sex steroid-binding globulin and thyroxine-binding globulin

67
Q

what does estrogen do to plasma lipids (3)

A 
increase HDL (good) decrease LDL (bad)
small increase in triglycerides
68
Q

what does estrogen do to HDL

A

increase

69
Q

what does estrogen do to LDL

A

decrease

70
Q

what does estrogen do to triglycerides

A

small increase

71
Q

what does estrogen do to salt and water intension and how

A

increase likely by ADH release

72
Q

what are 4 therapeutic uses of estrogen

A
  • primary hypogonadism
  • amenorrhea
  • birth control
  • postmenopausal hormonal therapy
73
Q

what is estrogen often combined with therapeutically

A

progesterone

74
Q

what is primary hypogonadism

A

failure of ovarian development

75
Q

what are 3 uses of postmenopausal hormonal therapy

A

decrease vasomotor symptoms
reduce genitourinary syndrome
reduce osteoporosis

76
Q

what are 4 vasomotor symptoms of menopause

A
  • hot flashes
  • inappropriate sweating
  • irritability, difficulty concentration, mood changes
  • insomnia
77
Q

what are 3 genitourinary symptoms of menopause

A
  • genital dry/burn/irritation
  • sexual pain / less lubrication
  • urinary urgency, dysuria, UTIs
78
Q

what is dysuria

A

painful or difficult urination

79
Q

what are 2 main untoward effects of estrogen

A

cancer (breast and endometrial)

embolisms

80
Q

what kinds of cancer are common with estrogen

A

breast and endometrial

81
Q

how can you reduce the risk of endometrial carcinoma with estrogen

A

progesterone supplement (prevents proliferation caused by E)

82
Q

what does estrogen do to embolisms

A

small increase risk of pulmonary embolism and venous thromboembolism

83
Q

what are 4 contraindications for estrogen

A
  • estrogen dependent cancer
  • undiagnosed genital bleeding
  • history of thromboembolic disorders
  • liver disease
84
Q

what was the point of the womens health initiative

A

assess the major health benefits and risks associated with the use of estrogen or combined estrogen/progestin preparation in hormone replacement therapy

85
Q

what is the most effective treatment for vasomotor symptoms and genito-urinary syndrome

A

hormone therapy

86
Q

what can hormone therapy do to bone loss and fracture

A

prevent

87
Q

who is hormone therapy most beneficial for

A

women under 60 or within 10 years of menopause with VMS and high risk for bone loss/fracture

88
Q

who is hormone therapy least beneficial for

A

women over 60 or more than 10 years of menopause due to coronary heart disease, stroke, thromboembolism, and dementia risk

89
Q

what was the conclusion of womens health initiative

A

therapy with estrogen/progestin or 5.6 years or estrogen for 7.2 years was not associated with all-cause, cardiovascular or cancer mortality during cumulative follow-up of 18 years

90
Q

what do anti-estrogen drugs do / mechanism of action (tamoxifen)

A

partial agonist inhibitor of estrogen receptor

91
Q

what is tamoxifen

A

anti-estrogen

92
Q

what is mechanism of action of tamoxifen

A

partial agonist inhibitor of estrogen receptor

93
Q

what does tamoxifen have estrogenic effects on (4)

A
  • bone (less osteoporosis)
  • plasma lipids (more HDL good)
  • endometrium (cancer!)
  • blood coagulation (clot!)
94
Q

what does tamoxifen have anti-estrogenic effects on (1)

A

breast tissue

95
Q

what are non estrogen receptor mediated actions if tamoxifen

A

modulation of signalling proteins and activation of apoptosis

96
Q

what can be a good use of tamoxifen and why

A

breast cancer because it has anti-estrogenic effects on breast tissue

97
Q

what are 2 types of aromatase inhibitors

A

steroidal or non steroidal inhibitor of aromatase

98
Q

what do aromatase inhibitors do

A

selective inhibition of estrogen synthesis

99
Q

what are aromatase inhibitors used for

A

breast cancer

100
Q

what does aromatase inhibitors do to estrogen synthesis

A

reduce

101
Q

do aromatase inhibitors stimulate endometrial tissue

A

no

102
Q

do aromatase inhibitors increase risk of uterine cancer

A

no

103
Q

do aromatase inhibitors increase risk of venous thromboembolism

A

no

104
Q

do aromatase inhibitors have a beneficial effect on bone

A

no

105
Q

what is the mechanism of action of clomiphene

A

anti-estrogen : reduces estrogen binding in gonadotropes, decrease in negative feedback

106
Q

what does anti-estrogen clomiphene do to gonadotrophins

A

increase secretion of them (LH FSH)

107
Q

what does anti-estrogen clomiphene do to estrogen secretion

A

increase

108
Q

what does anti-estrogen clomiphene do to ovulation

A

increase

109
Q

what is the use of anti-estrogen clomiphene

A

treatment of infertility and amenorrhea

110
Q

what are 5 unwanted effects of anti-estrogen clomiphene

A
  • ovarian enlargement
  • ovarian cysts
  • hot flashes
  • blurred vision
  • multiple births

PMCOL 343 (31 decks)

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