Estrogens - 13,14 Flashcards

1
Q

Estrogens

  • development and maintenance of female reproductive tissues (___, uterus, breast, ___)
  • regulation in ___ (temp, mood)
  • effects in ___ tissues (bone, cardiovascular, liver)
A
  • ovaries, vagina
  • CNS
  • peripheral
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Progesterone

  • development and maintenance of female reproductive tissues (___ and ___)
  • maintenance of ___
  • effects in other tissues (__)
A
  • uterus, breast
  • pregnancy
  • brain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

17β-Estradiol

  • most potent estrogen
  • produced mostly in the ___
  • synthesized most in the __ during pregnancy
  • plasma levels ___ ng/dL
  • ___ varies during the menstrual cycle
  • mostly bound to ___ and ___ only ___ free in circulation
A
  • ovaries
  • placenta
  • 5-85 ng/dL
  • cyclically
  • sex-hormone binding globulin (SHBG), albumin, 2%
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Regulation of estrogen synthesis

  1. hypothalamus: ___
  2. anterior pituitary: ___ and __
  3. Ovaries: ___ and ___ → physiological functions and positive/negative feedback loop
A
  • GnRH
  • FSH and LH
  • estrogens and progesterone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Menstrual cycle

  • Granulosa cells produce ___
  • Corpus luteum produces ___ and ___
A
  • estrogen
  • estrogen and progesterone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Menstrual cycle

Early follicular phase
* Estrogen suppresses the production
of ___.

A

FSH

prevents multiple eggs fro being released

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Menstrual cycle

Late follicular phase
* estrogen stimulates surge of __ and __ → ovulation and formation of ___

A
  • LH and FSH
  • corpus luteum
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Menstrual cycle

Luteal phase
* estrogen and __ suppresses the production of ___ and ___

A
  • progesterone
  • LH and FSH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Menstrual cycle

  • corpus luteum ___ if pregnancy does not occur
  • when production of estrogen and progesterone by the ___ declines, ___ occurs
A
  • degenerates
  • corpus luteum, menstruation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Menstrual cycle

if pregnancy occurs
* fertilized egg secretes ___, whichs acts as ___ to stimulate corpus luteum to produce ___ during the first trimester.
* higher ___ levels support maintenance of endometrium
* ___ is what is detected during a pregnancy tests.

A
  • human chorionic gonadotropin (hCG), LH, progesterone
  • progesterone
  • hCG

corpus luteum doesnt degrade, sticks around to make progesterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Biosynthesis of estrogens

  • Step 1: Androstenedione can be converted to ___ by aromatase, or it can be converted to ___ by 17B-hydroxysteroid dehydrogenase.
  • Step 2: estrone is then converted to 17B-estradiol by ___, or testosterone is converted to 17B-estradiol by ___

both estrone and 17B-estradiol are converted into ___, a weak estrogen

A
  • estrone, testosterone
  • 17B-hydroxysteroid dehydrogenase, aromatase
  • estriol

estrone & estriol - synthesized in the liver and peripheral tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Types of estrogens

Natural estrogens
* 17B-estradiol - ___ potent
* estrone - ___ potent
* estriol - less potent (dominant form during ___, synthesized in the ___)

A
  • most
  • less
  • pregnancy, placenta
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

types of estrogens

Synthetic estrogens
2 types: ___ and ___

A

steroidal, non-steroidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

types of estrogens

Phytoestrogens
Estrogen-mimetic compounds in ___

A

plants (flavonoids)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

types of estrogens

Environmental estrogens
Compounds used in the manufacture of ___

A

plastics (bisphenols, alkylphenols, phthalate phenols)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Metabolism and excretion of estrogen

  • Metabolized in the ___ mostly and excreted to the ___ and to the ___
  • Conjugated estrogens in the bile can be ____ in the ____ and reabsorbed (____ circulation).
  • ___ administered estrogens have a ___ ratio of hepatic to peripheral effects; can be avoided by using routes that avoid ___ liver exposure.
A
  • liver, bile, urine
  • hydrolyzed, intestine, enterohepatic
  • orally, high, first pass
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Physiologic effects of estrogen

Female maturation
* development of vagina, uterus, and ___
* ___ development and ___ growth in the breast
* accelerated growth phase and ___ closure
* growth of ___ and ___ hair
* body fat distribution
* ___ in the skin (nipples, areolae, and genital region)

A
  • uterine tubes
  • stromal, ductal
  • epiphyseal
  • axillary, pubic
  • pigmentation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Physiologic effects of estrogen

Endometrial effects
* development of ___ lining during menstrual cycles
* prolonged exposure leads to ___ of the endometrium and abnormal bleeding

A
  • endometrial
  • hyperplasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Physiological effects of estrogen

Metabolic and cardiovascular effects
* decrease in ___ resorption (estrogen deficiency can lead to ___)
* synthesis of ___ and ___
* alteration in the composition of ___ lipids (increase in ___, decrease in ___)
* blood ___
* CNS: ___

A
  • bone, osteoporosis
  • sex-homrone binding globulin (SHBG), transcortin
  • plasma, HDL, LDL
  • coagulation
  • mood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Clinical uses of estrogens

Hormone replacement therapy in postmenopausal women
* relief of ___ disturbances: ___, sweating, flushing
* used to treat symptoms of ____: vaginal dryness, increased risk of infections
* relief of psychological effects: ___, ___, depression, nervousness

A
  • CNS, hot flashes
  • urogenital atrophy
  • mood swings, insomnia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Clinical uses of estrogens

Osteoporosis
* for ___ osteoporosis only
* estrogen decrease the rate of ___ resorption

A
  • post-menopausal
  • bone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Clinical uses of estrogens

hormonal ___

A

contraception

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Clinical uses of estrogens

Replacement therapy in patients with primary ___
* failure of ___ development
* chromosomal disorders: ___ syndrome - absence of 1 or all ___ chromosomes
* ___ (ovarian cancer)

A

hypogonadism
* ovary
* Turner, sex
* oophorectomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Adverse effects

Uterine bleeding
* estrogen therapy is major cause of ___ uterine bleeding
* endometrial ___
* estrogen should be given ___
* can be prevented by the administration of a ___ in each cycle

A
  • postmenpausal
  • hyperplasia
  • cyclically
  • progestin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Adverse effects

Endometrial ___
* use of progestin reduces the risk

A

carcinoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Adverse effects

Breast cancer
* particularly ___term use
* addition of progestin does not have a ___ effect

A
  • long-term
  • protective
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Adverse effects

general adverse effects of estrogen (think PUP)

A
  • Nausea
  • headache
  • fluid retention
  • weight gain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Structure-activity relationship

  • ___ in A ring is required
  • ___at the 3 position is essential for activity
  • the 3-OH can be masked as a ___ derivative which is ___ in vivo
  • 16-OH ___ activity
  • 17a-ethynyl ___ metabolism and allows for ___ activity
  • ___ group at the 17B position required for activity. (can be temporarily blocked by an ___ for drug delivery)
A
  • aromaticity
  • hydroxyl
  • ester, hydrolyzed
  • decreases
  • blocks, oral
  • hydroxyl
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

17α-alkylated estrogens

examples

A
  • ethinyl estradiol
  • mestranol
  • quinestrol
30
Q

17α-alkylated estrogens

17α-alkylation prevents conversion to ___
* enhances ___ bioavailability and increases ___
* 3-alkylated ether is quickly ___ in
vivo

A
  • estrone
  • oral, half life
  • dealkylated
31
Q

Estrogenic esters

Esterification ___ solubility and ___ the absorption
* example: ___ absorption from the injection site (depo-provera) ___ the action → ___ frequent injections
* 2 examples: ___ and ___

A
  • decreases, slows
  • slow, prolongs, less
  • Estradiol valerate
  • Estradiol cypionate
32
Q

Conjugated estrogens

  • Premarin is collected from ___
  • mixture of estrogens: ___ estrone sulfate, ___ equilin sulfate, other estrogenic substances
A
  • pregnant mares’ urine
  • 50-60%, 20-30%
33
Q

Structure-activity relationship in nonsteroidal estrogens

  • an ___-substituted side chain blocks ___ and leads to antagonist/SERM activity
  • A rigid ___ is required to maintain proper space between 2 or 3 aromatic rings
  • ___ group required for agonist activity; should be ___ angstroms from other OH group.
  • the other hydroxyl enhances activities (___ is oxidized in vivo)
A
  • amine, helix-12
  • core
  • OH, 10-12
  • tamoxifen
34
Q

Non-steroidal estrogens

Diethyl stilbestrol (DES®)
* Used in 1940 – 1970 to prevent ___.
* Increased risk of vaginal ___ in women exposed in ___.
* Used in advanced ___.

A
  • miscarriage
  • adenocarcinoma, utero
  • prostate cancer
35
Q

Non-steroidal estrogens

Chlorotrianisene (Tace®)
* postpartum breast ___
* ___ symptoms
* ___ cancer

A
  • engorgement
  • menopause
  • prostate
36
Q

Selective estrogen receptor modulators (SERM)

  • “___” estrogens
  • ___ estrogen agonists
  • Estrogenic in some tissues and ___ in others
  • mostly ___ estrogens
  • alternative for estrogen ___ therapy.
A
  • designer
  • partial
  • antiestrogenic
  • nonsteroidal
  • replacement
37
Q

Structural basis of SERM activity

  • Helix 12 conformation allows for ___ binding.
A
  • coactivator
38
Q

Tamoxifen (Novaldex)

  • prodrug; oxidized in ___
  • ___ estrogen agonist

anti-estrogen actions
* treatment of ___ cancer
* ___of breast cancer in high risk women

estrogenic actions
* weak estrogen agonist at ___ cells
* increases the risk for ___ events
* prevents ___

A
  • vivo
  • partial
  • breast
  • prevention
  • endometrial
  • thromboembolic
  • osteoporosis
39
Q

Toremifene (FarestonTM)

  • structurally similar to ___
  • SERM
  • Used to treat advanced ___
A
  • tamoxifen
  • breast cancer
40
Q

Ospemifene (OspenaTM)

  • Structurally similar to ___
  • SERM
  • Estrogenic effects on the ___
  • Used to treat ___ in post-
    menopausal women.
A
  • toremifene
  • vaginal epithelium
  • dyspareunia
41
Q

Raloxifene (EvistaTM)

  • SERM; ___ estrogen agonist
  • tissue-specific activities

estrogen actions
* prevents osteoporosis in ___ women
* decreases ___ levels in blood
* increases the risk for ___

anti-estrogen actions
* decreases the risk for ___
* does not stimulate ___ cells
* may cause ____

A
  • partial
  • postmenopausal
  • LDL
  • blood clots
  • breast cancer
  • endometrial
  • hot flashes
42
Q

Bazedoxifene

Bazedoxifene is a recently approved analog with
similar activities to ___

A

Raloxifene

43
Q

Clomiphene (Clomid)

  • SERM; partial estrogen ___
  • increased secretion of ___ and ___ by inhibiting negative estradiol feedback
  • used to stimulate ___ in women with oligomenorrhea of amenorrhea and ovulatory dysfunction (polycycstic ovary syndrome)
A
  • agonist
  • FSH, LH
  • ovulation
44
Q

Polycystic ovary syndrome (PCOS)
* __% of women of reproductive age
* gonadotropin-___ ovarian hyperandrogenism
* anovulation and infertility

A
  • 7%
  • dependent
45
Q

Fulvestrant (Faslodex)

  • selective estrogen receptor ___ (SERD)
  • pure estrogen receptor ___ for the treatment of breast cancer
  • more effective than ___ in patients who have become resistant to ___
A
  • downregulator
  • antagonist
  • SERM, tamoxifen
46
Q

Aromatase inhibitors

  • Block the ___ of estrogens
  • Effective in some patients whose ___ has become resistant to ___.
  • ___ induction (off label use)
  • Gynecomastia

3 examples: ___, ___, and ___

A
  • biosynthesis
  • breast cancer, tamoxifen
  • ovulation
  • Anastrozole, Letrozole, Exemestane
47
Q

What is this?

A

17B-Estradiol

48
Q

What is this?

A

anastrozole

aromatase inhibitor

49
Q

What is this?

A

androstenedione

50
Q

What is this?

A

Bazedoxifene

SERM

51
Q

What is this?

A

Chlorotrianisene

Non-steroidal estrogen

52
Q

What is this?

A

Clomiphene

SERM

53
Q

What is this?

A

diethyl stilbestrol

Non-steroidal estrogen

54
Q

What is this?

A

Equilin sulfate

Conjugated estroge

55
Q

What is this?

A

Estradiol cypionate

Estrogenic esters

56
Q

What is this?

A

Estradiol valerate

Estrogenic esters

57
Q

What are these molecules?

A

estrone and estriol

58
Q

What is this?

A

Estrone Sulfate

Conjugated estrogens

59
Q

What is this?

A

Ethinyl estradiol

17α-alkylated estrogen

60
Q

What is this?

A

Exemestane

Aromatase inhibitor

61
Q

What is this?

A

Fulvestrant

Selective estrogen receptor downregulator (SERD)

62
Q

What is this?

A

Letrozole

Aromatase inhibitor

63
Q

What is this?

A

Mestranol

17α-alkylated estrogen

64
Q

What is this?

A

Ospemifene

SERM

65
Q

What is this?

A

progesterone

66
Q

What is this?

A

Quinestrol

17α-alkylated estrogen

67
Q

What is this?

A

Raloxifene

SERM

68
Q

What is this?

A

Tamoxifen

SERM

69
Q
A

testosterone

70
Q

What is this?

A

Toremifene

SERM