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IC 1.0 > Gonadal Hormones > Flashcards

Gonadal Hormones Flashcards

1
Q

Which hormones from the anterior pituitary stimulate release of gonadal hormones?

A

LH and FSH

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2
Q

How does pulsatile release of GnRH compare to non-pulsatile release?

A
  • pulsatile release stimulates release of LH/ FSH

- sustained release inhibits LH/FSH release

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3
Q

What hypothalamic signal stimulates LH/FSH release from the anterior pituitary?

A

GnRH

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4
Q

What is the effect of FSH?

A

spermatogenesis or follicular development

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5
Q

What is the effect of LH?

A

steroidogenesis

  • estrogen and progesterone release form the ovaries
  • testosterone from the testes
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6
Q

What is special about gonadorelin compared to other GnRH agonists?

A

gonadorelin has a very short half life and thus replicates the pulsatile release of GnRH that normally stimulates the release of LH and FSH

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7
Q

What are drugs that end in “-relin”?

A

GnRH agonist

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8
Q

What are drugs that end in “-relix”?

A

GnRH antagonists

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9
Q

What is the clinical use of depot ganirelix?

A
  • it is a GnRH antagonists used to control prostate cancer

- depot formulations allow for long-term use without frequent hospital visits

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10
Q

What are the primary uses of pulsatile GnRH agonists? Sustained GnRH agonists and antagonists?

A

pulsatile are used to stimulate gonadotropin release
- female and male infertility
- testing and diagnosis of problems with gonadotrophs in the anterior pituitary
sustained agonists and antagonists inhibit gonadotropin release
- suppress LH surge to control ovarian stimulation
- endometriosis
- uterine fibroids
- prostate cancer and occasionally ovarian cancer
- delay precocious puberty or puberty in transgender adolescents

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11
Q

What are the side effects of GnRH toxicities?

A
  • hypersensitivity reactions
  • menopausal-type symptoms in women
  • gynecomastia in men
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12
Q

What are urofillotropin and fillotropin?

A
  • FSH from urine of post-menopausal women

- recombinant FSH

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13
Q

How does chorionic gonadotropin compare to menotropins?

A
  • chorionic gonadotropin has far more LH than FSH activity

- menotropins have balanced LH and FSH activity

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14
Q

What is menotropin?

A

a gonadotropin obtained from menopausal women and thus known as hMH (human menopausal gonadotropin) with equal FSH and LH activity

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15
Q

How does hCG compare to hMH?

A

hCG has far more LH activity than FSH, while hMG has balanced activity

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16
Q

What are the primary uses of pharmacologic gonadotropins?

A
  • induce ovulation (in those with hypogonadotropism, polycystic ovaries, obesity, etc. or who are using assisted reproductive techniques)
  • treat male infertility
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17
Q

What is the risk of using gonadotropins to induce ovulation?

A

there is a risk for ovarian hyper stimulation syndrome and multiple pregnancies

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18
Q

How are gonadotropins used in the treatment of male infertility? Specifically which drugs are used and what is the time course?

A
  • start with hCG because it is least expensive and then move on to hMG
  • often takes 4-6 months before sperm can be detected
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19
Q

Gonadotropins carry what black box warning?

A

should not be used for the treatment of obesity

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20
Q

What is the primary endogenous estrogen produced by the human ovaries? What other forms are produced?

A
  • estradiol (E2) is produced in the greatest quantity

- estrone (E1) and estriol (E3) to a lesser extent

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21
Q

What is estropipate?

A

purified crystalline estrone

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22
Q

What benefit do estrogen esters offer compared to endogenous estrogens? What is their limitation?

A
  • they are metabolically-resistant pro hormones with improved bioavailability and longer half life
  • but are readily hydrolyzed once in the active form
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23
Q

How are conjugated estrogens produced?

A

they are equine estrogen sulfate sodium salts blended to a high, standardized potency

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24
Q

What is unique about ethanol estradiol?

A
  • it undergoes extensive hepatic metabolism into active metabolites
  • as a result it has excellent oral bioavailability
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25
Q

What is unique about diethylstilbestrol (DES)?

A

it is an estrogen historically used to prevent pregnancy complications but caused a variety of complications itself, including clear cell carcinoma of the vagina

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26
Q

Those women whose mothers used diethylstilbestrol need to be monitored for what?

A

clear cell carcinoma of the vagina

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27
Q

What is unique about esterified estrogens?

A

they are derived from soybeans and yams and consist mostly of estrone and equilin

28
Q

What is bisphenol A?

A

an estrogenic compound that leaches from plastics

29
Q

What is Genistein?

A

an estrogen that is often contained in herbal treatments for menopause

30
Q

Through what intracellular cascade do estrogens work?

A
  • they bind intracellular estrogen receptors located in the nucleus
  • this complex binds to the estrogen-response element and initiates gene transcription
31
Q

What are the primary uses for estrogen therapy?

A
  • primary hypogonadism
  • hormonal contraception
  • ovarian suppression for those with dysmenorrhea, endometriosis, e tc.
  • hormone replacement in post-menopausal women
32
Q

What is endometriosis?

A

growth of endometrium outside the uterus

33
Q

Which estrogen therapies have good oral bioavailability?

A
  • ethinyl estradiol

- esterified estrogens

34
Q

What are the adverse effects of estrogen therapy?

A

major concerns are proliferation of estrogen-responsive cancers and estrogen’s ability to induce a hypercoagulable state; may also cause:

  • nausea
  • beast tenderness
  • hyperpigmentation
  • migraine
  • cholestasis and gall bladder disease
  • hypertension
35
Q

Estrogen therapies carry what risk for malignancy?

A

uterine and breast cancer

36
Q

Under what circumstances is unopposed estrogen not to be used for replacement therapy? Why? What is used to oppose it?

A
  • postmenopausal women with a uterus

- estrogens stimulate proliferation of the endometrium and can promote cancer

37
Q

Post-menopausal women with a uterus who wish to undergo estrogen hormone replacement also need to be placed on what drug?

A

progestins, to decrease uterine proliferation

38
Q

How are most progestins administered? Which are available for IM?

A
  • most are given orally

- progesterone and medroxyprofesterone acetate are available for IM

39
Q

What is unique about desogestrol?

A

it is the cleanest progestin with very few non-progestin affects

40
Q

What are some common non-progestin effects of progestin agonists?

A
  • estrogenic
  • androgenic
  • antiestrogenic
  • antiandrogenic
  • anabolic
  • antimineralocorticoid
41
Q

Through what mechanism do progestins act?

A

they bind a nuclear receptor and initiate transcription by binding, as a complex, to the progesterone-response element

42
Q

What are the primary indications for progestins?

A
  • hormonal contraception
  • ovarian suppression for dysmenorrhea, endometriosis, etc.
  • postmenopausal hormone replacement
43
Q

What are the most common adverse effects associated with progestins?

A
  • may increase blood pressure

- those with more androgenic effects may decrease plasma HDL

44
Q

Most hormonal contraceptions use what sort of estrogen and progestin?

A
  • ethanyl estradiol

- norethindrone, L-norgestrel, desogestrel

45
Q

Through what mechanism does hormonal contraception work?

A
  • it suppresses the FSH/LH surge through negative feedback to inhibit ovulation
  • also thickens the cervical mucus and decreases fallopian tube motility
46
Q

What is the main concern or adverse effect associated with hormonal contraception?

A

risk of venous thromboembolism

47
Q

What are the purposes of peri- and post-menopausal hormone therapy?

A
  • decrease hot flashes, vaginal dryness, and other symptoms
  • prevent GU atrophy
  • prevent osteoporosis
  • prevent atherosclerosis
  • prevent dementia
48
Q

What risks are associated with peri- and post-menopausal hormone therapy?

A
  • heart disease, stroke, PE, and DVT
  • breast cancer (only when estrogen + progestin is used)
  • uterine cancer in those with a uterus receiving unopposed estrogen
  • increased triglycerides
49
Q

How long should post-menopausal hormone replacement last?

A

use for the shortest period and lowest dose possible to achieve treatment goals

50
Q

What is the primary use of tamoxifen?

A

treatment of breast cancer

51
Q

What are SERMs?

A
  • selective estrogen receptor modulators

- with tissue-specific partial agonist and partial antagonist activity at estrogen receptors

52
Q

What is the primary use of raloxifene?

A

treatment of osteoporosis

53
Q

What is clomiphene? How does it’s action suit it’s clinical use?

A
  • it is a SERM
  • it blocks estrogen feedback within the HPG axis
  • thereby increasing LH and FSH release to induce ovulation
54
Q

Which drug’s are used to induce ovulation?

A
  • clomiphene is used first because it is cheaper and easier to use
  • then hCG is used
55
Q

What is the primary use of fulvestrant?

A

it is an estrogen antagonist used in the treatment of tamoxifen-resistant breast cancer

56
Q

What mefiprisonte? How is it used clinically?

A
  • a progesterone antagonist

- primarily used as a postcoital contraceptive or abortifacient in combination with misprostol or PGE1

57
Q

What are aromatase inhibitors?

A

drugs that block the estrogen production in the periphery

58
Q

What is danazol?

A

a derivative of 17a-ethinyl-testosterone with weak progestin, androgen, and glucocorticoid activity used to suppress ovarian function

59
Q

What are aromatase inhibitors used for?

A

the treatment of breast cancer

60
Q

Through what mechanism do androgens effect cellular change?

A

they bind intracellular receptors and alter gene expression

61
Q

What are the primary uses of androgens in clinic?

A
  • androgen replacement
  • gynecologic disorders like endometriosis
  • as anabolic agents after trauma, disease, etc.
  • for growth stimulation in boys with delayed puberty
  • osteoporosis in men
  • aging
62
Q

What is the downside of using androgens for growth stimulation in boys with delayed puberty?

A

the androgens can cause premature closure o bone epiphyses

63
Q

What adverse effects are associated with androgen use?

A
  • acne
  • sleep apnea
  • gynecomastia through conversion to estradiol
  • testicular atrophy and azoospermia through feedback inhibition
  • hirsutism
  • sodium retension
  • hepatic dysfunction, cholestasis, jaundice
  • psychological dependence
  • aggression and psychosis
64
Q

What is the primary use of androgen antagonists and androgen suppression?

A

the treatment of prostate cancer

65
Q

What is unique about ketoconazole?

A

it inhibits adrenal and gonadal steroid synthesis, but increases the estrogen to testosterone ratio, contributing to gynecomastia

66
Q

What are the primary uses of cyproterone?

A

it is an androgen receptor inhibitor used for hirsutism in women and excessive sexual desire in men

67
Q

What is spironolactone?

A

a drug that competes with DHT and aldosterone

IC 1.0 (24 decks)

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