L 31-32 Sex Hormones and Gonadotropins

Question 1

Describe the HPG axis

Answer 1

This is the gonadal axis

GnRH is pulsatile and a constant signal will actually silence the axis

Also notice that Estrogen can inhibit and stimulate depending on concentration

Question 2

Where in the HPG axis do you treat for infertility and secondary sex characteristics?

Answer 2

Fertility: treat at the LH/FSH level

Secondary Sex: treat at the steroid level

Question 3

Gonadorelin (GnRH, Factrel)

Answer 3

Short acting GnRH

Used to treat infertility

Question 4

Leuprolide, Nafarelin (Synarel)

Goserelin (Zoladex)

Answer 4

Long-Acting GnRH analogues

Continuous administration suppresses LH and FSH after an initial stimulation of gonadotropin release

Used to shut down the HPG for infertility treatment, precocious puberty, prostate or breast cancer

Cause menopausal Sx and testicular atrophy

Question 5

Citrorelix (Cetrotide)

Ganirelix

Answer 5

GnRH antagonists

Suppress LH at low doses and FSH at higher doses

Has no initial surge of gonadotropins like the long-acting agonists would have

Used for ART and endometriosis

Question 6

Human menopausal gonadotropins (hMG)

Menotropins (Menopur)

Answer 6

Both FSH and LH but used as FSH

Question 7

Urofollitropin

Answer 7

Just FSH

Question 8

Follitropin alfa (Gonal F)

Follitropin beta (Follistim)

Answer 8

rFSH

Question 9

Human Chorionic Gonadotropin (hCG)

Answer 9

Similar structure and binds to LH receptors

Longer half-life than LH

Question 10

Choriogonadotropin alfa (Ovidrel)

Answer 10

rhCG

Same action as LH

Question 11

Lutropin (Luveris)

Answer 11

recombinant LH

Question 12

Effects of LH and FSH on men and women

Answer 12

Men: LH increases testosterone for up to one year, FSH then induces spermatogenesis (takes months)

Women: FSH (9-12 days) stimulates ovaries and estrogen, Single dose of LH given to induce ovulation

Opposite in order given between men and women

Question 13

How is estrogen metabolized?

Answer 13

Metabolized in the liver and excreted in the bile

Enterohepatic circulation–important for contraceptive use

Question 14

Estradiol

Answer 14

Naturally occuring estrogen and not orally active–used as a patch or a cream

Question 15

Ethinyl estradiol

Mestranol

Answer 15

Synthetic oral contraceptives that are estrogens

Question 16

Premarin

Cenest

Estratab

Menest

Answer 16

Conjugated estrogens used for hormone replacement therapy

Question 17

Diethylstilbesterol

Answer 17

Nonsteroidal estrogen

Not used much anymore

Question 18

When are estrogen drugs used?

Answer 18

In primary hypogonadism of 11-13 year old girls to stimulate growth

Postmenopausal hormone replacement therapy

Oral contraception

Suppress ovulation

Question 19

Side effects of estrogen use

Answer 19

Migraines

Gallbladder disease

Thromboembolism, blood clotting

Uterine hyperplasia

Nausea and breast tenderness

Question 20

Tamoxifen (Novaldex)

Answer 20

SERM (selective estrogen receptor modulator)

Agonist in uterus and bone

Antagonist in breast

Does not relieve hot flashes

Used to treat and prevent estrogen dependent breast cancer–DOC in premenopausal women

Question 21

Toremefine (Fareston)

Answer 21

Similar to tamoxifen (SERM), but better at increasing HDL

Question 22

Raloxifene (Evista)

Answer 22

SERM

Antagonist in breast and uterus

Agonist in liver and bone

Used to prevent postmenopausal osteoporosis

Does not relieve hot flashes

Question 23

Clomiphene (Clomid)

Answer 23

SERM

Typical DOC for infertility with intact HPG axis

Antagonizes negative feedback in the hypothalamus from estrogen to stimulate the release of LH and FSH inducing ovulation

Question 24

Fulvestrant (Faslodex)

Answer 24

Full estrogen receptor antagonist

Causes menopausal Sx

Question 25

Anastrazole (Arimidex) Letrozole (Femara) Exemastane (Aromasin)

Answer 25

Aromatase inhibitors that block all production of estrogen Exemastane is irreversible DOC–for postmenopausal breast cancer, advanced breast cancer after tamoxifen failure in postmenopausal women Will increase testosterone causing hursutism Will cause menopausal Sx

Question 26

Progesterone

Answer 26

Promotes gestation, maintains pregnancy, suppresses contractility during pregnancy, increases body temp Regulated by LH and produced by corpus luteum and placenta

Question 27

Medroxyprogesterone (Provera)

Answer 27

Progesterone derivative

Question 28

Megestrol (Megace)

Answer 28

Progesterone derivative

Question 29

Norethindrone (Aygestin)

Answer 29

Progestin More androgenic

Question 30

Norgestrel (Ovrette)

Answer 30

Progestin

Question 31

Levonorgestrel (Plan B)

Answer 31

Progestin

Question 32

Desogestrel (Desogen)

Answer 32

Progestin

Question 33

Norgestimate

Answer 33

Progestin

Question 34

Mifepristone (RU 486, Mifeprex)

Answer 34

Anti-progestin Progesterone receptor antagonist Terminates pregnancy Used to prevent implantation within 72 hours of intercourse

Question 35

Danazol (Danocrine)

Answer 35

Anti-progestin Weak progestin and androgen Suppresses ovarian function Used to treat endometriosis!!!!

Question 36

Drospirenone/ethinyl estradiol (Yaz)

Answer 36

Combination oral contraceptive Works by inhibiting ovulation, thickening cervical mucus, changing the endometrium decrease implantation This has less water retention than other contraceptives and anti-androgenic properties

Question 37

Adverse effects of combination oral contraceptives

Answer 37

Weight gain Nausea Edema Depression Clotting causing CV problems made worse by smoking or over 35 yo Migraine Teratogenesis Fertility can be suppressed for 3+ months Protects against ovarian and endometrial cancer for up to 15 years after use Do not use with thrombotic problems or estrogen-dependent neoplasms

Question 38

Oral contraceptive drug interactions

Answer 38

P450 inducers reduce effectiveness Antibiotics reduce effectiveness

Question 39

Adverse effects of hormone replacement therapy

Answer 39

Endometrial cancer–progesterone to prevent Breast cancer Gallbladder disease CV

Question 40

Ketoconazole (Nizoral) Spironolactone (Aldactone)

Answer 40

Androgen synthesis inhibitors

Question 41

Flutamide (generic) Bicalutamide (Casodex) Nilutamide (Nilandron)

Answer 41

Androgen receptor antagonists Used in prostate cancer with long-acting GnRH agonists to suppress the flare of gonadotropins with initiation of treatment Can be used topically for baldness and hirsutism

Question 42

Finasteride (Propecia) Dutasteride (Avodart)

Answer 42

5alpha-reductase inhibitors Suppress male sex accesory organs without affecting libido No DHT means affects the prostate and hair follicle the most Treats BPH and male pattern baldness Causes impotence Teratogenic