L32- Hypothalamic and Pituitary Hormones (gonadotropins)

Question 1

list the gonadotropins

Answer 1

• FSH
• LH
• hCG

Question 2

describe function of FSH, LH in women

Answer 2

FSH –> ovarian follicle development

FSH + LH –> ovarian steroidogenesis

Question 3

describe function of FSH, LH in men

Answer 3

FSH –> i) spermatogenesis, ii) conversion of Testosterone to Estrogen, iii) maintains high local [androgen] in area of developing cells

LH –> stimulates testosterone production

Question 4

what are the clinical applications of gonadotropins

Answer 4

Men –> stimulate spermatogenesis

Women –> induce ovulation (IVF)

Question 5

list the FSH analogs used (explain where they came from)

Answer 5

Follitropin α and β (rFSH) = recombinant FSH

Urofollitropin (uFSH) = purified human FSH extract

Question 6

list the LH analogs used (explain where they came from)

Answer 6

Lutropin alfa = recombinant LH (rLH)

Question 7

_____ = purified extract of FSH and LH

Answer 7

Menotropins or human menopausal gonadotropins (hMG)

Question 8

hCG is extracted / purified from (1) and is administered via (2)

(3) = recombinant hCG, administered via (4)

Answer 8

1- urine
2- IM

3- Choriogonadotropin α (rhCG)
4- SQ

Question 9

describe the different types of male infertility Tx

Answer 9

1) both FSH and LH
2) hCG alone
3) urofollitropin (uFSH), Follitropin α/β (rFSH ), Lutropin alfa (rLH)

Question 10

AEs of gonadotropins in women

Answer 10

• ovarian hyperstimulation syndrome
• multiple pregnancies (15-20%)

-HA, depression, edema, precocious puberty

Question 11

AEs of gonadotropins in men

Answer 11

gynecomastia

Question 12

GnRH agent = (1)
GnRH analog = (2)

-indicate the advantage one has over the other

Answer 12

1- gonadorelin (IV, SQ)

2- goserelin, leuprolide, nafarelin (SQ, IM, nasal spray, SQ implant)

**analogs are more potent, last longer

Question 13

GnRH is released in a (1) fashion in order to release FSH/LH. Gonadotropins stimulate (2) type receptors on target cells. (3) is the result if gonadotropins are released in opposite manner of (2).

Answer 13

1- pulsatile

2- G protein coupled receptors

3- (sustained / non-pulsatile) GnRH inhibits FSH/LH release => hypogonadism in men and women

Question 14

what are the 2 general uses of GnRH and its analogs

Answer 14

Stimulation

Suppression (mostly)

Question 15

list the stimulatory functions of GnRH and its analogs

Answer 15

• female infertility (uncommon, inconvenient, costly)
• male infertility, men w. hypothalamic hypogonadotropic hypogonadism (pulsatile gonadorelin)
• Dx of LH responsiveness: is puberty delayed b/c of constitutional delay or by hypogonadotropic hypogonadism

Question 16

Controlled ovarian hyperstimulartion:

• (1) are used for suppression
• critical to suppress (2) because of (3)

Answer 16

1- leuprolide, nafarelin (GnRH analogs)

2- endogenous LH surge

3- prevent premature ovulation

Question 17

Endometriosis:

• (1) are used for suppression
• suppression will abolish cyclical changes to (2) in order to decrease (3)
• Tx is limited to (4) amount of time

Answer 17

1- goserelin, leuprolide, nafarelin (GnRH analogs)

2- estrogen, progesterone (during menstrual cycle)

3- pain (during menstrual cycle)

4- 6 mos

Question 18

Fibroids = (1):

• (2) agent has (3) function
• combined with (4) supplement administration to improve (5)

Answer 18

1- uterine leiomyomata
2- goserelin, leuprolide, nafarelin (GnRH analogs)
3- reduce fibroid size
4- Fe
5- anemia

Question 19

Prostate Cancer:

• (1) and (2) are the main agents used in Tx
• this regimen is just as effective as (3) in terms of reducing serum testosterone

Answer 19

1- leuprolide, nafarelin (GnRH analogs)
2- androgen receptor antagonist
3- castration

Question 20

(1) are used to treat precocious puberty; (2) is very important before starting (1) treatment

Answer 20

1- leuprolide, nafarelin (GnRH analogs)

2- confirming diagnosis

Question 21

GnRH analogs are used to:

• treat (1) cancer
• treat (2) in women with PCOS
• prepares women for (3) procedure

Answer 21

1- advanced breast cancer, advanced ovarian cancer, prostate cancer

2- amenorrhea

3- endometrial ablation
for women with thinning of endometrial lining and dysfunctional uterine bleeding

Question 22

Gonadorelin = _____, + AEs

Answer 22

GnRH agent (not analog)
-HAs, lightheaded ness, nausea, flushing

• swelling at injection site
• generalized hypersensitivity rxn –> dermatitis (long-term use)
• acute hypersensitivity rxns (rare)

-sudden pituitary apoplexy / blindness in Pts with gonadotropin secreting pituitary tumor

Question 23

GnRH analogs women AEs + contraindication

Answer 23

• Menopausal Sxs: hot flushes, sweats, HAs
• depression, dec libido, generalized pain, vaginal dryness, breast atrophy
• ovarian cyst (generally resolves)
• reduced bone density / osteoporosis (long term use)

Contraindication- pregnant and breast feeding women

Question 24

GnRH analogs men AEs

Answer 24

• hot flashes, sweats, edema
• gynecomastia, dec libido
• reduced bone density
• asthenia
• injection site rxns

Question 25

GnRH receptor antagonists = (1):

• (2) MOA
• (3) use

Answer 25

1- cetrorelix, ganirelix

2- competitive antagonists of GnRH receptor

3- suppresses gonadotropin production –> prevents LH surge during controlled ovarian hyperstimulation