Reproductive Pharmacology

Question 1

What are the indications for pulsatile administration of GnRH v. long acting or continuous administration of GnRH agonists?

Answer 1

pulsatile: used to establish follicular development and ovulation in hypogonadtropic hypogonadism/Kallmann Syndrome

long acting/continuous: initial stimulation with following inhibition which is used in treatment of precocious puberty, endometriosis, fibroids, fertility treatment (with assistive technology) or androgen deprivation for prostate cancer

*also in LHRH testing for precocious and delayed puberty

Question 2

What are the adverse effects of GnRH agonists?

Answer 2

non-pulsatile agonists create a chemical menopause and side effects include hot flashes, low-libido, amenorrhea and infertility

in certain cases “add-back” therapy may supplement a small amount of estrogen to support bone health

Question 3

What are the therapeutic uses of FSH, LH and HCG?

Answer 3

used in futility treatment and endocrine support

FSH injections stimulate ovarian follicle development and sperm production

hCG can be used in place of LH to stimulate ovulation and progesterone production, enhances spermatogenesis and testosterone secretion

Question 4

Give two expamples of dopamine receptor agonists.

Answer 4

bromocriptine and cabergoline- these dopamine receptor agonists inhibit prolactin production

Question 5

Describe the general mechanism by which nuclear receptor superfamily function and which of hormones work via nuclear receptor mechanism.

Answer 5

receptors, located in the nucleus of target cells are bound by hormone and release heat shock proteins

two receptors dimerize and subsequently bind to target DNA sequences and regulate gene transcription

hormones acting by this mechanism: estrogen

Question 6

Where are estradiol, estriol and estrone produced?

Answer 6

estradiol E2 principal ovarian estrogen potency+++
estriol E3 principle placental estrogen potency +
estrone E1 major ovarian estrogen post menopause potency ++

Question 7

What is the effect of estrogen at the liver?

Answer 7

stimulates hepatic production of sex hormone binding globulin, thyroid hormone binding globulin and blood clotting factors

Question 8

What are the three major therapeutic uses of estrogens?

Answer 8

estrogen deficiency as in premature ovarian failure or menopause (stimulate development of secondary sex characteristics, or tx. of symptoms of estrogen deficiency)

prevention and treatment of osteoporosis and contraception (normally as part of a combo OC)

Question 9

What is the MOA of selective estrogen receptor modifiers? Name 3 examples.

Answer 9

drugs have mixed agonist/antagonist activity and their action varies from tissue to tissue

examples include clomiphene, tamoxifen and raloxifine

Question 10

What is the therapeutic indication for clomiphene? What are the adverse effects?

Answer 10

works centrally at hypothalamus

prevents normal feedback regulation of estrogen leading to increased secretion of GnRH and gonadotropins, stimulating ovarian follicle development, used in ovulation induction

adverse effects: multiple births, hot flashes, thick mucous/thick endometrium

Question 11

What is the therapeutic indication for tamoxifen? What are the adverse effects?

Answer 11

acts as an estrogen antagonist in breast tissue, acts as week agonist at endometrium, used as treatment in breast cancer (ER+)

adverse effects: endometrial hyperplasia, hot flashes, multiple births

Question 12

What is the therapeutic indication for reloxifene? What are the adverse effects?

Answer 12

acts as an estrogen agonist in bone and an estrogen antagonist in breast tissue, used in prevention and treatment of osteoporosis

Question 13

When is use of an aromatase inhibitor indicated? What are the adverse effects?

Answer 13

type 1 irreversible inhibitors are often used to reduce endometrial hyperplasia and breast cancer and type 2 reversible inhibitors can be used in ovulation induction

adverse effects: hot flashes, bone loss

Question 14

What’s important to remember regarding the route of progesterone administration?

Answer 14

progesterone undergoes extensive first pass metabolism and can be administered high dose PO, IM infection or as a vaginal preparation

Question 15

What type of progesterone is included in combination OC and why?

Answer 15

progestins are structural derivatives of progesterone with better pharmacokinetics , can also be used in HRT

older agents have more androgenic activity (contraindicated in pregnancy) while drospirenon is antiandrogenic

Question 16

What are the therapeutic uses of progestins? (3)

Answer 16

can be used to prevent endometrial hyperplasia with postmenopausal hormone therapy

as part of a combined contraceptive

in support of pregnancies (with donor egg/embryo when CL is not present)

**mifiprisone is a progesterone and glucocorticoid receptor antagonist

Question 17

What are the risks of HRT?

Answer 17

HRT associated with increased risk of DVT and stroke, no protective against heart disease and increases risk of breast cancer—usually given at the lowest possible dose for the shortest period of time

(does improve bone mineral density)

Question 18

Describe the receptor that testorone and DHT act through.

Answer 18

both act through a single androgen receptor which is present in the cytoplasm working through the same mechanism of the nuclear receptor superfamily

Question 19

What are the therapeutic uses of androgens?

Answer 19

replacement in males with testosterone (DOES NOT HELP WITH FERTILITY)

other effects: virilization, development of secondary sexual characteristics in men, stimulates linear growth and enhances sex drive and libido

**monitor for erthryocytosis and PSA for occult prostate cancer

Question 20

What are the different vehicles for androgens?

Answer 20

injection (high levels for day(s)
patch and topical (more steady application)

CANNOT BE GIVEN ORAL (first pass)

Question 21

What is the MOA of anti androgen spironolactone? When is it used?

Answer 21

acts as a weak blocker of AR and weak inhibitor of testosterone synthesis as well as blocker of the mineralocorticoid receptor

used in: tx of hirsutism in women, hypertension and CHF, primary hyperaldosteronism

adverse effects: hyperkalemia, irregular menses, gynecomastia

Question 22

What are the clinical uses of flutamide?

Answer 22

acts as a competitive antagonist of the AR, used in hormonal therapy for prostate cancer and hirsutism

can cause hepatotoxicity

Question 23

What is the clinical indication for finasteride?

Answer 23

acts as an inhibitor of 5-a reductase and is used to treat BPH and male-batters baldness and hirsutism

can cause hepatotoxicity