DLA9- Gonadal Hormones

Question 1

describe feedback for gonadal hormones

• men
• women
• hint: more than just steroids…

Answer 1

Men: (estrogen +) Testosterone –> inhibit GnRH (hypothalamus) and FSH/LH release (pituitary) release

Women: Estrogen (mainly) –> inhibit GnRH (hypothalamus) and FSH/LH release (pituitary) release
-at ovulation, estrogen –> stimulates FSH/LH release

NOTE (ovaries/testes):

• inhibin –> dec FSH/LH (pituitary)
• activin –> inc FSH/LH (pituitary)

Question 2

LH and FSH function in women

Answer 2

FSH- follicle development

LH/FSH- androgen production (LH, theca cells) –> conversion to estrogen (FSH, granuloma cells)

Question 3

LH and FSH function in men

Answer 3

FSH (sertoli) –> spermatogenesis, maintain high [androgens], androgen binding protein production

LH (leydig) –> testosterone production

Question 4

list the general groups of gonadal pharmalogical agents

Answer 4

All: GnRH agonists + receptor antagonists

DHT: 5α-reductase inhibitors. androgen receptor antagonists

Estrogen: -aromatase inhibitors, SERMs, SERDs

Progesterone: anti-progestins

Question 5

list major natural and analog estrogren hormones

Answer 5

Natural: estradiol (E2) > estrone (E1) > estriol (E3)

Synthetic:

• ethinyl estradiol
• mestranol (ethinyl estradiol prodrug)

Question 6

list the MAJOR effects of estrogen

Answer 6

• female maturation: secondary sex characteristics
• endometrial proliferation
• metabolic effects

Question 7

Estrogen effects:

• (1) lipids
• (2) proteins
• (3) fluid balance

Answer 7

1- inc HDL, dec LDL

2- inc hepatic protein production (SHBG)

3- Na/H2O retention

Question 8

Estrogen effects:

• (1) coagulation
• (2) vasculature
• (3) bone

Answer 8

1- inc hepatic production of factor II, factor VII, factor IX, factor X, fibrinogen + dec antithrombin III activity –> inc risk thrombolytic events

2- inc NO and prostacyclin

3- dec resorption –> inc mass

Question 9

list clinical uses of estrogen

Answer 9

• postmenopausal therapy
• primary hypergonadism (start 11-13 y/o, after 1st period augment with progestins)

-Tx androgen dependent prostate cancer

• OCPs
• menstrual abnormalities

Question 10

what is the basis of postmenopausal replacement therapy

Answer 10

(estrogen)
-dec risk osteoporosis (not Tx)

• reestablish feedback –> dec NE secretion –> dec hot flashes
• reverse atrophy of vulva, vagina, urethra, trigone

Question 11

list the MINOR estrogen AEs

Answer 11

• uterine bleeding
• nausea
• breast tenderness
• melasma (inc melanocyte production)
• peripheral edema

Question 12

list the MODERATE / SEVERE estrogen AEs

Answer 12

-inc risk endometrial cancer (offset with progestin combination)

• inc migraine frequency
• cholestasis / gall bladder disease
• HTN
• thromboembolism
• depression

Question 13

the main contraindication for estrogen use is…..

Answer 13

cytochrome inducer use —> inc CYP450 –> inc estrogen metabolism –> severely reduce estrogen efficacy

Question 14

list SERMs + major effects

Answer 14

(selective estrogen receptor modulators)
Tamoxifen:
-breast antagonist
-rest of body (+ uterine/endometrial, liver, bone) agonist (inc endo. CA risk)

Raloxifene:

• breast and uterine antagonist
• bone agonist (inhibits resorption)

Clomiphene:
-hypothalamus antagonist (prevents normal feedback inhibition)

Question 15

main SERD + use + AEs

Answer 15

(selective estrogen receptor degraders/downregulators)
Fulvestrant:
-adjunct in ER+/PR+ breast cancer (if resistant to 1st line anti-estrogens)
-AEs: hot flashes, arthralgia, myalgias

Question 16

Aromatase inhibitors + uses + AEs

Answer 16

Anastrozole, Letrozole, Exemestrane:

• adjunct in ER+ breast CA
• AEs: hot flashes, nausea, fatigue, alopecia, dermatitis

Question 17

list synthetic progestins

Answer 17

norgestrol
norethindrone
medroxyprogesterone
desogestrel
drospirenone

Question 18

main effects of progestins

Answer 18

• dec growth / inc vascularization of endometrium (prevent endometrial hyperplasia)
• thickening of cervical mucus (inhibits sperm movement)
• maintain pregnancy
• associated with inc in body T

Question 19

main clinical applications of progestins

Answer 19

• OCPs
• endometrial cancers
• abnormal uterine bleeding
• HRT
• infertility
• Dx test of estrogen secretion

Question 20

Progestins AEs

Answer 20

uterine bleeding
HA
rarely thromboembolic events
dec HDL (androgenic progestins)

weight gain
insulin resistance

depression
changes in libido

Question 21

____ = antiprogestin, MOA, clinical use, AEs

Answer 21

Mifepristone:
-competitive receptor inhibitor

• combo with misoprostol as abortifacent
• n/v/d, abdominal / pelvic pain, uterine bleeding

Question 22

list androgens and effects paired with uses

Answer 22

Testosterone, Methyl-testosterone, Danazol

• male maturation: hypogonadism (unapproved PED)
• sexual function
• metabolic: cancer / HIV Pts (prevents wasting), burn recovery

Question 23

androgen receptor antagonists + uses + AEs

Answer 23

Flutamide, Spironolactone:

• prostate cancer (Flu.)
• PCOS, aldosteronism, diuretic (Spir)

AEs: gynecomastia

Question 24

5α-reductase inhibitor + use + AEs

Answer 24

Finasteride:
-BPH, baldness

AEs: gynecomastia, rarely impotence

Question 25

Steroid Synthesis inhibitor + use + AEs

Answer 25

Ketoconazole:
-Cushing’s syndrome, prostate cancer

AEs: gynecomastia, amenorrhea, CYP450 inhibitor