Gonadal Hormones

Question 1

Name 3 natural estrogens?

Answer 1

• Estrone (E1)
• Estradiol (E2)
• Estriol (E3)

Question 2

Where do conjugated estrogens come from?

Answer 2

• Conjugated estrogens are blended equine estrogens
either isolated from the urine of pregnant mares or
synthetically produced.

Question 3

Name 2 synthetic estrogens?

Answer 3

Steroidal
• Ethinyl estradiol
• Mestranol (pro-drug converted to ethinyl estradiol)

Question 4

MOA of estrogens?

Answer 4

Mechanism of action
• Estradiol bind to the estrogen receptor to form a
steroid hormone receptor complex
• Hormone-receptor complex → cell nucleus
→ changes in gene expression

Question 5

Effects of Estrogen: Female maturation, endometrial, and Metabolic?

Answer 5

Female Maturation
• Development of female secondary sex characteristics

Endometrial
• Endometrial proliferation

Metabolic
• The effects of estrogens on selected aspects of mineral,
lipid, carbohydrate, and protein metabolism are
important for understanding their pharmacological
actions.

Question 6

Effects of Estrogens: Bone, Lipids, and Coagulation?

Answer 6

Bone
• Decreases resorption of bone (increases mass)

Lipids
• Increase in HDL and decrease in LDL

Coagulation
• Increase hepatic production of factors 2, 7, 9 & 10 and fibrinogen
• Decreases antithrombin III activity
• Increases risk of thromboembolic events

Question 7

Effects of Estrogen: protein synthesis, vasculature, and fluid balance? Other effects?

Answer 7

Protein Synthesis
• Increase in hepatic production of binding proteins eg, SHBG

Vasculature
• Increase production of NO
• Increase production of prostacyclin

Fluid Balance
• Na+ and H20 retention

Other Effects
• Reproductive Function
• Sexual Behavior
• GI Tract

Question 8

PK of Estrogens?

Answer 8

Route of Delivery
• Oral, parenteral, intravaginally, or transdermal patch

Metabolism
• Conjugation by cytochrome enzymes
• Use enterohepatic circulation (metabolized in liver, excreted in bile, hydrolyzed by intestinal bacteria and reabsorbed as active drug)

Question 9

Clinical uses of estrogens?

Answer 9

Postmenopausal Hormonal Therapy
• Decreases risk of osteoporosis (does not treat
osteoporosis)
• Reestablishes feedback on hypothalamic control of NE
secretion, leading to decreased frequency of hot flashes
• Reverses postmenopausal atrophy of the vulva, vagina,
urethra, and trigone of the bladder

Primary Hypogonadism
• Treatment begun with estrogen between ages 11-13
• Progestin added after first uterine bleeding

Treatment of Androgen-Dependent Prostate cancer

Oral Contraceptives

Menstrual Abnormalities

Question 10

Minor AE of estrogens and Contraindications?

Answer 10

Minor
• Uterine bleeding
• Nausea
• Breast tenderness
• Melasma
• Peripheral edema

Contraindications
• Cytochrome inducers can lead to reduction in efficacy

Question 11

Moderate to severe AE of Estrogens?

Answer 11

Moderate/Severe
• Increased risk of endometrial cancer (can be offset by combining estrogen with progestin)
• Increase in frequency of migraines
• Cholestasis and gallbladder disease
• Hypertension
• Thromboembolism
• Depression

Question 12

Names 3 Selective Estrogen Receptor Modulators(SERMS)

Answer 12

Tamoxifen
Raloxifene
Clomiphene

Question 13

MOA of each SERM?

Answer 13

Mechanism of Action
They bind to estrogen receptors but can act as
antagonists or agonists depending on the tissue.

Tamoxifen – Antagonist in breast tissue; agonist in nonbreast tissues (endometrium, liver, bone)

Raloxifene – Antagonist in uterus and breast tissue;
agonist in the bone (inhibits resorption)

Clomiphene – Antagonist in hypothalamus (prevents
normal feedback inhibition)

Question 14

Clinical Use of each SERM?

Answer 14

Tamoxifen
• Prevention and treatment of hormone-responsive breast cancer

Raloxifene
• Prevention of hormone-responsive breast cancer
• Prevention and treatment of osteoporosis in postmenopausal
women

Clomiphene
• Treatment of infertility associated with anovulatory
cycles (eg, PCOS)

Question 15

AE of Tamoxifen?

Answer 15

Tamoxifen
• Hot flashes and nausea
• Endometrial hyperplasia (increased risk of cancer)
• Thromboembolism

Question 16

AE of Raloxifene?

Answer 16

Raloxifene
• Hot flashes and nausea
• Leg cramps
• Thromboembolism
• NO RISK of endometrial hyperplasia

Question 17

AE of Clomiphene?

Answer 17

Clomiphene
• Hot flashes, nausea, vomiting, weight gain, breast
tenderness
• Ovarian hyper-stimulation
• Multiple simultaneous pregnancies (10%)
• Visual disturbances

Question 18

Name on Selective estrogen receptor degrader/downregulator?

Answer 18

Fulvestrant

Question 19

MOA and clinical use of SERDs?

Answer 19

Mechanism of Action
They bind to estrogen receptors and cause the receptor to be degraded and thus downregulated in all tissues

Clinical Uses
Adjuvant treatment of hormone-receptor positive
metastatic breast cancer that is resistant to first-line
antiestrogen (tamoxifen) therapy

Question 20

PK and AE of SERDS?

Answer 20

Pharmacokinetics
Given IM

Adverse Effects
• Hot flashes
• Arthralgias
• Myalgias.

Question 21

Name 3 aromatase inhibitors? MOA of each?

Answer 21

Anastrozole (non-steroidal)
Letrozole (non-steroidal)
Exemestrane (steroidal)

Mechanism of Action
Inhibit peripheral conversion of androgens to estrogen
• Anastrozole and Letrozole are competitive, reversible
inhibitors
• Exemestrane is an irreversible inhibitor

Question 22

Clinical use and AE of aromatase inhibitors?

Answer 22

Used as adjuvant chemotherapy in estrogen receptor positive breast cancer

AE
• Hot flashes 
• Nausea 
• Fatigue 
• Alopecia 
• Dermatitis

Question 23

Name Natural and Synthetic progestins(there are 6 synthetic)

Answer 23

Natural Progestins
• Progesterone

Synthetic Progestins 
• Medroxyprogesterone 
• Norgestrol 
• Norethindrone 
• Norgestimate 
• Desogestreol 
• Drospirenone

Question 24

MOA of Progestins?

Answer 24

Mechanism of action
• Progestins enter the cell and bind progesterone
receptors
• The lipid-receptor complex binds to a progesterone
response element (PRE) and activates gene expression

Question 25

Main Effect of Progestins?

Answer 25

• Decreases growth and increases vascularization of
endometrium (prevents endometrial hyperplasia)
• Thickening of cervical mucus (inhibits movement of
sperm)
• Associated with an increase in body temperature
• Maintenance of pregnancy

Question 26

PK and Metabolism of Progestins

Answer 26

Route of Delivery
• Oral, parenteral and transdermal patch
Metabolism
• Conjugation by cytochrome enzymes
• Use enterohepatic circulation (metabolized in liver,
excreted in bile, hydrolyzed by intestinal bacteria and
reabsorbed as active drug)

Question 27

Clinical use of progestins?

Answer 27

• Oral Contraceptives
• Endometrial Cancer
• Abnormal Uterine Bleeding
• Hormone Replacement Therapy
• Infertility
• Diagnostic test of estrogen secretion

Question 28

AE of progestins?

Answer 28

• Uterine bleeding
• Weight gain
• Insulin resistance
• Depression
• Changes in libido
• Headache
• Thromboembolic events (rare)
• Decrease HDL levels (androgenic progestins)

Question 29

Name antiprogestin, moa, clinical use, and AE?

Answer 29

Mifepristone

MOA
Competitive inhibitor at progesterone receptor

Clinical Uses
Used in combination with misoprostol as abortifacient

Adverse Effects
Vomiting, diarrhea, abdominal / pelvic pain and uterine bleeding

Question 30

Name 3 androgens?

Answer 30

Testosterone
Methyltestosterone
Danazol

Question 31

MOA of androgens?

Answer 31

Mechanism of action
• In skin, prostate seminal vesicles, and epididymis,
testosterone is converted to 5a-dihydrotestosterone
(DHT) by 5a-reductase and binds to the intracellular
androgen receptor

Question 32

Main Effects of Androgens?

Answer 32

Male Maturation
• Development of male secondary sex characteristics
• Increases lean body mass, stimulate body hair growth
and sebum secretion

Sexual function
• Increased libido

Metabolic
• Reduction of hormone binding and other carrier proteins
• Increased synthesis of clotting factors, triglyceride lipase, a1-antitrypsin, haptoglobin and sialic acid

Question 33

PK of Androgens?

Answer 33

Testosterone
• Given IM, transdermally, topically and as buccal tablets
• Metabolized before being excreted in the urine

Testosterone Derivatives
• Methyltestosterone and danazol can be given orally

Question 34

Clinical use of androgens?

Answer 34

Testosterone / Methyltestosterone
• Males with primary or secondary hypogonadism
• Chronic wasting associated with HIV or cancer
• Stimulate anabolism to promote recovery after burns or other injuries
• Increase lean body mass and endurance in athletes
(unapproved)

Danazol (also has anti-estrogen activity)
• Endometriosis
• Fibrocystic breast disease

Question 35

AE of androgens in males and females?

Answer 35

Females
• Masculinization, acne, facial hair growth, deepening of
the voice, male pattern baldness, excessive muscle
development
• Menstrual irregularities

Males
• Priapism, impotence, decreased spermatogenesis
• Gynecomastia
• Gonadal atrophy

Question 36

AE in children and generally?

Answer 36

Children
• Abnormal sexual maturation
• Growth disturbances due to premature closing of the
epiphyseal plates

General
• Increase LDL and decrease HDL
• Fluid retention → edema

Question 37

AE of androgens in athletes?

Answer 37

Athletes
• Reduction in testicular size (high doses)
• Hepatic abnormalities
• Increased aggression

Question 38

Name 3 Anti androgen drugs?

Answer 38

Androgen Receptor Antagonists
Flutamide
Spironolactone

5a-reductase Inhibitor
Finasteride

Steroid Synthesis Inhibitor
Ketoconazole

Question 39

Flutamide overview, clinical use, and AE?

Answer 39

Flutamide
Non-steroidal competitive inhibitor at androgen receptors

Clinical use: Prostate carcinoma

Adverse effects: mild gynecomastia, hot flashes,
reversible hepatotoxicity

Question 40

Spironolactone overview, clinical use, and AE?

Answer 40

Spironolactone
Mineralocorticoid receptor and androgen receptor
antagonist

Clinical use: Reduction of androgenic symptoms due to PCOS (hirsutism), aldosteronism, diuretic

Adverse effects: Gynecomastia, amenorrhea,
hyperkalemia