Endoc- Gonadal hormones and Inhibitors

Question 1

Sex Steroids

Answer 1

 Estrogens  Progestins  Androgens  Antiestrogens  Antiprogestins  Antiandrogens

Question 2

Estrogens

Answer 2

 Diethylstilbestrol (DES)

 Estradiol

 Estriol

 Estrone

 Ethinyl estradiol

Question 3

Antiestrogens Selective Estrogen Receptor Modulators (SERMs)

Answer 3

 Clomiphene  Tamoxifen  Raloxifene

Question 4

Estrogens: Indications For Use

Answer 4

 1) Replacement in estrogen deficiency

 Female hypogonadal or postmenopausal

 Prevention & treatment of osteoporosis

 2) Oral contraceptive therapy (combined with progestins)

 3) Hirsutism

 4) Amenorrhea

5) Dysmenorrhea

Question 5

Physiologic effects of estrogens

Answer 5

Physiologic effects of estrogens

 1) Normal female maturation

 -secondary sex characteristics

 -stimulates stromal and ductal growth of the breast

 2) Accelerated growth phase at puberty, closing of long bone epiphyseal plate

 3) Antagonizes the effect of PTH on bone resorption - increases bone density

 4) Promotes growth of endometrium - prolonged unopposed exposure causes hyperplasia

 5) Maintains skin & blood vessel integrity

6) Alters liver metabolism - primarily when given orally

 Increases production of plasma proteins (Transport proteins, Proteins related to hemostasis)

 Alters plasma lipid/lipoprotein profile

 Increases: HDL and TG

 Decreases: cholesterol and LDL

 7) Enhances blood coagulability

 8) Alters vascular reactivity - affects vascular smooth muscle cells and endothelial cells

 Decreases: endothelin-1, TXA2 receptor number, angiotensin II receptor number, decreases or scavenges free radicals

 Increases: expression of nitric oxide synthase (NOS), NOS activity

 9) Facilitates movement of fluid into extravascular space (decrease in plasma volume) with compensatory sodium and water retention.

 10) Others - increases angiotensinogen

Question 6

Pharmacokinetics of estrogens

Answer 6

 Strongly bound to sex hormone binding globulin (SHBG) and with lower affinity to albumin

 Estradiol is metabolized to estrone in peripheral tissue.

 Estradiol is metabolized to estriol, estrone and 2-hydroxyestrone in the liver.

 The hydroxylated derivative is conjugated (with glucuronic acid or sulfate) and secreted in the bile.

Conjugated metabolites may undergo enterohepatic circulation. Thus, more effects are seen on the liver when estrogens are administered orally than by other routes

Question 7

Estrogens: Adverse effect

Answer 7

s  Nausea, vomiting

 Breast tenderness

 Postmenopausal uterine bleedin

g  Endometrial hyperplasia, cancer

 Edema (sodium, water retention), hypertension

 Weight gain

 Hypertriglyceridemia

 Cholestasis, gallbladder disease

 Migraine headaches

Question 8

Estrogen-progestin combinations: Adverse effects

Answer 8

 Increased risk for breast cancer

 Slight increase in coronary artery disease

 Increased risk for thromboembolic episodes (e.g., stroke, pulmonary embolism, deep vein thromboses)

Question 9

_________ - most active endogenous estrogen, and has highest affinity for estrogen receptor. Metabolites estrone and estriol have weak uterine effects.

Answer 9

Estradiol

” Dikit”

Question 10

 - more effect on levels of CBG, SHBG, and other liver proteins (e.g., angiotensinogen) than transdermal preparations.

Answer 10

Oral preparations

Question 11

l  Associated with cervical & vaginal carcinoma in daughters of women who took the drug during pregnancy

Answer 11

Diethylstilbestrol

Question 12

Selective Estrogen Receptor Modulators (SERMs)

 Nonhormonal pharmacological agents that bind to the estrogen receptors

Answer 12

 Tamoxifen

 Raloxifene

 Clomiphene

” CaRT”

Question 13

partial estrogen agonist in breast, full agonist in bone & endometrium

Answer 13

Tamoxifen

” thats why in CA patient taking hormonal therapy has an adverse result of endometrial ca”:

Question 14

_____________ – estrogenic activity in bone, antagonist in both breast and endometrial tissue

Answer 14

 Raloxifene

Question 15

 Used in treatment of breast cance

r  Increased incidence of endometrial cancer

Answer 15

SERMs: Tamoxifen

Question 16

____________

 Used in prevention and treatment of osteoporosis

 Prophylaxis of breast cancer in women at risk

Answer 16

SERMs: Raloxifene

Question 17

Good effects of Raloxifene

Answer 17

1. Lowers LDL
2. Prevents breast ca
3. prevents uterine CA
4. Strengthens the bones

Question 18

What are the bad effects of Raloxifene?

Answer 18

Increases blod clot risk

**No relief for hot flashes **

Question 19

Progestins

Answer 19

 Progesterone

 Hydroxyprogesterone

 Medroxyprogesterone

 Megestrol

 Norethindrone

 Norgestrel

Question 20

Antiprogestins

Answer 20

l Mifepristone

Question 21

Indications for the use of progesterone/progestins Progestins are synthetic progesterone-like compounds

Answer 21

 1) Primary use in contraceptive therapy

 2) With estrogen for replacement therapy

 3) May be used in treatment of dysfunctional uterine bleeding (DUB), dysmenorrhea, endometriosis

 4) May delay premature labor

Question 22

Physiologic effects of progesterone

Answer 22

 1) Stimulates lipoprotein lipase & favors fat deposition

 2) Increases basal insulin levels & increases insulin response to glucose

 3) Competes with aldosterone at the renal tubule therefore antagonizes aldosterone-mediated Na+ & water retention

 4) Increases ventilatory response to CO2

 5) Responsible for alveolobular development of secretory apparatus in the breast

 6) Relaxes smooth muscle - including inhibition of uterine contraction

 7) Participates in preovulatory LH surge and causes maturation, secretory changes in the endometrium that are seen following ovulation

 8) depressant and hypnotic effects on the brain

Question 23

Contraception

Answer 23

Contraception

 Combination Oral (Estrogen and Progestin combination)

 Monophasic

 Multiphasic

 Progestin only

Question 24

 1) An oral combination of estrogen and progestin is given at a ___________________

Withdrawal bleeding occurs during “off” period.

Answer 24

constant dose for 21 days followed by 7 days without hormone.

Question 25

 Monophasic

 each of the 21 pills per month have the same amount and proportion of estrogen and progestin

Question 26

 Progestin dose is_______________, i.e. estrogen dominance early in the cycle and progestin dominance later.

Answer 26

varied over the 21 days (“on”) to more closely mimic menstrual cycle

Question 27

Contraception: Mechanism of action

_______________ – Negative feedback on the hypothalamus and anterior pituitary to inhibit the surge of LH and thus inhibit ovulation

Answer 27

Primary Secondary

Question 28

 _________- - Estrogen and progesterone suppresses FSH - blocking follicular development

• • Progestin causes thickening of cervical mucus - interfering with sperm migration
• • Progestins (out of sequence) cause disturbances in endometrium making it unsuitable for implantation
• Progestins may impair tubal transport of ovum (due to relaxant effect of progestin on smooth muscle in fallopian tube)
•  Effectiveness: 2 to 3 pregnancies per 100 women years (theoretical 0.1/100 women yrs)

Answer 28

SECONDARY

Question 29

 2______________ - ora

l  Used when estrogen is contraindicated

 Mechanisms of action

 Thickening of cervical mucus

.  Inhibition of ovulation

 As listed above for progestin component of combination OC.

 Effectiveness: 3 pregnancies per 100 women years

Answer 29

) Progestin only minipill

Question 30

Oral Contraceptives: Beneficial effects

 Reduced risk for:

Answer 30

 Ovarian cysts

 Ovarian & endometrial cancer

 Benign breast disease

 Ectopic pregnancy

 Fe deficiency

 Rheumatoid arthritis

Question 31

Oral Contraceptives:

Other uses Amelioration of:

Answer 31

 Premenstrual symptoms  Dysmenorrhea  Endometriosis  Acne  Hirsutism

Question 32

Contraceptives: CONTRAINDICATIONS

Answer 32

 Thrombophlebitis/thromboembolic disorders

 Cerebral vascular or coronary artery disease

 Uncontrolled hypertension

 Known or suspected estrogen-dependent neoplasm (e.g., breast, endometrium)

 Cholestatic jaundice or history with prior pill use

 Hepatic adenomas, carcinomas, benign liver tumors

l Markedly impaired liver function
l Severe hypertriglyceridemia
l Known or suspected pregnancy

Question 33

Contraceptives: RELATIVE CONTRAINDICATIONS

Answer 33

 Migraine or vascular headache

 Cardiac or renal dysfunction

 Hypertension

 Psychic depression

 Varicose veins

 History of worsening of a chronic condition during pregnancy (e.g. cholestatic jaundice)

 Over age 35 and a cigarette smoker or over age 45

Question 34

Progestins: ADVERSE REACTIONS

Answer 34

 Hypertension  Reduce plasma HDL, hirsutism, acne (especially androgenic progestins)  Slightly increases breast cancer risk in combination with estrogen  Irregular uterine bleeding  Depression