GONADAL HORMONES

Question 1

17 α-hydroxylase deficiency

Answer 1

leads to ↓sex hormones and cortisol and ↑ in mineralocorticoids.

Question 2

Patients presents with ↑BP,↓K+
 XY: ↓DHT may show cryptorchidism and indistinct genitalia.
Rx: androgens, glucocorticoids and Anti-hypertensives
XX outwardly Phenotypic female with normal internal sex organs but lack 20 sexual characteristics. Rx: Estrogens, anti-HTN

Answer 2

17 α-hydroxylase deficiency

Question 3

21-hydroxylase deficiency

Answer 3

↑ sex hormones and ↓ cortisol and in mineralocorticoids.

Question 4

Presents with ↓BP; ↑K+;↑renin activity and volume depletion.
Over masculinization – pseudohermaphroditism in females.
 Rx: fluids + salt repletion & administer cortisol to ↓ACTH

Answer 4

21-hydroxylase deficiency

Question 5

11β-hydroxylase deficiency

Answer 5

leads to ↑ sex hormones and ↓ cortisol and in mineralocorticoid (aldosterone) but ↑11-deoxycorticosterone.

Question 6

Patients present with ↑BP due to ↑mineralocorticoid 11-deoxycorticosterone
Over masculinization. Rx: estrogens, anti-HTN

Answer 6

11β-hydroxylase deficiency

Question 7

WHICH ESTROGEN IS THE MOST POTENT

Answer 7

Estradiol is more potent than Estrone and Estriol

Question 8

Important physiological effects of estrogens on:

- Pro-coagulation state

Answer 8

–Increases factor II, VII, IX, X and XII in higher doses

–Decreases antithrombin III, protein C and S

Question 9

Important physiological effects of estrogens on:

- Lipid profile

Answer 9

•Favorable Lipid profile
–Increase HDL
–Decrease LDL

Question 10

Important physiological effects of estrogens on:
HORMONE LEVELS
AND CHOLESTEROL

Answer 10

•Effect on hormone levels
–Increases the transport protein level of various hormones (cortisol, thyroxine, sex steroids)
–free hormone level is unaffected
•Increase cholesterol in bile –formation of gall stone

Question 11

Estrogens NAMES

Answer 11

1. Ethinyl estradiol
2. Conjugated estrogen
3. Mestranol
4. Diethylstilbestrol
5. Estradiol
6. Estrone
7. Estriol

Question 12

a prodrug is converted into Ethinyl estradiol, present in some contraceptives. ↑bio-availability, ↑half-life and ↓FSH & LH via feed-back

Answer 12

MESTRANOL

Question 13

ESTORGENS METANOLIZED BY?

Answer 13

P450

Combination with P-450 inducers can lead to failure of contraceptive effectiveness.

Question 14

what kind of estrogens are used in females with hypogondadism?

Answer 14

I.M. Long acting estrogen preparations

Question 15

Estrogens AE

Answer 15

• Increased incidence of thromboembolism.
• Increased incidence of breast cancers
• Endometrial hyperplasia & cancers (unless progestin is added).
• Migraine, Cholestasis, and mood changes.
• Nausea, breast tenderness and bloating
• Diethylstilbestrol (DES) –a nonsteroidal estrogen agonist use in pregnancy results in female child to infertility, vaginal cancer

Question 16

SERMs

Answer 16

Tamoxifen
Toremifene
Raloxifene
- Mixed mechanism of actions: They exhibit agonistic action in some tissue and antagonists in other tissues.

Question 17

•Fulvestrant:
PK
USE
AE

Answer 17

IM
•Used in the treatment breast cancer in tamoxifen resistant patients.
•A.E: Hot flushes, injection site reactions & headache

Question 18

Aromatase inhibitors
Drug names?
PK
AE

Answer 18

•Inhibits conversion of androgens to estrogen
Letrozole
Anastrozole
Exemestane –an irreversible aromatase inhibitor
•Used in treatment of breast cancer (estrogen dependent) as 2nd line drugs following tamoxifen resistant.
•Oral administration
•A.E: hot flushes, decreased bone mineral density.

Question 19

Clomiphene?
PK
AE

Answer 19

Fertility drug - used in anovulatory infertility

• Acts as estrogen antagonist in hypothalamus and anterior pituitary
• prevents feedback inhibition of GnRH release by hypothalamus

ORAL
AE:
–Ovarian hyper-stimulation leading to enlargement of ovary.
–Multiple pregnancy 10%
–Hot flushes, nausea, vomiting, breast tenderness and weight gain.

Question 20

Progestins

Answer 20

• Progesterone
• Medroxyprogesterone
• Norgestrel
• Norethindrone
• Norgestimate
• Desogestrel
• Drospirenone

Question 21

Antiprogestin

Answer 21

Mifepristone

- therapeutic abortificient

Question 22

PROGESTERONE - Preps:

Medroxyprogesterone, Norgestrel, Norethindrone, Norgestimate, Desogestrel

Answer 22

–newer preps lacking of androgenic and antiestrogenic effects.

Question 23

–a spironolactone derivative used as O.C. antagonize aldosterone effects useful in acne in females.

Answer 23

Drospirenone

Question 24

Progestins –Adverse effects

Long term use may result in:

Answer 24

1. Weight gain
2. Glucose intolerance
3. Androgenic –hirsutism & acne
4. Anti-estrogenic (blocks lipid changes)
5. Depression,
6. Edema, acne
7. increased HDL, decreased LDL & hypertension

Question 25

``` Antiprogestins - RU 486 or Mifepristone PD PK AE ```

Answer 25

Competitive inhibitor of progesterone & glucocorticoid receptors. •Controversial “morning after” drug used as an abortifacient. •It is given concomitantly with PG-E or PG-F to increase myometrial contraction. •Adverse effects: Excessive bleeding, gastrointestinal effects as nausea, vomiting, anorexia and abdominal pain.

Question 26

ANDROGENS

Answer 26

``` •Testosterone –natural Synthetic androgens –17alkyl derivatives with increased anabolic effects: •Oxandrolone •Methyltestosterone •Stanozolol •Fluoxymesterone •Nandrolone •Oxymetholone •Danazol ```

Question 27

Antiandrogens | MOA and drug name?

Answer 27

``` Receptor Antagonist: - Flutamide 5-α-Reductase Inhibitor: - Finasteride Synthesis Inhibitors: - Ketoconazole •Bicalutamide •Nilutamide •Cyproterone •Spironolactone GnRH Agonists ```

Question 28

GnRH inhibitors?

Answer 28

Degarelix Abarelix (remember same as Ganirelix and cetrorelix)

Question 29

Androgen overdose can result in?

Answer 29

feminization (gynecomastia, testicular shrinkage, infertility, azoospermia) as a result of feedback inhibition (HPG axis) & conversion of exogenous testosterone into estrogen.

Question 30

Danazol MOA USE AE

Answer 30

•Danazol is an inhibitor of P450 in gonadal steroid synthesis. •It an androgen derivative, a partial agonist of progestin, and glucocorticoid receptors. •Used in endometriosis and fibrocystic disease of breast. •AE: hepatitis –abnormal liver function tests and drug interaction due to P-450 inhibition. It is a modified testosterone shows some signs of musculinising effects – acne, hirsutism, menstrual disturbances.

Question 31

Androgen receptor blockers –used for androgen-receptor-positive cancers.

Answer 31

Flutamide –a substituted anilide. Bicalutamide Nilutamide •Primarily used in conjunction with GnRH analogs e.g., leuprolide (to ↓initial tumor flare-ups of prostate carcinoma).

Question 32

Spiranolactone: MOA | USE?

Answer 32

blocks aldosterone and competes androgen receptors. It is used in hirsutism.

Question 33

Cyproterone: MOA USE

Answer 33

it has progesteronal effect suppresses LH & FSH. Used in hirsutism and to ↓excessive sexual drive in men

Question 34

Ketoconazole PK USE AE

Answer 34

– oral administration •Adrenal and gonadal steroid synthesis inhibitor •Use: in prostate cancer but not 1st line drug. •AE: May have drug interactions with other steroids due to P-450↓

Question 35

5-α reductase inhibitor - name drug - PK - MOA - USE - AE

Answer 35

* Finasteride (PROPECIA): * Oral administration * Inhibit conversion of testosterone to dihydrotestosterone. * Use: BPH and promotes hair growth. * AE: gynecomastia, teratogenicity and impotence