GONADAL HORMONES Flashcards
17 α-hydroxylase deficiency
leads to ↓sex hormones and cortisol and ↑ in mineralocorticoids.
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
17 α-hydroxylase deficiency
21-hydroxylase deficiency
↑ sex hormones and ↓ cortisol and in mineralocorticoids.
Presents with ↓BP; ↑K+;↑renin activity and volume depletion.
Over masculinization – pseudohermaphroditism in females.
Rx: fluids + salt repletion & administer cortisol to ↓ACTH
21-hydroxylase deficiency
11β-hydroxylase deficiency
leads to ↑ sex hormones and ↓ cortisol and in mineralocorticoid (aldosterone) but ↑11-deoxycorticosterone.
Patients present with ↑BP due to ↑mineralocorticoid 11-deoxycorticosterone
Over masculinization. Rx: estrogens, anti-HTN
11β-hydroxylase deficiency
WHICH ESTROGEN IS THE MOST POTENT
Estradiol is more potent than Estrone and Estriol
Important physiological effects of estrogens on:
- Pro-coagulation state
–Increases factor II, VII, IX, X and XII in higher doses
–Decreases antithrombin III, protein C and S
Important physiological effects of estrogens on:
- Lipid profile
•Favorable Lipid profile
–Increase HDL
–Decrease LDL
Important physiological effects of estrogens on:
HORMONE LEVELS
AND CHOLESTEROL
•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
Estrogens NAMES
- Ethinyl estradiol
- Conjugated estrogen
- Mestranol
- Diethylstilbestrol
- Estradiol
- Estrone
- Estriol
a prodrug is converted into Ethinyl estradiol, present in some contraceptives. ↑bio-availability, ↑half-life and ↓FSH & LH via feed-back
MESTRANOL
ESTORGENS METANOLIZED BY?
P450
Combination with P-450 inducers can lead to failure of contraceptive effectiveness.
what kind of estrogens are used in females with hypogondadism?
I.M. Long acting estrogen preparations
Estrogens AE
- 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
SERMs
Tamoxifen
Toremifene
Raloxifene
- Mixed mechanism of actions: They exhibit agonistic action in some tissue and antagonists in other tissues.
•Fulvestrant:
PK
USE
AE
IM
•Used in the treatment breast cancer in tamoxifen resistant patients.
•A.E: Hot flushes, injection site reactions & headache
Aromatase inhibitors
Drug names?
PK
AE
•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.
Clomiphene?
PK
AE
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.
Progestins
- Progesterone
- Medroxyprogesterone
- Norgestrel
- Norethindrone
- Norgestimate
- Desogestrel
- Drospirenone
Antiprogestin
Mifepristone
- therapeutic abortificient
PROGESTERONE - Preps:
Medroxyprogesterone, Norgestrel, Norethindrone, Norgestimate, Desogestrel
–newer preps lacking of androgenic and antiestrogenic effects.
–a spironolactone derivative used as O.C. antagonize aldosterone effects useful in acne in females.
Drospirenone
Progestins –Adverse effects
Long term use may result in:
- Weight gain
- Glucose intolerance
- Androgenic –hirsutism & acne
- Anti-estrogenic (blocks lipid changes)
- Depression,
- Edema, acne
- increased HDL, decreased LDL & hypertension
Antiprogestins - RU 486 or Mifepristone PD PK AE
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.
ANDROGENS
•Testosterone –natural Synthetic androgens –17alkyl derivatives with increased anabolic effects: •Oxandrolone •Methyltestosterone •Stanozolol •Fluoxymesterone •Nandrolone •Oxymetholone •Danazol
Antiandrogens
MOA and drug name?
Receptor Antagonist: - Flutamide 5-α-Reductase Inhibitor: - Finasteride Synthesis Inhibitors: - Ketoconazole •Bicalutamide •Nilutamide •Cyproterone •Spironolactone GnRH Agonists
GnRH inhibitors?
Degarelix
Abarelix
(remember same as Ganirelix and cetrorelix)
Androgen overdose can result in?
feminization (gynecomastia, testicular shrinkage, infertility, azoospermia) as a result of feedback inhibition (HPG axis) & conversion of exogenous testosterone into estrogen.
Danazol
MOA
USE
AE
•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.
Androgen receptor blockers –used for androgen-receptor-positive cancers.
Flutamide –a substituted anilide.
Bicalutamide
Nilutamide
•Primarily used in conjunction with GnRH analogs e.g., leuprolide (to ↓initial tumor flare-ups of prostate carcinoma).
Spiranolactone: MOA
USE?
blocks aldosterone and competes androgen receptors. It is used in hirsutism.
Cyproterone:
MOA
USE
it has progesteronal effect suppresses LH & FSH. Used in hirsutism and to ↓excessive sexual drive in men
Ketoconazole
PK
USE
AE
– 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↓
5-α reductase inhibitor
- name drug
- PK
- MOA
- USE
- AE
- Finasteride (PROPECIA):
- Oral administration
- Inhibit conversion of testosterone to dihydrotestosterone.
- Use: BPH and promotes hair growth.
- AE: gynecomastia, teratogenicity and impotence
