This document discusses adrenal steroids, sex hormones, and their clinical uses and adverse effects. It covers glucocorticoids like prednisone and mineralocorticoids like fludrocortisone. It also discusses estrogens like estradiol, progestins, oral contraceptives, androgens, and drugs that antagonize these hormones. The key uses and side effects of these classes of hormones are summarized.

1. Endocrine Pharmacology
Adrenal Steroids & The Sex
Hormones
Dr. Salman Iftikhar

2. Adrenal Steroids
Glucocorticoids: prednisone, dexamethasone
Mineralocorticoid: fludrocortisone

3. Adrenal Steroids
• Nonendocrine uses: Used in inflammatory
disorders
• Endocrine uses of glucocorticoids (e.g.,
prednisone, dexamethasone), mineralocorticoids
(fkudrocortisone):
1. Addison disease – replacement therapy
2. Adrenal insufficiency staes (infection, shock,
trauma) – supplementation
3. Premature delivery to prevent respiratory distress
syndrome – supplementation
4. Adrenal hyperplasia – feedback inhibition of ACTH

4. Adrenal Steroids
• Adrenal steroid antagonists:
1. Spironolactone:
 Blocks aldosterone and androgen receptos
2. Mifepristone:
 Blocks glucocorticoid and progestin receptors
3. Synthesis inhibitors
 Metyrapone (blocks 11-hydroxylation)
 Ketoconazole

5. SEX hormones

6. Contraception

16. Estrogens
• Estradiol is the major natural estrogen
• Conjugated equine estrogens
(premarin)– natural
• Ethinyl estradiol and mestranol –
steroidal
• Diethylstilbestrol (DES) – nonsteroidal

17. Estrogens
• Clinical Uses
1. Female hypogonadism
2. Hormone replacement therapy (HRT) in
menopause
3. Contraception –feedback  of
gonadotropins
4. Dysmenorrhea
5. Uterine bleeding
6. Prostate CA

18. Estrogens
• Adverse Effects
1. General
 Nausea
 Breast tenderness
 Endometrial hyperplasia
  gallbladder disease, cholestasis
 Migraine

19. Estrogens
• Adverse effects
2.  blood coagulation (only high doses)
3. Cancer risk
•  endometrial cancer (unless progestins are
added)
•  breast cancer – questionable, but caution if
other risk factors are present
• DES given during breast feeding  vaginal
adenocarcinoma cancer in offspring

20. Estrogens
1. Anastrozole
• Aromatase inhibitor  estrogen synthesis
• Use: Estrogent – dependant postmenopausal
breast cancer
2. Clomiphene (fertility pill)
•  feedback inhibition  FSH and LH 
ovulation  pregnancy
• Use: fertility drug
• Adverse effect:  multiple births

21. Estrogens
• Selective estrogen – receptor modulators
(SERMs)
1. Tamoxifen
• Action is variable depending on “target” tissue
• E-receptor agonist (bone), antagonist (breast),
partial agonist (endometrium)
• Possible inc. risk of endometrial cancer
• Used in estrogen-dependant breast cancer and
for prophylaxis in high – risk patients

22. Estrogens
• Selective estrogen – receptor
modulators (SERMs)
2. Raloxifene
• E-receptor agonist (bone), antagonist
breast and uterus
• When used in menopause there is no inc.
risk of cancer
• Use: prophylaxis of post menopausal
osteoporosis

23. Progestin
• Progesterone is the major natural
progestin
• Drugs:
1. Levonorgestril
2. Medroxyprogesterone
3. Norethindrone
4. Desogestrel – a synthetic progestin
devoid of androgenic and anti-estrogenic
activities, common to other derivative

24. Progestin
• Clinical uses:
1. Contraception (oral with estrogens)
2. HRT with estrogens to decrease endometrial CA
• Adverse effects
1. HDL and  LDL
2. Glucose intolerance
3. Breakthrough bleading
4. Androgenic (hirsutism)
5. Antiestrogenic (block lipid changes)

25. Progestin
• Antagonist: mifeprostone –
abortifacient (used with PGs)

26. Oral Contraceptives
• Pharmacology:
1. Combination of estrogens (ethinyl estradiol,
mestranol) with progestins (norgestrel,
norethindrone) in varied dose with mono-, bi-,
and triphasic variants
2. Supress gonadotropins, esp. midcycle LH surge
• Adverse effects
1. Estrogen
• Nausea, bloating, headache, mastalgia
2. Progestins
• Weight gain, hirsutism, acne, tiredness,
depression, dec. HDL and inc. LDL
3. Liver adenoma

27. Oral Contraceptives
• Interactions: Dec. contraceptive
effectiveness when used with
antimicrobials and enzyme inducers
• Benefits
1.  risk of endometrial and ovarian cancer
2.  Dysmenorrhea
3.  endometriosis
4.  PID
5.  osteoporosis

28. • The combination agents are divided into
monophasic forms (constant dosage of
both components during the cycle) and
biphasic or triphasic forms (dosage of
one or both components is changed once
or twice during the cycle)

31. Androgens
• Methyltestosterone and 17-alkyl
derivatives with increased anabolic
actions, e.g., oxandrolone, nandrolone
• Uses:
1. Male hypogonadism and for anabolic
actions
2. Illicit use in athletics

32. Androgens
• Adverse effects
1. Excessive masculinization
2. Premature closure of epiphysis
3. Cholestatic jaundice
4. Aggression – “roid rage”
5. Dependence

33. Androgens
• Antagonists:
1. Flutamide: androgen receptor blocker
– used for prostate cancer
2. Leuprolide: GnRH analog: repository
form used for CA prostate

34. Androgens
• Antagonists:
3. Finasteride:
• 5- alpha reductase inhibitor, preventing
conversion of testosterone to
dihydrotestosterone (DHT)
• DHT is responsible for hair loss and
prostate enlargement
• Uses: BPH, male pattern baldness
• CAUTION: Teratogenicity

35. Androgens
• Antagonists:
4. Ketoconazole
• Synthesis inhibitor – used in androgen
receptor positive prostate cancer