Androgens and Anabolic Steroids

Source & Biosynthesis

• Mainly by Leydig cells of testis (95% by leydig cells, 5% by adrenals)
• In females, both ovaries and adrenals convert estradiol.
• Same biosynthesis pathway as estrogen.

Classification

A. Natural

• Testosterone
• Dihydrotestosterone
• Dehydroepiandrosterone
• Androstenedione

B. Synthetic

Testosterone Esters

• Testosterone cypionate
• Testosterone enanthate

Alkylated Androgens

• Methyltestosterone
• Fluoxymesterone

Anabolic Androgens

• Oxymetholone
• Oxandrolone
• Nandrolone decanoate

Mechanism of action

Steroidal receptors, androgenic receptors intracellularly present, binding leads to changes in pattern of synthesis of estrogen.

Pharmacokinetics

Routes of administration –oral, sublingual, transderma, topical

Protein binding – bind sex hormone binding globulin SHBG

5α-reductase – converts testosterone into dihydrotestosterone

Conjugation occurs and excreted in form of urates

Physiological & Pharmacological Effects

Development of primary sex characteristics

Development in utero and whole life.

Development of secondary sex characteristics

Like changes in growth of hair patterns, change in skin thickness, which becomes oilier, deepness of voice due to growth of larynx and vocal cords, muscular, skeletal growth.

Effect on growth & Ca⁺² metabolism

Increased deposition, thickness of bones is increased

Epiphyseal closure is accelerated

Increase in muscular mass esp. shoulder girdle.

Metabolic effects

Androgens increase synthesis of hepatic proteins, clotting factors, triglyceride lipase, alpha 1 antitrypsin and other proteins.

Effect on water & electrolytes

Increased resorption of sodium from distal convulated tubules leading to edema in susceptible patients.

Effect on blood

Increased secretion of erythrocytes, increased RBCs

Anabolic effects

Increased activity, increased protein anabolism decreased catabolism

Increased Na, K, Ca, N

Increased tolerance in athletes.

Therapeutic Uses

1. Replacement therapy in male

•             Primary hypogonadism
•             Castration

2. Gynaecological disorders in female
3. Male contraception
4. Catabolic & wasting states –anabolic effects
5. Anemia –refractory cases, now replaced by recombinant erythropoietin
6. Osteoporosis
7. Growth stimulators

In those young boys having delayed puberty and growth but used with caution. Also cause closure of epiphysis and can retard growth.

8. Aging

Used to slow down aging process.

9. Anabolic steroids in sports

Not therapeutic use but misuse, to increase performance because of anabolic effects.

Adverse Effects

In females

1. Acne
2. Hirsuitism

In infants

1. Affects CNS
2. Growth
3. Sexual functions

In males

Hepatic dysfunction

a.      Increased bilirubin
b.      Cholestasis
c.       Jaundice
d.      Increased incidence of adenoma and carcinoma of liver
e.       Some reports of hepatic failure with use

Urogenital system

1. Prostate hyperplasia –benign prostatic hyperplasia, urinary retention especially in older patients
2. Also increase incidence of prostatic cancer
3. Suppress sperm production -azospermia

CNS

1. Aggression
2. Psychotic behavior
3. Psychological dependence

CVS

1. Na retention
2. hypertension

Blood

Erythrocytosis

Polycythemia

Other effects

1. Acne
2. Gynecomastia

Contraindications & Cautions

•       Pregnant females causing masculinization of female fetus or under masculinization of male fetus.
•       Infants
•       Hepatic / CVS / Renal / Cancer patients (prostatic, breast)

Anti-androgens

• Anti androgens are the inhibitors of testosterone secretion
• They are released in non pulsatile nature,

1. GnRH analogs – Goserelin / Nafarelin are used in Prostate Cancer
2.  Steroid synthesis inhibitors – Ketoconazole antifungal, inhibits many enzymes of steroid synthesis
3. 5α-reductase inhibitors – Finasteride inhibits conversion of testosterone into dihydrotestosterone.

Uses BPH / Male pattern baldness / Hirsutism

Androgen receptor inhibitors

•             Flutamide / Bicalutamide
•             Cyproterone 
•             Spironolactone –inhibition of androgen and aldosterone receptor

Uses Hirsutism /   androgenic activity / Prostate Ca

Danazol

•       Drug having Progestational / Androgenic / Glucocorticoid activity
•       Weak glucocorticoid activity, Suppression of ovarian functions
•       Major active metabolite Ethisterone

Uses

1.             Endometriosis
2.             Fibrocystic disease of breast
3.             Hematological & allergic disorders
4.             Hemophilia
5.             Idiopathic thrombocytopenia purpura
6.             Angioneurotic edema

Adverse effects

1. Weight gain
2. edema
3. headache
4. hot flushes
5. hirsutism
6. acne
7. breast size
8. voice deepening