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Definition.

These are a group of steroids that have anabolic and musculinizing effects in both males and females.

Examples.

Testosterone .5a-dihydrotestosterone(DHT) .Androstenedione
Dehydroepiandrosterone(DHEA)

Source.

Testes .Ovary .Adrenal gland

Regulation of secretion of Testosterone

Testosterone secretion by leydig cells is controlled by GnRH from the hypothalamus.
This stimulates the anterior pituitary gland to secrete FSH and LH.

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LH stimulates steroidogenesis in the leydig cells.
FSH is necessary for spermatogenesis.
Testosterone or DHT inhibits production of GnRH through a negative feedback loop thereby regulating testosterone production.

Why require androgens.?

Normal maturation in the male.
Sperm production.
Increased synthesis of muscle proteins and hemoglobin
Decreased bone resorption.

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REGULATION OF SECRETION OF TESTOSTERONE

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Mechanism of action.

Androgens bind to a specific nuclear receptor in a target cell.

E.g. testosterone in tissues like the prostate, seminal vesicles,epididymis and the skin is converted by 5a- reductase to DHT which binds to the receptor.

In the brain, liver and adipose tissue, is biotransformed to estradiol by cytochrome P450 aromatase.

The hormone-receptor complex binds to DNA and stimulates the synthesis of specific RNAs and proteins.

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Therapeutic uses.

Androgenic effects.

Primary hypogonadism
Secondary hypogonadism

Anabolic effects.

Senile osteoporosis
Chronic wasting due to HIV or Cancer.
Adjunct therapy in burns.

Endometriosis.

Danazol

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Pharmacokinetics.

Testosterone is ineffective orally because of inactivation by first-pass metabolism.
It is rapidly absorbed and metabolized to inactive compds excreted in the urine.
The esters e.g. testosterone cypionate or enanthate are administered i.m.
Transdermal patches
Topical gels
Buccal tablets of testosterone.

Testosterone derivatives.

Alkylation of the 17a-position of testosterone allows oral administration of the hormone.

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Fluoxymesterone.

Has a 1:2 androgenic to anabolic ratio.

Oxandrolone

Has anabolic activity 3 to 13 times that of testosterone.

Adverse effects.

In females

Masculinization
Menstrual irregularities.

In males

Priapism .Impotence .Gynecomastia . < Spermatogenesis.

In children

Abnormal sexual maturation and growth disturbances.

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Cardiovascular

Increased serum LDL:HDL ratio
Fluid retention

In athletes

DHEA or Nandrolone.

Reduced testicular size
Increased aggression
Mood disorders.

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Antiandrogens.

They counter male hormonal action by interfering with the synthesis of androgens or by blocking their receptors.

Examples

Ketoconazole

Finasteride
Dutasteride

Flutamide
Bicalutamide
Nilutamide

5a-Reductase inhibitors.

Competitive inhibitors

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Probable questions.

QI. Young athletes who abuse androgens should be made aware of the side effects of these drugs. Which one of the following is however, not of concern?

a. Increased muscle mass b. anemia due to bone marrow failure. C. overly aggressive behavior. D. decreased spermatogenesis. e. stunted growth.

Q2. A 70 year old woman is being treated with raloxifene for osteoporosis. There is an increased risk of her developing: a. breast cancer. b. uterine cancer. C. vein thrombosis. D. atrophic vaginitis. E.hypercholesterolemia .

Q3. A 23 year old girl has failed to become pregnant after 2 years of unprotected intercourse. Which of the following would be effective in treating infertility due to anovulatory cycles? A. a combination of an estrogen and progestin. B. estrogen alone. C. clomiphene. D. raloxifene.

Q4. Which of the following is inappropriate for treating osteoporosis? A. DHEA. B. estradiol. C. tamoxifen. D. norethindrone. E. mestranol.

Q5. Estrogen replacement therapy in menopausal women : A. restores bone loss accompanying osteoporosis. B. may induce hot flashes. C. may cause atrophic vaginitis. D. is most effective if instituted at the first signs of menopause. E. requires higher doses of estrogen than with oral contraceptive therapy.