Androgen Suppression & Antiandrogens Male contraceptives Dr keli

Androgens supression
Androgens effects can be eliminated by Suppression of gonads by Orchidectomy Large doses of oestrogen !! Gynaecomastia GnRH analogue adminstered contonously

Anti-Androgens
Compounds that block the synthesis or action of androgens. They are useful in the management of

hyperplasia acne, male-pattern

and carcinoma of the prostate,

baldness, virilizing syndromes in women precocious puberty in boys To inhibit of sex drive in men

Modes of Antiandrogens effects

1. Steroid synthesis inhibition ketoconazole It inhibits adrenal and gonadol steroid synthesis

it does not affect the ovarian aromatase but affects the placental
aromatase activity Not usefull in women due to its toxcity Experimetal rx of prostatic ca It causes gynaecomastia in men due to increased ratio ofesradiol:testosterone

Antiandrogens

Androgen Receptor inhibitors 1. Cyproterone and Cyproterone acetate inhibit androgens at their target organs Use hirsutism has contraceptive effects, to reduce excessive sexual drive in men 2. Flutamide NSAID Rx of ca prostrate behaves like a competitive antagonist of androgen receptors Ae mild gynaecomastia mild hepatotoxicity ? Mx of excess androgens in women

Androgen receptor inhibitors

3. Bicalutamide Nilutamide potent ant androgens for Rx of metastatic prostrate ca use with GnRH analogues to reduce tumour flare 4. Spironolactone competes for androgen receptors with dihydrotestosterone reduces 17 a hydroxylase activity lowering testosterone and androstenedione Rx of

hirsutim in women

Conversion of steroid precursors to androgens

This occurs via Inhibition of the conversion of progesterone or pregnelone to androgens via inhibition

of 17 hydroxylase by Abiraterone and Dutasteride

Inhibition of 5 a reductase, reduces the levels of dihydrotestosterone an androgen in the prostrate

Finasteride Rx of prostrate ca Dutasteride Slow OOA & longer DOA Dose 5mg/d Both not approved for use in women or children

Receptor inhibitors
Cyproterone Cyproterone Flutamide Bicalutamide Nilutamide

acetate

Spironolactone

Spironolactone

A competitive inhibitor of aldosterone Also competes with DHT for androgen receptors in target tissues Also reduces 17 hydroxylase activity, lowering plasma levels of testosterone & androstenedione Treatment of hirsuitism in women As effective as other finasteride, Cyproterone & Flutamide Dose: 50-200mg/d

Danazol
FSH & LH release in both sexes Binding of steroids to receptors Enzymes needed for steroid synthesis Weak androgenic, anabolic, progestational & glucocorticoid action Uses:
Endometriosis
Menorrhagia Fibrocystic Hereditary

Side effects:

Dose related
Amenorrhea (High doses) Androgenic side effects

breast disease angioneurotic oedema

Gynecomastia Infertility

SILDENAFIL

Hypothalamus ANS

Parasympathetic

Sympathetic

Noradrenaline
Acetyl choline vasoconstriction
Muscarinic Receptors

Penile erection

Penile flaccidity

Sildenafil

Inhibits PDE5 in the corpus cavernosa of the penis 50mg, p.o. 1 h before sexual activity potentiate nitrates hypotension activity ketoconazole & erythromycin increases its level renal & hepatic disease increases its level Side effects: headache, flushing, dyspepsia, myalgia

MALE CONTRACEPTION
Condom Vasectomy Male oral contraception with androgens and with cotton seed oil Immunological contraception

Still at investigative stage.

Do men want new options?

Over 40% of US couples rely on the currently available male contraceptives

Source: CDC (2006) Health, United States

Chemical Contraception in Men

Testosterone and testosterone enanthate in a dose of 400 mg a month Testosterone + Danazole well tolerated but not more effective than testosterone enathate Testosterone enanthate 100 mg weekly + levonorgestrel 500 mg daily produce azoospermia

Under investigation
Gossypol a cottonseed derivative it destroys semineferpous epithelium AE Hypokalemia Has been tried as an intravaginal contraceptive Risk of lack of normal near normal reversibility of sperm amounts

Cotton seeds

Cotton plant