543 androgens/anti androgens 1/12

actions of androgens

reproductive tract development, secondary sex characteristics; spermatogenesis; anabolic effects; pubertal growth spurt; sebaceous gland secretions

testosterone as 3 hormones

directly binds to androgen receptors; metabolism to dihydrotestosterone; metabolism to estradiol

enzyme that converts testosterone to dihydrotestosterone

5a-reductase (type 1 in the liver/scalp and type 2 in the reproductive tissues, liver, and scalp)

enzyme that converts testosterone to estradiol

CYP19 (aromatase)

binding site of dihydrotestosterone and testosterone

androgen receptors

things dihydrotestosterone affects

external genitalia and hair follicles

things testosterone affects

internal genitalia, skeletal muscles, erythropoiesis, bone growth

things estradiol affects

bone; libido

illnesses replacement therapy (testosterone) is meant to treat

male hypogonadism (mainly primary and not secondary of fertility is wanted) and andropause (senescent hypogonadism)

17a-alkyl derivatives (stanozolol, danazol)

androgenic and anabolic steriods

use of androgenic and anabolic steroids

weight gain after burns, in wasting syndromes; sports use

risk of using androgenic and anabolic steroids

liver and testes damage

ADR of androgens

masculinization; hepatic dysfunction (increased AST); lowered HDL and increased LDL; increased hematocrit; promotion of prostatic carcinoma

classes of androgen suppressants

GnRH analogs; synthesis suppression; 5a-reductase inhibitors; androgen receptor antagonists

use of androgen suppressants

if patient is producing too much testosterone or to treat prostatic carcinoma

MOA of GnRH analogs

idea is that GnRH release from the hypothalamus is pulsatile, but using the drug, there is continuous stimulation of gonadotropes in the pituitary. This leads to less LH and FSH release which leads to less testosterone production

GnRH drugs

Leuprolide acetate, Goserelin; Histrelin; Triptorelin

Leuprolide acetate ADR

increase in androgens early on which we can use another suppressant to help; long term use can lead to decreased bone mineral density

drugs that suppress steroid synthesis

ketoconazole (nizoral), spironolactone (aldactone); abiraterone (zytiga)

ketoconazole facts

inhibits steroid synthesis enzymes (P450C17, P450C11); can lead to gynecomastia by changing ratio; Levoketoconazole can be used for Cushing’s

spironolactone facts

inhibits 17a-hydroxylase and competes with testosterone at the androgen receptors; can treat hirsutism in women

Abiraterone facts

reduces androgen production in testes, adrenals, and tumor; given in combination with prednisone; ADR of adrenal insufficiency; mineralocorticoid excess, hepatic dysfunction, musculoskeletal symptoms

5a-reductase inhibitor drugs

finasteride, dutasteride

MOA of finasteride

inhibit 5a-R and reduces DHT within 8 hours; mainly inhibits type 2

dutasteride

inhibits both type 1 and type 2

ADR of 5a-R inhibitors

sexual dysfunction (erection, ejaculation, orgasm); gynecomastia; rash, oligospermia (number and quality of sperm production)

uses of 5a-R inhibitors

treatment in prostatic carcinoma; mixed results in preventing prostate cancer (might promote); use with caution in oligospermia and when fertility is wanted (evidence is that there is a sharp increase in sperm count when D/C)

androgen receptor antagonist drugs

flutamide, bicalutamide, nilutamide, enzalutamide

flutamide

competitive antagonist for androgen receptors; used in prostate cancer with GnRH agonists; ADR of gynacomastia and reversible liver damage; interaction with low dose ASA