B-21. Androgens, anabolic steroids, antiandrogens. Flashcards
The testes main function? Controlled by? Main androgen secreted? Letter amount of DHEA secreted?
- Gametogenic functions (controlled by FSH)
- Endocrine functions:
- The main androgen secreted by the testes is testosterone (Leydig cells – stimulated by LH)
- Smaller amounts of dihydrotestosterone (potent), androstenedione and dehydroepiandrosterone (weak androgens) are also secreted
Testosterone pharmokinetics
Testosterone - IC receptor → gene activation
Good absorption, but low oral bioavailability (first pass metabolism) → injection of transdermal use
Testosterone Pharmacological actions
- Testosterone Pharmacological actions:
- In young men: development of secondary sex characteristics
- In adult women: facial and body hair, deepening of voice, enlargement of the clitoris, frontal baldness etc.
- In adult men: maintenance of libido, spermatogenesis
- Anabolic effects:
- Reduced nitrogen excretion, increased protein synthesis, decreased protein breakdown (more pronounced in women and children)
Steroids with androgenic/anabolic actions?
Testosterone
Nandrolone
Clinical uses of androgens and related steroids
- Clinical uses of androgens and related steroids
- Androgen replacement:
- Hypogonadism in men, after castration
- Protein anabolic agents after trauma, surgery, prolonged immobilization
- Gynecologic disorders:
- Danazol (weak androgen) for endometriosis
- Illegal use (sports)
- Danazol, stanozolol- for hereditary angioedema (long-term therapy- increased synthesis of C1-esterase-inhibitor in the liver)
- Androgen replacement:
Adverse effects of androgens and related steroids
- Adverse effects of androgens and related steroids
- Masculinizing action in women and children (hirsutism, acne, deepening of voice etc.)
- Some androgens with progestational activity- increased cardiovascular risk, endometrial bleeding upon discontinuation in women
- Sodium retention, edema
- C-17-alkyl-substituted steroids (most anabolic agents) – hepatic dysfunction (AST, bilirubin, cholestasis, hepatic tumors)
- Older males – prostate hyperplasia
Contraindications of steroids
Contraindications: Pregnancy, prostate cancer, infants and young children, breast cancer in males
Antiandrogen classes
- Androgenic suppression with GnRH-analogues
- Steroid synthesis inhibitors
- 5alpha-reductive inhibitors
- Androgen receptor antagonist
Steroid synthesis inhibitor drugs
- Ketoconazole
- 17-hydroxylase inhibitors
- Abiraterone
Ketoconazole Function as a antiandrogen? Clinical trials? Side effects?
- Antifungal drug, inhibitor of adrenal and gonadal steroid synthesis
- Clinical trails in hirsutism (women) and prostate cancer are not encouraging
- Causes sexual disturbances during the antifungal treatment
5alpha-reductase inhibitors drugs
- Finasteride
- Dutasteride
5alpha-reductive inhibitor effects? Useful in?
Moderately effective in reducing prostate size in men with benign prostate hyperplasia ▪ May be useful in male baldness and female hirsutism
Androgen receptor antagonist drugs
Flutamide Bicalutamide Nilutamide Enzalutamide Cyproterone acetate Spironolactone
Androgen receptor antagonist (Flutamide, bicalutamide, nilutamide, enzalutamide) Used in treatment of? Side effect?
- Strong and pure androgen antagonists
- Used in treatment of metastatic prostate cancer
- Flutamide has a mild hepatotoxicity
Cyproterone acetate -Activity? Treatment of? Combined with?
- Strong progestational activity
- Treatment of hirsutism in women, decreases excessive sexual drive in men, useful in prostate cancer, and used in alopecia in women (combination therapy with ethynylestradiol)
Spironolactone use as an antiandrogen
Diuretic agent, aldosterone and androgen antagonist, inhibits testosterone synthesis, used in the treatment of hirsutism in women
GnRH drugs
- Leuprolide
- Nafarelin
- Goserelin
- Histerelin
GnRH analogues are what and produced where? Controls? Half life? Given?
- Decapeptide, produced by the arcuate nucleus of the hypothalamus
- Controls the release of the gonadotropins FSH and LH
- GnRH analogs have a longer half-life (3 hours compared with GnRH – 4 minutes) and can be given intranasally
GnRH (Leuprolide, Nafarelin, Goserelin, Histerelin) analogues diagnostic use
- Diagnostic use:
- Delayed puberty
- Constitutional delay – normal LH response
- Hypogonadotropic hypogonadism due to pituitary/hypothalamic disease – impaired LH response
- Delayed puberty
GnRH (Leuprolide, Nafarelin, Goserelin, Histerelin) analogues therapeutic uses
- Therapeutic uses:
- Stimulation – pulsatile GnRH (gonadorelin) therapy:
- Every 90 minutes – infertility caused by hypothalamic hypogonadotropic hypogonadism in both sexes
- Suppression – continuous therapy (GnRH analogs):
- Prostate cancer, uterine fibroids, endometriosis, polycystic ovary syndrome, precocious puberty
- In vitro fertilization programs:
- Suppression followed by exogenous gonadotropins – synchronous follicular development
- Stimulation – pulsatile GnRH (gonadorelin) therapy:
GnRH antagonist and function
- Ganirelix
- Abarelix
- Degarelix
- Cetrorelix
Treatment of prostate cancer, in vitro fertilization programs
FSH is? Stimulates?
- Glycoproteins hormone produced in the anterior pituitary
- Stimulates gametogenesis and follicular development in women and spermatogenesis in men
FSH drugs
- Follitropen Beta
- Modified FSH for therapeutic use
- Urofollitropin
- Human FSH extracted from the urine of postmenopausal women without LH
- hMF (menotropins)
- FSH-LH combination
FSH drugs indication
Pituitary or hypothalamic hypogondaism with infertility, in vitro fertilization programs
LH produced by? Primarily responsible for?
- Primarily responsible for regulation of gonadal steroid hormone secretion
- No LH preparation in clinical use
- Human chorionic gondotropin (hCG)- LH substitute
Diagnostic use of LH
Prepubertal boys with undescended gonads- distinguished truly retained (cryptochid) testis from retracted (pseudocryptochid)
Therapeutic use of LH
- Therapeutic use
- Induce ovulation (in combination with human menotropins)
- Stimulate testosterone secretion (hypogonadotropic hypogonadism)
- AIDs-related Kaposi’s sarcoma- injection into the lesions causes regression
