8. Androgens, anabolic steroids, antiandrogens. Agents affecting the sexual activity Flashcards
Androgens
testosterone:
- testosterone-undecanoate
- effective after p.o. - Nandrolone
(Oxandrolone)
(mesterolone -> older men)
- Male reproductive development and function → growth of genital organs, appearance of secondary sexual characteristics
- Maintains secondary sexual characteristics, fertility and libido
- Acts on hair follicle cells to cause male-pattern baldness
- Anabolic effects → increased muscle mass and strength, increased RBC’s production
Side effects – Testosterone:
- Females
- Virilization (hirsutism, enlarged clitoris, deepened voice)
- Menstrual irregularity
*Males -
- Feminization (due to feedback inhibition of the pituitary)
- Prostate pathology
(in older males)
- Both sexes
- Cholestatic jaundice
- Elevation of liver enzymes - Hepatocellular carcinoma
Contraindications – Testosterone:
- Pregnancy
- Cautions in children
- Prostate cancer
- Cautions in liver disease
- CHF
Anti-androgens
Receptor inhibitor:
Bicalutamide, (flutamide)
- longer T1/2
- competitive
- SARM - selective androgen receptor modulator
- oseteoporosis, hypogonadism, muscle-waiting
- prostate cc.
Spironolactone
- mineralocorticoid receptor antagonist
5-alpha-reductase inhibitor:
Finasteride
- BPH, prostate cc.
GnRH analogue
Leuprolide
Goserelin
high continious administration suppresses GnRH release
GnRH antagonist
Degarelix
androgen and glucocorticoid enzyme inhibitor etc.
Ketoconazole is an antifungal agent that, in high doses, inhibits testicular and adrenal steroid synthesis
While ketoconazole blocks the synthesis of the sterol ergosterol in fungi, in humans, at high dosages (>800 mg/day), it potently inhibits the activity of several enzymes necessary for the conversion of cholesterol to steroid hormones such as testosterone and cortisol.[20][22] Specifically, ketoconazole has been shown to inhibit cholesterol side-chain cleavage enzyme, which converts cholesterol to pregnenolone, 17α-hydroxylase and 17,20-lyase,[22] which convert pregnenolone into androgens, and 11β-hydoxylase, which converts 11-deoxycortisol to cortisol.[28] All of these enzymes are mitochondrial cytochrome p450 enzymes.[29] Based on these antiandrogen and antiglucocorticoid effects, ketoconazole has been used with some success as a second-line treatment for certain forms of advanced prostate cancer[22][30] and for the suppression of glucocorticoid synthesis in the treatment of Cushing’s syndrome
Cimetidine
Cimetidine is a potent inhibitor of certain cytochrome P450 (CYP) enzymes,[24][36] including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4
Antiandrogenic and estrogenic effects
Cimetidine has been found to possess weak antiandrogenic activity at high doses.[34][43][44][45] It directly and competitively antagonizes the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT)
progesterone derivative: cyproterone acetate
possible side effects of CPA include low sex hormone levels, reversible infertility, sexual dysfunction, fatigue, depression, weight gain, and elevated liver enzymes.
CPA is used as an antiandrogen to treat high androgen levels and associated symptoms such as masculinization due to conditions like polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH) in women
CPA has antiandrogenic activity,[1][147] progestogenic activity,[1][147] weak partial glucocorticoid activity,[148] weak steroidogenesis inhibitor activity,[149] and agonist activity at the pregnane X receptor.[150][151][152] It has no estrogenic or antimineralocorticoid activity.[1] In terms of potency, CPA is described as a highly potent progestogen, a moderately potent antiandrogen, and a weak glucocorticoid.[51][142][40] Due to its progestogenic activity, CPA has antigonadotropic effects, and is able to suppress fertility and sex-hormone levels in both males and females.
agents affecting sexual activity
erectile dysfunction :
- hormone
- psychological
- drugs: BB, CCB, alpha-antagonist (retrograde ejaculation), anti-depressants, SSRI, diuretics, cytostatic drugs, cimetidine
parasym. : erection
symp. : ejaculation
require sexual stimulation as well
erection-agent
PDE-5-inhibitor:
1. sildenafil
(tadalefil)
(Varendafil)
nitrates are contraindicated
40-60 min before sex
Intracavernous treatment:
- Papaverine
- Phentolamine
- Alpostadil (also intraurethral)
yohimbin
SNRI
apomorphin
hormon-therapy
Testosterone
- Transdermal, buccal, subcutaneous implant
indications:
- Hypogonadism in boys
- Hormone replacement therapy in male
- Weight gain in patients with ‘wasting syndrome’
- Stimulate red blood cell production in certain anemias (old age male)
- Illicit use in athletes
- Male reproductive development and function → growth of genital organs, appearance of secondary sexual characteristics
- Maintains secondary sexual characteristics, fertility and libido
- Acts on hair follicle cells to cause male-pattern baldness
- Anabolic effects → increased muscle mass and strength, increased RBC’s production
Side effects – Testosterone:
- Females
- Virilization (hirsutism, enlarged clitoris, deepened voice)
- Menstrual irregularity
*Males -
- Feminization (due to feedback inhibition of the pituitary)
- Prostate pathology
(in older males)
- Both sexes
- Cholestatic jaundice
- Elevation of liver enzymes - Hepatocellular carcinoma
Contraindications – Testosterone:
- Pregnancy
- Cautions in children
- Prostate cancer
- Cautions in liver disease
- CHF
Testosterone undecanoate
- Synthetic analogue
- Orally active
indications:
- Hypogonadism in boys
- Hormone replacement therapy in male
- Weight gain in patients with ‘wasting syndrome’
- Stimulate red blood cell production in certain anemias (old age male)
- Illicit use in athletes
- Male reproductive development and function → growth of genital organs, appearance of secondary sexual characteristics
- Maintains secondary sexual characteristics, fertility and libido
- Acts on hair follicle cells to cause male-pattern baldness
- Anabolic effects → increased muscle mass and strength, increased RBC’s production
Side effects – Testosterone:
- Females
- Virilization (hirsutism, enlarged clitoris, deepened voice)
- Menstrual irregularity
*Males -
- Feminization (due to feedback inhibition of the pituitary)
- Prostate pathology
(in older males)
- Both sexes
- Cholestatic jaundice
- Elevation of liver enzymes - Hepatocellular carcinoma
Contraindications – Testosterone:
- Pregnancy
- Cautions in children
- Prostate cancer
- Cautions in liver disease
- CHF
Nandrolone
Oxandrolone
- Synthetic analogues (‘anabolic steroids’)
- Parenteral
indications:
- Hypogonadism in boys
- Hormone replacement therapy in male
- Weight gain in patients with ‘wasting syndrome’
- Stimulate red blood cell production in certain anemias (old age male)
- Illicit use in athletes
- Male reproductive development and function → growth of genital organs, appearance of secondary sexual characteristics
- Maintains secondary sexual characteristics, fertility and libido
- Acts on hair follicle cells to cause male-pattern baldness
- Anabolic effects → increased muscle mass and strength, increased RBC’s production
Side effects – Testosterone:
- Females
- Virilization (hirsutism, enlarged clitoris, deepened voice)
- Menstrual irregularity
*Males -
- Feminization (due to feedback inhibition of the pituitary)
- Prostate pathology
(in older males)
- Both sexes
- Cholestatic jaundice
- Elevation of liver enzymes - Hepatocellular carcinoma
Contraindications – Testosterone:
- Pregnancy
- Cautions in children
- Prostate cancer
- Cautions in liver disease
- CHF
Bicalutamide
Flutamide
Anti-androgens
- receptor inhibitors
- Competitive inhibitor of androgen receptors
- Oral
- Prostate cancer
- Precocious puberty
- Side effects: gynecomastia, hot flushes, impotence,
hepatoxicity
Spironolactone
Anti-androgens
- receptor inhibitors
- Mineralocorticoid receptor antagonist used mainly as K+-sparing diuretic; also has androgen-receptor antagonist activity
- Hirsutism in women
Mineralocorticoid receptor antagonists
K+-sparing agents
Competitively inhibit mineralocorticoid (aldosterone) receptors in the distal convoluted tubule to promote sodium and water excretion and potassium retention
- Natriuresis (Na+ reabsorption ↓)
- K+ and H+ retention (hyperkalemic metabolic acidosis)
- Oral
- Slow onset and offset of effect
- Duration of action 24-48 h’
- Weak antagonist of androgen receptor
- Hyperaldosteronism (Conn’s syndrome, secondary)
- Hypokalemia caused by K+-wasting diuretics
- Congestive heart failure (also reduce mortality) (2nd line)
- Antiandrogenic effects (female hirsutism, PCOS)
- Side effects: hyperkalemic metabolic acidosis,
anti-androgenic effects (gynecomastia, impotence)
Anti-hypertensive double/triple therapy
- Initial approach →
ACE inhibitor or ARB + Ca2+-channel blocker or diuretic
- If resistant, progress with →
ACE inhibitor or ARB + Ca2+-channel blocker + diuretic
- If resistant, add additional agent →
Spironolactone or β-blocker
HF:
- reduce muscle remodelling
- improve survival
Finasteride
Anti-androgen
5α-reductase inhibitors
Catalyzes the conversion of testosterone into dihydrotestosterone in DHT-dependent tissues (prostate, hair-follicles)
- Oral
- Since it does not interfere with testosterone action, less likely than other drugs to cause impotence, infertility, and loss of libido
- Benign prostatic hyperplasia
- Prevent male baldness (low dose)
Goserelin
Leuprolide
- Synthetic peptide with GnRH agonist activity
- Parenteral
- Long-acting
- Continuous administration of GnRH agonists suppresses gonadotropin secretion and thereby inhibits ovarian production of estrogens and progesterone
→ inhibits the release of FSH and LH → both androgen and estrogen syntheses are reduced
indications:
- Ovarian suppression in women undergoing controlled ovulation induction
- Ovarian suppression in endometriosis, leiomyoma
- Central precocious puberty
- Prostate cancer
- Breast cancer
Side effects:
- headache,
- nausea,
- injection site reaction,
- symptoms of hypogonadism with continuous treatment (impotence in male)
Degarelix
Degarelix
- GnRH antagonist
- Parenteral
- GnRH receptor inhibition → altered release FSH and LH → testosterone synthesis ↓
- Prostate cancer
- Controlled ovarian stimulation (suppress endogenous LH and FSH) (1st stage)
Side effects:
- Nausea, vomiting
- Headaches
