Term
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Definition
| testosterone, androstenedione, and dehydroepiandrosterone (DHEA - sold as a supplement) |
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Term
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Definition
| this enzyme is involved in some estrogen production |
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Term
| where are the androgens produced? |
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Definition
| in the testes (leydig cells), adrenal glands, and the ovaries (theca cells). they are then transported to target tissues. |
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Term
| what is the major product of the testis? at what rate? how much is stored? |
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Definition
| testosterone is produced at a rate of 5-7 mg/day and 9 ug is stored in the testis. |
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Term
| where is testosterone produced in women? at what rate? |
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Definition
| testosterone is produced in the ovaries and adrenals in women at a rate of .25 mg/24 hrs (may be higher in some women and interrupt the menstrual cycle). |
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Term
| does testosterone production include CYP? |
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Definition
| yes, progesterone is converted to androstenedione via CYP. this plays a role in some of the drugs prescribe for prostate CA (want to reduce testosterone production). |
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Term
| what happens to testosterone when it reaches the prostate? what is the implication of this for anti-prostate CA drugs? |
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Definition
| *5-alpha reductase metabolizes testosterone to 5-alpha dihydro-testosterone (DHT) in the prostate. (5 alpha reductase also does this in the testes, hair follicles, and adrenal glands - but testosterone is unchanged muscle/kidney). b/c in prostate CA testosterone levels need to be lower - this enzyme is often the target of anti-prostate CA drugs. |
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Term
| is DHT more powerful than testosterone? |
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Definition
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Term
| what is testosterone production stimulated by? |
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Definition
| luteinizing hormone (LH), which is produced by the anterior pituitary. receptors for LH are found on leydig cells. estradiol is also stimulated by LH. |
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Term
| what is the path of hormonal stimulation for the androgen production in the gonads? |
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Definition
| hypothalamus: gonadotropin releasing hormone -> pituitary: LH/FSH -> gonads: testosterone, estrogen, progesterone |
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Term
| what is the path of hormonal stimulation for the androgen production in the adrenal cortex? |
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Definition
| hypothalamus: corticotropin releasing hormone -> pituitary: adrenocorticotropin -> adrenal cortex: glucocorticoids, mineralocorticoids, and androgens (5% of testosterone) |
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Term
| what is the function of the sertoli cells? how are they regulated hormonally? |
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Definition
| the sertoli cells are where spermatogenesis occurs as well as production of transferrin (androgen-binding) and inhibin (negative feedback for FSH) occur. the sertoli cells are primarily stimulated by FSH from the anterior pituitary. |
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Term
| what androgens are produced by the adrenal glands? |
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Definition
| dehydro*epi*androsterone, androstenedione and testosterone |
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Term
| what does adrenocorticotropin stimulate production of? |
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Definition
| adrenocorticotropin stimulates production of cortisol and sex steroids by the adrenals |
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Term
| what is sex hormone binding globulin? what agents increase its levels? |
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Definition
| sex hormone binding globulin is a serum glycoprotein derived from the liver which strongly binds to testosterone - inactivating it, and thus regulating its bioavailability in circulation. *estrogen will increase its levels (females 2-3 x males) as will *thyroxine. *androgens, growth hormone, and insulin will decrease sex hormone binding globulin levels. |
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Term
| what are the pharmacological actions of anabolic steroids (subgroup of androgens)? |
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Definition
| stimulation of sperm production, erythropoiesis, positive nitrogen balance, and growth/development of hair/bone/muscle. |
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Term
| what is the major clinical use of anabolic steroids? |
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Definition
| primary testicular insufficiency |
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Term
| what are the available injectable androgen products? |
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Definition
| testosterone cypionate (2-3 wks), testosterone enanthate (2-3 wks), and testosterone propionate (1-3 days). these are all IM injection and have rapid biotransformation. |
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Term
| what is the transdermal androgen product available? ADRs? |
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Definition
| the transdermal testosterone patch is applied to scrotum/abdominal/upper arm skin and is thinner than the epidermis. FDA warning: accelerated development of 2ndary sex characteristics in young pediatric pts in contact w/pt using this product. |
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Term
| what are the androgen products "out there"? |
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Definition
| fluoxymesterone, oxandrolone, oxymetholone, methyltestosterone, and nandrolone |
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Term
| what are the anabolic steroids? |
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Definition
| a subgroup of androgens, synthetic derivatives of testosterone which have more *anabolic action than androgenic. this includes: increased muscle mass, increased physical performance, and increased linear growth in children. |
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Term
| what are the anabolic steroid products available? |
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Definition
| oxandrolone, oxymetholone, and stanozolol |
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Term
| how can androgen therapy help treat pts with primary testicular failure? |
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Definition
| androgen therapy increases expression of secondary sex characteristics: hair/beard growth, deepening of voice, muscle development, and phallic enlargement in boys. however androgen therapy will not help with infertility. |
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Term
| what is secondary testicular failure? can androgens be used to treat it? |
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Definition
| secondary testicular failure: insufficient stimulation of the testes by pituitary gonadotropins or hypogonadotropic hypogonadism. androgens can be used to treat this. |
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Term
| can androgens be given to short children/teenagers to increase height? |
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Definition
| yes, though this is controversial due to the fact that the role of androgens is not completely established, and the fact that androgens can cause premature closure of epiphyseal plates (if too much is used and negative feedback gets tripped) as well as virilization. if androgens are used for short children/teens, growth hormone is preferably combined (better mimics the natural system). |
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Term
| why might androgens be used to tx aplastic anemia? |
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Definition
| androgens can increase stimulation of erythropoiesis |
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Term
| can androgens be used to tx inoperable breast CA? |
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Definition
| yes, which will decrease estrogen levels |
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Term
| can androgens be used to tx malnutrition? |
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Definition
| yes, this will help stave off protein breakdown in critical areas such as heart muscle |
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Term
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Definition
| a weaker androgen used to tx endometriosis, fibrocystic breast disease and PMS (MOA: reduction of estrogen) |
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Term
| is there an association between lower endogenous testosterone levels and fall risk in elderly pts? |
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Definition
| yes. lower endogenous testosterone levels did not correlate w/overall performance - just fewer falls. |
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Term
| how has testosterone supplementation been shown to affect MS pts? |
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Definition
| MS pts treated w/testosterone (12 mo of 100 mg testosterone in a 10 g gel daily) showed an increased cognitive performance, slowing of brain atrophy, and an increase in lean body mass. |
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Term
| what ADRs are associated with androgen supplementation? |
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Definition
| priapism, suppression of gonadotropin, gynecomastia, wt gain, Na+ retention (edema/HTN), decreased HDLs (possible *atherosclerosis), hepatoxicity (jaundice/*peliosis hepatitis*/hepatocellular CA), virilization (stop if appears: irreversible), BPH/prostatic CA, and decreased size of testis/spermatogenesis (due to negative feedback). *ADRs: dose-related* |
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Term
| can androgens ever be prescribed to pregnant pts? |
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Definition
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Term
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Definition
| a feeling of invincibility to physical challenges associated w/androgen |
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Term
| can anabolic drugs also cause inappropriate enlargement of genitalia (penis/clitoris), premature development of pubic hair, advanced bone age (restricts growth), increased libido, and aggressive behavior? |
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Definition
| yes - this has to be included on androgel/tesim boxes now |
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Term
| can testosterone supplements increase prostate CA growth/metastasis? |
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Definition
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Term
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Definition
| a possible ADR associated w/anabolic steroid use |
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Term
| what are male contraindications for androgen supplementation? |
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Definition
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Term
| what are female contraindications for androgen supplementation? |
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Definition
| pregnancy (known/suspected) |
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Term
| what are contraindications for androgen supplementation in all pts? |
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Definition
| serious cardiac, hepatic or renal disease |
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Term
| what are the 2 different kinds of anti-androgen action? what might these be used for? |
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Definition
| suppression of androgen synthesis or blockade of androgen receptors. possible application: tx of androgen stimulated tumors. |
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Term
| what anti-androgens are used to suppress androgen synthesis? what is their MOA? |
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Definition
| goserelin, leuprolide, and nafarelin are gonadotropin releasing hormone analogues which inhibit androgen synthesis via negative feedback inhibition. |
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Term
| what are indications for goserelin, leuprolide, and nafarelin, the gonadotropin releasing hormone analogues? ADRs? |
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Definition
| prostate CA pts. ADRs: small increased risk for DM, heart attack, stroke, and sudden death. |
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Term
| what characterizes leuprolide? why might it cause increased testosterone synthesis at the start of tx? does it treat the prostate CA or it's symptoms? how can it be used to tx women/children? |
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Definition
| this synthetic nona-peptide analog of GnRH suppresses synthesis of androgens via negative feedback. there is an *initial increase in testosterone levels (worsening of symptoms) at the start of tx* until the body adjusts to what is happening. leuprolide will tx the symptoms of prostate CA (decreases testosterone), but *not the CA itself. leuprolide will also tx symptoms of endometriosis in women (decreases estrogen), but is category X for pregnant pts. leuprolide can also be used to tx precocious puberty in children. |
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Term
| what characterizes goserelin as an anti-androgen? |
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Definition
| this is installed as an implant and is a synthetic decapeptide analogue of *luteinizing hormone-releasing hormone* - also known as a GnRH agonist analogue. it is used as palliative tx for advanced prostate CA. |
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Term
| what characterizes nafarelin as an anti-androgen? |
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Definition
| nafarelin is a nasal spray and *powerful GnRH agonist analog which suppresses synthesis of androgens via negative feedback. used BID, after 4 wks (and an initial increase in androgens), gonadal steroidogenesis will decrease. nafarelin is used for hormonal mangement of endometriosis - *including pain relief and reduction of endometric lesions (can treat the problem rather than just giving pt NSAIDs or narcotics). |
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Term
| how can ketoconazole be used as an anti-androgen? |
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Definition
| ketoconazole reduces CYP in testicular microsomes, which reduces synthesis and hydroxylation of androgens. this can give some feminizing effects such as gynecomastia/impotence/oligospermia. it is being investigated in tx for prostate CA or GnRH-independent precocious puberty in boys. |
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Term
| what is the MOA for 5-alpha reductase inhibitors as an anti-androgen? |
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Definition
| 5-alpha reductase inhibitors decrease the biotransformation of steroid precursors to active androgens - *DHT, not testosterone is active in the prostate |
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Term
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Definition
| finasteride is a PO steroid-like inhibitor of 5-alpha reductase, which can decrease DHT levels in 8 hrs and lasts 24 hrs (40-50% metabolized). finasteride looks very similar to androgens, which is why it is able to block their processing enzyme. |
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Term
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Definition
| similar to finasteride, but a slower onset of action and a greater half-life |
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Term
| what is flutamide? major ADR? |
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Definition
| a nonsteroidal androgen receptor *blocker which is used w/LHRH agonists in tx of prostatic/metastatic CA. major ADR: hepatic injury (not recommended w/ALT > 2x ULN) |
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Term
| can spironolactone be used to block androgen receptors? |
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Definition
| yes. it is a steroid and also decreases CYP in testicular microsomes. |
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