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27 Cards in this Set
- Front
- Back
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Testosterone is the principal androgen in male circulation. What are the precursors? Do they have any andgrogenic action?
Is testosterone a precursor for any other active compounds? |
Androstenedione and DHEA are weak androgens.
Dihydrotestosterone is produced from testosterone and is a highly potent androgen. |
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Where is GnRH produced? How is it secreted? Where does it go?
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GnRH is produced in the hypothalamus and secreted into the hypothalamic-pituitary portal system. It is secreted in pulses every 90-120 minutes. Testosterone feeds back and inhibits release of GnRH and FSH/LH.
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The majority of testicular volume is made up of?
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Seminiferous tubulues with mature sperm and sertoli cells. Small testes indicates deficiency in these elements.
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Starting with cholesterol, describe androgen biosynthesis.
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Cholesterol is transported into cells (thanks to ACTH and LH).
Cholesterol --> Pregnenelone Pregnenelone --> progesterone (3-betahydroxysteroid dehydrogenase) Progesterone --> androstenedione (two step- 17 beta hydroxylase) UP TILL THIS POINT- processes in testes and adrenals are identical Androstenedione --> testosterone (17 beta hydroxysteroid dehydrogenase) |
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95% of testosterone is secreted by?
Where is the rest synthesized? Are any of the intermediates active androgens? |
Leydig cells
Adrenals Dihydroepiandrosterone and androstenedione are WEAK androgens |
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what is the fate of testosterone? Is it active?
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Testosterone is active and can interact with receptors. However, some testosterone is converted to dihydrotestosterone by 5-alpha reductase and some is converted to estrogen by aromatase.
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Is most testosterone found in the free or bound state? What does it bind to? What is the definition of bioavailable testosterone?
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Most testosterone (98%) is bound to plasma proteins (40% bound to sex hormone binding globulin and the rest weakly bound to albumin) + 2% is free and bioactive.
Bioavailable testosterone refers to the amount of free testosterone + the amount of testosterone bound to albumin. |
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What are the targets/roles of testosterone/DHT/estrogen?
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Testosterone- targets Wolffian duct, brain, muscle, spermatogenesis, libido
DHT- external genitalia, body hair, prostate Estrogen- maintains bone strength |
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Notable causes of primary hypogonadism
Secondary |
Klinefelters, cryptorchidism, Mumps orchitis (during adulthood), torsion, aging
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What are the effects of aging on gonads
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Decline in leydig cell number and volume, impaired hormone synthesis, decreased spermatogenesis and sperm motility, decreased free testosterone level
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What is Kallman's syndrome
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An x-linked congenital abnormality that gives rise to secondary hypogonadism.
in X linked form, deletion of gene on X chromosome short arm, lack of expression of KALIG-1 molecule (inability of GnRH secreting neurons to migrate to hypothalamus --> deficient GnRH secretion) |
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Other notable congenital causes of secondary hypogonadism?
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Prader Willi, Laurence-Moon-Bardet-Biedl syndrome
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Other acquired conditions that give rise to secondary hypogonadism?
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Mass lesion of pituitary or hypothal, infiltrative disease (sarcoidosis, histiocytosis X, hemochromatosis), pituitary apoplexy/infarct
Also androgen insensitivity syndrome and androgen abuse |
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Other than secondary hypogonadism, what physical findings are seen in Kallman's syndrome?
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Red-green color blindness, midline facial abnormalities and sensorineural hearing loss
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What are the manifestations of a person with primary hypogonadism affecting them in utero?
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Depending on deficiency of testosterone- varies (hypospadias/partial virilization/ambiguous/female external genitalia)
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What are the manifestations of a person with secondary hypogonadism? Why?
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The problem is higher up (hypothalamic), will have normal differentiation of external genitalia. HCG is responsible for differentiation of external genitalia in first trimester (not GnRH).
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What are the manifestations of androgen deficiency in third trimester?
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Micropenis, otherwise normal male differentiation.
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Manifestations of androgen deficiency before anticipated onset of puberty?
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Delayed or absent puberty with:
Absence of development of sexual hair, absence of deepening of voice, absence of increased muscle mass/libido, euchnoid proportions |
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What are eunuchoid proportions?
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Lower body segment is more 5 cm greater than upper body segment and arm span is 5 cm longer than height
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Manifestations of androgen deficiency after puberty/during adulthood?
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Decrease in libido/erectile dysfunction/decrease energy/decrease in bone mineral density/changes in body composition/decrease in lean body mass and increased body fat
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Which is more likely to cause decreased sperm production & gynecomastia- primary or secondary hypogonadism?
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Primary hypogonadism
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What is Tanner staging?
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A scale which defines physical measurements of development based on external primary and secondary sexual characteristics (size of genitalia and development of sexual hair)
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Define a fertile sample in a sperm count. When is a sample considered abnormal?
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>20 million/cc and motility in >50%. If abnormal samples are measured on 3 separate occasions during a 3 month period, something is abnormal.
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Effects of testosterone replacement in hypogonadal men?
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Improves libido and sexual performance, increases bone mineral density, increased lean body mass and decreased body fat
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Side effects of testosterone
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Acne, gynecomastia, testicular atrophy with prolonged treatment.
RBC mass increases and hyperviscosity syndrome can cause HEART FAILURE, STROKE, SLEEP APNEA |
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Can testosterone replacement be used in men with prostate cancer?
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NO!!! Absolutely contraindicated. But testosterone does not increase risk of prostate cancer.
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If restoring fertility is the goal of treatment, what should be given? How is it dosed?
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GnRH will be administered in a pulsatile manner with a pump. GnRH cannot be given continuously as it will downregulate receptors and decrease FSH/LH production.
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