Son gonad-13

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  • 1. Erkek reme Sistemi Seksel farkllama Virilizasyon Pubertedeki hormonal deiimi Spermatogenez Fertiliteyi regle eder

2. LHGonadotropin reglasyonu Seksel diferansiyonHedef hcre TT5-a-redktazTRWolf stimlasyonu Eksternal virilizasyon Pubertede sekselDHTolgunlama testisREestradiol Androjen etki mekanizmas 3. Serbest testosteron-Eksternal genital organ geliimi -Prostat bymesi -Akne -Yz ve vcut kllanmas -Kafa derisinde sa kayb-Wolf kanal uyarlr -Kemik formasyonu -Kas kitlesi -Spermatogenez-Hipotalmopititer feedback -Kemik rezorpsiyonu Epifizlerin kapanmas -Jinekomasti -Vaskler etkiler -Davransal etkiler 4. T sekresyonu, tanmas: T, testislerde 20 ug depolanr. %38i albumine, %60 SHBG (TeBG) bal olarak tanr. %1-3 serbesttir. Albuminden ayrlan ksm ve serbest T bioavailable T olarak adlandrlr, hcreye kolayca girer. SHBGi arttranlar: -estrojen, tamoksifen, fenitoin, tiroid hor kullanm, hipertiroidi, siroz. SHBGi azaltanlar: -eksojen androjen, glukokortikoid, byme hor, akromegali, hipotiroidi, obezite 5. A perif metabolizmas: T, 5-alfa redktaz ile DHTa dnr. KCde metabolize olur, androsteron, etiocholanolone mg, glukuronik veya slfirik asitle konjuge olur, idrarla 17 ketosteroid eklinde artlr. %20-30u gonad kaynakl. testisadrenalperiferikT95% of Chinese men. Because of concern about long-term adverse effects of supraphysiologic testosterone doses, regimens that combine other gonadotropin inhibitors, such as GnRH antagonists and progestins with replacement doses of testosterone, are being investigated. Oral etonogestrel daily in combination with intramuscular testosterone decanoate every 46 weeks induced azoospermia or severe oligozoospermia (sperm density 19) or with baseline prostate-specific antigen (PSA) >3 ng/mL without a urologic evaluation. Testosterone replacement should not be administered to men with baseline hematocrit 50%. Testosterone can induce and exacerbate sleep apnea because of its neuromuscular effects on the upper airway. Testosterone should not be administered to men with congestive heart failure with class III or IV symptoms. 79. Monitoring Potential Adverse Experiences The clinical effectiveness and safety of testosterone replacement therapy should be performed 3 and 6 months after initiating testosterone therapy and annually thereafter (Table 340-5). Potential adverse effects include acne, oiliness of skin, erythrocytosis, breast tenderness and enlargement, leg edema, induction and exacerbation of obstructive sleep apnea, and increased risk of prostate cancer, though it may increase the incidence of detection rather than the actual occurrence rate. In addition, there may be formulation-specific adverse effects such as skin irritation with transdermal patch, risk of gel transfer to a sexual partner with testosterone gels, buccal ulceration and gum problems with buccal testosterone, and pain and mood fluctuation with injectable testosterone esters. 80. Hemoglobin Levels Administration of testosterone to androgen-deficient men is typically associated with a 35% increase in hemoglobin levels, but the magnitude of hemoglobin increase may be greater in men who have sleep apnea, a significant smoking history, or chronic obstructive lung disease. Erythrocytosis is the most frequent adverse event reported in testosterone trials in middle-aged and older men and is also the most frequent cause of treatment discontinuation in these trials. The frequency of erythrocytosis is higher in older men than younger men and higher in hypogonadal men treated with injectable testosterone esters than in those treated with transdermal formulations, presumably due to the higher testosterone dose delivered by the typical regimens of testosterone esters. If hematocrit rises above 54%, testosterone therapy should be stopped until hematocrit has fallen to 2 years; a change of >0.40 ng/mL per year merits closer urologic follow-up. 82. Cardiovascular Risk Assessment The long-term effects of testosterone supplementation on cardiovascular risk are unknown. Testosterone effects on lipids depend on the dose (physiologic or supraphysiologic), the route of administration (oral or parenteral), and the formulation (whether aromatizable or not). Physiologic testosterone replacement by an aromatizable androgen has a modest effect on HDL or no effect at all. In middle-aged men with low testosterone levels, physiologic testosterone replacement has been shown to improve insulin sensitivity and reduce visceral obesity. In epidemiologic studies, testosterone concentrations are inversely related to waist-to-hip ratio and directly correlated with HDL cholesterol levels. These data suggest that physiologic testosterone concentration is correlated with factors associated with reduced cardiovascular risk. However, no prospective studies have examined the effect on testosterone replacement on cardiovascular risk. 83. Androgen Abuse by Athletes and Recreational BodybuildersThe illicit use of androgenic steroids to enhance athletic performance is widespread among professional and high school athletes and recreational bodybuilders. Although androgen supplementation increases skeletal muscle mass and strength, whether and how androgens improve athletic performance is unknown. The most commonly used androgenic steroids include testosterone esters, nandrolone, stanozolol, methandienone, and methenolol. Athletes generally use increasing doses of multiple steroids in a practice known as stacking. A majority of athletes who abuse androgenic steroids also use other drugs that are perceived to be muscle-building or performance-enhancing, such as growth hormone; IGF-1; insulin; stimulants such as amphetamine, clenbuterol, ephedrine, and thyroxine; and drugs perceived to reduce adverse effects such as hCG, aromatase inhibitors, or estrogen antagonists. The adverse effects of androgen abuse include a marked decrease in plasma HDL cholesterol and an increase in LDL cholesterol, changes in clotting factors, suppression of spermatogenesis resulting in reduced fertility, and increase in liver enzymes. Elevations of liver enzymes, hepatic neoplasms, and peliosis hepatis have been reported, mostly with the use of oral, 17- alkylated androgenic steroids but not with parenterally administered testosterone or its esters. There are anecdotal reports of the association of androgenic steroid use with "rage reactions." Breast tenderness and enlargement are not uncommon among athletes abusing aromatizable androgens. Oral 17- alkylated androgens also can induce insulin resistance and glucose intolerance. A serious, underappreciated adverse effect of androgen use is the suppression of the hypothalamic-pituitary-testicular axis. Upon discontinuation of exogenous androgen use, the suppressed hypothalamic-pituitary axis may take weeks to months to recover. During this period when testosterone levels are low, the athletes may experience sexual dysfunction, hot flushes, fatigue, and depressed mood, causing some athletes to resume androgen use and thus perpetuating the cycle of abuse, withdrawal symptoms, and dependence. Also, the use of nonsterile needles confers the risk of local infection, sepsis, hepatitis, and HIV infection. Disproportionate gains in muscle mass and strength without commensurate adaptations in tendons and other connective tissues may predispose to the risk of tendon injuries. Accredited laboratories use gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to detect anabolic steroid abuse. In recent years, the availability of high-resolution mass spectrometry and tandem mass spectrometry has further improved the sensitivity of detecting androgen abuse. Illicit testosterone use is detected generally by the application of the measurement of urinary testosterone to epitestosterone ratio and further confirmed by the use of the 13C:12C ratio in testosterone by the use of isotope ratio combustion mass spectrometry. Exogenous testosterone administration increases urinary testosterone glucuronide excretion and consequently the testosterone to epitestosterone ratio. Ratios above 6 suggest exogenous testosterone use but can also reflect genetic variation. Synthetic testosterone has a lower 13C:12C ratio than endogenously produced testosterone and these differences in 13C:12C ratio can be detected by isotope ratio combustion mass spectrometry, which is used to confirm exogenous testosterone use in individuals with a high testosterone to epitestosterone