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Testosterone, an androgen responsible for male secondary sexual characteristics, is produced primarily in the testes (95%) and also in small amounts by the adrenal glands (5%). Testosterone is the main sex hormone for men, regulating various functions such as libido, bone density, red blood cell count, male characteristics, and male behaviors. Testosterone is also the fundamental hormone in the regulation of prostate cancer growth. Blood levels of total testosterone are composed of bound and free forms of testosterone. Most of the circulating testosterone is bound to either albumin or sex hormone-binding globulin (SHBG). As its name implies, most of the sex hormones in males and females are bound to SHBG, a protein produced by the liver, as they circulate through the body. In addition to protection from degradation, SHBG serves to regulate the amount of free testosterone that is available for biological activity by keeping it bound and therefore inactive. Free testosterone is the metabolically active form of testosterone that carries out the biological functions that are associated with its activity.3 For the purpose of this manuscript, the terms free testosterone and bioavailable testosterone are synonymous and are used that way throughout.
Obviously, one of the limitations to the standardization of free and total testosterone levels constitutes the assays used to measure them. There may be assay differences related to the ability to detect low levels of the forms of the hormone in the blood. The primary techniques utilized for the measurement of testosterone are liquid chromatography-mass spectrometry (LC/MS), RIA, and chemiluminescence. The assays and associated instrumentation used to measure testosterone are important to consider because of the reliability, accuracy, sensitivity, ability to be standardized, and comparability of the results, when making any conclusions regarding clinically appropriate testosterone levels and cutoffs to define castration.
Termed the gold standard by the Endocrine Society, LC/MS is a technique from analytical chemistry with huge potential for clinical use.8 There are validated LC/MS methods that measure free and total testosterone.10 The advantages of using LC/MS include higher sensitivity, higher precision, analytical specificity, performance, and excellent diagnostic ability.11 Disadvantages include that it is more expensive than RIA, there is a lack of standardization and generalizability, and that noise may influence the machinery's extreme sensitivity. In order to obtain clinical proficiency as measured by the US Centers for Disease Control and Prevention (CDC) certification for standardization, laboratories have to demonstrate a mean bias of 6.4%.12
Only 2% of all testosterone in the body is unbound and free. According to the free hormone hypothesis, only the 2% of testosterone which is free can diffuse into cells and bind to the AR.25 As free testosterone is the biologically active form of testosterone, it should be given more attention in the treatment of PCa.
A cross-sectional study evaluating assays which measure free testosterone, the goal of which was to determine the concordance of the various assays to one another, was conducted on fifty males.26 This study demonstrated that there was a significant correlation among the free testosterone index, free testosterone by EqD, and bioavailable testosterone. The free testosterone value was calculated by the Vermeulen method, a formula relying on the total testosterone and SHBG values obtained from immunoassay.27 This approach is a practical measure of bioavailable testosterone as a result of its simplicity and efficiency in detecting hypogonadism.26
Patients with advanced PCa that achieve lower free testosterone levels have been shown to have overall better survival rates.5 Despite these findings, more studies need to be conducted examining the levels of serum free testosterone and determining any correlations with PCa disease progression. A study published in Oncology Letters examining a group of 34 patients illustrated that the mean free testosterone was a significant prognostic factor of cancer-specific survival; also, cancer-specific survival (43.6 vs 17.3 months, P = 0.0063) was statistically significantly longer in patients with free testosterone levels below the cutoff level than patients above it.24 Thus, suppressing biologically active testosterone (free testosterone) would appear to be a primary goal of ADT.
A comprehensive literature search was conducted to identify and analyze all studies measuring free and total testosterone. Information collected includes the type of ADT used, the number of patients, the timing of the measurement, the method/assay of measurement, patient demographics, and length of time on ADT, if available. Unfortunately, from our review of the literature, only four published studies4,28,29,30 directly addressed these important points, the summaries of which are included here.
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Big Sister Davina McCall filled us in as the multi-pierced peroxide-blond former basketballer and wrestler, Dennis Rodman, exited his limo and entered the house (in men's clothes, sadly, rather than the crack-whore duds he seems to favour on his tranny days). He'd been partying at Stringfellows - of course - until the early hours. He'd brought extra large condoms and no underwear. He made his first movie with Mickey Rourke and Jean Claude Van Damme, which tells you all you need to know about his post-basketball movie career. He's also known as \"Worm\", apparently because, like a ringworm, he gets under your skin.
however, in a post-sexual revolution sex positive rich western societies, prostitution is not exploitation, it is vocation. as long as prostition is freely chosen by its participants, and there is no duress for them to get into it or stay there, then prostitution is not female disempowerment. it is not economic exploitation if the participant freely chooses the money that is being made there and has a range of economic choices and can get out any time they like
still, there needs to be more oversight of prostitution to make sure its participants are freely choosing the vocation, rather than being forced into it, which is still possible, and does still go on in rich western societies
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