Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively. It is bound 65% to sex hormone-binding globulin (SHBG) and 33% bound weakly to albumin. The plasma protein binding of testosterone is 98.0 to 98.5%, with 1.5 to 2.0% free or unbound. The amount of testosterone synthesized is regulated by the hypothalamic–pituitary–testicular axis (Figure 2). In the final and rate limiting step, the C17 keto group androstenedione is reduced by 17β-hydroxysteroid dehydrogenase to yield testosterone. In contrast to testosterone, DHEA and DHEA sulfate have been found to act as high-affinity agonists of these receptors. Testosterone has been found to act as an antagonist of the TrkA and p75NTR, receptors for the neurotrophin nerve growth factor (NGF), with high affinity (around 5 nM). For these individuals, testosterone might be a causative rather than symptomatic treatment for their hypertension. For the same reason but in a reverse way, the statistically significant side-effect of testosterone replacement therapy does not mean that the side-effect occurs in all the individuals. Rather, the conclusions depend heavily on statistical analysis, which has the limitation of discounting the responses of a subpopulation within the case group. The presence of these ubiquitous steroids in a wide range of animals suggest that sex hormones have an ancient evolutionary history. They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. Immunofluorescence assays exhibit considerable variability in quantifying testosterone concentrations in blood samples due to the cross-reaction of structurally similar steroids, leading to overestimating the results. In measurements of testosterone in blood samples, different assay techniques can yield different results. In women with hyperandrogenism, mean levels of total testosterone have been reported to be 62.1 ng/dL. In women, mean levels of total testosterone have been reported to be 32.6 ng/dL. Total levels of testosterone in the body have been reported as 264 to 916 ng/dL (nanograms per deciliter) in non-obese European and American men age 19 to 39 years, while mean testosterone levels in adult men have been reported as 630 ng/dL. For example, when male and female athletes are compared when competing, no differences have been observed (Crewther et al., 2016; Jiménez et al., 2012). Moreover, skydiving is a predominantly male sport (Westman & Bjornstig, 2007) and women who choose to skydive may represent a unique female population. Second, it is possible that testosterone reactivity does differ between men and women, but differences may be obscured by sampling factors. First, it is possible that testosterone reactivity does not differ between men and women. In addition, the amount of testosterone produced by existing Leydig cells is under the control of LH, which regulates the expression of 17β-hydroxysteroid dehydrogenase. The number of Leydig cells in turn is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Testosterone is also synthesized in far smaller total quantities in women by the adrenal glands, thecal cells of the ovaries, and, during pregnancy, by the placenta.
