We were not able to fully evaluate the effects of testosterone supplementation, but found no significant differences between those that had been treated and those that had not. However, in our recent cohort study we were able to assess laboratory data related to incidence of thrombosis in men with KS (Chang, Christiansen, et al., 2019). Also, thrombin generation, an overall marker of coagulation, was lower in the 27 testosterone treated compared with 18 untreated men with KS (Chang, Biltoft, et al., 2019). The annual expenses for testosterone supplementation for a man with KS under these circumstances are currently around 2000 DKR (≈300 USD; 270 EURO). However, most prescription medications, including testosterone preparations for KS, are subject to own payment, but with a considerable public subsidy. Others argue that one should not start testosterone supplementation before serum total testosterone falls below normal ranges. Clinical practice in most countries has been that testosterone supplementation should be timed with the natural onset of puberty if testosterone production is inadequate and/or LH and follicle stimulating hormone rise above normal limits, which is the strategy that we use in our clinic (Gravholt et al., 2018). A review of the current KS literature yielded only a few studies which have focused on the impact of living with KS (Close, Fennoy, Smaldone, & Reame, 2015; de Ronde, de Haan, & Drent, 2009; Fjermestad & Stokke, 2018; Herlihy, McLachlan, et al., 2011; Skakkebaek, Moore, Chang, Fedder, & Gravholt, 2018; Turriff, Levy, & Biesecker, 2015). Although medical outcomes for patients with KS have been researched to some extent, the impact of living with KS has only been investigated sparsely. Although the oxandrolone protocol in prepubertal boys with KS tried to replicate normal physiology with consistent low-dose androgen exposure, nearly 25% of the boys Davis et al., 2018). While testosterone replacement therapy is very successful for some people, it doesn’t work for everybody. These treatments are particularly important if you have Klinefelter syndrome, a genetic condition that affects your body’s ability to produce testosterone. As more adolescent and young adult (AYA) patients with KS seek care, it becomes increasingly important to investigate their understanding of information about testosterone supplementation and infertility. The results do not support universal adoption of testosterone treatment into current clinical practice for infants with XXY. This consideration may partially explain the undertreatment of KS patients with TRT. First, the retrospective nature of our study may introduce incomplete or inaccurate capture of data. Hypogonadism poses a significant burden on the quality of life of men. A total of 1581 men (29.6%) received a laboratory measurement of their testosterone level on the day of diagnosis or later (Fig. 2). Descriptive analysis of comorbidities revealed 350 (6.5%) patients with a diagnosis of intellectual disability, 761 (14.2%) with type 2 diabetes mellitus, 995 (18.6%) with obesity, 919 (17.2%) with hypertension, 246 (4.6%) with osteoporosis, 757 (14.2%) with hyperlipidemia, 153 (2.9%) with history of pulmonary embolism, and 60 (1.1%) with a history of vascular thrombosis. There were in total 6071 men in the initial cohort with diagnosis of KS in the TriNetX database. Individuals with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone (primary testicular insufficiency). Unauthorized use of these marks is strictly prohibited. The strongest associations were with body fat, indicating that metabolic dysfunction may be a key regulator of contact activation system activity. Contact activation system mediates crosstalk between coagulation, fibrinolysis, and inflammation and may contribute to thromboinflammatory risk. While hypogonadism and metabolic dysfunction are known contributors, the role of the contact activation system in Klinefelter syndrome remains unexplored. However, in our experience, most adult men with KS have overt hypogonadism at presentation and further, by including laboratory data from Danish hospitals, we were able to demonstrate biochemical signs of hypogonadism in those men with KS without testosterone prescriptions (Chang, Christiansen, et al., 2019). Two-thirds of responders agreed that the optimal timing for initiation of testosterone supplementation in KS was between 10 and 16 years of age, although there was no real consensus on whether to monitor testosterone levels, gonadotropin levels, or to look for clinical signs of delayed puberty or hypogonadism, to decide the actual timing of initiating treatment in the individual patient (Zganjar et al., 2019). However, the impact of testosterone supplementation on biological paternity in KS is still debatable, since others do not find that testosterone treatment impairs chances of fertility (Zganjar, Nangia, Sokol, Ryabets, & Samplaski, 2019). In November 2024, Nicklow's advocacy broadened when another TikTok video addressing potential bans on gender-affirming care, including testosterone shots, also went viral. This genetic condition affects individuals assigned male at birth, characterized by an extra X sex chromosome (XXY) instead of the typical XY. As a result, some of the body's cells have the usual one X chromosome and one Y chromosome (46,XY), and other cells have an extra copy of the X chromosome (47,XXY). Autoimmune disorders are a large group of conditions that occur when the immune system attacks the body's own tissues and organs. Affected individuals also have an increased risk for attention-deficit/hyperactivity disorder (ADHD), though they tend to have problems with attention and distractability rather than hyperactivity. Affected individuals have an increased risk for learning disabilities, most commonly problems with reading (dyslexia) and written expression.
