Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6-15% of osteoporosis and of 25-48% of osteopenia. Reduced bone mass has been described since adolescence and it might be related to both reduced bone formation and higher bone resorption. Although reduced testosterone levels are clearly involved in the pathogenesis, this relation is not always evident. Importantly, fracture risk is increased independently from bone mineral density (BMD) and testosterone levels. Here we discuss the pathogenesis of osteoporosis in patients with KS, with a particular focus on the role of testosterone and testis function. In fact, other hormonal mechanisms, such as global Leydig cell dysfunction, causing reduced Insulin-like factor 3 (INSL3) and 25-OH vitamin D levels, and high FSH and estradiol levels, might be involved. Furthermore, genetic aspects related to the supernumerary X chromosome might be involved, as well as androgen receptor expression and function. Notably, body composition, skeletal mass and strength, and age at diagnosis are other important aspects. Although Dual-Energy X-ray Absorptiometry (DXA) is recommended in the clinical workflow for patients with KS to measure BMD, recent evidence suggests that alterations in the microarchitecture of the bones and vertebral fractures might be present even in subjects with normal BMD. Therefore, analysis of trabecular bone score (TBS), high resolution peripheral quantitative CT and vertebral morphometry seem promising tools to better estimate the fracture risk of patents with KS. This review also summarizes the evidence on the best available treatments for osteoporosis in men with KS, with or without hypogonadism.
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Giuseppe Grande, Andrea Graziani, Antonella Di Mambro, Riccardo Selice, and Alberto Ferlin
Willem de Ronde and Diederik L Smit
experience, we discuss the management of steroid abuse and give treatment recommendations for the clinical endocrinologist. What are AAS? AAS comprise a group of compounds that are structurally similar to testosterone and have similar actions when
Alessandra Gambineri and Carla Pelusi
androgens, in both sexes, there are different synthesis pathways; a classic pathway where testosterone is synthesized directly in testicular Leydig cells in men and ovarian theca cells in women. Androgens are parallel produced from Δ5- and Δ4-precursors, and
Miranda Scharff, Chantal Maria Wiepjes, Maartje Klaver, Thomas Schreiner, Guy T’Sjoen, and Martin den Heijer
oral estradiol valerate a day or 100 µg/24 h estradiol patch twice a week. People older than 40 years were advised to be treated with transdermal estrogens, because of thrombosis risk ( 12 ). Transmen were treated with testosterone. They could choose
Christos Tsatsanis, Angel Elenkov, Irene Leijonhufvud, Katerina Vaporidi, Åsa Tivesten, and Aleksander Giwercman
to be regulated by sex hormones. BAFF suppression by testosterone has been demonstrated in animal studies and indirectly in humans when comparing men with high and low testosterone levels ( 4 ). In contrast, estrogens have been demonstrated to induce
Andre Madsen, Anders Juul, and Lise Aksglaede
the study period as previously described ( 19 ). Serum concentrations of total testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), androstenedione (4A), SHBG, follicle-stimulating hormone (FSH), luteinizing hormone
Yael Sofer, Nava Nevo, Michal Vechoropoulos, Gabi Shefer, Etty Osher, Nathan Landis, Karen Tordjman, Geoffrey L Hammond, and Naftali Stern
glucose, insulin, lipids, liver enzymes and testosterone levels. A glucose tolerance test (GTT) was done after an overnight fast with an intra-peritoneal injection of glucose (2 mg/kg). Glucose was measured at the following time points: 0, 15, 30, 60, 90
Lukas Ochsner Ridder, Agnethe Berglund, Kirstine Stochholm, Simon Chang, and Claus H Gravholt
(follicle-stimulating hormone, luteinizing hormone) and 65–85% of KS patients having decreased testosterone levels ( 6 ). KS patients may have signs of hypogonadism regardless of testosterone levels within the normal range. Even though current guidelines
Dorte Glintborg, Hanne Mumm, Jens Juul Holst, and Marianne Andersen
free testosterone ( 14 ). OCP may increase body weight ( 15 ) and insulin resistance ( 14 , 16 ), which could be associated with decreased GLP-1 levels. In contrast, animal studies suggested that estradiol and progesterone treatment could increase the
Jan Roar Mellembakken, Azita Mahmoudan, Lars Mørkrid, Inger Sundström-Poromaa, Laure Morin-Papunen, Juha S Tapanainen, Terhi T Piltonen, Angelica Lindén Hirschberg, Elisabet Stener-Victorin, Eszter Vanky, Pernille Ravn, Richard Christian Jensen, Marianne Skovsager Andersen, and Dorte Glintborg
PCOS is undetermined. Testosterone levels could be an important modifier of vascular health in PCOS, but whether testosterone has a protective or unfavorable impact on the risk of CVD in PCOS is debated ( 7 , 15 ). We are not aware of studies
