title: Late-onset hypogonadism: beyond testosterone.
abstract: Late-onset hypogonadism is defined as a combination of low testosterone (T) levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell (dys)function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone (LH) and 25-hydroxyvitamin D levels. These markers help in identifying the so-called "subclinical" hypogonadism (normal T, high LH levels). Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option (cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D) in these patients. We studied 66 patients with classic hypogonadism (total T [TT] <12 nmol l-1 , LH ≥ 8 IU l-1 ) (n = 26) and subclinical hypogonadism (TT ≥ 12 nmol l-1 , LH ≥ 8 IU l-1 ) (n = 40) and low 25-hydroxyvitamin D (<50 nmol l-1 ). Subjects received cholecalciferol (5000 IU per week) (n = 20) or calcidiol (4000 IU per week) (n = 46), and 25-hydroxyvitamin D and parathyroid hormone (PTH) were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PTH levels in both groups of men with hypogonadism (primary, n = 16 and subclinical, n = 30), whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D (calcidiol), and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism.
authors.affiliation: Department of Medicine and Centre for Human Reproduction Pathology, University of Padova, Padova 35128, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
authors.forename: Aldo E
authors.initials: AE
authors.lastname: Calogero
authors.forename: Francesco
authors.initials: F
authors.lastname: Lombardo
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferlin
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002112:Calcifediol / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000627:therapeutic use*; D005058:Eunuchism / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D057285:Precision Medicine; D013739:Testosterone / Q000097:blood / Q000172:deficiency*; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D015415:Biomarkers; D010281:Parathyroid Hormone; D014807:Vitamin D; D002762:Cholecalciferol; D013739:Testosterone; D007986:Luteinizing Hormone; C104450:25-hydroxyvitamin D; D002112:Calcifediol