Fabbri E, An Y, Gonzalez-Freire M, Zoli M, Maggio M, Studenski SA, et al. Bioavailable Testosterone Linearly Declines Over A Wide Age Spectrum in Men and Women From The Baltimore Longitudinal Study of Aging. J Gerontol A Biol Sci Med Sci. 2016;71(9):1202–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93(7):2737–45.

Article  CAS  PubMed  Google Scholar 

Li H, Gu Y, Shang X, Zhou Y, Zhang H, Zuo L, et al. Decreased testosterone secretion index and free testosterone level with multiple symptoms for late-onset hypogonadism identification: a nationwide multicenter study with 5980 aging males in China. Aging (Albany NY). 2020;12(24):26012–28.

Article  CAS  PubMed  Google Scholar 

Handelsman DJ, Yeap B, Flicker L, Martin S, Wittert GA, Ly LP. Age-specific population centiles for androgen status in men. Eur J Endocrinol. 2015;173(6):809–17.

Article  CAS  PubMed  Google Scholar 

Zitzmann M. Testosterone and the brain. Aging Male. 2006;9(4):195–9.

Article  CAS  PubMed  Google Scholar 

Shigehara K, Izumi K, Kadono Y, Mizokami A. Testosterone and Bone Health in Men: A Narrative Review. J Clin Med. 2021;10(3):520.

Article  Google Scholar 

Kaur H, Werstuck GH. The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data. CJC Open. 2021;3(10):1238–48.

Article  PubMed  PubMed Central  Google Scholar 

Mohamad NV, Wong SK, Wan Hasan WN, Jolly JJ, Nur-Farhana MF, Ima-Nirwana S, et al. The relationship between circulating testosterone and inflammatory cytokines in men. Aging Male. 2019;22(2):129–40.

Article  CAS  PubMed  Google Scholar 

Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295(11):1288–99.

Article  CAS  PubMed  Google Scholar 

Wittert G, Bracken K, Robledo KP, Grossmann M, Yeap BB, Handelsman DJ, et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet Diabetes Endocrinol. 2021;9(1):32–45.

Article  CAS  PubMed  Google Scholar 

Marriott RJ, Murray K, Flicker L, Hankey GJ, Matsumoto AM, Dwivedi G, et al. Lower serum testosterone concentrations are associated with a higher incidence of dementia in men: The UK Biobank prospective cohort study. Alzheimers Dement. 2022;18(10):1907–18.

Article  CAS  PubMed  Google Scholar 

Chen Z, Zhang E, Gan L, Jiang G, Duan Q, Huang M, et al. Analysis of the association between testosterone and cardiovascular disease potential risk factor apolipoprotein B in adult males without cancer: national health and nutrition examination survey 2011–2016. Front Endocrinol (Lausanne). 2024;15:1304344.

Article  PubMed  Google Scholar 

Yeap BB, Marriott RJ, Antonio L, Chan YX, Raj S, Dwivedi G, et al. Serum Testosterone is Inversely and Sex Hormone-binding Globulin is Directly Associated with All-cause Mortality in Men. J Clin Endocrinol Metab. 2021;106(2):e625–37.

Article  PubMed  Google Scholar 

Ohlander SJ, Lindgren MC, Lipshultz LI. Testosterone and Male Infertility. Urol Clin North Am. 2016;43(2):195–202.

Article  PubMed  Google Scholar 

McBride JA, Carson CC 3rd, Coward RM. Testosterone deficiency in the aging male. Ther Adv Urol. 2016;8(1):47–60.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jefcoate C. High-flux mitochondrial cholesterol trafficking, a specialized function of the adrenal cortex. J Clin Invest. 2002;110(7):881–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simpson ER, Waterman MR. Regulation by ACTH of steroid hormone biosynthesis in the adrenal cortex. Can J Biochem Cell Biol. 1983;61(7):692–707.

Article  CAS  PubMed  Google Scholar 

Rone MB, Midzak AS, Issop L, Rammouz G, Jagannathan S, Fan J, et al. Identification of a dynamic mitochondrial protein complex driving cholesterol import, trafficking, and metabolism to steroid hormones. Mol Endocrinol. 2012;26(11):1868–82.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fan J, Papadopoulos V. Evolutionary origin of the mitochondrial cholesterol transport machinery reveals a universal mechanism of steroid hormone biosynthesis in animals. PLoS ONE. 2013;8(10): e76701.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Miller WL. Mechanism of StAR’s regulation of mitochondrial cholesterol import. Mol Cell Endocrinol. 2007;265–266:46–50.

Article  PubMed  Google Scholar 

Miller WL. Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol transporter. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2007;1771(6):663–76.

Article  CAS  PubMed  Google Scholar 

Aghazadeh Y, Rone MB, Blonder J, Ye X, Veenstra TD, Hales DB, et al. Hormone-induced 14-3-3γ adaptor protein regulates steroidogenic acute regulatory protein activity and steroid biosynthesis in MA-10 Leydig cells. J Biol Chem. 2012;287(19):15380–94.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aghazadeh Y, Martinez-Arguelles DB, Fan J, Culty M, Papadopoulos V. Induction of androgen formation in the male by a TAT-VDAC1 fusion peptide blocking 14-3-3ɛ protein adaptor and mitochondrial VDAC1 interactions. Mol Ther. 2014;22(10):1779–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang Y, Chen F, Ye L, Zirkin B, Chen H. Steroidogenesis in Leydig cells: effects of aging and environmental factors. Reproduction. 2017;154(4):R111–22.

Article  PubMed  PubMed Central  Google Scholar 

Anawalt BD, Matsumoto AM. Aging and androgens: Physiology and clinical implications. Rev Endocr Metab Disord. 2022;23(6):1123–37.

Article  PubMed  PubMed Central  Google Scholar 

Keenan DM, Veldhuis JD. Age-dependent regression analysis of male gonadal axis. Am J Physiol Regul Integr Comp Physiol. 2009;297(5):R1215–27.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Keenan DM, Takahashi PY, Liu PY, Roebuck PD, Nehra AX, Iranmanesh A, et al. An ensemble model of the male gonadal axis: illustrative application in aging men. Endocrinology. 2006;147(6):2817–28.

Article  CAS  PubMed  Google Scholar 

Roelfsema F, Liu PY, Takahashi PY, Yang RJ, Veldhuis JD. Dynamic Interactions Between LH and Testosterone in Healthy Community-Dwelling Men: Impact of Age and Body Composition. J Clin Endocrinol Metab. 2020;105(3):e628–41.

Article  PubMed  Google Scholar 

Campbell RE, Coolen LM, Hoffman GE, Hrabovszky E. Highlights of neuroanatomical discoveries of the mammalian gonadotropin-releasing hormone system. J Neuroendocrinol. 2022;34(5): e13115.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gruenewald DA, Naai MA, Marck BT, Matsumoto AM. Age-related decrease in hypothalamic gonadotropin-releasing hormone (GnRH) gene expression, but not pituitary responsiveness to GnRH, in the male Brown Norway rat. J Androl. 2000;21(1):72–84.

Article  CAS  PubMed