Safety Aspects and Rational Use of Testosterone Undecanoate in the Treatment of Testosterone Deficiency: Clinical Insights

References

• Trabado S, Maione L, Salenave S, et al. Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment. Fertil Steril. 2011;95(7):2324–2329.e3. doi:10.1016/j.fertnstert.2011.03.091
   PubMed Web of Science ®Google Scholar
• Anaissie J, DeLay KJ, Wang W, Hatzichristodoulou G, Hellstrom WJ. Testosterone deficiency in adults and corresponding treatment patterns across the globe. Transl Androl Urol. 2017;6(2):183–191. doi:10.21037/tau.2016.11.16
   PubMed Web of Science ®Google Scholar
• Cohen J, Nassau DE, Patel P, Ramasamy R. Low testosterone in adolescents & young adults. Front Endocrinol Lausanne. 2019;10:916. doi:10.3389/fendo.2019.00916
   PubMed Web of Science ®Google Scholar
• Vartolomei MD, Kimura S, Vartolomei L, Shariat SF. Systematic review of the impact of testosterone replacement therapy on depression in patients with late-onset testosterone deficiency. Eur Urol Focus. 2020;6(1):170–177. doi:10.1016/j.euf.2018.07.006
   PubMedGoogle Scholar
• Kumar P, Kumar N, Thakur DS, Patidar A. Male hypogonadism: symptoms and treatment. J Adv Pharm Technol Res. 2010;1(3):297–301. doi:10.4103/0110-5558.72420
   PubMedGoogle Scholar
• Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–624. doi:10.1056/NEJMoa1506119
   PubMed Web of Science ®Google Scholar
• Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423–432. doi:10.1016/j.juro.2018.03.115
   PubMed Web of Science ®Google Scholar
• Rochira V. Hypogonadism in systemic diseases. In: Vitti P, Hegedus L, editors. Thyroid Diseases. Endocrinology. Springer International Publishing; 2017:1–51. doi:10.1007/978-3-319-29456-8_28-1
   Google Scholar
• Gurayah AA, Mason MM, Masterson JM, Kargi AY, Ramasamy R. U-shaped association between prevalence of secondary hypogonadism and body mass index: a retrospective analysis of men with testosterone deficiency. Int J Impot Res. 2022. doi:10.1038/s41443-022-00533-z
   PubMed Web of Science ®Google Scholar
• Dhingra OP, Bernstein J, Barnes SD, VanLaanen H, Wadlington N, Chang J. Novel oral testosterone formulation improves male well being without compromising international prostate symptom scores. In: © The Author(s) 2021. Vol. 5. Published by Oxford University Press on behalf of the Endocrine Society.; 2021:A760. doi:10.1210/jendso/bvab048.1546
   Google Scholar
• Scovell JM, Ramasamy R, Wilken N, Kovac JR, Lipshultz LI. Hypogonadal symptoms in young men are associated with a serum total testosterone threshold of 400 ng/dL. BJU Int. 2015;116(1):142–146. doi:10.1111/bju.12970
   PubMed Web of Science ®Google Scholar
• Dandona P, Rosenberg MT. A practical guide to male hypogonadism in the primary care setting. Int J Clin Pr. 2010;64(6):682–696. doi:10.1111/j.1742-1241.2010.02355.x
   PubMed Web of Science ®Google Scholar
• Valancy D, Blachman-Braun R, Kuchakulla M, Nackeeran S, Ramasamy R. Association between low testosterone and anaemia: analysis of the National Health and Nutrition Examination Survey. Andrologia. 2021;53(11):e14210. doi:10.1111/and.14210
   PubMed Web of Science ®Google Scholar
• Straftis AA, Gray PB. Sex, energy, well-being and low testosterone: an exploratory survey of U.S. men’s experiences on prescription testosterone. Int J Env Res Public Health. 2019;16(18):3261. doi:10.3390/ijerph16183261
   PubMed Web of Science ®Google Scholar
• Wheeler KM, Smith RP, Kumar RA, Setia S, Costabile RA, Kavoussi PK. A comparison of secondary polycythemia in hypogonadal men treated with clomiphene citrate versus testosterone replacement: a multi-institutional study. J Urol. 2017;197(4):1127–1131. doi:10.1016/j.juro.2016.10.068
   PubMed Web of Science ®Google Scholar
• Liu PY, Swerdloff RS, Anawalt BD, et al. Determinants of the rate and extent of spermatogenic suppression during hormonal male contraception: an integrated analysis. J Clin Endocrinol Metab. 2008;93(5):1774–1783. doi:10.1210/jc.2007-2768
   PubMed Web of Science ®Google Scholar
• Hudson J, Cruickshank M, Quinton R, et al. Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. Lancet Healthy Longev. 2022;3(6):e381–e393. doi:10.1016/S2666-7568(22)00096-4
   PubMedGoogle Scholar
• Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med. 2013;10(1):245–284. doi:10.1111/j.1743-6109.2012.02783.x
   PubMed Web of Science ®Google Scholar
• Morgentaler A, Dobs AS, Kaufman JM, et al. Long acting testosterone undecanoate therapy in men with hypogonadism: results of a pharmacokinetic clinical study. J Urol. 2008;180(6):2307–2313. doi:10.1016/j.juro.2008.08.126
   PubMed Web of Science ®Google Scholar
• von Eckardstein S, Nieschlag E. Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: a Phase II study. J Androl. 2002;23(3):419–425. doi:10.1530/eje.0.1400414
   PubMedGoogle Scholar
• Corona G, Vignozzi L, Sforza A, Maggi M. Risks and benefits of late onset hypogonadism treatment: an expert opinion. World J Mens Health. 2013;31(2):103–125. doi:10.5534/wjmh.2013.31.2.103
   PubMedGoogle Scholar
• Shoskes JJ, Wilson MK, Spinner ML. Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol. 2016;5(6):834–843. doi:10.21037/tau.2016.07.10
   PubMed Web of Science ®Google Scholar
• Jockenhövel F, Minnemann T, Schubert M, et al. Comparison of long-acting testosterone undecanoate formulation versus testosterone enanthate on sexual function and mood in hypogonadal men. Eur J Endocrinol. 2009;160(5):815–819. doi:10.1530/EJE-08-0830
   PubMed Web of Science ®Google Scholar
• Saad F, Kamischke A, Yassin A, et al. More than eight years’ hands-on experience with the novel long-acting parenteral testosterone undecanoate. Asian J Androl. 2007;9(3):291–297. doi:10.1111/j.1745-7262.2007.00275.x
   PubMed Web of Science ®Google Scholar
• Horst HJ, Höltje WJ, Dennis M, Coert A, Geelen J, Voigt KD. Lymphatic absorption and metabolism of orally administered testosterone undecanoate in man. Klin Wochenschr. 1976;54(18):875–879. doi:10.1007/BF01483589
   PubMedGoogle Scholar
• Bagchus WM, Hust R, Maris F, Schnabel PG, Houwing NS. Important effect of food on the bioavailability of oral testosterone undecanoate. Pharmacotherapy. 2003;23(3):319–325. doi:10.1592/phco.23.3.319.32104
   PubMed Web of Science ®Google Scholar
• Skakkebaek NE, Bancroft J, Davidson DW, Warner P. Androgen replacement with oral testosterone undecanoate in hypogonadal men: a double blind controlled study. Clin Endocrinol. 1981;14(1):49–61. doi:10.1111/j.1365-2265.1981.tb00364.x
   PubMed Web of Science ®Google Scholar
• Nieschlag E, Mauss J, Coert A, Kićović P. Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Acta Endocrinol. 1975;79(2):366–374. doi:10.1530/acta.0.0790366
   PubMedGoogle Scholar
• Park NC, Yan BQ, Chung JM, Lee KM. Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency. Aging Male. 2003;6(2):86–93. doi:10.1080/tam.6.2.86.93
   PubMedGoogle Scholar
• Emmelot-Vonk MH, Verhaar HJJ, Nakhai Pour HR, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA. 2008;299(1):39–52. doi:10.1001/jama.2007.51
   PubMed Web of Science ®Google Scholar
• Jungwirth A, Plas E, Geurts P. Clinical experience with Andriol Testocaps--the first Austrian surveillance study on the treatment of late-onset hypogonadism. Aging Male. 2007;10(4):183–187. doi:10.1080/13685530701495088
   PubMed Web of Science ®Google Scholar
• Wittert GA, Chapman IM, Haren MT, Mackintosh S, Coates P, Morley JE. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol a Biol Sci Med Sci. 2003;58(7):618–625. doi:10.1093/gerona/58.7.m618
   PubMed Web of Science ®Google Scholar
• Yin AY, Htun M, Swerdloff RS, et al. Reexamination of pharmacokinetics of oral testosterone undecanoate in hypogonadal men with a new self-emulsifying formulation. J Androl. 2012;33(2):190–201. doi:10.2164/jandrol.111.013169
   PubMedGoogle Scholar
• Frey H, Aakvaag A, Saanum D, Falch J. Bioavailability of oral testosterone in males. Eur J Clin Pharmacol. 1979;16(5):345–349. doi:10.1007/BF00605634
   PubMed Web of Science ®Google Scholar
• Schnabel PG, Bagchus W, Lass H, Thomsen T, Geurts TBP. The effect of food composition on serum testosterone levels after oral administration of Andriol Testocaps. Clin Endocrinol (Oxf). 2007;66(4):579–585. doi:10.1111/j.1365-2265.2007.02781.x
   PubMed Web of Science ®Google Scholar
• Swerdloff RS, Wang C, White WB, et al. A new oral testosterone undecanoate formulation restores testosterone to normal concentrations in hypogonadal men. J Clin Endocrinol Metab. 2020;105(8):dgaa238. doi:10.1210/clinem/dgaa238
   PubMed Web of Science ®Google Scholar
• Meyer L. FDA approves new oral testosterone capsule for treatment of men with certain forms of hypogonadism. FDA NEWS RELEASE; 2019. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-new-oral-testosterone-capsule-treatment-men-certain-forms-hypogonadism. Accessed March 16, 2023.
   Google Scholar
• Khodamoradi K, Khosravizadeh Z, Parmar M, Kuchakulla M, Ramasamy R, Arora H. Exogenous testosterone replacement therapy versus raising endogenous testosterone levels: current and future prospects. FS Rev. 2021;2(1):32–42. doi:10.1016/j.xfnr.2020.11.001
   PubMedGoogle Scholar
• Patel M, Muthigi A, Ramasamy R. JATENZO®: challenges in the development of oral testosterone. Int J Impot Res. 2022;34(7):721–724. doi:10.1038/s41443-021-00461-4
   PubMed Web of Science ®Google Scholar
• Swerdloff RS, Dudley RE. A new oral testosterone undecanoate therapy comes of age for the treatment of hypogonadal men. Ther Adv Urol. 2020;12:1756287220937232. doi:10.1177/1756287220937232
   Web of Science ®Google Scholar
• Clarus Therapeutics, Inc. JATENZO- testosterone undecanoate capsule, liquid filled. Package insert; 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206089s000lbl.pdf. Accessed March 16, 2023.
   Google Scholar
• DelConte A, Papangkorn K, Kim K, et al. A new oral testosterone (TLANDO) treatment regimen without dose titration requirement for male hypogonadism. Andrology. 2022;10(4):669–676. doi:10.1111/andr.13153
   PubMed Web of Science ®Google Scholar
• DelConte A, Patel MV, Papangkorn K, et al. SAT-052 A Novel Oral Testosterone Therapy (TLANDO) safely restores testosterone to eugonadal levels with fixed dose treatment. J Endocr Soc. 2020;4(Supplement_1):SAT–052. doi:10.1210/jendso/bvaa046.684
   Google Scholar
• Anthony D, Nachiappan C, Kongnara P, et al. MP45-15 a novel oral testosterone therapy restores testosterone to eugonadal levels without dose titration. J Urol. 2020;203(Supplement4):e670–e670. doi:10.1097/JU.0000000000000900.015
   PubMedGoogle Scholar
• Antares Pharma, Inc. TLANDO- testosterone undecanoate capsule, liquid filled. Package insert; 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/208088s000lbl.pdf. Accessed March 16, 2023.
   Google Scholar
• White WB, Dobs A, Carson C, et al. Effects of a novel oral testosterone undecanoate on ambulatory blood pressure in hypogonadal men. J Cardiovasc Pharmacol Ther. 2021;26(6):630–637. doi:10.1177/10742484211027394
   PubMed Web of Science ®Google Scholar
• Globe Newswire. CORRECTION -- Marius pharmaceuticals receives FDA approval of KYZATREXTM, an oral testosterone replacement therapy; 2022. Available from: https://www.globenewswire.com/en/news-release/2022/09/21/2520385/0/en/CORRECTION-Marius-Pharmaceuticals-Receives-FDA-Approval-of-KYZATREX-an-Oral-Testosterone-Replacement-Therapy.html. Accessed October 4, 2022.
   Google Scholar
• Marius Pharma. Marius pharmaceuticals completes efficacy Phase 3 study; 2018. Available from: https://www.mariuspharma.com/. Accessed March 16, 2023.
   Google Scholar
• Marius Pharmaceuticals. KYZATREX- testosterone undecanoate capsule, liquid filled. Package insert; 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213953s000lbl.pdf. Accessed March 16, 2023.
   Google Scholar
• White WB, Bernstein JS, Rittmaster R, Dhingra O. Effects of the oral testosterone undecanoate KyzatrexTM on ambulatory blood pressure in hypogonadal men. J Clin Hypertens Greenwich Conn. 2021;23(7):1420–1430. doi:10.1111/jch.14297
   PubMed Web of Science ®Google Scholar
• Edel Y, Sagy I, Pokroy-Shapira E, et al. A cross-sectional survey on the preference of patients with rheumatoid arthritis for route of administration of disease-modifying anti-rheumatic drugs: oral target-specific versus parenteral biologic. Isr Med Assoc J. 2020;22(3):154–159.
   PubMed Web of Science ®Google Scholar
• Sánchez Martínez I, Cerdán Sánchez M, López Román J, et al. Possible influence of the route of treatment administration on treatment adherence in patients with multiple sclerosis. Clin Ther. 2020;42(5):e87–e99. doi:10.1016/j.clinthera.2020.03.005
   PubMed Web of Science ®Google Scholar
• Partsch CJ, Weinbauer GF, Fang R, Nieschlag E. Injectable testosterone undecanoate has more favourable pharmacokinetics and pharmacodynamics than testosterone enanthate. Eur J Endocrinol. 1995;132(4):514–519. doi:10.1530/eje.0.1320514
   PubMed Web of Science ®Google Scholar
• Zhang GY, Gu YQ, Wang XH, Cui YG, Bremner WJ. A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men. J Androl. 1998;19(6):761–768.
   PubMedGoogle Scholar
• Behre HM, Abshagen K, Oettel M, Hübler D, Nieschlag E Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. European Journal of Endocrinology. 1999 May;140(5):414–419. doi: 10.1530/eje.0.1400414.
   PubMed Web of Science ®Google Scholar
• Middleton T, Turner L, Fennell C, et al. Complications of injectable testosterone undecanoate in routine clinical practice. Eur J Endocrinol. 2015;172(5):511–517. doi:10.1530/EJE-14-0891
   PubMed Web of Science ®Google Scholar
• Adam JA, Pastuszak AW, Christensen MB, et al. Occurrence of pulmonary oil microembolism (POME) with intramuscular testosterone undecanoate injection: literature review. Int J Impot Res. 2022. doi:10.1038/s41443-022-00585-1
   PubMed Web of Science ®Google Scholar
• Krakowsky Y, Conners W, Davidson E, Rawji A, Morgentaler A. Initial clinical experience with testosterone undecanoate therapy (AVEED) in men with testosterone deficiency in the United States. Urology. 2017;109:27–31. doi:10.1016/j.urology.2017.07.007
   PubMed Web of Science ®Google Scholar
• Endo Pharmaceuticals. AVEED (testosterone undecanoate) injection, for intramuscular use. Package insert; 2014. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022219s000lbl.pdf. Accessed March 16, 2023.
   Google Scholar
• Turner L, Ly LP, Desai R, et al. Pharmacokinetics and acceptability of subcutaneous injection of testosterone undecanoate. J Endocr Soc. 2019;3(8):1531–1540. doi:10.1210/js.2019-00134
   PubMed Web of Science ®Google Scholar
• Schubert M, Minnemann T, Hübler D, et al. Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism. J Clin Endocrinol Metab. 2004;89(11):5429–5434. doi:10.1210/jc.2004-0897
   PubMed Web of Science ®Google Scholar
• Yassin AA, Saad F. Treatment of sexual dysfunction of hypogonadal patients with long-acting testosterone undecanoate (Nebido). World J Urol. 2006;24(6):639–644. doi:10.1007/s00345-006-0120-0
   PubMed Web of Science ®Google Scholar
• Moon DG, Park MG, Lee SW, et al. The efficacy and safety of testosterone undecanoate (Nebido(®)) in testosterone deficiency syndrome in Korean: a multicenter prospective study. J Sex Med. 2010;7(6):2253–2260. doi:10.1111/j.1743-6109.2010.01765.x
   PubMed Web of Science ®Google Scholar
• Rostom M, Ramasamy R, Kohn TP. History of testosterone therapy through the ages. Int J Impot Res. 2022;34(7):623–625. doi:10.1038/s41443-021-00493-w
   PubMed Web of Science ®Google Scholar