Research Article|Articles in Press

One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy



      Although intracordal trafermin injection has been performed in the treatment of age-related vocal fold atrophy, the effects of single high dose trafermin injections are unknown. In this study, we examined the 1 year outcomes and longitudinal changes in voice improvement with single high dose intracordal trafermin injections.

      Study Design

      Retrospective study with approval by our Ethics Committee.


      The medical records of 34 patients who underwent single high dose (50ug per side) intracordal trafermin injections under local anesthesia for vocal fold atrophy were retrospectively reviewed at 1 month pre-injection and 1 month, 6 months and 1 year post injection.


      Maximum phonation time (MPT), pitch range (PR), Japanese version of voice handicap index (VHI), grade of GRBAS evaluation, and jitter% improved significantly at 1-year post-injection compared to 1-month pre-injection. MPT and PR improved as early as 1-month post-injection and continued to improve most at 1-year post-injection. VHI showed negative progression from 6-months to 1-year post-injection, during which time the speaking fundamental frequency (SFF) changed to the high pitch in men.


      Single high dose intracordal trafermin injections can be expected to improve voice in the early post-injection period and to maintain its effect for 1 year. SFF may play a role in worsening VHI in men.

      Level of evidence

      level 4.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Voice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Hirano S
        • Kishimoto Y.
        Clinical application of regenerative medicine to the vocal fold.
        Japan Soc Logop Phoniatr. 2016; 57: 255-260
        • Berg EE
        • Hapner E
        • Klein A
        • et al.
        Voice therapy improves quality of life in age-related dysphonia: a case-control study.
        J Voice. 2008; 22: 70-74
        • Hirano S
        • Takagita S
        • Yamashita M
        • et al.
        Modefied Gore-Tex thyroplasty.
        J Jpn Bronchoesophagol Soc. 2005; 56: 439-444
        • Hirano S
        • Bless DM
        • Muñoz del Río A
        • et al.
        Therapeutic potential of growth factors for aging voice.
        Laryngoscope. 2004; 114: 2161-2167
        • Ohno T
        • Yoo MJ
        • Swanson ER
        • et al.
        Regenerative effects of basic growth factor on extracellular matrix production in aged rat vocal folds.
        Ann Otol Rhinol Laryngol. 2009; 118: 559-564
        • Hirano S
        • Nagai H
        • Tateya I
        • et al.
        Regeneration of aged vocal folds with basic fibroblast growth factor in a rat model: a preliminary report.
        Ann Otol Rhinol Laryngol. 2005; 114: 304-308
        • Efthimiadou A
        • Nikolettos NK
        • Lambropoulou M
        • et al.
        Angiogenic effect of intramuscular administration of basic fibroblast growth factor in atrophied muscles: an experimental study in the rat.
        Br J Sports Med. 2006; 40: 355-358
        • Menetrey J
        • Kasemkijwattana C
        • Day CS
        • et al.
        Growth factors improve muscle healing in vivo.
        J Bone Joint Surg Br. 2000; 82: 131-137
        • Hirano S
        • Sugiyama Y
        • Kaneko M
        • et al.
        Intracordal injection of basic fibroblast growth factor in 100 cases of vocal fold atrophy and scar.
        Laryngoscope. 2020; 131: 2059-2064
        • Sueyoshi S
        • Umeno H
        • Kurita T
        • et al.
        Long-term outcomes of basic fibroblast growth factor treatments in patients with vocal fold scarring, aged vocal fold, and sulcus vocalis.
        Auris Nasus Larynx. 2021; 48: 949-955
        • Suzuki H
        • Makiyama K
        • Hirai R
        • et al.
        Efficacy of a single dose of basic fibroblast growth factor: clinical observation for 1 year.
        J Voice. 2016; 30 (e11-761.e17): 761
        • Miura R
        • Matsuzaki H
        • Suzuki H
        • et al.
        Effect of a single injection of basic fibroblast growth factor into the vocal folds: a 36-month clinical study.
        J Voice. 2021; 8:S0892-1997(21)00036-9, 2021
        • Hiwatashi N
        • Hirano S
        • Suzuki R
        • et al.
        Comparison of ASCs and BMSCs combined with atelocollagen for vocal fold scar regeneration.
        Laryngoscope. 2016; 126: 1143-1150
        • Li X
        • Wang H
        • Xu W.
        HGF and bFGF secreted by adipose-derived mesenchymal stem cells revert the fibroblast phenotype caused by vocal fold injury in a rat model.
        J Voice. 2022; 36: 622-629
        • Yamada T
        • Kumai Y
        • Kodama H
        • et al.
        Effect of pirfenidone injection on ferret vocal fold scars: a preliminary in vivo study.
        Laryngoscope. 2020; 130: 726-731
        • Özgürsoy SK
        • Tunçkaşık F
        • Tunçkaşık ME
        • et al.
        Histopathologic evaluation of hyaluronic acid and plasma-rich platelet injection into rabbit vocal cords: an experimental study.
        Turk Arch Otorhinolaryngol. 2018; 56: 30-35
        • Sheehan SM
        • Allen RE
        Skeletal muscle satellite cell proliferation in response to members of the fibroblast growth factor family and hepatocyte growth factor.
        J Cell Physiol. 1999; 181: 499-506
        • Gospodarowicz D
        • Ferrara N
        • Schweigerer L
        • et al.
        Structural characterization and biological functions of fibroblast growth factor.
        Endocr Rev. 1987; 8: 95-114
        • Saksela O
        • Moscatelli D
        • Rifkin DB.
        The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells.
        J Cell Biol. 1987; 105: 957-963
        • Folkman J
        • Klagsbrun M.
        Angiogenic factors.
        Science. 1987; 235: 442-447
        • Rifkin DB
        • Moscatelli D.
        Recent developments in the cell biology of basic fibroblast growth factor.
        J Cell Biol. 1989; 109: 1-6
        • Sheehan SM
        • Allen RE.
        Skeletal muscle satellite cell proliferation in response to members of the fibroblast growth factor family and hepatocyte growth factor.
        J Cell Physiol. 1999; 181 (3<499::AID-JCP14>3.0.CO;2-1): 499-506
        • Kimura Y
        • Ozeki M
        • Inamoto T
        • et al.
        Time course of de novo adipogenesis in matrigel by gelatin microspheres incorporating basic fibroblast growth factor.
        Tissue Eng. 2002; 8: 603-613
        • Okui A
        • Konomi U
        • Kanazawa T
        • et al.
        Trapeutic efficacy of basic fibroblast growth factor in patients with vocal fold atrophy.
        Laryngoscope. 2020; 130: 2847-2852
        • Goto T
        • Ueha R
        • Sato T
        • et al.
        Single, high-dose local injection of bFGF improves thyroarytenoid muscle atrophy after paralysis.
        Laryngoscope. 2020; 130: 159-165
        • Tamura E
        • Yamada C
        • Iida M
        • et al.
        Phonatory Functions in healthy elderly persons.
        Nippon Jibiinkoka Gakkai Kaiho (Tokyo). 2020; 123: 1175-1182
        • Titze IR.
        Mechanisms underlying the control of fundamental frequency.
        Vocal Fold Physiololgy. Jan Gauffin and Britta Hammarberg. Singular Publishing Group, San Diego1993: 129-138 (Vol. 3)
        • Sakaguchi Y
        • Kanazawa T
        • Okui A
        • et al.
        Assessment of dysphonia using the japanese version of the voice handicap index and determination of cutoff points for screening.
        J Voice. 2020; 36 (e1-144.e9): 144
        • Sato K
        • Sakaguchi S
        • Hirano M.
        Histologic investigation of bowing of the aged vocal folds.
        Larynx Jpn. 1996; 8: 11-14