Table 2.

Characteristics of anti-inflammatory corticosteroids that were included in the systematic review and their main outcomes.

References	Design	Population	Age	Gender	Treatment	Noise Exposure	Type, Dose, and Duration of Intervention	Parameters Analyzed	Main Outcomes
1. Panevin (2018). St. Petersburg (Russia) [53]	Prospective cohort	Wistar	-	Male	Hydrocortisone acetate suspension	5 kHz (110–112 dB) for 2 h	IV 0.05% hydrocortisone acetate suspension (5 mg/kg) + 0.01% lidocaine hydrochloride solution (1 mg/kg)	DPOAE: −1 d and +1 h; +24 h +7 d	There was a partial recovery of the DPOAE amplitude at 4 kHz, 1 h after the injection of hydrocortisone. The same status was recorded only by day 7 in response to the hydrocortisone solution. The functional activity of the acoustic receptor recovered completely in response to the hydrocortisone suspension during this period for all checkpoints of OAE. The detected differences could be attributed to the presence of the dispersed drug (povidone particles) that contained the hydrocortisone suspension
2. Muller (2016). Heidelberg (Germany) [54]	Prospective cohort	Guinea pig	-	-	Prednisona (PD) or methylprednisolone (MTP)	Impulse noise bursts (500 ms) at (0.25–4 kHz; 140–144 dB SPL); 15, 30, 45, 60, and 120 bursts were carried out	Osmotic pump implanted in the RWM delivering glucocorticoids (0.5 μL/h) for 2 weeks: PD (25 mg/mL) or MTP (12.5 mg/mL)	Hearing threshold measured using the compound action potential (CAP): 0 d and +14 d	At 15–30 impulse noise bursts, there was great variability in the threshold and partial loss of OHCs At 60–120 impulse noise bursts, the loss of threshold and hair cells was complete. With 45 impulse noise bursts, a loss of 75% of hair cells was observed. A reduction in hearing loss was observed after 2 weeks of high exposure to PD at 25 mg/mL without a significant reduction in the percentage of damaged OHCs. With the use of MTP at 12.5 mg/mL, a reduction in hearing loss and a decrease in the loss of OHCs were observed at 45 impulse noise bursts
3. Chang (2017). Yangju (South Korea) [35]	Prospective cohort	Humans	21–22 years	Male	PD and Dexamethasone (DEX)	Gunshot noise (149 dB) measured at 1 m; 20 shots per session, 3–5 times sequentially	Oral PD (60 mg) daily for 10 d with tapering for 4 d + oral Ginkgo biloba (40 mg) twice a day ITSI DEX (5 mg/mL) in 4 applications every 2 days	Pure tone air conduction threshold audiometry: 0 d, +1 month	Group 2 (ITSI group) showed a significant improvement compared to group 1 (PD group) at all frequencies
4. Choi (2019). Ansan-si (South Korea) [34]	Retrospective cohort		20–21 years		PD	Gunshot noise exposure	Oral Prednisone (60 mg)	Pure tone thresholds	The post-treatment hearing threshold of group 1 showed a significant improvement (p < 0.05) while group 2 did not. The regression coefficient for the association between the initial hearing level and the hearing gain was 0.45
5. Heinrich U-R (2016). Mainz (Germany) [55]	Prospective cohort	Guinea pig	2 weeks		DEX	90 dB noise exposure	IT DEX (0.1 mL) 4 h before NE	ABRs: 0 d, +2 h	There was a significant reduction (p = 0.0013) in the mean hearing thresholds of the DEX group (23 dB) compared to the NE (31.99) and saline (28.5) groups at the end of the treatment. The increase in staining intensity in GR expression was only significant for the DEX group (p = 0.0344). Strong associations were detected when comparing the GR expression in the fibrocytes of the limbus with the spiral ganglion cells, the interdental cells, or the nerve fibers (p < 0.001)
6. Harrop-Jones (2016). California (US) [56]			6–8 weeks		DEX in poloxamer vehicle (OTO-104)	Narrowband noise (4–8 kHz at 105–110 dB) for 2 h	IT bilateral OTO-104 prior to NE	ABR	a. Doses of 2% and 6% OTO-104 exhibited otoprotection against NIHL b. But only the intratympanic injection of 6% OTO-104 showed significant otoprotection after NIHL
7. Gumrukcu (2017). Istanbul (Turkey) [57]		Wistar	Adults	Female	DEX	110 dB for 25’	IT DEX 1 mL (4 mg/mL) on days 0, 2, and 4	DPOAE: 0 d, +7 d, and +10 d	DEX treatment group showed a significant difference in DPOAE measurements on days 7 and 10 at all frequencies compared to the saline group
8. Zhu C (2018). Viena (Austria) [58]		Guinea pig	Adults	Both	DEX and triamcinolone acetonide (TAAC) in thermoreversible poloxamer 407 (POX-407) hydrogels	120 dB SPL for 3 h	Hydrogels applied post-NE into the RWM	.ABR: −1 week and +1 d, +2 d, +7 d, +14 d, +21 d, and +28 d	a. DEX (6%) group showed significantly higher threshold shifts than the TAAC (6%) group on day 14 and exhibited a significantly smaller hearing threshold shift at 16 kHz compared to the control hydrogel on day 7 b. SGC showed the highest density on the second turn in the DEX (6%) group, but no statistically significant difference was detected
9. Shih (2018). Taipei (Taiwan) [59]			Adults	Male	DEX +USMB	118 dB SPL for 5 h	IT DEX/MB US or DEX/MB without US. US irradiation: 3 w/cm2 for 3 consecutive 1’ course duty cycle 50%. In the MB group, they used 2 preparations: one called SonoVue made of phospholipids, and the other with albumin	.ABR: 0 d and +1 d, +7 d, +14 d, +28 d	a. DEX concentration was significantly higher in the US MB SonoVue groups with frequencies of 0.5 MHz, 3 MHz, and 5 mhZ than in the RWS group. Albumin MBs also significantly increased the perilymphatic DEX levels in the USM group compared to the RWS b. DEX delivery was significantly higher for a US frequency of 1 MHz than for 0.5 MHz US group showed significant differences on days 7, 14, and 28 than the control group
10. Park (2020). Seul (South Korea) [60]		Sprague Dawley	-	-	DEX in different vehicles: saline, hyaluronic acid (HA), and methoxy polyethylene glycol-b-polycaprolactone block copolymer (MP)	120 dB SPL for 3 h	IT DEX (10 mg) + MP; 3 h NE	a. ABR: 0 d, +1 h NE, +3 h after vehicle/drug injection, and +4 d, +8 d, +30 d, and +45 d after IT b. Endoscopic examination TM c. Microcomputed tomography: +2 h, +4 h, +8 h, +30 h, and +45 h after IT	All 4 groups improved the hearing threshold after treatment, but there was a difference in degree. The HA + D group was significantly better than the MP + D group (p = 0.043). The difference between the HA + D group and the saline + D group was not statistically significant (p = 0.083). The duration of vehicle/drug in the bulla was significantly longer for the MP + D group than the saline + D and HA + D groups (p = 0.038)
11 Jeong (2021). Seul (South Korea) [61]			7–8 weeks	Male	DEX and sodium caprate (SC)	115 dB SPL for 5’	IT DEX sodium phosphate (5 mg/mL) + Sodium caprate (1.94 mg/mL)	ABR	a. Perilymphatic DEX concentration was significantly elevated in the DEX + SC group compared to the DEX-alone group: at 30’ post-NE (p = 0.0255) and at 90’ (p = 0.0206) b. SC co-treatment accelerates the recovery of NIHL c. SC did not show any signs of loss or death of IHCs and OHCs 14 days after treatment