Research Article: A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere’s Disease—A Pilot Study

Date Published: June 30, 2016

Publisher: Public Library of Science

Author(s): Tadashi Kitahara, Hidehiko Okamoto, Munehisa Fukushima, Masaharu Sakagami, Taeko Ito, Akinori Yamashita, Ichiro Ota, Toshiaki Yamanaka, Russell R. Lonser.


Meniere’s disease, a common inner ear condition, has an incidence of 15–50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere’s disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere’s patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I < II = III = IV). Hearing was improved in 7.1% of patients in Group-I, 35.7% in Group-II, 34.9% in Group-III, and 31.7% in Group-IV (statistically I < II = III = IV). Plasma vasopressin concentrations decreased more in Groups-II, -III, and -IV than in Groups-I (statistically I < II = III = IV), although patients’ stress/psychological factors had not changed. Physicians have focused on stress management for Meniere’s disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere’s disease, even though these therapies did not alter reported mental/physical stress levels.

Partial Text

Meniere’s disease, characterized by recurrent vertigo, fluctuating hearing loss and persistent tinnitus, is a common disease with an incidence of 15–50 per 100,000 [1]. It has been reported that Meniere’s disease is usually triggered by various kinds of stimuli, i.e. genetic, infectious, vascular, dietary, allergic, autonomic, endocrine, autoimmune, or other insults to the inner ear, associated with a small misplaced malfunctioning endolymphatic sac [2]. In spite of these undetermined insults, so many ENT doctors have had an impression of strong relationships between stress and Meniere’s disease. This disease is supposedly triggered by mental and/or physical stress caused by participating in stressful daily activities and by interactions within stressful social environments. Several studies have reported psychological and cognitive therapies for Meniere’s disease [3]. Many physicians advise their patients to take adequate time out for stress management. However, it is difficult, indeed often unrealistic, for most of Meniere’s patients to undertake long-term psychological treatment and/or change their work situation to reduce stress in their daily life.

This clinical study was registered with (identification number: NCT01099046). The use of all the patients’ data in the present study was approved not only by the patients as written consents but by the Ethics Committee of Osaka Rosai Hospital (identification number: 2263).

Relevant data of patients with definite Meniere’s disease are shown in Table 1. There were no significant differences in these variables among the four groups studied.

There have been several basic and clinical reports of abundant water intake [14,21], tympanic ventilation tubes [15,22] and sleeping in the dark [16,23,24] having possible therapeutic effects on Meniere’s disease. In the present study, one aim was to examine whether these treatments have the feasibility to avoid making a decision of surgery for intractable Meniere’s disease and another was to evaluate which of them is superior. In comparison with a control group, number of vertigo attacks and hearing were significantly better in the water, tube and sleep groups; there were no significant differences between these three groups. Similarly, in comparison with a control group, pAVP concentrations also significantly decreased in the water, tube and sleep groups, again with no significant differences between the three groups. AVP, a stress-related hypothalamic–pituitary releasing hormone, acts via V2R and AQP2 on water metabolism at the level of the renal collecting ducts [25]. Researchers have found that pAVP concentrations are significantly higher in Meniere’s patients than in controls without inner ear hydrops [8,17,26]. Takeda has also shown that systemic administration of vasopressin induces bilateral inner ear hydrops and hearing deterioration in guinea pigs [6]. Additionally, long-lasting decreases in pAVP after endolymphatic sac surgery correlate with better surgical results [27]. All these findings suggest that decreased pAVP concentrations after treatment of patients with Meniere’s disease assist control of symptoms.