Pregnancy and Ménière’s Disease

Pregnancy is well known to cause further progression of the clinical symptoms of Ménière’s disease. However, mild low-tone hearing loss and ear fullness, similar to the hearing impairment of Ménière’s disease, is often recognized in the ears of pregnant women who are not originally impaired. These phenomena seem to have a common backland to form endolymphatic hydrops. As to this background, various hypotheses have been proposed and developed. Hormonal changes and changes in body fluids due to pregnancy are considered in common to be based in these phenomena. In the present paper, theses hypotheses are reviewed.

Pregnancy is important and wonderful time for women, but the exhausting side effects are known to often accompany. The representative symptoms include tinnitus, ear fullness and more rarely, hearing loss. The most common otological manifestation is slight low-tone deafness, imaging endolymphatic hydrops. However, this hearing loss is known not to reach pathologic levels in any case and returned to normal in the post-partum period [1-4]. Exacerbation of symptoms due to pregnancy is also noted in Ménière’s disease [5-9]. In cases of Ménière’s disease, it is thought that exacerbation of endolymphatic hydrops is in the background.

The pathology of the deafness during pregnancy is still unknown. But there seems to be a common pathophysiology between these two symptoms. Hormonal changes and changes in body fluids due to pregnancy have been cited as causes, especially through the Arginine Vasopressin (AVP) system [8], but there is not yet definitive theory. In the present paper, these possible hypotheses are reviewed.

It is recognized that pregnancy can potentially contribute to the exacerbation of certain otolaryngological conditions, including a patulous eustachian tube, nasal congestion, epistaxis, gingivitis, and reflux esophagitis. It is thought that these changes may be related to metabolic, endocrinological, and physiologic shifts that occur during pregnancy [10]. Some studies have also suggested that there might be a potential link between pregnancy and sensorineural deafness and vertigo/dizziness. With regard to sensorineural deafness, some have suggested that there may be a reduction in hearing levels at 125 Hz, which could potentially begin in the first trimester and intensify in the second and third trimesters. Similarly, findings were also observed at 250 and 500 Hz. It is also important to consider that frequencies above 500 Hz did not show a significant correlation [1,11]. While this low-frequency hearing loss may resemble Ménière's disease, it is reassuring to note that it did not reach pathological levels and returned to normal in the postpartum period [12].

It is not uncommon for pregnant women to experience vertigo and dizziness, which are among the most frequently reported complaints in primary care. These patients are rarely referred to ENT departments, as the majority of cases appear to be related to non-vestibular causes [13]. It would seem that there is a paucity of literature reporting on the course of Ménière's disease during pregnancy. However, it has been demonstrated that this condition can be exacerbated during the late luteal phase of the menstrual cycle [14]. Furthermore, the symptoms of Ménière's disease can potentially worsen in a pre-existing case, and that patients may experience more attacks during pregnancy. There is evidence to suggest that attacks of vertigo may increase with the decline in serum osmolality during pregnancy [5,11,15].

Uchide presented a detailed account of the clinical course of Ménière's disease during pregnancy [5]. In this particular case, there was a notable increase in the frequency of vertigo attacks, reaching up to 10 times per month during the early stages of pregnancy. This coincided with a significant decline in serum osmolality, which was recorded at 268 mosm/kg, a value that fell below the normal range. As the pregnancy progressed, the serum osmolality returned to normal levels and the frequency of vertigo attacks decreased. In addition, we came across three cases where dizziness was linked to a worsening of low-tone sensorineural hearing loss. In these cases, osmolarity was low as well.

With regard to low-tone deafness during pregnancy, the majority of the literature suggests that it may be caused by hormonal sensory dysfunction resulting from fluid retention associated with hormonal changes. However, the supporting evidence is limited, and further investigation may be beneficial. It is thought that the worsening of symptoms in Ménière's disease may be linked to a decline in serum osmolality during pregnancy [6,12]. It seems plausible to suggest that a similar scientific basis may be responsible for these clinical features, namely the low-tone deafness in pregnancy and the exacerbation of symptoms of Ménière's disease during pregnancy.

It would seem that water homeostasis in pregnant women is quite distinctive and different compared with the nonpregnant state [4]. There is evidence to suggest that systemic arterial vasodilation occurs very early in the first trimester of pregnancy [16]. This change in the arterial circulation happens before maturation of the placenta. It may be the case that the arterial vasodilation is caused by Nitric Oxide (NO) upregulated by estrogens.

The systemic arterial vasodilation in the first trimester of pregnancy is also associated with stimulation of thirst, increased water intake, and a decline in plasma osmolality of approximately 8 to 10 mOsm/kg H2O (4 to 5 mEq/L decline in serum sodium concentration) [16]. In addition to the nonosmotic stimulation of thirst, a similar nonosmotic release of 8-Arg-Vasopressin (AVP) would be expected with the systemic arterial vasodilation of pregnancy. The increases in plasma and hypothalamic AVP were confirmed by animal experiments [17], which lends further support to this hypothesis. There is other evidence for the role of AVP in pregnancy [18,19]. AVP is known to regulate the expression of Aquaporin 2 (AQP2) water channels in principal cells along the collecting duct. Actually, the nonosmotic stimulation of AVP in rat pregnancy increases the medullary expression of AQP2 and its trafficking to the apical membrane. These effects on AQP2 during pregnancy were confirmed to be reversed by a Vasopressin (VP) V2-receptor antagonist [18]. Moreover, urinary AQP2 has been shown to increase in human pregnancy as compared with the nonpregnant state [19]. Thus, the modest lowering of the osmotic threshold for plasma AVP in pregnancy may be most likely to be secondary to systemic arterial vasodilation, leading to the nonosmotic stimulation of AVP and upregulation of AQP2. This is compatible with the peripheral arterial vasodilation hypothesis of sodium and water retention in pregnancy.

There is another very interesting and important event related to AVP in pregnancy. This is the role of vasopressinase, a cystine aminopeptidase produced by placental trophoblasts during pregnancy [16]. It is thought that some peptide hormones produced by human fetuses may play an important role in fetal development and growth. However, the exchange of some peptide hormones between the mother and fetus should be restricted in order to maintain feto-maternal homeostasis. The inability of AVP to cross the placenta contributes partially to such restrictions. Metabolic Clearance Rates (MCR) of AVP have been confirmed to markedly increase between gestational weeks 7 and 8 and mid-pregnancy, which parallels the period of the greatest rise in both the trophoblastic mass and plasma vasopressinase. Plasma vasopressinase, which was undetectable within 7-8 gestational weeks, increases markedly by mid-gestation and slightly more by late gestation [20].

Finally, relationships between plasma AVP and urine osmolality were similar before, during, and after pregnancy. However, animal experiments indicate that mRNA of AQP2 in the renal inner medulla (papilla) of pregnant rats is increased early during pregnancy and AQP2 protein is also increased during pregnancy. That is, both AQP2 mRNA and protein in pregnancy upregulate without a significant, concomitant increase in the plasma AVP concentration. Therefore, a non-AVP factor present in pregnancy is considered to play a role in control of the excretion of AQP2 water channels. A recent study indicated that Oxytocin (OT) has an antidiuretic effect and increases the urinary excretion of AQP2 in humans, and that the antidiuretic action of OT is mediated not by the OT receptor but by the VP V2-receptor, although affinity for the VP V2-receptor is low [21,22]. From these experiments, expression of AQP2 in the inner ear is also suspected to be increased, although there is currently no experimental data to support this. In our three cases, plasma AVP was within the normal limit despite Ménière’s attack. The low-tone deafness in pregnancy and exacerbation of symptoms of Ménière’s disease during pregnancy is understandable on considering that the formation and/or development of endolymphatic hydrops is caused by the upregulation of AQP2 in the inner ear.

Pregnancy causes various physical changes in women due to changes in body fluids. One of these disorders is inner ear damage, resulting in low-tone deafness and vertigo attack. In cases with Ménière’s disease, a worsening of symptoms is recognized. These changes may be related to metabolic, endocrinological, and physiologic shifts that occur during pregnancy, which influence water homeostasis inner ear. However, it should be noted that these changes occur only during pregnancy, which would mean that treatment would not be necessary.

Taizo Takeda: Writing - Original Draft. Setsuko Takeda: Writing - Review & Editing. Akinobu Kakigi: Writing - Review & Editing. All authors contributed to the writing of the final manuscript.

Financial disclosures/conflicts of interest: This study was funded by grants from The Ministry of Education, Science, Culture and Sports, Japan (#2 2 K 0 9 7 2 5). There are no conflicts of interest, financial, or otherwise.

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