Conclusion: ER alpha and ER beta are present in the inner ear and are up- and down-regulated depending on the stage of maturation, development and pregnancy, suggesting that estrogen may have an effect on the cochlea during various stages of life. No estrogen receptors (ERs) were found in the cochlea of the developing fetus, which suggests that estrogen does not have an effect on the cochlea during gestation. Objective: To investigate the distribution of ERs in the cochlea during pregnancy, maturation and development in a female rat model. Materials and methods: The cochleas of 24 rats in 4 groups in different time periods of maturation (21 and 56 days old) and pregnancy (day 8 and 18 of pregnancy) and 16 fetuses at gestational ages of 8 and 18 days were collected. All specimens were stained for ERs using standard immunohistochemical techniques. Results: ERs are present in the cochlea of the rat and vary during maturation and pregnancy. No ERs were found in the fetal cochleas. Of the non-fetal time points measured, the expression levels of ERs in the rat cochlea were highest at the postnatal age of 21 days and were lowest during late pregnancy (day 18).

There are well known differences between males and females in hearing. In the present study, the role of estrogen receptor-beta (ER-beta; listed as ESR2 in the MGI Database) in hearing was investigated by comparing hearing and morphology of the inner ear in ER-beta knock-out mice (ER-beta(-/-)) with that of wild-type (WT) littermates. Hearing was analyzed with auditory brainstem response audiometry at 3 and 12 months. The ER-beta(-/-) mice were deaf at 1 year of age, and the morphological analysis showed absence of hair cells and loss of the whole organ of Corti initiated in the basal turn of the cochlea. Furthermore, in ER-beta(-/-), but not in WT mice, the spiral ganglion was lacking many of its neurons. Immunostaining showed the presence of both ER-alpha (listed as ESR1 in the MGI Database) and ER-beta in the nuclei of some neurons in the inner ear in WT mice, but no ER-beta was found in the ER-beta(-/-) mice as expected. ER-alpha staining was predominant in the nuclei of large neurons and ER-beta in nuclei of small neurons and fibroblasts. These results reveal that both ERs are present in the inner ear at specific localizations suggesting subtype-specific functions. It is concluded that ER-beta is important for the prevention of age-related hearing loss. These findings strengthen the hypothesis that estrogen has a direct effect on hearing functions.

A disturbance in the immune system has been described in Turner syndrome (45,X), with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45,X), thyroiditis being the most common. Other autoimmune diseases seen are inflammatory bowel disease, insulin dependent diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite.

Is the female sex steroid estrogen the key to preserved hearing in the aging human? This question remains unanswered, but hearing loss is more profound in elderly males than females. There are also well-known sex differences in the auditory brainstem response (ABR), i.e. women have shorter latencies than men. Moreover, menopausal women who are administered hormone replacement therapy have slightly better hearing than those who are not, and women with Turner's syndrome (45,X), who are biologically estrogen-deficient, show longer ABR latencies and early presbyacusis. These findings are also supported by animal experiments. When boosted with estrogen or testosterone the non-reproductive female midshipman fish alters its inner ear auditory mechanism so that it can hear the male's hum-like call. If estrogen receptor beta is knocked out in mice, severe progressive hearing loss occurs, leading to early deafness. In apparent contradiction to these findings, there have been case reports suggesting that hormone replacement therapy and oral contraceptive use can lead to hearing loss, but of another type, namely acute sudden deafness. Such contradictory aspects of the action of estrogen are commonly found and may spring from the fact that there are two estrogen receptors, alpha and beta, both of which are present in the inner ear of mice, rats and humans. Knowing how sex steroids can alter hearing ability may give important clues as to how estrogen can preserve hearing in humans. In this review we present a summary of current knowledge about hearing and estrogen.

Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X), thyroiditis being the most common. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency) ear problems are common (recurrent otitis media and progressive sensorineural hearing disorder). Levels of IgG, IgA, IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte subpopulations were investigated in 15 girls with Turners syndrome to examine whether an immunodeficiency may be the cause of their high incidence of otitis media. No major immunological deficiency was found that could explain the increased incidence of otitis media in the young Turner girls.

Cervical necrotizing fasciitis is a serious, rapidly progressive infection along fascia planes that sometimes involves skin, subcutaneous tissue and muscle (myositis). The condition, often of dental or pharyngeal origin, is associated with high morbidity and mortality. Thirteen consecutive cases of cervical necrotizing fasciitis treated with hyperbaric oxygen at the Karolinska Hospital during the period 1997-2003 were reviewed. Eight male and five female patients, 33 to 78 years old, were treated according to the Karolinska Hospital guidelines for severe soft tissue infections. All patients recovered. Eleven of thirteen patients required intensive care and eight inotropic drugs. Streptococcus milleri was the predominant pathogen found in initial cultures. Three case reports are presented. Our findings lend further support to the literature on the importance of a prompt multidisciplinary approach with aggressive surgical intervention, broad-spectrum antibiotic therapy and hyperbaric oxygen therapy.

Older women in the normal population tend to develop less severe hearing loss as compared to males in the same age. In Turner syndrome (45,X), estrogen deficiency is one of the predominant problems. Ear and hearing problems are common among these patients. Does estrogen have an impact on the hearing organ? Twenty-four rats were ovariectomized and treated with vehicle (controls), estradiol or selective estrogen receptor modulators such as tamoxifen and ICI182780, in order to study the effects on the estrogen receptor levels and distribution in the inner ear. The cochleas were stained immunohistochemically using antibodies against estrogen receptor alpha and beta. No major difference in estrogen receptor content in the cochleas was observed among groups. There was however a potential down regulation of estrogen receptor alpha in the marginal cells of stria vascularis in the rats that were substituted with ICI182780 (pure antiestrogen) as compared to those given estradiol or tamoxifen. When investigating the tissues with light microscopy no change in inner ear anatomy could be observed.

Estrogen receptors have earlier been shown in the normal mouse, rat and human inner ear. If estrogens are important in normal hearing and development of presbyacusis in the normal population is not known. However it is known that patients with Turner syndrome, where a lack of estrogens is one of the main characteristics, commonly develop an early presbyacusis. A 'Turner mouse' has been developed, as a model for the ear problems in Turner syndrome, and it shows otitis media and a premature aging of the hearing. Estrogen receptors exist in an alpha and a beta form. In this study inner ear tissue, from the Turner mouse and an estrogen receptor beta knockout mouse (betaERKO), was investigated regarding estrogen receptor alpha and beta using immunohistochemistry. Results show that the Turner mouse has the same pattern of inner ear labeling, both concerning the estrogen receptor alpha and beta, as that of a normal CBA/Ca mouse, with positive staining in the organ of Corti and spiral ganglion. The betaERKO mice show close to normal inner ear morphology and positive estrogen receptor alpha immunostaining at the same locations as the CBA/Ca mouse.

The influence of estrogens, the female sex hormone, on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The presence of estrogen receptors α and β has earlier been shown in the inner ear of mice and rats. The aim of this study was to map possible estrogen receptors in the human inner ear. Inner ear tissue from human adults, aborted human normal fetuses and fetuses with Turner’s syndrome were collected. Paraffin embedded sections of adult and fetal inner ears were immunostained with antibodies against estrogen receptors α and β. Estrogen receptor α containing cells were found in the adult human inner ear only in the spiral ganglion, and estrogen receptor β in the stria vascularis solely. The human fetal inner ear tissue from both normal and Turner fetuses showed a very weak staining of estrogen receptor α in the spiral ganglion cells, but no specific labeling of the Kölliker’s organ of Corti at 13, 14 and 18 weeks of age. No staining of estrogen receptor β was seen in the fetal inner ear.

Turner's syndrome is due to total (45,X) or partial (mosaicism) loss of one X-chromosome. The main features are short stature, ovarian dysgenesis with no estrogen production and infertility. In addition to ear and hearing disorders, middle ear problems including acute/serous otitis media and chronic middle ear disease are frequent. Sensorineural hearing loss is often seen with a dip in the mid-frequencies and also an early high frequency loss. In this study, middle-and inner-ear pathology was characterized using physiological and morphological techniques in a 'Turner mouse' that has been generated with the chromosomal aberration X,0. Otitis media was found in some of these X,0 animals, a symptom that is seldom found in control animals. The auditory brainstem responses (ABR) of the Turner mouse showed a progressive hearing loss in the high frequency region that exceeded the normal age-related hearing loss of control mice and increased latencies of the first ABR wave. Outer hair cell loss was apparent in the cochlear basal turn of Turner mice. Decreases in the amplitude of distortion product otoacoustic emissions were correlated with the loss of ABR threshold sensitivity. These results indicate that hearing problems in the Turner mouse seems to be of cochlear origin with an eighth nerve component. This Turner mouse model appears to have ear and hearing problems quite similar to humans and can therefore be used as a model to determine the auditory pathology underlying this syndrome.

The sex hormone estrogen is classically known to influence growth, differentiation and function of peripheral tissues of both the female and male reproductive tract, mediated through the estrogen receptors alpha and beta. The influence of estrogens on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The aim of this study was to map eventual estrogen receptors in the inner ear in mouse and rat. Paraffin embedded sections of mouse and rat inner ear were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptors alpha and beta containing cells were found in the inner ear, showing a unique distribution pattern, both in the auditory pathways and in the water/ion regulating areas. The presence of estrogen receptors indicates that estrogens may have an effect on the inner ear and hearing functions.

Ear and hearing disorders are common problems among girls and women with Turner's syndrome. During infancy and childhood the girls often suffer from repeated attacks of acute otitis media and later in life the women frequently complain of a rapid onset of social hearing problems due to sensorineural hearing impairment. A study of 56 girls aged 4–15 years with Turner's syndrome was performed to investigate the prevalence of eardrum pathology and hearing impairment in young children and teenagers with Turner's syndrome. A possible relation to karyotype was also investigated. A high prevalence (61%) of recurrent acute otitis media was found in the study group and 32% had been treated with ventilation tubes. Fifty-seven percent showed eardrum pathology, such as effusion, myringosclerosis, atrophic scars, retraction pockets and perforations. Auricular anomalies were noted in 23% of the cases, most commonly in the 45,X group. The audiometric analysis showed conductive hearing loss (air–bone gap>10 dB HL) in 43% and the typical sensorineural dip in the middle frequencies was found in 58% of the girls, of whom the youngest was 6 years old. Four percent were using hearing aids. The data of this study further confirm that the dip is progressive over time and may be detectable as early as at the age of 6, giving a chance to predict a future hearing loss. The findings emphasize the importance of regular otological examinations and audiological evaluations of all girls with Turner's syndrome early in life.