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Maggi; Clinical and therapeutic aspects of Klinefelter's syndrome: Basic science of reproductive medicineVolume 16, Issue 6, 1 JunePages —, https: Klinefelter's syndrome KS is the most common sex chromosomal aberration among men, with estimated prevalence of about 1 in newborn males.

The classical phenotype of KS is widely recognized, but many affected subjects present only very mild signs. While the association between KS and infertility has been well documented, few studies have investigated sexual function in the KS patients.

In the present paper we reviewed studies addressed to emotional processing and sexual function in KS. We searched the following databases Medline, Pubmed, Embase, for Klinefelter's syndrome, sexuality.

We focus on the peculiar contribution of genetic and hormonal background, which characterizes sexual dysfunction in KS. Abnormal structure and function of the emotional brain circuits have been described in KS.

These alterations were less pronounced when the patients underwent to testosterone replacement therapy suggesting that they were mediated by testosterone deficiency.

Accordingly, clinical studies indicate that sexual dysfunctions, eventually present in KS, are not specifically Jm marquez wife sexual dysfunction with the syndrome but are related to the underlying hypogonadism.

In conclusion, androgen deficiency more than chromosomal abnormality is the major pathogenic factor of sexual dysfunction in KS. InHarry Klinefelter and colleagues described a male syndrome characterized by tall stature with eunochoidal body proportions, small testes, azospermia, gynecomastia and increased urinary excretion of FSH Klinefelter et al. The XXY karyotype occurs in 1 in live male births and is the most common type of human chromosome anomaly Smyth and Bremner, Unlike chromosomal abnormalities on autosomes, the 47,XXY karyotype leads to a relatively mild clinical presentation.

This mildness is probably due to inactivation of most genes on the supernumerary X chromosome Heard et al. However, there are genes that lie in the pseudo-autosomal region on the X chromosome that have homologues on the Y chromosome Jegalian and Page,and tend to escape the silencing during the supernumerary X chromosome inactivation process Carrel et al.

Nowadays, it is well recognized that Klinefelter's "Jm marquez wife sexual dysfunction" description of the syndrome is too limiting, because it represents a broad spectrum of phenotypes, professions, incomes and socio-economic statuses Lanfranco et al.

The issue related to infertility in KS have been significantly improved during the last 10 years by the advent of combined testicular sperm extraction, TESE Devroey, and assisted reproductive technologies ART Romundstad et al. This topic has been extensively covered by several recent reviews Paduch et Jm marquez wife sexual dysfunction. In contrast, the issue related to KS sexual function and dysfunction is less studied.

The evidence base on erectile...

In this review we provide an overview of available research studies investigating the pathogenesis of sexual function and dysfunction in KS. Sexual differentiation and behaviour is a multi-step process, which begins early in fetal life, according to the sex difference of the chromosomes established at conception chromosomal sex.

In fact, chromosomal sex determines gonadal production of androgens and the Mullerian inhibiting hormone gonadal sexwhich finally dictate the appearance of external and internal genitalia anatomic or phenotypic sex.

Sex differences between male and female brain organization and cognitive process occur either under the control of a complex series of genetic sex determining region YSRY; silencing of X chromosome; several epigenetic eventsbut also hormonal gonadal steroid hormones and their receptors events. SRY is the testis-determining gene, which causes the embryonic undifferentiated Jm marquez wife sexual dysfunction to develop into a testis rather than an ovary Goodfellow and Lovell-Badge, This event represents the primary developmental decision that will determine whether an individual will be and behave as a male or a female.

Indeed the embryonic testis secretes sex steroids, particularly the surge of testosterone during the early Jm marquez wife sexual dysfunction of development an epoch of extreme sensitivity to the environment that enters the brain causing a masculine pattern of brain development and behaviour. Sexual behaviour is controlled by a set of brain regions that do Jm marquez wife sexual dysfunction operate independently, but function in a background in which genetic and hormonal factors are crucial Pfaus, Hence, in order to answer the question of which is the main determinant of sexual dysfunctions, eventually present in KS subjects, we focused on the potential contribution of the peculiar genetic and hormonal background, which characterizes the syndrome.

A systematic search was performed using Medline up to February The search was limited to English-language papers. Sexual behaviour is controlled by a set of complex neuroanatomical and neurochemical pathways, which are commonly referred to as the emotional brain.

Among these, the amygdala occupies a very geometric centre and is deemed to be a highly connected hub. In particular, amygdala projections broadcast important regulatory signals widely to the prefrontal cortex and the hypothalamus Alheid, ; Swanson, Amygdala activation has been evidenced in rodents Minerbo et al.

More recently research in humans has found amygdala activation in response to sexual stimuli using functional magnetic resonance imaging MRI Karama et al. Previous studies in rats Cooke et al. Interestingly, a volume reduction in left temporal gray matter Patwardhan et al. A decreased cortical thickness in the temporal regions has been reported to be present also in child KS patients Rose et al. Taken together, findings from MRI studies show structural abnormalities of brain regions that form part of a neural network subserving social cognition and emotion Aleman et al.

Recently it has been proposed that in 47, XXY men reduced activation in the amygdala is responsible for the less accurate perception of socio-emotional cues and impairment in emotional prosody in comparison to the general population Van Rijn Jm marquez wife sexual dysfunction al. Interestingly, amygdala, the central hub in the emotional brain, is recognized to be subject to a high degree of androgen-dependent plasticity, even in the adulthood Cooke, as will be discussed below.

The reduced size of the amygdala Patwardhan et al. In particular, in a small study involving 10 subjects with KS, variation in brain morphology associated with supernumerary X chromosome was not present in the subgroup of KS subjects that had received testosterone supplementation since puberty. This suggests that the human brain retains plasticity to be continually modified by externally supplemented hormones, such as testosterone.

They demonstrated that female guinea pig exposed to testosterone during the fetal life permanently masculinized their sexual behaviour Phoenix et al. It is now well known that exposure to testosterone during gestation induces masculinization of the brain Arnold, ; Blaustein and McCarthy, ; Thornton et al.

Nevertheless, when prenatal testosterone was investigated in amniotic fluid, no significant difference was observed between XXY fetuses and XY controls, and both showed higher levels than the XX fetuses Ratcliffe et al.

Also in the neonatal period no indisputable hypoandrogenism Jm marquez wife sexual dysfunction apparent in KS subjects because of studies reporting a normal Ratcliffe, ; Aksglaede et al.

Recently, Neufang et al. Indeed, during puberty, neural connections between amygdala and frontal areas are strengthened Walker and Bollini, supporting a role for post-pubertal hormonal changes in the maturation and refinement of the limbic circuitry.

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