Mechanisms of Central Hypogonadism

Barber, Thomas M.; Kyrou, Ioannis; Kaltsas, Gregory; Grossman, Ashley; Randeva, Harpal S.; Weickert, Martin O.

doi:10.3390/ijms22158217

Cited by 28 publications

(15 citation statements)

References 121 publications

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“…Regarding psychosis spectrum disorders, in the presence of obesity the male overrepresentation typically observed in epidemiological studies only occurred in the first half of life with women matching male diagnoses rates around the age of 40 and surpassing them beyond this age. This may be owed to a reduced protective effect of female sex hormones against psychosis onset in women with obesity, potentially mediated by altered hypothalamus-pituitary-adreno signaling that accelerates the rise in psychosis spectrum disorders commonly observed in perimenopausal states [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Obesity as pleiotropic risk state for metabolic and mental health throughout life

et al. 2023

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Obesity, a highly prevalent disorder and central diagnosis of the metabolic syndrome, is linked to mental health by clinical observations and biological pathways. Patients with a diagnosis of obesity may show long-lasting increases in risk for receiving psychiatric co-diagnoses. Austrian national registry data of inpatient services from 1997 to 2014 were analyzed to detect associations between a hospital diagnosis of obesity (ICD-10: E66) and disorders grouped by level-3 ICD-10 codes. Data were stratified by age decades and associations between each pair of diagnoses were computed with the Cochran-Mantel-Haenszel method, providing odds ratios (OR) and p values corrected for multiple testing. Further, directions of the associations were assessed by calculating time-order-ratios. Receiving a diagnosis of obesity significantly increased the odds for a large spectrum of psychiatric disorders across all age groups, including depression, psychosis-spectrum, anxiety, eating and personality disorders (all pcorr < 0.01, all OR > 1.5). For all co-diagnoses except for psychosis-spectrum, obesity was significantly more often the diagnosis received first. Further, significant sex differences were found for most disorders, with women showing increased risk for all disorders except schizophrenia and nicotine addiction. In addition to the well-recognized role in promoting disorders related to the metabolic syndrome and severe cardiometabolic sequalae, obesity commonly precedes severe mental health disorders. Risk is most pronounced in young age groups and particularly increased in female patients. Consequently, thorough screening for mental health problems in patients with obesity is urgently called for to allow prevention and facilitate adequate treatment.

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Section: Discussionmentioning

confidence: 99%

Obesity as pleiotropic risk state for metabolic and mental health throughout life

et al. 2023

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“…INSR and other components of insulin signaling are present in all of these populations of hypothalamic neurons, although they are not found in GnRH-expressing neurons. It is important that the adipokine leptin uses the same mechanisms to stimulate GnRH production, being an insulin synergist in the activation of the hypothalamic links of the gonadal axis [ 354 , 355 ].…”

Section: Intranasal Insulin and The Gonadal And Thyroid Systemsmentioning

confidence: 99%

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

Zorina

Derkach

2023

IJMS

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A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI). Currently, INI is being considered as a promising drug to treat Alzheimer’s disease and mild cognitive impairment. The clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. At the same time, much attention has recently been paid to the prospects of using INI for the treatment of cerebral ischemia, traumatic brain injuries, and postoperative delirium (after anesthesia), as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes. This review is devoted to the prospects and current trends in the use of INI for the treatment of these diseases, which, although differing in etiology and pathogenesis, are characterized by impaired insulin signaling in the brain.

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“…However, in obese people, the hypothalamus becomes resistant to leptin. This leads to reduced expression of the gene for kisspeptin, and consequently, reduced GnRH secretion [ 184 ]. It was found that leptin might also modulate the expression and release of gonadotropins [ 183 ].…”

Section: Schizophrenia and Obesitymentioning

confidence: 99%

The Hypothalamic-Pituitary-Gonadal Axis in Men with Schizophrenia

Matuszewska

Kowalski

Jawień

et al. 2023

IJMS

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Schizophrenia is a severe mental disorder with a chronic, progressive course. The etiology of this condition is linked to the interactions of multiple genes and environmental factors. The earlier age of onset of schizophrenia, the higher frequency of negative symptoms in the clinical presentation, and the poorer response to antipsychotic treatment in men compared to women suggests the involvement of sex hormones in these processes. This article aims to draw attention to the possible relationship between testosterone and some clinical features in male schizophrenic patients and discuss the complex nature of these phenomena based on data from the literature. PubMed, Web of Science, and Google Scholar databases were searched to select the papers without limiting the time of the publications. Hormone levels in the body are regulated by many organs and systems, and take place through the neuroendocrine, hormonal, neural, and metabolic pathways. Sex hormones play an important role in the development and function of the organism. Besides their impact on secondary sex characteristics, they influence brain development and function, mood, and cognition. In men with schizophrenia, altered testosterone levels were noted. In many cases, evidence from available single studies gave contradictory results. However, it seems that the testosterone level in men affected by schizophrenia may differ depending on the phase of the disease, types of clinical symptoms, and administered therapy. The etiology of testosterone level disturbances may be very complex. Besides the impact of the illness (schizophrenia), stress, and antipsychotic drug-induced hyperprolactinemia, testosterone levels may be influenced by, i.a., obesity, substances of abuse (e.g., ethanol), or liver damage.

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Mechanisms of Central Hypogonadism

Cited by 28 publications

References 121 publications

Obesity as pleiotropic risk state for metabolic and mental health throughout life

Obesity as pleiotropic risk state for metabolic and mental health throughout life

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

The Hypothalamic-Pituitary-Gonadal Axis in Men with Schizophrenia

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