Gender Differences in the Clinical Manifestation of Depression and Related Neurotransmitters / 생물치료정신의학

Depression is almost twice as prevalent in women than men. Atypical symptoms, somatic complaints, and comorbid anxiety disorders are more common in women, whereas suicide and comorbid substance use disorders are more common in men. Previous studies have also reported gender differences in the efficacy of and tolerability to specific classes of antidepressants. Various psychosocial and biological factors have been proposed to explain the gender differences in clinical characteristics of depression. The predominant theory of depression pathogenesis is the monoamine hypothesis, and consequently, monoamine neurotransmitters have been the primary target of antidepressants. In the first section of this review, study findings of clinical differences in depression by gender are summarized. Then, we provide an overview of the findings from human and rodent studies of gender differences in serotonin, norepinephrine, dopamine, and glutamate neurotransmitter systems. Total level, rate of synthesis, and receptor profiles of neurotransmitters seem to differ by gender in the euthymic state, depressed state, and in responses to stress or antidepressants. Furthermore, these neurotransmitters interact with gonadal hormones and the hypothalamic-pituitary-adrenal axis, systems that innately exhibit gender differences. Although most of the studies conducted so far are limited to animal models and results of the studies are heterogeneous, growing evidence suggests that gender differences exist in neurotransmitter systems, which possibly leads to gender differences in depression. More intensive studies in this field are needed to build gender-specific treatment strategies.

Consideraciones clínicas y endocrinológicas en mujeres con trastorno bipolar / Clinical and endocrine considerations in bipolar women

El trastorno bipolar es una de las enfermedades mentales más discapacitantes. Existen diferencias en cuanto al tipo de episodios más frecuentes, la polaridad predominante y la frecuencia de comorbilidad según el sexo. En la mujer es importante considerar la etapa de vida reproductiva en que se encuentra, pues se sabe que puede influir en el curso de la enfermedad. Se ha informado una elevada comorbilidad del trastorno bipolar con trastorno disfórico premenstrual y una exacerbación de los síntomas en el período premenstrual en el 44% al 65%, que puede conducir a un peor curso de la enfermedad. El embarazo no parece incrementar la presencia de episodios de la enfermedad; sin embargo, el tratamiento se complica de forma importante, mientras que la suspensión de la medicación puede llevar a recaídas, el mantenerlo puede llevar a resultados obstétricos negativos, malformaciones congénitas e incluso alteraciones del neurodesarrollo. De tal manera que la evaluación de riesgo-beneficio en estas pacientes tiene que ser muy cautelosa. En el posparto, claramente se relaciona con un incremento en el riesgo de presentar algún episodio afectivo. Al llegar a la transición a la menopausia parecieran incrementarse los episodios de tipo depresivo. La relación entre el ciclo reproductivo y la presencia de episodios de enfermedad, así como los estudios en otras entidades psiquiátricas, han llevado a considerar que una relación entre las hormonas gonadales y los neurotransmisores podrían subyacer a esta entidad. En el presente artículo describimos algunas de las observaciones relacionadas con estrógenos, progesterona y sus metabolitos, testosterona y deshidroepiandrosterona

Bipolar disorder is one of the most disabling psychiatric illnesses. Some characteristics of the disorder vary with sex, such as predominant polarity, frequency and type of comorbidity, and type of episodes presented. In the case of bipolar women, it is important to consider reproductive events, due to their influence in the course of the disorder. High comorbidity of bipolar disorder and premenstrual dysphoric disorder with an exacerbation of symptoms in the premenstrual period has been reported in 44% to 65% which may lead to a worse disease course. In general, women with premenstrual symptom exacerbation show more affective - particularly depressive - episodes, more frequent relapses, and more severe symptomatology. Pregnancy does not appear to increase presence of bipolar episodes, but significantly complicates treatment. On the one hand, stopping the treatment, particularly abruptly, increases the risk of relapse; while on the other, the use of mood stabilizers represents a risk for the newborn. Poor neonatal outcomes, congenital malformations and neurodevelopment alterations in children of mothers exposed to mood stabilizers during pregnancy have been reported. So, a meticulous benefit-risk assessment should be carried out in pregnant bipolar women. In the postpartum period, a clearer relation with increased risk of affective episode has been observed; while the perimenopause increases depressive episodes. The inter-relation between reproductive cycle and bipolar episodes suggests that gonadal hormones are involved in their physio-pathology. Here we discuss some of the observations related to testosterone, dehydroepiandrosterone, estrogens, and progesterone

Male sexual dysfunction, leptin, pituitary and gonadal hormones in Nigerian males with metabolic syndrome and type 2 diabetes mellitus

Background: Pituitary and gonadal dysfunctions resulting from increased adiposity leading to disturbances of sexual and reproductive functions have been reported in males with metabolic syndrome [MS] and type 2 diabetes mellitus [DM2]. The aim of this study was to evaluate sexual dysfunction, leptin, and reproductive hormones in Nigerian males with MS and DM2

Methods: Participants were 104 men [34 males with DM2, 17 men with MS and 53 men with normal body mass index [18.5-24.9 Kg/m[2]] without MS [controls]]. The International Diabetes Federation [2005] criteria were used for MS diagnosis. Reproductive history, anthropometry, blood pressure [BP] and 10 ml fasting blood samples were obtained by standard methods. Fasting plasma glucose, total cholesterol, triglycerides and high density lipoprotein cholesterol were determined by enzymatic methods while low density lipoprotein cholesterol was calculated. Leptin, follicle stimulating hormone [FSH], luteinising hormone [LH], prolactin, testosterone and oestrogen were determined by enzyme immunoassay [leptin by Diagnostic Automation, Inc.; others by Immunometrics [UK] Ltd.] while oestrogen-testosterone ratio was calculated. Data analyzed using ANOVA, Chi square and multiple regression were statistically significant at p<0.05

Results: Testosterone was significantly lower in MS than controls while oestradiol and ETR were significantly higher in MS compared with controls and DM2 group [p<0.05]. ETR significantly predicted testosterone in all groups [p<0.05]. Significantly lower libido was observed in men in MS than controls and DM2 groups [p<0.05]

Conclusion: Sexual and reproductive dysfunction may be related to increased conversion of testosterone to oestrogen in increased adipose mass in men with metabolic syndrome and type 2 diabetes mellitus

Comparison of oral dydrogesterone with vaginal progesterone for luteal support in IUI cycles: arandomized clinical trial

The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone [cyelogest] for luteal support in intrauterine insemination [IUI] cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency [LPD] can reasonably be assumed. This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyelogest on luteal phase support in the IUI cycles. This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone [20 mg] as group A and vaginal cyelogest [400 mg] as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone [7 days after IUI] and patient satisfaction were compared between two groups, The mean serum progesterone levels was significantly higher in group A in comparison with group B [p=0.001]. Pregnancy rates in group A was not statistically different in comparison with group B [p =0.58]. Abortion rate in two groups was not statistically different [p =0.056] although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B [p<0.001]. We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyelogest group

Premature ovarian failure: a critical condition in the reproductive potential with various genetic causes

Premature ovarian failure [POF] is identified as a heterogeneous disorder leading to amenorrhea and ovarian failure before the age of 40 years. The first known symptom of the disease is having irregular menstrual periods. The phenotype appearance of POF depends significantly on the variations in hormones. Low levels of gonadal hormones [estrogens and inhibins] and increased level of gonadotropins [luteinizing hormone [LH] and Follicle stimulating hormone [FSH]] [hypergonadotropic amenorrhea] are well documented as causes of POF. There is an association between the failure of germ cell development and complete ovarian failure, and consistently decreased number of germ cells is more likely associated with partial ovarian failure resulting in secondary amenorrhea. A literature review on recent findings about POF and its association with genomic alterations in terms of genes and chromosomes. POF is a complex heterogeneous disorder. Some of POF cases are carriers of a single gene mutation inherited in an autosomal or X-linked manner while a number of patients suffer from a chromosome abnormality like Turner syndrome in mosaic form and manifest secondary amenorrhea associated with ovarian dysgenesis. Among many of the known involved genes in POF development, several are prove to be positively associated to the disease development in different populations. While there is a promising association between X chromosome anomalies and specific gene mutations with POF, genome-wide analysis could prove a powerful tool for identifying the most important candidate genes that influence POF manifestation

Sexual hormones modulate compensatory renal growth and function / Las hormonas sexuales modulan el crecimiento renal compensador (CRC) y la función renal en la uninefrectomía (uNx)

The role played by sexual hormones and vasoactive substances in the compensatory renal growth (CRG) that follows uninephrectomy (uNx) is still controversial. Intact and gonadectomized adult Wistar rats of both sexes, with and without uNx, performed at 90 days age, were studied at age 150 days. Daily urine volume, electrolyte excretion and kallikrein activity (UKa) were determined. Afterwards, glomerular filtration rate and blood pressure were measured, the kidneys weighed and DNA, protein and RNA studied to determine nuclei content and cell size. When the remnant kidney weight at age 150 days was compared with the weight of the kidney removed at the time of uNx, male uNx rats showed the greatest CRG (50%) while growth in the other uNx groups was 25%, 15% and 19% in orchidectomized, female and ovariectomized rats, respectively. The small CRG observed in the uNx female rats was accompanied by the lowest glomerular filtration value, 0.56 ± 0.02 ml/min/g kwt compared, with the other uNx groups, p < 0.05. Cell size (protein or RNA/DNA) was similar for all the groups except for uNx orchidectomized rats. In this group the cytoplasmatic protein or RNA content was lower than in the other groups while DNA (nuclei content) was similar. Some degree of hyperplasia was determined by DNA content in the uNx groups. Male sexual hormones positively influenced CRG and its absence modulated cell size. Female sexual hormones, instead, did not appear to stimulate CRG. The kallikrein kinin system may not be involved in CRG.

La importancia que pueden tener las hormonas sexuales y sustancias vasoactivas sobre el crecimiento renal compensador (CRC) que sigue a la uninefrectomía es aún materia de debate. Se estudiaron ratas Wistar de ambos sexos, a los 150 días de vida, intactas y gonadectomizadas con y sin uNx, realizada a los 90 días de vida. Se midió volumen urinario diario y excreción de electrolitos y actividad de kalikreína urinaria. Se midió filtrado glomerular y presión arterial media extrayéndose luego los riñones que fueron pesados y preparados para estudios histológicos y determinación de ADN, ARN y proteínas para estimar contenido nuclear y tamaño celular. El CRC fue calculado comparando el peso del riñón al momento de las uNx (90 dias de vida) con aquel obtenido a los 150 días de vida. En las ratas macho uNx se observó el mayor CRC (50%) mientras que, en los otros grupos uNx solo alcanzó un 25%, 15% y 19%. El filtrado glomerular acompañó los cambios morfológicos observándose el menor filtrado en las ratas hembras uNx respecto al resto de los grupos 0.56 ± 0.02, p < 0.05. El tamaño celular (proteína o ARN/ ADN) fue similar para todos los grupos excepto para los orquidectomizados uNx, cuyo contenido citoplasmático fue menor. El contenido nuclear (ADN) fue semejante en todos los grupos. Se observó que el CRC está influenciado positivamente por las hormonas sexuales masculinas y su ausencia modula el tamaño celular. La falta de hormonas sexuales femeninas, en cambio, afecta negativamente el CRC. El sistema kalikreína kinina no parecería estar involucrado en el CRC.

Irritable Bowel Syndrome and Migraine: Bystanders or Partners?

Irritable bowel syndrome (IBS) and migraine are distinct clinical disorders. Apart from the characteristics of chronic and recurrent pain in nature, these pain-related disorders apparently share many similarities. For example, IBS is female predominant with community prevalence about 5-10%, whereas that of migraine is 1-3% also showing female predominance. They are often associated with many somatic and psychiatric comorbidities in terms of fibromyaglia, chronic fatigue syndrome, interstitial cystitis, insomnia and depression etc., even the IBS subjects may have coexisted migraine with an estimated odds ratio of 2.66. They similarly reduce the quality of life of victims leading to the social, medical and economic burdens. Their pathogeneses have been somewhat addressed in relation to biopsychosocial dysfunction, heredity, genetic polymorphism, central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain network, gonadal hormones and abuses etc. Both disorders are diagnosed according to the symptomatically based criteria. Multidisciplinary managements such as receptor target new drugs, melantonin, antispasmodics, and psychological drugs and measures, complementary and alternatives etc. are recommended to treat them although the used agents may not be necessarily the same. Finally, the prognosis of IBS is pretty good, whereas that of migraine is less fair since suicide attempt and stroke are at risk. In conclusion, both distinct chronic pain disorders to share many similarities among various aspects probably suggest that they may locate within the same spectrum of a pain-centered disorder such as central sensitization syndromes. The true pathogenesis to involve these disorders remains to be clarified in the future.

Aportes al conocimiento del hipogonadismo hipogonadotrófico congénito / Contribution to the knowledge of the congenital hypogonadotropic hypogonadism

El hipogonadismo hipogonadotrófico congénito (HHC) es una forma clínica prepuberal de insuficiencia gonadal de origen hipotalámico por deficiencia congénita de la secreción de la hormona liberadora de gonadotrofinas (GnRH), vinculada a defectos cromosómicos. Material y métodos: Se describe 35 casos de HHC, 24 con alteración olfatoria correspondientes al síndrome de Kallmann, 21 varones y 3 mujeres y 11 con HH idiopático sin alteración olfatoria, 8 varones y 3 mujeres, de 12 a 40 años, promedio 20.9 años, que fueron evaluados clínicamente y mediante determinaciones de LH, FSH, testosterona (T), pruebas de GnRH e hipoglicemia insulínica, edad ósea, función tiroidea. Resultados: En todos se comprobó manifestaciones de hipogonadismo prepuberal, genitales infantiles, ausencia de caracteres sexuales secundarios, ausencia de interés y actividad sexual, amenorrea primaria en las 6 mujeres, proporciones eunucoides, edad ósea menor que la edad cronológica,concentraciones bajas de LH, FSH,T, las pruebas de GnRH e hipoglicemia fueron positivas, función tiroidea normal y cromatina sexual normal. Conclusiones: Se concluye que se trata de pacientes con hipogonadismo hipogonadotrófico hipotalámico congénito por deficiencia de GnRH.

The congenital hypogonadotropic hypogonadism (CHH) is a prepuberal clinical form of gonadal hypofunction due to a congenital hypothalamic deficiency of the gonadotropin releasing hormone (GnRH) related to chromosomial defects. Material and methods: A total of 35 cases of CHH, 24 with olfaction defects corresponding to the Kallman´s syndrome, 21 male and 3 female and 11 to the idiopathic hypogonadothrophic hypogonadism without olfactory defects, 8 male and 3 female, 12 to 40 years old, mean 20.9 years are described. Clinical evaluations as well as determinations of LH, FSH, testosterone (T), GnRH and insulin hypoglycemic tests, radiological bone age, thyroid function tests, sexual chromatin determinations were conducted. Results: All of them had clinical manifestations of prepuberal hypogonadism characterized by infantile genitalia, absence of secondary sexual characteristics, no sexual interest and activity, primary amenorrhea in the 6 female patients, eunuchoidal body proportions, bone age lower than the chronological one. These patients had low basal LH, FSH, T concentrations in blood, positive GnRH and hypoglycemia tests, normal thyroid function and normal sex chromatin. Conclusions: It is concluded that these patients suffered from a congenital hypothalamic hypogonadothropic hypogonadism due to GnRH deficiency.

Effects of prenatal lipopolysaccharide exposure on reproductive activities and serum concentrations of pituitary-gonadal hormones in mice offspring

Maternal infection during pregnancy is a risk factor for some behavioral problems with neurodevelopmental origin. This study aimed to evaluate the effects of exposure of pregnant mice to the bacterial lipopolysaccharide [LPS] on sexual behaviour and serum level of pituitary-gonadal hormones of offspring in adulthood. In this Expremental study, pregnant NMRI mice [n=7/group] were treated with intra-peritoneal administration of LPS [1, 5 and 10 micro g/kg] at day 10 of gestation. Induction of the pro-inflammatory cytokines, Tumor necrosis factor-alpha [TNF-alpha], interleukin-1beta [IL-1beta] and interleukin-6 [IL-6] were measured in maternal serum 2 hours following the maternal LPS challenge. Behavior in the adult male offspring reproductive activity was investigated using receptive female mice. Concentrations of testosterone, luteinizing hormone [LH] and follicle-stimulating hormone [FSH] in adult offspring serum were measured using the enzyme-linked immunosorbent assay [ELISA] method [at postnatal day 60, n=10/group]. One-way ANOVA showed that LPS administration induces a significant increase in TNF-alpha, IL-1beta and IL-6 levels of maternal serum. Prenatal LPS exposure reduces sexual behavior and serum concentration of LH and testosterone in adult male offspring. The overall results suggest that prenatal exposure to LPS increases pro-inflammatory cytokine levels, affects development of neuroendocrine systems and results in the inhibition of reproductive behaviors and reactivity of hypothalamic-pituitary-gonadal [HPG] axis in adult male offspring

Men Associated with Good Prognosis after Return of Spontaneous Circulation after Out-of Hospital Cardiac Arrest: a Retrospective Study in One Emergency Center / 대한구급학회지

BACKGROUND: The aim of this study was to analyze the gender factors associated with good or bad prognosis after return of spontaneous circulation after out-of hospital cardiac arrest. METHODS: The patients admitted to the intensive care unit after successful resuscitation after out-of hospital cardiac arrest were retrospectively identified and evaluated. Thirty days mortality after admission, and neurologic outcome at 6 months after hospital discharge (cerebral performance category [CPC]) were evaluated. RESULTS: One hundred forty-two patients were evaluated in this study; there were 101 males (71.1%). The median age was 52 years old (43-63). Thirty days after admission, 85 patients (59.9%) survived, 40 patients had a good neurologic outcome (CPC 1-2). The factors associated 30 days mortality were cause of arrest (non-cardiac, p = 0.03), lactate in emergency department (p = 0.05) and the factors associated with good neurologic outcome were males (p = 0.007), young age (p = 0.01), body weight and height (p = 0.001), cause of death (cardiac, p = 0.000). Alcohols and smoking were not associated with mortality and neurologic outcome. In multiple logistic regression analysis, men had a 8-fold increased good neurologic outcome (CPC 1-2) (odds ratio [OR] 8.038, 95% Confidence Interval [CI] 1.079-59.903). Other factors associated with good neurologic outcome were cardiac cause of death (OR 5.523, 95% CI 1.562-19.533) and young age (OR 1.055, 95% CI 1.009-1.103). CONCLUSIONS: Men had a good neurologic outcome after return of spontaneous circulation after out-of hospital cardiac arrest in one emergency center. Other additional factors including gonadal hormones should be evaluated.

Effects of Carthamus tinctorius on Semen Quality and Gonadal Hormone Levels in Partially Sterile Male Rats

PURPOSE: Traditional herbal medicine is just one of the many different approaches using plants in the remedy of diseases. Carthamus tinctorius (CT) or safflower is a popular plant that is used for coloring and flavoring in food industries. The effect of CT on spermatogenesis and sperm parameters has been reported in traditional medicine but has not yet been confirmed scientifically. Therefore, this study was designed to determine the effects of CT on spermatogenesis and the male reproductive system in an animal model. MATERIALS AND METHODS: Sixty male rats were divided into five groups. Four groups were injected with 5 mg/kg of busulfan as a model of partial infertility. Then, the experimental groups were treated with 10 mg/kg, 25 mg/kg, or 50 mg/kg of CT extract for 35 days. The control was treated with busulfan (infertile control) or distilled water only. After this period, the animals were sacrificed and blood samples were taken for hormonal assay. The semen was collected from the epididymis and the reproductive organs were assessed. Sperm count and motility were measured and smears were prepared for assessment of the other parameters. RESULTS: The results indicated that the percentage of sperm with good morphology, motility, and count increased significantly in the group treated with 10 mg/kg CT (p=0.002, p=0.03, and p=0.00001, respectively). The effects on hormonal changes and genital organ weights were also positive. CONCLUSIONS: It is probable that the CT extract affects spermatogenesis and as a result sperm quality. Further studies are needed.

Eight years evaluation of children with ambiguous genitalia attending the endocrinology clinic of Alexandria university children's hospital: a retrospective study

Ambiguous genitalia is a real problem in Egypt representing 5.5% of total number of endocrine patients in our study. There is a wide variation of the age at presentation. More than one third of our patients presented with adrenal crisis which is the most serious complication of ambiguous genitalia. Management of cases of DSD requires an experienced multidisciplinary team that is usually found in tertiary centers. Gender assignment in cases of DSD is a difficult challenge. Lack of some laboratory investigations or their higher cost as well as unavailability of some genetic analysis in developing countries are important causes of delayed diagnosis in these cases. The aim of the work was to review the clinical characteristics of children with ambiguous genitalia who attended the endocrinology clinic of Alexandria University Children's Hospital between 2002-2009 to categorize them depending on their clinical, laboratory and radiological findings and to study the response to therapy. All the records of children with ambiguous genitalia who attended the endocrinology clinic in Alexandria University Children's Hospital in the period from 2002 to 2009 were reviewed to obtain data from files regarding history, clinical examination, genital examination and grading, laboratory investigations, karyotyping, radiological findings, laparoscopic findings, final diagnosis, management plan, and gender assignment. This study included 77 children with ambiguous genitalia: Clinically, the sex of presentation was 49 females [63.6%], 21 male patients [27.3%], and 7 cases presented with undetermined sex [9.1%] while according to DSD classification, our patients were classified into 46 XX DSD [79.2%],46 XY DSD [19.5%], and Ovotesticular DSD [only one case]. The age of presentation ranged from 0.23-120 months with a mean of 11.07 +/- 20.03 months. Consanguinity among patient's parents was observed in 36.4%. 39% of our patients presented with adrenal crisis, and 5.2% were associated with other congenital anomalies. 3.8% had pubic hair at presentation and only one case had hypertension. In cases of 46 XXDSD, salt-losing type of congenital adrenal hyperplasia [21-Hydroxylase deficiency] was the commonest type representing 78.7%. In cases of 46 XYDSD, the most frequent diagnosis was androgen insensitivity syndrome that was present in 53.3%. Regarding to gender assignment, 48 cases were reared as females [62.3%] and ten cases were reared as males [13%], the same as their initial sex assignment by their families. 14 cases [18.2%] changed their gender from males to females and five cases [6.5%] had changed from female to male. From our study, we concluded that ambiguous genitalia is a real problem in our country representing 5.5% of total number of endocrine patients in our study. Management of cases of DSD requires an experienced multidisciplinary team that is usually found in tertiary centers. Gender assignment in cases of DSD is a difficult challenge. Lack of some laboratory investigations or their higher cost as well as unavailability of some genetic analysis in developing countries may delay and affects the final diagnosis of some cases of ambiguous genitalia

Male infertility and its association with metabolic syndrome and hypogonadism

Hormonal profile alteration is seen in men with metabolic syndrome. Obese men have elevated levels of estrone and estradiol and there is also an attenuation of the pulse amplitude of luteinizing hormone [LH] which leads to a reduction of testicular production of testosterone. This study was conducted to assess the sperm morphology, prevalence of metabolic syndrome and association between gonadal hormones and parameters of metabolic syndrome among men diagnosed with infertility. Out of 434 men referred to the laboratory of Gulf Medical College Hospital and Research Centre, Ajman, UAE, 184 were diagnosed as infertile based on seminal parameters. Prevalence of metabolic syndrome and gonadal hormonal level among these infertile men were also studied. Data were analyzed with PASW 18 software and student t-test used for the significance. Mean age of the men referred for seminal analysis was 33 +/- 7.2 years. Forty two percent of the men were found to be infertile based on seminal parameters. Majority had total forward progression abnormality followed by abnormalities of head, tail and neck. Prevalence of metabolic syndrome among these men was found to be 19%. FSH and LH levels were significantly lower and prolactin levels were significantly higher [p<0.01] in men with metabolic syndrome. Estradiol and total testosterone levels showed no difference. High prevalence of metabolic syndrome was found among men diagnosed with infertility. Significant hypogonadism was found associated with metabolic syndrome among these men

Effects of Long-Term Combination Treatment with Valproate and Atypical Antipsychotics on Bone Mineral Density and Bone Metabolism in Premenopausal Patients with Bipolar Disorder: A Preliminary Study

OBJECTIVE: We investigated bone mineral density (BMD) and bone metabolism in female bipolar patients who were undergoing long-term treatment with valproate combined with a low-dose atypical antipsychotic. METHODS: Nineteen premenopausal women with bipolar disorder who were treated with valproate combined with atypical antipsycho-tics for at least 2 years were evaluated. The BMD was measured at lumbar spine and femur sites using dual-energy X-ray absorptiometry (DE-XA). The biochemical markers of bone turnover and circulating levels of gonadal hormones were assessed. Subjects with abnormal DEXA scans were compared to those with normal scans. RESULTS: Nine (47%) of nineteen subjects showed osteopenia or osteoporosis. The T-score for subjects with abnormal DEXA scans was -1.988. Decreased BMD was more prominent in the proximal femur than in the lumbar spine. Subjects with abnormal DEXA scans had high phosphorus and low testosterone levels relative to subjects with normal scans (p=0.008 and p=0.028, respectively). There was a significant negative correlation between phosphorus, osteocalcin, and femur neck BMD (p<0.05). However, multivariate analysis did not show a significant association between femur and lumbar BMD and biochemical markers of bone turnover. CONCLUSION: Long-term treatment with valproate combined with low-dose atypical antipsychotics may adversely affect BMD in premenopausal women with bipolar disorder. A prospective, controlled-study with a larger population is warranted, and assessment of BMD and bone metabolism should be taken into consideration in long-term therapy with valproate and atypical antipsychotics.

Serum leptin levels in type-I diabetic children and adolescents versus healthy controls: relationship to age, gender, body mass index, gonadal hormones and pubertal stages

Since childhood and puberty are periods of major metabolic and endocrine changes, the present study was conducted to: [I] Evaluate developmental changes of serum leptin levels in children and adolescents with type-1 diabetes mellitus in comparison with matched healthy controls in respect with chronological age and pubertal stages [2] Evaluate if leptin concentration would be related to obesity observed in children and adolescents with type-1 diabetes during puberty. The study included 60 children diagnosed as type-1 diabetes mellitus by the criteria of American Diabetes Association [ADA] as well as 48 healthy children with matchable age and sex with diabetic patients. The patient and control children were grouped according to their chronological age into 4 groups [6-7yr, 8-10yr, 11-13 yr and 14-16yr] and according to stages of puberty into 3 groups: pre puberty P[1] early puberty P[2] and overt puberty P[3]. Serum leptin levels and BMI were measured to all patients and controls. Also, serum testosterone in boys and serum estradiol in girls were measured by ELISA method. Serum leptin levels significantly increased parallel with age and with pubertal stages both in control and diabetic girls. The maximum levels were observed at 14-16yr age group and at overt stage of puberty. Serum leptin levels were significantly higher in diabetic girls than controls at all studied groups. In control boys, leptin levels were significantly higher at 8-10yr and during P[1] stage then a significant decline occurred thereafter. In contrast, the diabetic boys showed no such decline either with age or with pubertal staging. Diabetic boys had significantly higher leptin levels than control boys at all studied groups. Serum leptin levels in girls were significantly higher than boys either in control or diabetic children. Diabetic children [girls and boys] were significantly older than controls during P[2] and P[3] stage. BMI was significantly increased In diabetic children [girls and boys] than controls during P[1], P[2] and P[3] stage whereas serum estradiol in diabetic girls and testosterone in diabetic boys were significantly lower than controls during P[2] and P[3] stages. Significant positive correlations were observed between serum leptin levels versus age, BMI and estradiol hormone in control girls. Also significant positive correlations were found in diabetic girls between serum leptin levels and each of age, BMI and estradiol hormone. In control boys significant negative correlations were observed between serum leptin level and each of age and testosterone hormone whereas non significant with BMI. Significant positive correlations were found in diabetic boys between serum leptin levels and each of age and BMI, while the correlation with testosterone was non significant. In conclusion leptin appears to participate in various endocrinological and physiological process in human body. Among the more notable are obesity and pubertal delay-associated diabetes. Thus, it may be involved in regulation of body weight and signaling the onset of puberty and maintenance of reproductive function thereafter

Molecular genetic and biochemical evaluation of ghrelin hormone as a novel signal of gonadal function in adult male rats

It is well known that reproductive function is regulated by the interplay of the hypothalamus, pituitary and gonads, which form the so called reproductive axis. A number of factors primarily involved in the control of energy balance and metabolism have been proven as putative modulators of the gonadal axis, thus providing the basis for the link between energy homeostasis and fertility. Ghrelin is a 28 amino acid peptide. It is predominantly produced by the endocrine X/ A- like cells of the stomach submucosa and mobilized by food deprivation. Ghrelin concentrations were observed to change with fasting and refeeding in mammals. The potential reproductive role of ghrelin has received attention recently. The Objective of this work is to study the effect of chronic food restriction on ghrelin level in adult male rats and it's relation to reproductive hormones. The present study was carried out on 32 adult male Sprague Dawley rats divided into 4 groups: Group I [control group] comprised 8 rats fed ad libitum for 30 days, Group II, III and IV [food-restricted groups for 10, 20 and 30 days respectively] each consisted of 8 rats fed 50% of ad libitum intake determined by the amount of food consumed by the control group. Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced significant increase of serum ghrelin with significant decrease of both gastric and hypothalamic ghrelin accompanied with significant increase in its gene expression in stomach and hypothalamus. Testosterone, follicle- stimulating hormone [FSH] and luteinizing hormone [LH] levels showed significant decrease correlated with down- regulation of gonadotropins, aromatase and kisspeptin [Kissl] genes in food restricted rats compared with control group. Ghrelin could be one of the hormones responsible for the suppression of male reproductive axis in case of negative energy balance. Thus, ghrelin could provide a link between energy homeostasis and reproductive capacity in adult male rats

Association of GnRH1 Polymorphisms with Rheumatoid Arthritis in a Korean Female / 대한정형외과학회잡지

PURPOSE: Rheumatoid arthritis (RA) is a common, chronic inflammatory arthritis that develops most often in women. Gonadal hormones may account for the sexual dimorphism in the immune response and for the greater incidence of autoimmune disease in females. Gonadotrophin-releasing hormone (GnRH), one of the gonadal hormones, plays an important role in immune system modulation. This study examined the effects of single nucleotide polymorphisms (SNP) in GnRH on gender differences in the pathophysiology of RA. MATERIALS AND METHODS: The presence of SNPs rs2659590, rs2321248, rs6186, rs6185, and rs2321049 in the human GnRH1 gene was confirmed in Korean RA patients by Taqman(R) SNP genotyping assays. A total of 153 unrelated female, Korean RA patients and 96 female Korean controls participated. RESULTS: There were no significant associations between GnRH1 polymorphisms and RA. However, we found that the rs2659590, rs6185 and rs2321248 polymorphism might be associated with a susceptibility to aberrantly high erythrocyte sedimentation rates in female RA patients. CONCLUSION: Additional studies, with a larger number of patients and in different populations will be required to assess whether GnRH1 polymorphisms and these haplotypes could be used as susceptibility or resistance markers in RA. To our knowledge, this study is the first to analyze associations between SNPs of GnRH1 and RA.

Effect of catgut implantation at acupoint on gonadal hormone and beta-endorphin in patients of climacteric syndrome / 中国针灸

<p><b>OBJECTIVE</b>To explore the clinical therapeutic effect of catgut implantation at acupoint on climacteric syndrome (CS) and its mechanism.</p><p><b>METHODS</b>Sixty cases were randomly divided into a catgut implantation group and a western medicine group, 30 cases in each group. The catgut implantation group was treated by catgut implantation at Shenshu (BL 23), Zigong (EX-CA 1), Sanyinjiao (SP 6). The western medicine group was treated by oral administration of Diethylstilbestrol tablet. Their therapeutic effects and changes of content of follicle-stimulating hormone (FSH), luteotrophic hormone (LH), estradiol (E2) and beta-endorphin (beta-EP) in serum were observed.</p><p><b>RESULTS</b>The total effective rate was 93.3% in the catgut implantation group and 70.0% in the western medicine group with a significant difference between the two groups (P < 0.05). After treatment, the beta-EP concentration in the catgutation implant group was significantly increased (P < 0.05), the FSH concentration was significantly reduced and E2 concentration was significantly increased as compared with those in the western medicine group (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Catgut implantation at acupoint has an obvious therapeutic effects on CS. It can significantly improve the ovaries function and has a favorable regulative action on the endogenous opioid peptides.</p>

Síndrome da apnéia-hipopnéia obstrutiva do sono. Fisiopatologia / Physiopathology of obstructive sleep apnea-hypopnea syndrome

A fisiopatogenia da apnéia obstrutiva do sono é multifatorial. O sexo, a obesidade, os fatores genéticos, anatômicos e hormonais e o controle da ventilação interagem diversamente na fisiopatogenia e expressão clínica da doença. A obesidade é o principal fator de risco, sendo a elevação do índice de massa corpórea, da gordura visceral e da circunferência do pescoço, fortes preditores de sua ocorrência. A progesterona, por aumentar a atividade dos músculos dilatadores das vias aéreas superiores, tem papel protetor nas mulheres antes da menopausa, justificando a maior prevalência da doença na pós-menopausa, no sexo masculino e na síndrome dos ovários policísticos. Evidências apontam para o fato de que o aumento da idade promove diminuição do tônus muscular, com redução da luz das vias aéreas superiores. O dismorfismo crânio-facial, como na retrognatia ou micrognatia, está associado ao posicionamento posterior da língua, e pode resultar em estreitamento da luz das vias aéreas superiores. Finalmente, comando ventilatório reduzido tem sido detectado em pacientes com síndrome de apnéia obstrutiva do sono e hipercapnia.

The physiopathology of obstructive sleep apnea syndrome is multifactorial. Gender and obesity status, as well as genetic, anatomic, and hormonal factors, together with ventilatory drive, interact in a diverse manner in the physiopathology and clinical expression of the disease. Obesity is the main risk factor, since increases in body mass index, visceral fat, and neck circumference are strong predictors of the disease. Progesterone increases the activity of the upper airway dilator muscles and therefore plays a protective role in premenopausal women. This explains the fact that the prevalence of the disease is higher in postmenopausal patients, in patients with polycystic ovary syndrome, as well as in males. Evidence supports the fact that, as individuals grow older, there is a decrease in muscle tonus, with a consequent reduction in the dimensions of the upper airway lumen. Craniofacial anomalies, such as in retrognathia or micrognathia, are accompanied by posterior positioning of the tongue and can result in narrowing of the upper airway lumen. Finally, decreased ventilatory drive has been detected in patients with obstructive sleep apnea syndrome and hypercapnia.