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ABSTRACT: OBJECTIVE: The aim of the present study was to clarify the changes in circulating cytokines and chemokines in women during the menopausal transition by using a detailed classification. MATERIALS AND METHODS: A total of 554 women were recruited for this study from the outpatient clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. We divided the women into seven stages by menstrual regularity and FSH level: mid-reproductive stage, late reproductive stage, early menopausal transition, late menopausal transition, very early postmenopause, early postmenopause and late postmenopause. We measured serum concentrations of nine cytokines (IL-1β, IL-5, IL-6, IL-7, IL-8, IL-10, TNF-α, MIP-1β and MCP-1). RESULTS: Serum IL-8 concentrations in postmenopausal women were significantly (p=0.001) higher than those in women in the mid- or late reproductive stage and women in early or late menopausal transition. Serum MCP-1 levels in women in late menopausal transition and postmenopause were significantly (p<0.001) higher than those in women in the mid- or late reproductive stage and women in early menopausal transition. MCP-1 level showed a significant positive correlation (r=0.215, p<0.01) with FSH level in women in menopausal transition. CONCLUSION: By using a detailed classification of menopausal transition, patterns of changes in IL-8 and MCP-1 levels during the menopausal transition were found to be different. IL-8 level showed a high level after menopause, while MCP-1 level showed a high level in menopausal transition. MCP-1 may be sensitive to hormonal change and may be involved in the development of estrogen deficiency diseases.
Cytokine 03/2013; · 3.02 Impact Factor
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ABSTRACT: Secretion of glucocorticoids is widely known as a key endocrine response to stresses. Prenatal dexamethasone administration induces intrauterine growth retardation and delayed onset of puberty in female rats independent of the hypothalamic Kiss1-gonadotropin-releasing hormone (GnRH) system. The aim of this study was to evaluate the influence of chronic intracerebroventricular (central, CD) or subcutaneous (peripheral, PD) dexamethasone administration to prepubertal female rats on the onset of puberty and body weight change. Rats administered dexamethasone from day 25 to day 34 (CD and PD) showed significantly reduced body weight gain throughout the experimental period and delayed onset of vaginal opening compared with rats administered saline centrally (CS) or peripherally (PS). At 34 days old, hypothalamic Kiss1r mRNA levels were significantly lower with CD than with CS. No significant differences were seen between rats administered saline and rats administered dexamethasone with regard to hypothalamic Kiss1, GnRH and NPY mRNA levels or serum LH levels. Serum leptin concentrations were higher in CD and PD than in the controls (CS and PS). These results suggest that the delayed onset of puberty induced by prepubertal dexamethasone administration occurs independent of the hypothalamic Kiss1-GnRH system.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 09/2012; 30(7):596-601. · 2.03 Impact Factor
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ABSTRACT: We examined (1) the change in circulating adiponectin in women during the menopausal transition and (2) the associations of adiponectin levels with estrogen, androgen and sex hormone-binding globulin (SHBG) in women during the menopausal transition.
We conducted a cross-sectional study in 235 healthy women and divided them into 7 stages by menstrual regularity and follicle-stimulating hormone (FSH) level. Serum levels of adiponectin, estradiol, total testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and SHBG were measured. Levels of free and bioavailable testosterone were calculated by using total testosterone, albumin and SHBG.
Serum adiponectin levels showed a U-curve, levels being low in early and late menopausal transition and gradually becoming higher after menopause. Adiponectin levels were negatively correlated with levels of free testosterone, bioavailable testosterone and DHEA-S and were positively correlated with SHBG in postmenopausal women for whom more than 1 year had passed since menopause. Adiponectin level was not correlated with estradiol level.
Circulating adiponectin level shows a U-curve during the menopausal transition and adiponectin level is associated with levels of free and bioavailable testosterone and DHEA-S in postmenopause.
Maturitas 08/2012; 73(3):255-60. · 2.77 Impact Factor
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Sumika Matsui,
Toshiyuki Yasui,
Anna Tani, Kotaro Kunimi,
Hirokazu Uemura,
Satoshi Yamamoto,
Akira Kuwahara,
Toshiya Matsuzaki,
Naoko Tsuchiya,
Mitsutoshi Yuzurihara,
Yoshio Kase,
Minoru Irahara
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ABSTRACT: The purpose of this study was to determine (1) the influence of estrogen deficiency induced by gonadotropin-releasing hormone (GnRH) agonist administration on insulin sensitivity as well as hormones and factors related to insulin resistance and (2) the differences in the influence for these parameters by the degree of basal insulin sensitivity.
Thirty-five women diagnosed with leiomyoma were enrolled in this study. Serum levels of fasting glucose, insulin, sex steroid hormones, sex hormone-binding globulin (SHBG), vascular inflammatory markers and cytokines before and at 6months after commencement of GnRH agonist administration were examined.
In all women, levels of insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) were not significantly changed. However, in women who had a low HOMA-IR before treatment, levels of insulin, glucose and HOMA-IR showed significant increases and total testosterone level showed a significant decrease. In women who had a high HOMA-IR, levels of insulin, HOMA-IR and SHBG were significantly decreased and levels of highly sensitive C-reactive protein, soluble intercellular adhesion molecule-1, E-selectin and monocyte chemoattractant protein-1 were significantly increased.
Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment.
Clinica chimica acta; international journal of clinical chemistry 02/2012; 413(11-12):960-5. · 2.54 Impact Factor
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ABSTRACT: Menopausal symptoms, bone loss, changes in lipid profiles and reduction of insulin sensitivity due to an abrupt decrease in circulating estrogen level are well known in women during the menopausal transition. On the other hand, the effect of androgen on women's health has not been fully elucidated. Circulating levels of testosterone and dehydroepiandrosterone sulfate (DHEA-S) gradually decrease with age in postmenopausal women, although transient increases have been observed during the menopausal transition. High testosterone level has been suggested to be associated with increased risk of cardiovascular disease, increased triglyceride, insulin resistance and increase in the risk of developing breast cancer in postmenopausal women. Circulating DHEA-S level does not affect the risk of cardiovascular disease, mortality or lipid profiles in women. Female androgen insufficiency, which is characterized by the presence of reduced androgen level in circulation, leads to an impairment in sexual drive, reduced libido, depressed mood, and signs and symptoms of limited androgen exposure such as decreased muscle mass, reduced bone density and decreased sense of well-being. An appropriate level of androgen may play important roles in metabolic, psychological and sexual functions in women. In addition, the roles of testosterone and DHEA-S in women's health may be different.
The Journal of Medical Investigation 02/2012; 59(1-2):12-27.
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Kotaro Kunimi,
Masahiko Maegawa,
Masaharu Kamada,
Satoshi Yamamoto,
Toshiyuki Yasui,
Toshiya Matsuzaki,
Akira Kuwahara,
Hiroyuki Furumoto,
Yasukazu Ohmoto,
Hiroshi Kido,
Minoru Irahara
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ABSTRACT: Myeloid-related protein-8 (MRP-8), MRP-14, and MRP-8/14 are found in a variety of inflammatory conditions and are involved in the host defense system. The objective of this study was to determine the concentrations of MRP-8, MRP-14, and MRP-8/14 in human cervical mucus and the associations between MRP-8/14 and proinflammatory cytokines. Samples of cervical mucus were obtained using a syringe from sexually active women (n=97) during the preovulatory phase. Samples from seven women were obtained using a swab placed in the cervical canal during the proliferative, preovulatory, and luteal phases. Concentrations of MRP-8, MRP-14, MRP-8/14, IL-1alpha, IL-6, IL-8, and granulocyte elastase were measured using an ELISA. The mean levels of MRP-8, MRP-14, and MRP-8/14 in cervical mucus were 1.87, 0.46, and 23.90microg/ml, respectively. The concentration of MRP-8/14 showed positive correlations with concentrations of IL-1alpha (p<0.0001), IL-8 (p<0.0001), and granulocyte elastase (p<0.0001). However, there were no significant differences in MRP-8/14 levels in the cervical mucus of each patient during the menstrual cycle. MRP-8/14 was mainly detected in human cervical mucus and showed a positive correlation with proinflammatory cytokines. The MRP-8/14 level in cervical mucus may be useful as a marker of inflammation of the uterine cervix.
Journal of Reproductive Immunology 08/2006; 71(1):3-11. · 2.97 Impact Factor
