Anna Tani

Association of circulating adiponectin with testosterone in women during the menopausal transition

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.

Different circulating levels of monocyte chemoattractant protein-1 and interleukin-8 during the menopausal transition

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.

Associations of estrogen and testosterone with insulin resistance in pre- and postmenopausal women with and without hormone therapy.

Background Estrogen deficiency due to natural menopause or surgical menopause has been suggested to have an adverse effect on insulin resistance. Testosterone and sex hormone–binding globulin (SHBG) as well as estrogen are also associated with insulin resistance in women. However, to date, the associations of estradiol, testosterone and SHBG with insulin resistance according to estrogen level have not been clarified. Objectives We examined the associations of estradiol, testosterone and SHBG with insulin resistance in pre- and in postmenopausal women and postmenopausal women who had received hormone therapy to clarify whether the associations differ depending on the estrogen status. Patients and Methods Twenty premenopausal women and thirty-two postmenopausal women were enrolled in this study. Fifteen postmenopausal women received oral conjugated equine estrogen (CEE) (0.625 mg) everyday for 12 months. Serum levels of estradiol, testosterone, SHBG and insulin and plasma levels of glucose were measured. Results Serum estradiol levels tended to have a negative correlation with homeostasis model assessment of insulin resistance (HOMA-IR) in premenopausal women but not in postmenopausal women. On the other hand, free testosterone levels tended to have a positive correlation with HOMA-IR in postmenopausal women but not in premenopausal women. Serum SHBG levels showed significant negative correlations with HOMA-IR in both pre- and postmenopausal women. SHBG level was significantly increased, free testosterone level was significantly decreased and HOMA-IR was significantly decreased at 12 months after CEE administration. However, there were no significant correlations of changes between estradiol, SHBG or free testosterone and HOMA-IR. Conclusions The associations of sex steroid hormones with insulin resistance are different depending on the estrogen status.

Effect of ultra-low-dose estradiol and dydrogesterone on arterial stiffness in postmenopausal women

Abstract Background Ultra-low-dose estradiol is known to improve menopausal symptoms and increase bone mineral density. However, the effect of ultra-low-dose estradiol on vascular function has not been clarified. Objectives We examined the effects of ultra-low-dose estradiol on brachial-ankle pulse wave velocity (baPWV) and circulating markers of cardiovascular risk. Patients and methods Twenty-eight postmenopausal women were enrolled in this study. Fourteen women received oral estradiol (0.5 mg) and dydrogesterone (5 mg) every day for 12 months (ultra-low-dose group) as hormone replacement therapy (HRT) and 14 women as a control group did not receive HRT. The baPWV, lipid profiles, homeostasis model assessment of insulin resistance (HOMA-IR) and vascular inflammatory markers were measured. Results The baPWV level significantly decreased in the ultra-low-dose group (p = 0.037), while the baPWV level did not significantly change in the control group. HOMA-IR tended to decrease in the ultra-low-dose group (p = 0.076). Systolic blood pressure and diastolic blood pressure did not change significantly in either group. Conclusion An HRT regimen using oral ultra-low-dose estradiol and dydrogesterone has an effect on arterial stiffness and insulin resistance.

High adiponectin level in late postmenopausal women with normal renal function

BACKGROUND We examined whether high circulating adiponectin level is associated with renal function and is favorable for lipid and glucose metabolism in late postmenopausal women with normal renal function. METHODS We conducted a cross-sectional study in 115 postmenopausal women and divided the subjects into 2 groups (early postmenopausal women and late postmenopausal women). Serum levels of adiponectin, blood urea nitrogen, creatinine (Cr), glucose, insulin and lipid profiles were measured. Glomerular filtration rate (GFR) was estimated by age and Cr. RESULTS Serum adiponectin level in late postmenopausal women was significantly higher than that in early postmenopausal women, and eGFR in late postmenopausal women was significantly lower than that in early postmenopausal women. Adiponectin level showed a negative correlation with eGFR and tended to have a negative correlation with eGFR after adjustments for age, BMI and bioavailable testosterone in all subjects, but adiponectin level did not show a significant correlation with eGFR in late postmenopausal women. Adiponectin level in late postmenopausal women showed a significant negative correlation with triglyceride (TG) and a positive correlation with high-density lipoprotein cholesterol (HDL-C) after adjustments for age and BMI. CONCLUSION In late postmenopausal women with normal renal function, high adiponectin level is associated with favorable lipid profiles. High adiponectin level may be involved in not only eGFR but also other factors in late postmenopausal women.

Arterial stiffness is increased in young women with endometriosis

Endometriosis is a chronic gynaecological disorder that is accompanied by inflammation and oxidative stress. Atherosclerosis has a long subclinical progression in arteries of children and young adults decades before overt clinical manifestations of the disease. In this study, we determined arterial stiffness by measuring brachial-ankle pulse wave velocity (baPWV) in women with endometriosis to assess the presence of subclinical atherosclerosis. We also measured markers of inflammation and oxidative stress in women with endometriosis. baPWV in women with endometriosis aged over 30 years was significantly higher than that in women without endometriosis aged over 30 years (p < 0.05), but not in women aged less than 30. Serum high-sensitivity C-reactive protein level in women with endometriosis was significantly higher than that in controls (p < 0.05). Young women with endometriosis show significantly increased arterial stiffness, suggesting that women with endometriosis need to be cautious of the future onset of atherosclerosis.

Circulating levels of monocyte chemoattractant protein-1 and interleukin-7 in women who have undergone bilateral salpingo-oophorectomy.

Purpose The aim of the study reported here was to determine the effect of surgical menopause by bilateral salpingo-oophorectomy (BSO) on circulating levels of cytokines and chemokines related to the pathogenesis of atherosclerosis. Patients and methods A total of 110 women were recruited for this study from the outpatient clinic of our facility. We divided the women into three groups: 1) women with a regular menstrual cycle, 2) women in whom less than 5 years had passed since their BSO, and 3) women in whom 5 years or more had passed since their BSO. Concentrations of nine cytokines and chemokines in serum were measured. Results The serum monocyte chemoattractant protein-1 (MCP-1) level in women in whom less than 5 years had passed since their BSO was significantly higher than in women with a regular menstrual cycle (P<0.05). There were significant differences in serum interleukin (IL)-7 among the three groups (P=0.035). MCP-1 showed a significant positive correlation (r=0.320, P=0.008) with follicle-stimulating hormone in women with a regular menstrual cycle and in women in whom less than 5 years had passed since their BSO. Conclusion A hypoestrogenic state due to BSO induced changes in MCP-1 and IL-7 levels. MCP-1 level showed a significant increase in the early period after BSO, while IL-7 level showed a significant decrease in the late period after BSO.

Difference in the ratio of high-molecular weight (HMW) to total adiponectin and HMW adiponectin in late post-menopausal women.

Objective: High-molecular weight (HMW) isoform level and HMW ratio have been shown to be better predictors of insulin sensitivity and metabolic syndrome than total adiponectin level. We examined the changes in circulating levels of HMW adiponectin and ratios of HMW to total adiponectin in women during the menopausal transition. Methods: We conducted a cross-sectional study in 217 healthy women and divided them into 4 stages: 58 women in pre-menopausal, 69 women in perimenopausal, 62 women in early post-menopausal and 28 women in late post-menopausal phase. Serum levels of total adiponectin and HMW adiponectin were measured by an enzyme-linked immunosorbent assay. Results: In late post-menopausal women, HMW adiponectin level was significantly higher than that in peri-menopausal women and the HMW to total adiponectin ratio was significantly lower than that in early post-menopausal women. In peri-menopausal women, HMW adiponectin level was significantly lower than that in pre-menopausal women and HMW to total adiponectin ratio was significantly lower than the ratios in pre-menopausal and early post-menopausal women. Conclusion: The ratio of HMW to total adiponectin is low in late post-menopausal women, though both levels of total and HMW adiponectin were high after menopause in our cross-sectional study.

Changes in insulin sensitivity during GnRH agonist treatment in premenopausal women with leiomyoma

OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION Change in insulin sensitivity caused by GnRH agonist administration for premenopausal women with leiomyoma differs depending on baseline insulin sensitivity before treatment.