Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables

The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but <7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) <30 kg/m(2). Adiponectin values were higher (P < 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/- 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P < 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P < 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle-aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status.     

Impact of the age at menarche on adult body composition in healthy pre- and postmenopausal women

The present study focuses on the impact of age at menarche on body composition development during adulthood. With 459 healthy middle-class women between 18 and 67 years (x = 41.5) the association between age at menarche and body composition was tested. Body composition, described by absolute and relative amount of fat mass, lean body mass, and bone mass, was estimated by means of dual energy x-ray absorptiometry. In order to exclude the influence of the menopausal transition on body composition, pre- and postmenopausal females were examined separately. The absolute amount of body fat was significantly lower within the group of women whose menarche occurred later. However, postmenopausal females exhibit less significant relations between the two trait systems than premenopausal women. This may be due to the impact of menopausal transition which affected the hormone levels and body composition development independently from the adolescent hormonal transition. While in both proband groups the quantitative amount of body fat was significantly related to menarcheal age, a significant relation between menarcheal age and adult body fat distribution could not be verified. Am J Phys Anthropol 105:9–20, 1998. © 1998 Wiley-Liss, Inc.     

Anthropometric and body composition characteristics in pre- and postmenopausal Asian Indian women: Santiniketan women study

The present cross-sectional study was aimed to investigate anthropometric and body composition characteristics in pre- and postmenopausal Asian Indian women. A total of 245 healthy women aged 25 to 65 years took part in the study. A random sampling procedure using a local voters' registration list was followed to select the participants. All participants belonged to the Bengalee population and were inhabitants of the Bolpur-Santiniketan area (lying in between 23 degrees 40' north latitude and 87degrees 43' east longitude) West Bengal, India. Before the actual commencement of the study, written information was communicated to select individuals, and an appointment was requested at their respective houses. Anthropometric measures, namely height, weight etc., were collected using standard techniques. Percentages of body fat (%BF) and body mass index (BMI) were measured using an Omron body fat analyser. All subjects were categorized into two groups: premenopausal (Group I; n = 145, mean age = 32.66 +/- 5.75 years) and postmenopausal (Group II; n = 100, mean age = 52.72 +/- 5.62 years). It was observed that 80.00% women were cohabited and 80.82% were housewife with 44.08% of them having an education up to secondary level. Furthermore, 62.45% subjects had monthly family expenditure of > or = 5000 Indian Rupees. One way ANOVA revealed that there was significant group difference for age, age at menarche, MWC, WHR, FM, FFM and %BF across the groups. Intercorrelation matrix (Pearson's correlation) showed that age had significantly positive association with MWC (p < 0.01), MHC (p < 0.05), WHR (p < 0.01), FM (p < 0.01), and %BF (p < 0.01), whereas FFM has had negative association with age. Most interestingly, it was observed that there was significant difference [chi2 (1) = 9.73] for central obesity status across the groups. It seems reasonable to argue that onset of menopause does play a vital role to alter body composition and in turn CVD risk factors.     

Association of eating frequency with body fatness in pre- and postmenopausal women

Objective: To examine associations between eating frequency (EF) and body fatness in pre‐ and postmenopausal women, after excluding potential low‐energy reporters. Research Methods and Procedures: In this cross‐sectional study of 220 free‐living women, 64 pre‐ and 50 postmenopausal non‐low‐energy‐reporting women were further analyzed (age, 24 to 74 years; BMI, 18.5 to 38.6 kg/m²). Anthropometric and body composition measurements (DXA) were performed in all study participants. EF, energy, and macronutrient intake were assessed by 3‐day food record. Physical activity level and energy expenditure were assessed by self‐reported questionnaire. Results: No association between EF and adiposity indices was detected in premenopausal women. In contrast, EF was positively correlated with percentage body fat in postmenopausal women (r = 0.30, p = 0.03). EF was positively correlated with total energy intake in both groups and with total energy expenditure in premenopausal women only (r = 0.34, p = 0.02). Multivariate analysis revealed that, in postmenopausal women, EF was a significant predictor of body fatness (standardized β = 0.41, p = 0.01). Discussion: Frequent eating was not found to be related to adiposity in premenopausal women, but it was associated with increased body fat in postmenopausal women. Possible explanations could be that the frequent eating is not associated with a physically active lifestyle in postmenopausal women or that frequent eating predisposes women after menopause to a higher energy intake by increasing food stimuli and rendering it more difficult for them to control energy balance.     

Excretion and metabolism of desogestrel in healthy postmenopausal women

The metabolism of desogestrel (13-ethyl-11-methylene-18,19-dinor-17-pregn-4-en-20-yn-17-ol), a progestagen used in oral contraceptives and hormone replacement therapy, was studied in vivo after a single oral administration of 150 μg [¹⁴C]-labeled desogestrel and 30 μg ethinylestradiol under steady state conditions to healthy postmenopausal women. After this oral administration, desogestrel was extensively metabolized. The dosed radioactivity was predominantly (60%) excreted via urine, while about 35% was excreted via the feces. Desogestrel was metabolized mainly at the C3-, C5-, C6- and C13-CH₂CH₃ positions. At the C3-position, the 3-keto moiety was found and in addition, 3β-hydroxy and 3-hydroxy groups were observed in combination with a reduced Δ⁴-double bond (5-H). Hydroxy groups were introduced at the C6- (6β-OH), the C13-ethyl (C13-CH₂CH₂OH) and possibly the C15- (15-OH) position of desogestrel. Conjugation of the 3-hydroxy moiety with sulfonic acid and conjugation with glucuronic acid were also major metabolic routes found for desogestrel in postmenopausal women. The 3-keto metabolite of desogestrel (the biologically active metabolite) was the major compound present in plasma at least up to 24 h after administration of the radioactive dose. Species comparison of the metabolic routes of desogestrel after oral administration indicates that in rats and dogs desogestrel is also mainly metabolized at the C3-position, similar to what is now found for postmenopausal women. Most other metabolic routes of desogestrel were found to differ between species. Finally, major metabolic routes found in the present study in postmenopausal women are in line with outcome of previous in vitro metabolism studies with human liver tissue (microsomes and postmitochondrial liver fractions) and intestinal mucosa.     

Estrogen receptor alpha and vitamin D receptor gene polymorphisms and bone mineral density: association study of healthy pre- and postmenopausal Chinese women

In the present study, we tested the association between the estrogen receptor alpha (ER-alpha) and vitamin D receptor (VDR) genes with bone mineral density (BMD). A total of 649 healthy Chinese women, classified as pre-menopausal (N=388) and post-menopausal (N=261) groups, were genotyped at the ER-alpha PvuII, XbaI, and VDR ApaI sites. BMDs at the lumbar spine (L(1)-L(4)) and total hip were measured by dual-energy X-ray absorptiometry. For the VDR ApaI locus, AA carriers had lower spine BMD than Aa (p=0.02) and aa carriers (p<0.01) in the pre-menopausal group. For the ER-alpha gene, carriers of haplotype px had lower spine BMD than the non-carriers (p=0.03) in the pre-menopausal group. Furthermore, we observed significant interaction between the ER-alpha and VDR genes in the post-menopausal group: with AA genotype (or A allele) at the VDR ApaI locus, pX carriers had higher spine BMD than the non-carriers (p=0.02), and PX carriers had lower hip BMD than the non-carriers (p=0.04). Our data suggest that the ER-alpha and VDR genes may be associated with the BMD variation in Chinese women.     

Adiponectin and negative mood in healthy premenopausal and postmenopausal women

Negative mood and stress are associated with cardiovascular and metabolic disease. There are likely many physiological mechanisms underlying the poor health outcomes. The relationship of psychological states (negative mood, life stress, and stress-responsive hormones) and adiponectin, an adipokine that promotes insulin sensitivity, was investigated in two separate studies. The two groups of participants included 52 healthy, premenopausal women, and 63 postmenopausal women with a range of stress levels. The relationship between adiponectin and psychological state (perceived stress and negative mood) was examined cross-sectionally in both groups of participants, but also prospectively (1 year later) in the group of postmenopausal women.In premenopausal women, negative mood and nocturnal urinary epinephrine were significantly related to adiponectin, independent of BMI. In postmenopausal women, negative mood was not associated with adiponectin cross-sectionally, but negative mood was a significant predictor for lower levels of adiponectin 1 year later, independent of initial adiponectin concentrations and changes in body mass index. Lastly, having a depressive disorder was related to lower adiponectin. As adiponectin levels are associated with insulin resistance, obesity, and diabetes mellitus, these findings suggest there may be an adiponectin-mediated pathway explaining in part how negative mood affects metabolic health. Mechanistic studies are needed to explore this potential relationship further.     

Hormone and metabolic factors associated with leptin mRNA expression in pre- and postmenopausal women

Recent information has extended leptin's action, beyond the control of appetite, to various sites of metabolic regulation. To better understand leptin's role we studied its production in subcutaneous and visceral fat compartments before and after menopause. During elective abdominal surgery, biopsies of subcutaneous and omental tissues were taken from 20 women at pre- (BMI 28.4 +/- 4.5 kg/m2) and 10 at postmenopause (BMI 30.6 +/- 7.7 kg/m2). In both groups serum leptin levels were similar, and highly correlated with BMI. In subcutaneous adipose tissue, leptin mRNA expression was significantly higher in pre- than in postmenopausal women (50.4 +/- 20.5 amol/microg total RNA versus 34.5 +/- 24.9 amol/microg total RNA, respectively). Leptin mRNA expression in subcutaneous tissue was independently correlated with fasting glucose (R = 0.89, P < 0.006) at premenopause, and with serum estradiol (R = 0.77, P < 0.04) at postmenopause. Leptin mRNA expression in visceral fat was correlated with DHEAS (R = 0.86, P < 0.001), at premenopause. These results indicate that in both compartments, leptin production is sensitive to different but overlapping stimuli, conveying information about energy availability to central and peripheral sites under different conditions of estrogen exposure.     

Blood pressure risk factors in healthy postmenopausal women: physical activity and hormone replacement

Stevenson, Edith T., Kevin P. Davy, Pamela P. Jones,Christopher A. Desouza, and Douglas R. Seals. Blood pressure risk factors in healthy postmenopausal women: physical activity and hormonereplacement. J. Appl. Physiol. 82(2):652-660, 1997.The prevalence of cardiovascular disease (CVD)increases with advancing age in women, particularly after menopause.CVD risk is lower in physically active women relative to theirsedentary peers, but the responsible mechanisms are not wellunderstood. The aims of this study were to test the hypotheses that1) physically active postmenopausalwomen demonstrate more favorable blood pressure (BP)-related riskfactors for CVD than do sedentary healthy women and2) women on hormone replacementtherapy (HRT) also have more favorable levels of these CVD riskfactors. BP-related CVD risk factors were measured in physically activewomen (n = 18; age 55 ± 1 yr;n = 8 on HRT) and in healthyless-active controls (n = 34; age 59 ± 1 yr; n = 17 on HRT). Maximaloxygen consumption was higher in the active group, whereas waist-to-hipratio and waist circumference were lower (allP < 0.005). The activewomen demonstrated marginally lower (5-8 mmHg;P  0.10) levels of casual, 24-h, anddaytime systolic BP (SBP). They also tended to have lower(P = 0.11) daytime SBP loads(percentage of BP recordings >140/90 mmHg) and lower daytime andnighttime BP variabilities (P = 0.04)and a reduced (P < 0.007) SBPresponse to submaximal exercise. Women on HRT tended to have lower(3-4 mmHg; P = 0.07) levels of24-h and nighttime diastolic BP (DBP) relative to the nonusers andsmaller (P < 0.04) daytime and 24-hDBP loads. Stepwise multiple regression indicated that waistcircumference was the primary predictor of most of the SBP-related CVDrisk factors while HRT use was the best predictor for DBP loads. Thesefindings indicate that, in general, physically active postmenopausalwomen demonstrate more favorable SBP-related CVD risk factors relative to their less-active healthy peers, which may be mediated, in part, bytheir lower levels of abdominal adiposity. In addition, HRT use tendsto be associated with lower levels of DBP-related CVD risk factors.

     

Hormone replacement therapy increases renal kallikrein excretion in healthy postmenopausal women

Hypertension and its related increase in cardiovascular morbidity in postmenopausal women is a major public health problem. The hypotensive property of urinary kallikrein has been described since 1909. Despite the controversy surrounding the effects of hormone replacement therapy on blood pressure regulation, its mechanisms remain incompletely understood, and no evidence has yet been provided for its effects on renal kallikrein excretion in postmenopausal women. In a double-blind, randomized study we examined the effects of hormone replacement therapy in the form of 2 mg 17-beta estradiol (ERT) or 2 mg 17-beta estradiol combined with continuous 5 mg medroxyprogesterone acetate (HRT) on urinary kallikrein excretion in postmenopausal women. Thirty-nine postmenopausal women collected their urine for 24 hours on two separate occasions 3 months apart. During the 3 month period women were randomized to placebo, ERT, or HRT. Urine samples were assayed for kallikrein activity, normalized to urine creatinine and expressed as mU/gm creatinine. Urinary kallikrein excretion increased significantly after 3 months in the ERT (p < 0.001) and HRT (p < 0.01) groups, and decreased non-significantly in the placebo group (p > 0.06). There were no significant blood pressure changes after 3 months of therapy. The findings demonstrate that hormone replacement therapy in the form of estrogen or estrogen combined with continuous medroxyprogesterone is effective in increasing urinary kallikrein excretion. Given that a decrease in kallikrein excretion may mark risk for development of hypertension, the findings of this study are of value in demonstrating a novel mechanism underlying cardioprotective properties of postmenopausal hormone replacement therapy in women without pre-existing coronary disease.     

Relations between anxiety, psychophysiological variables and menstrual cycle in healthy women

The present study was designed to explore whether changes occur in psychophysiological variables in healthy women not suffering from premenstrual tension. Variations in electroencephalogram frequencies, reaction time, somatosensory evoked potentials, and nerve conduction velocity were examined in a sample of 30 women, in relation to scores from the Hamilton Psychiatric Rating Scale for Depression and the State-Trait Anxiety Inventory. Trials and recordings were done weekly. EEG frequencies decreased before menstruation in all subjects. However, there were no significant changes for reaction time, nerve conduction velocity, HAMILTON nor State-Trait Anxiety scales associated with subperiods of the menstrual cycle. To explore the impact of anxiety, high and low anxiety groups were formed. The high anxiety group showed the highest scores in the A-Trait form, longer reaction time, enlarged latencies of the P100, but shorter nerve conduction velocity. Anxiety scores as well as reaction time increased during the premenstrual period only for the low anxiety group. The authors conclude that for some women premenstrual anxiety may be related to previous and continuous high levels of anxiety, which associated with some subtle neurological differences as compared with women who rated in low scores for anxiety.     

Differential influence of peripheral and systemic sex steroids on skeletal muscle quality in pre- and postmenopausal women

Aging is associated with gradual decline of skeletal muscle strength and mass often leading to diminished muscle quality. This phenomenon is known as sarcopenia and affects about 30% of the over 60-year-old population. Androgens act as anabolic agents regulating muscle mass and improving muscle performance. The role of female sex steroids as well as the ability of skeletal muscle tissue to locally produce sex steroids has been less extensively studied. We show that despite the extensive systemic deficit of sex steroid hormones in postmenopausal compared to premenopausal women, the hormone content of skeletal muscle does not follow the same trend. In contrast to the systemic levels, muscle tissue of post- and premenopausal women had similar concentrations of dehydroepiandrosterone and androstenedione, while the concentrations of estradiol and testosterone were significantly higher in muscle of the postmenopausal women. The presence of steroidogenetic enzymes in muscle tissue indicates that the elevated postmenopausal steroid levels in skeletal muscle are because of local steroidogenesis. The circulating sex steroids were associated with better muscle quality while the muscle concentrations reflected the amount of infiltrated fat within muscle tissue. We conclude that systemically delivered and peripherally produced sex steroids have distinct roles in the regulation of neuromuscular characteristics during aging.     

Excretion balance and metabolism of the progestagen Org 30659 in healthy postmenopausal women

Metabolism of Org 30659 ((17alpha)-17-hydroxy-11-methylene-19-norpregna-4, 15-dien-20-yn-3-one), a new potent progestagen currently under clinical development by NV Organon for use in oral contraception and hormone replacement therapy, was studied in vivo after oral administration to healthy postmenopausal women. After oral administration of [14C]-Org 30659 to postmenopausal women, the compound was extensively metabolized. The dosed radioactivity was predominantly excreted via urine. Org 30659 was to a large extent metabolized at the C3- and the C17-positions. Phase II metabolism, and in particular conjugation with glucuronic acid at the 17beta-hydroxy group, is the major metabolic route for Org 30659 in vivo. Not only phase II metabolism was observed for Org 30659 after oral administration to postmenopausal volunteers, but also metabolism in the A-ring occurred, especially reduction of the 3-keto-Delta(4) moiety to give 3alpha-hydroxy, 5alpha(beta)-dihydro and 3beta-hydroxy, 5alpha-dihydro derivatives. Oxidative metabolism (6beta-hydroxylation) observed in human liver preparations in vitro, was not observed to a significant extent in vivo. So, in vitro human metabolism is different from the in vivo metabolism, indicating that the in vitro-in vivo extrapolation is far from straightforward, at least when only liver preparations are used. The proper choice of the in vitro system (e.g., microsomes, hepatocytes, slices or individually expressed enzymes) and the substrate concentration can be very important determinative factors for the predictability of the in vitro system for the in vivo situation. Species comparison of the metabolic routes of Org 30659 after oral administration indicated that the monkey seems to be a better representative species than the rat for the metabolism of Org 30659 in humans.     

Cardiovascular, anthropometric and neurocognitive features of healthy postmenopausal women: effects of hormone replacement therapy

Randomized clinical trials have not shown long-term benefit of postmenopausal hormone replacement therapy (PHT) nor have they shown conclusively that the harmful consequences outweighs the benefits of the treatment. Rather, it is possible that an individualized hormone replacement therapy in questionably clinically healthy postmenopausal women may lead to different results than randomized trials. DESIGN: In this cross-sectional study we evaluated anthropometric parameters, body composition, serum lipids, blood pressure, heart rate variability (HRV) and neurocognitive functions in 39 healthy postmenopausal women PHT users or not users (n=13, age 53.0+/-3.3 and n=26, age=53.3+/-5.0 SD, respectively) as well as in 27 younger controls (ages=33.3+/-7.1). RESULTS: Demographic parameters were similar in women PHT users and not users. Postmenopausal women showed a significantly increase of body mass index (BMI) as well as of waist circumference, compared to younger controls, but in PHT users the values of fat free mass were intermediate between the ones of not treated and younger women. The study of HRV showed a reduction in low frequency (LF) component (sympathetic modulation) during the day, and a reduction in high frequency (HF) component (parasympathetic modulation), particularly in postmenopausal women without PHT. PHT users were characterized by autonomic parameters intermediate between younger controls and age-matched women without PHT. CONCLUSIONS: The impact of PHT on the age-dependent changes of anthropometric features and body composition seems to be modest but positive. Furthermore, PHT seems to play a positive role on the autonomic modulation of cardiac function, through a shift of LF/HF ratio values towards those of young controls.     

Soy isoflavones, diet and physical exercise modify serum cytokines in healthy obese postmenopausal women

Objectives

Evaluate the effect of diet, physical exercise, and a daily oral intake of a soy isoflavones extract (Fisiogen^®) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) on leptin and other adipokines plasma levels in healthy obese postmenopausal women.

Methods

A multicentric randomized longitudinal prospective cohort study was conducted in a sample of 87 healthy obese postmenopausal women. Patients were randomly assigned to a 1200 kcal diet and exercise group (control group) or a group of 1200 kcal diet, exercise, and daily oral intake of daily oral intake of a soy isoflavones extract (Fisiogen^®) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) (soy isoflavones group) along 6 months. Main outcome measures were: anthropometric measures, body composition, leptin, adiponectin, TNF-alpha, homocysteine, C-reactive protein, glucose, insulin, lipid profile and oestradiol serum levels, Kupperman index and Cervantes Scale.

Results

Mean serum leptin and TNF-alpha levels declined after 6 months in both groups of the study, but only women in the soy isoflavones group showed a significant increase of mean serum levels of adiponectin.

Conclusions

Diet, physical exercise and daily oral intake of a soy isoflavones extract (Fisiogen^®) contained 200 mg of Glycine max, which corresponded to 80 mg of isoflavone (60.8 mg of genistein, 16 mg of daidzein and 3.2 mg of glicitein) have a beneficial effect on serum leptin, adiponectin and TNF-α in healthy obese postmenopausal women after 6 months of treatment.     

The prolactin response to intravenous dextroamphetamine in normal young men and postmenopausal women

D-amphetamine was administered intravenously in doses of 0.1 mg/kg and 0.15 mg/kg to normal young men and postmenopausal women in both morning and evening. No suppression of PRL secretion after amphetamine was found, and, in the postmenopausal women, no significant change in PRL levels in any dose or time condition occured. However, a significant and relatively consistent PRL release was induced in the young men in the evening by the higher dose. This latter response suggests that, in humans, dextroamphetamine can actually stimulate prolactin perhaps by a mechanism other than alteration in dopaminergic tone.