The Study Of Androgen Variation And Correlation Of Androgen Levels With Body Fat Mass And Fat Distribution In Middle-aged Women

Objectives1. To investigate the variation of DHEA, total testosterone, FAI level with menopause status and age in Chinese women aged40-60;2. To inspect the relationships between androgen level, AR gene polymorphism and body fat mass and fat distribution in Chinese women aged40-60;3. To explore the correlations of menopause status, age, physical activity with body fat mass and fat distribution, and analyze the impacts of androgen on these correlations.Methods1. Clinical data collection:Healthy women who were undergoing their annual health examination in PUMCH were recruited. General data was recorded with unified survey tables. Height and body weight was measured. BMI was calculated.2. Serum sex steroid hormone measurement:DHEA was measured by radioimmunoassay, while FSH and total testosterone by electrochemiluminescence method and SHBG by "sandwich"-like immunoradiometric method. FAI was calculated according to the following formula:(TT(nmol/L) X100)/SHBG(nmol/L).3. Assessments of physical activity level:Physical activity time in one week was recorded with the Chinese version of international physical activity questionnaire (IPAQ) short form. Energy expenditure was calculated via multiplication by corresponding metabolic equivalent.4. Measurements of body fat mass and fat distribution:Total and local fat tissue mass, fat-free tissue mass and fat tissue percent was measured by dual-energy X-ray absorptiometry.5. Androgen receptor gene CAG repeats determination:After PCR amplification, CAG repeats number was determined by GeneScan method with ABI3730XL sequencer.6. Statistical analysis:Statistical software SPSS16.0was used. The comparison between groups was conducted via one-way ANOVA. Pearson correlation and multivariants regression were performed. Nonparametric analysis was performed when necessary. The significance level was setted at0.05.Results1. Demographic results:The androgen level analysis included222cases with an average age of50.90and mean BMI of23.57. The average time since menopause in postmenopausal women was4.68years.The analysis of body fat mass and fat distribution involved138cases with an average age of52.28and mean BMI of23.40. The average time since menopause was4.92years.2. Comparison of DHEA, total testosterone and FAI levels among differen menopause status and age groups:DHEA level:DHEA of women aged51-55was higher than women aged47-51(borderline significance, P=0.057) and women aged55and over (P=0.001), but similar with women aged less than47. There was an increasing trend of DHEA level in late perimenopausal women, but it didn't reach statistical significance (P=0.064)Total testosterone level:There was no significant difference in total testosterone between reproductive age women and perimenopausal women, but an increasing trend in late perimenopausal women. Total testosterone level in postmenopausal women was lower than reproductive age women and perimenopausal women, with P value of0.001,0.035and0.001. As for the effect of age, total testosterone level in women aged55or more was significantly lower than women aged less than47.FAI:Compared with reproductive age women, there was no significant difference but a trend of increase of FAI in perimenopausal women. FAI level in postmenopausal women was lower than reproductive age women and perimenopausal women, with P value of0.014,0.027and0.010. As for the effect of age, no difference in FAI level was found among age groups in present study.3. Relationship of androgen levels, polymorphism of AR gene, menopause status, age and physical activity with body fat mass and fat distribution:Androgen levels:DHEA level was positively related with total body fat percentage, and the correlation was mild but significant (r=0.18, P=0.039). DHEA didn't related with A/G ratio. Total testosterone and FAI were correlated with total fat percentage. Before and after adjustment of BMI, FAI was always associated with A/G ratio.AR gene CAG repeats polymorphism:No difference of body fat mass or fat distribution was found among different genotypes of AR gene.Menopause status:After adjustment of BMI, body fat mass was related with menopause status. Compared with reproductive age women, total fat mass increased, and fat-free mass decreased in postmenopausal women. Even after adjustment of FAI, menopause status was associated with fat distribution parameters. Compared with reproductive age women, A/G ratio increased in perimenopausal and postmenopausal women. Age:After adjusted the effect of menopause status, the association between age and fat mass and fat distribution disappeared.Physical activity:PA energy expenditure was negatively associated with total fat mass. However, after adjustment of FAI level, this association disappeared. No effect of PA on fat distribution was found in present study.Conclusions1. The level of DHEA declined with age in general, but increased transiently at the age stage of51～55, and a similar trend was observed in TT level. However, the mechanism of these increases are unclear. This phenomenon may help to determine the start time of exogenous DHEA supplementation. DHEA was mild and positively related with total fat percentage. So exogenous DHEA supplementation should be administered with cautions and changes of CVD risk should be monitored.2. Higher level of FAI was related with increased total fat mass and centrally distributed fat mass. In late perimenopausal stage, the relative androgen excess occured and might be one cause of fat mass change in middle-life women.3. The impact of menopausal status on fat mass was not totally mediated by FAI, and the exact mechanism calls for further studies.4. In late perimenopausal stage, the relative androgen excess occured and body fat trend to deposit centrally. More benefit might be gained if certain management innitiated at late perimenopausal stage.