Diana Jędrzejuk1 , Andrzej Milewicz1 , Anna Arkowska1 , Urszula Mieszczanowicz1, Jerzy Chudek2 and Tomasz Zdrojewski3
(1)
Department of Endocrinology, Diabetology and Isotopes Therapy, Wroclaw Medical University, Pasteura 4, Wroclaw, 50-367, Poland
(2)
Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Francuska 20-24, Katowice, 40-027, Poland
(3)
Department of Preventive Medicine and Education, Medical University of Gdańsk, Dębinki 7, Gdańsk, 80-211, Poland
Diana Jędrzejuk
Email: diana.jedrzejuk@gmail.com
Andrzej Milewicz (Corresponding author)
Email: andrzej.milewicz@umed.wroc.pl
Anna Arkowska
Email: anna.arkowska@umed.wroc.pl
Jerzy Chudek
Email: chj@poczta.fm
Tomasz Zdrojewski
Email: tz@gumed.edu.pl
15.1 Introduction
Aging in women is associated with several hormonal and metabolic disorders. Sex hormone transformation in aging women is associated with fat distribution changes caused by insulin resistance and atherogenic lipids profile. Cardiovascular diseases (CVD) are the most common reason for mortality in women over 50 years of age. Several predictors can be recommended to recognize the risk of CVD such as body mass index (BMI) >30.0 kg/m2, waist circumference over 80 cm for women and 94 cm for men, serum fasting glucose >100.0 mg% (5.6 mmol/l), serum triglycerides >150.0 mg% (1.7 mmol/l), serum high-density lipoprotein (HDL) cholesterol <50.0 mg% (1.1 mmol/l) for women and <40.0 mg% (0.9 mmol/l) for men, and hypertension >130/85 mmHg [1].
15.2 Materials and Methods
The assumptions of the PolSenior study was described in detail elsewhere [2]. This study included subjects randomly selected out of 15.574 from the whole of Poland. A total of 1.971 women and 2.087 men aged 50–100 years old were studied. Anthropometric parameters (BMI, waist circumference), fasting glucose and homeostatic model assessment (HOMA), fasting triglycerides and HDL cholesterol were estimated using standard methods. Serum insulin, estradiol, testosterone, sex hormone-binding globulin (SHGB) were evaluated using radioimmunoassay (RIA) methods and the free androgen index (FAI) and the free estradiol index (FEI) were calculated.
15.3 Aim
The aim of the study was to answer questions:
1.
2.
3.
4.
15.4 Frequency of CVD Predictors in Aging Polish Women
Among the women participating in the PolSenior study the frequency of obesity was 39 % (overweight – 36 %). It is very difficult to compare this result with those of the rest of Europe because of the various methods of measurements and geographical and race differentiation (≥30 % according to a WHO report [3]). In our study obesity was most common among women between 65 and 74 years old (41 %). We also diagnosed malnutrition; the highest frequency (4.8 %) was detected among women over 90 years of age. There was a very large group of women with abdominal obesity – metabolic obesity with a waist circumference above 80 cm (86 %). On the other hand, serum fasting glucose above 100 mg% was detected only in 36 % of women. A more accurate measurement indicating glucose intolerance (HOMA) was calculated and 43 % of participating women had abnormal results. Lipid disturbances were also frequent; serum HDL cholesterol below 50 mg% was measured in 44 %, and serum triglycerides above 150 mg% in 30 % of aging women. The frequency of ideal metabolic women (the women met all the IDF Consensus Berlin criteria) was 8.8 %. These criteria are strongly connected with CVD morbidity. However, the correlation (p = 0.002) between age and BMI is negative (which can be concluded from the results described above). The correlation between age and serum HDL cholesterol is also negative and statistically significant (p = 0.012), which indicated the great influence of aging on increasing CVD risk factors.
We conclude that the frequency of obesity in Polish aging women (39 %) is higher in comparison to Europe (30 %) and the USA (33 %). Aging has a significantly negative influence on BMI and serum HDL cholesterol levels in women.
15.5 Sex Hormone Levels Correlate with CVD Predictors in Aging Women
Serum estradiol in aging, postmenopausal women is very low (most commonly less than 20–30 pg/ml). The increase in CVD risk factors after the menopause is often connected to lowering estradiol concentrations. In our results estradiol and FEI play an important negative role in aging women. The statistically significant positive correlations between estradiol and FEI were found with BMI, waist circumference, serum triglycerides, glucose, and HOMA, and the negative with HDL cholesterol. The relationship between serum estradiol and CVD risk factors is probably not linear.
Testosterone levels correlated positively only with BMI and HOMA, but FAI correlated positively with BMI, waist circumference, triglycerides, glucose concentration and HOMA with p = 0.0001, and negatively with HDL cholesterol (p = 0.0001). Serum SHBG is also expected to correlate with the same factors, but negatively (only HDL cholesterol correlates positively); p = 0.0001.
Many publications show the important role that endogenous dehydroepiandrosterone (DHEAS; weak androgen) concentrations play in CVD prevention [4, 5]. In our study serum DHEAS correlates with BMI and triglycerides positively (p = 0.035 and 0.005 respectively), which indicates the abnormal influence of endogenous DHEAS in elderly women.
Physiologically, the serum levels of sex hormones should be expected to lower with age. In the PolSenior study only serum testosterone did not correlate with age; serum estradiol, DHEAS, FAI, FEI and SHBG correlated significantly negatively with age in aging women.
We conclude that serum estradiol, the free estradiol index and free androgen index significantly correlated with CVD predictors in women. SHGB has a significant influence on CVD predictors in women but the influence of aging must be also included.
15.6 Endogenous Vitamin D Concentration Is Related to CVD Predictors in Women
The 3rd National Health and Nutrition Examination Survey (NHANES III) study assessed the mortality in 13,331 persons over 20 years of age in 1994–2000 and showed that the highest mortality rate was revealed in persons with vitamin D (25 OHD) deficiency; serum vitamin D level below 17.8 ng/ml is an independent mortality risk factor [6]. For bone health a vitamin D level of 30 ng/ml is optimal. Another observation of 182,152 persons shows a significant correlation between mortality and vitamin D deficiency [7]. In the PolSenior study we observed the negative correlation between serum vitamin D concentration and age (r = (−) 0.286; p = 0.001). After dividing the whole group of women into those below and those above a vitamin D level of 20 ng/ml we realized that there is no difference in the BMI, percentage of body fat, waist circumference and carbohydrate metabolism. Only total cholesterol and LDL cholesterol were statistically significantly higher in the group with a lower vitamin D concentration.
We conclude that endogenous serum vitamin D concentration decreases with biological age. In aging women with a level of vitamin D lower than 20.0 ng/ml, significantly higher serum total cholesterol and LDL cholesterol levels were observed. The serum vitamin D levels were not associated with obesity and carbohydrate metabolism disturbances in aging Polish women.
15.7 Thyroid Function in Aging Women
Serum TSH levels changes did not correlate with biological age in women participating in the PolSenior study. 47.9 % of women and 28.04 % of the men had elevated titers of anti-TPO. The thyroid disturbances were more often recognized in women than in men; the frequency of hypothyroidism was 10.35 and 5.3 % respectively, hyperthyroidism 3.52 and 2.38 %. What is most important is that up to 57.8 % of subjects with abnormal thyroid hormone concentrations were not treated. Another question is whether or not they should be treated, because subclinical hypothyroidism is not an absolute indication for the treatment.
15.8 Summary
1.
2.
3.
4.
5.
References
1.
Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group (2005) The metabolic syndrome – a new worldwide definition. Lancet 366(9491):1059–1062PubMedCrossRef
2.
Bledowski P, Mossakowska M, Chudek J et al (2008) Medical, psychological and socioeconomic aspects of aging in Poland: assumptions and objectives of the PolSenior project. Exp Gerontol 46(12):1003–1009. doi:10.1016/j.exger.2011.09.006CrossRef
3.
Branca F, Nikogosian H, Lobstein T (2007) The challenge of obesity in the WHO European Region and the strategies for response. WHO Library Cataloguing in Publication Data. World Health Organization. http://www.euro.who.int/__data/assets/pdf_file/0010/74746/E90711.pdf
4.
Savineau JP, Marthan R, Dumas de la Roque E (2013) Role of DHEA in cardiovascular diseases. Biochem Pharmacol 85(6):718–726. doi:10.1016/j.bcp.2012.12.004PubMedCrossRef
5.
Weiss EP, Villareal DT, Ehsani AA et al (2012) Dehydroepiandrosterone replacement therapy in older adults improves indices of arterial stiffness. Aging Cell 11(5):876–884. doi:10.1111/j.1474-9726.2012.00852.xPubMedCentralPubMedCrossRef
6.
Melamed ML, Michos ED, Post W et al (2008) 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 168(15):1629–1637. doi:10.1001/archinte.168.15.1629PubMedCentralPubMedCrossRef
7.
Saliba W, Barnett O, Rennert HS et al (2012) The risk of all-cause mortality is inversely related to serum 25(OH)D levels. J Clin Endocrinol Metab 97(8):2792–2798. doi:10.1210/jc.2012-1747PubMedCrossRef