Grażyna Bednarek-Tupikowska
1, Anna Jodkowska
2,
Jolanta Antonowicz-Juchniewicz
2Zinc, Cooper, Manganese, and Selenium Status
in Pre- and Postmenopausal Women During Sex
Hormone Therapy
Stężenia cynku, miedzi, manganu i selenu u kobiet menopauzalnych
przyjmujących terapię hormonalną
1 Department of Endocrinology, Diabetology, and Isotope Treatment, Wroclaw Medical University, Poland 2 Department of Internal Medicine, Occupational Diseases, and Hypertension, Wroclaw Medical University,
Poland
Abstract
Background. The impact of estrogen deficiency after menopause on trace minerals has not been widely studied.
Objectives. The aim of this study was to compare trace mineral levels of postmenopausal women with those of premenopausal women of similar age and to determine the impact of estrogen (ET) and estro-progestin (HT) therapy on them.
Material and Methods. E2, FSH, Cu, Zn, Se, and Mn concentrations in serum and/or whole blood in 80 post-menopausal women (M1 group: 26 with surgically induced and 54 with physiological menopause) and in 40 pre-menopausal controls (C) were determined. In the M1 group the measurements were repeated after 4 months of ET or HT.
Results. The study showed that trace mineral status in the postmenopausal women was slightly different from that of the C. The serum Zn level after menopause was considerably higher than that of the C and tended to decrease after ET, whereas it remained unchanged after HT. Serum Mn level after menopause was similar to that of the con-trols, but it decreased significantly after ET, whereas it remained unchanged after HT. The rest of the trace element concentrations showed only slight changes.
Conclusions. The precise impact of estrogen deficiency after menopause and hormonal therapy on trace mineral status needs further large-population studies (Adv Clin Exp Med 2010, 19, 3, 337–345).
Key words: copper, zinc, selenium, manganese, menopause, hormonal therapy.
Streszczenie
Wprowadzenie. Wpływ niedoboru estrogenów na stężenia metali śladowych u kobiet po menopauzie nie został dotychczas dobrze poznany.
Cel pracy. Zbadano, czy stężenia Zn, Cu, Se i Mn w surowicy i krwi pełnej kobiet przed i po menopauzie różnią się oraz oceniono wpływ terapii estrogenowej (ET) i estroprogestagenowej (HT) na stężenia tych metali.
Materiał i metody. Porównano 80 zdrowych kobiet po menopauzie (54 – naturalnej, 26 – chirurgicznej) i 40 przed menopauzą (K). Oznaczano stężenia E2, FSH w surowicy oraz Zn, Cu, Se i Mn w surowicy i krwi pełnej, przed i po
4-miesięcznej terapii: u kobiet z zachowaną macicą – HT, u kobiet z menopauzą chirurgiczną – ET.
Wyniki. Wykazano, że stężenia metali śladowych u kobiet po menopauzie nieznacznie różnią się od stężeń obser-wowanych w grupie kontrolnej. Stężenie cynku w surowicy było większe u kobiet po menopauzie niż w grupie kontrolnej i pod wpływem terapii estroprogestagenowej (HT) nieznacznie zmniejszało się, pozostając bez zmian pod wpływem terapii estrogenowej (ET). Wyjściowo porównywalne między badanymi grupami stężenie man-ganu w surowicy istotnie zmniejszyło się pod wpływem ET i pozostało niezmienione pod wpływem HT. Stężenia pozostałych badanych mikroelementów zmieniały się jedynie w nieistotnym zakresie.
Wnioski. Dokładne określenie wpływu niedoboru estrogenów na stężenia metali śladowych u kobiet po menopau-zie i znaczenia terapii hormonalnej w tym aspekcie wymaga przeprowadzenia dalszych badań na większej populacji (Adv Clin Exp Med 2010, 19, 3, 337–345).
Słowa kluczowe: miedź, cynk, selen, mangan, menopauza, terapia hormonalna.
Adv Clin Exp Med 2010, 19, 3, 337–345 ISSN 1230-025X
OrIGINAl PAPErS
The decrease in sex steroid hormones during menopause in women causes a number of distur-bances in the metabolisms of different organs. In this period of life, the risk of osteoporosis, cardio-vascular diseases, arterial hypertension, impair-ment of glucose metabolism, breast cancer, and degenerative cognition diseases rises. The detailed mechanisms of this effect are still being investi-gated. The impact of estrogen deficiency after menopause on trace minerals has not yet been widely studied, but the expected menopause-related alterations in trace mineral status may have an impact on the above pathologies [1–4]. Several trace elements, particularly Ca, Mg, Cu, Mn, and Zn, are essential in bone metabolism [5, 6]. The authors previously examined the serum and whole-blood Ca and Mg concentrations in pre- and postmenopusal women before and after hormonal therapy, showing that menopausal women have significantly higher blood calcium levels than premenopausal women, which prob-ably results from higher bone resorption of those cations. The authors observed that the blood Ca level decreased after four months of therapy with estrogens or estro-progestins, becoming compa-rable to that of premenopausal subjects. The Mg concentration showed a similar, but not statisti-cally significant tendency to Ca concentration [7]. Some investigators have also shown that in post-menopausal women serum Zn level negatively correlates with serum glucose level, whereas in pre-menopausal ones it correlates positively. This may suggest that menopause induced changes in Zn metabolism may have an impact on glucose tolerance [47].
Some trace minerals are cofactors of antioxida-tive enzymes. Se is a cofactor of glutathione peroxi-dase (GSH-Px), one of the most important enzymes of the free-radical defense system. Zn and Cu mol-ecules are integrated elements of superoxide mutase (Cu/Zn-SOD). Manganese superoxide dis-mutase (MnSOD) is a major enzyme responsible for the detoxification of reactive oxygen species in the mitochondria. The protective activities of the enzymes are dependent on the redox capability of the cations. The authors recently demonstrated that total antioxidant status (TAS) in untreated postmenopausal women is lower and after hor-monal therapy it rises to a level comparable to that of premenopausal women [8]. It is thought that disturbances in trace mineral status during menopause may impair the antioxidative defense of postmenopausal women, enhancing the oxida-tive stress involved in most degeneraoxida-tive organ processes. It is documented that hormonal therapy has beneficial impact on the prooxidant-antioxi-dant balance in postmenopausal women [8–11].
Some investigators have shown that hormonal replacement therapy antagonizes the decrease in SOD activity that occurs after menopause [12]. It is also supposed that hormonal therapy may influ-ence trace mineral status.
The aim of this study was to compare the trace mineral status of postmenopausal women with that of healthy, regularly cycling women of similar age and to determine the impact of estrogen and estro-progestin therapy on it.
Material and Methods
Constitution of the Groups
One hundred and twenty healthy women were investigated. The study group consisted of 80 post-menopausal women (M1 group) who were divid-ed into two subgroups: 26 women with surgically induced menopause (ET1 group) with a mean age of 50.9 ± 2.9 years and 54 women with physiologi-cal menopause (HT1 group) with a mean age of 50.5 ± 3.0 years. The control group (C) comprised 40 premenopausal healthy volunteers with a mean age of 48.3 ± 2.3 years. Every subject underwent physical and laboratory examination. Each of investigated women presented normal findings of blood cell count test, liver function test, serum glu-cose, urea and creatinine tests. None of the subjects were on a special diet, none were cigarette smok-ers, and none had used any medication during the four months proceeding the onset of the study. All the patients were informed about the aims and the methods of the study and gave their informed consent. The study protocol was approved by the Bioethics Committee of the Wroclaw Medical University, Poland.
All the postmenopausal women were treated for four months (M2 – the postmenopausal group after treatment). The ET1 group received estra-diol (E2) transdermally (estrogen therapy – ET) in a dose of 50 μg daily (the ET1 group after treat-ment was designated as the group ET2). The HT1 group received combined hormonal therapy (HT) consisting of E2 given transdermally in a dose of 50 μg daily and medroxyprogesterone acetate (MPA) administered in sequential fashion in a dose of 5 mg daily for 12 days in the second phase of the cycle (the HT1 group after treatment was desig-nated as the group HT2).
Sample Collection
Trace Mineral and Hormone
Analyses
Serum E2 concentration was determined by radioimmunoassay (rIA, Diagnostic Products Corporation, los Angeles, CA, USA) and serum FSH concentration was determined by immuno-radiometric assay (IrMA, Biodata Diagnostics, rome, Italy).
Blood samples for Se measurement were microwave digested with nitric acid in a self-contained system. A Plazmatronika-Servis BM-11 Microwave Digestion Unit with high-density Teflon vessels was used. The digestion of samples was followed by a reduction step with concentrat-ed hydrochloric acid to convert Se(VI) to Se(IV). Se levels were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) on an Arl 3410 ICP vacuum spectrometer using the 196.094 nm spectral line with hydride genera-tion (the online Arl hydride generator produced by rOTH, Karlsruhe, Germany, and 1.43% potas-sium borohydride solution were used). The cali-bration curves were obtained using blood, a sele-nium reference solution (Aldrich), and the Merck 9976 Titrisol reference solution. Nycomed refer-ence materials were controls.
Cu, Zn, and Mn concentrations in serum and whole blood were determined by atomic absorption spectrophotometry on a SOlAAr M6 (Thermo Elemental). For Cu and Zn measurements an air-acetylene flame was used at the 324.8 nm wave-length for Cu and 213.9 nm for Zn with deuterium background correction. The reference material PEAK PErFOrMANCE certified by ICP-NIST SrM 3114 was used. For the Mn measurement an electrographite cuvette was used at the wavelength of 279.5 nm with Zeeman’s background correc-tion. Seronorm Whole Blood 3 SPEX Certiprep 2 (Dalston Gardens Stanmore Middlesex HA7 1BQ, UK) was used as the reference material.
Statistical Analysis
Statistical analysis was performed using Student’s t-test; p-values < 0.05 were considered statistically significant. Correlation analysis was performed by calculating Pearson’s or Spearman’s correlation coefficients. results were considered statistically significant with p < 0.05.
Results
The postmenopausal women had a signifi-cantly lower mean serum E2 level and higher FSH level than the C group. After HT and ET, serum E2
rose significantly and serum FSH fell significantly in the postmenopausal groups (Table 1).
The whole-blood (Znb, Cub, Seb) and serum
(Zns, Cus, Ses, Mns) trace metal concentrations in
postmenopausal women before and during substi-tution therapy and in the control group are pre-sented in Table 2. The whole-blood Zn, Se, and Cu concentrations were not statistically different between the groups M1, M2, and C. Zn serum level was significantly higher in group M1 than in C and did not change after sex hormone therapy. In the ET1 and HT1 groups the serum level of Zn was significantly higher than in the C group. After ET the serum Zn concentration tended to decrease, but the difference was not statistically significant, whereas in the group treated with estro-proge-stin (HT), the serum Zn concentration remained unchanged after therapy. The whole-blood Zn concentration in M1 was not significantly higher than in C and after administration of both types of therapy it tended to decrease slightly, becoming similar to C. Whole-blood and serum Se concen-trations in the M1 and M2 groups did not differ significantly from those of the group of healthy controls. It rose slightly in whole blood, whereas it rather tended to decrease in plasma after both types of therapy, but all the differences were not statistically significant. Whole-blood and serum Cu concentrations in M1 were not significantly lower than in C and showed a tendency to rise after both types of therapy, becoming comparable to those of C. The serum Mn concentrations in the M1 and M2 groups were not significantly different from that of the controls (C). It decreased after estrogen therapy, achieving a significantly lower level in the ET2 group than before therapy (in ET1) and in the premenopausal controls (C), whereas in the group treated with estro-progestin (HT), the serum Mn concentration remained unchanged after therapy.
There were no statistically significant cor-relations in each group of women between the concentrations of the studied trace minerals in the serum or whole blood and serum hormone concentrations before and after both types of sex hormone therapy. There were also no correlations observed between the trace metal levels and clini-cal features, such as BMI or systolic and diastolic blood pressure.
Discussion
of Zn in serum and whole blood than premeno-pausal, but the difference is significant only for the serum Zn level. Similarly, a previous study of a Czech population reported that blood Zn con-centration increased with age in women [13]. In another study, higher urinary Zn loss in post-menopausal non-HT women was observed which was also associated with higher Ca and Mg uri-nary loss [14]. Own study shows that hormonal therapy does not significantly alter elevated serum and whole-blood Zn concentrations in postmeno-pausal women, but a slight tendency to decrease is observed. It is suggested that higher Zn concen-tration in postmenopausal women, which is also involved in bone metabolism, might be an effect of the increased bone resorption that appears with
estrogen deficiency. Studies by some investiga-tors have demonstrated a decrease in plasma Zn concentration accompanied, in some cases, by a reduction in urinary Zn loss, both induced by the administration of estrogens to postmenopausal women [14–18]. An indirect confirmation of these data is also a decrease in Zn serum level reported in a study of healthy pregnant women [19]. Own study is compatible and confirms the already exist-ing observations. The decrease in Zn level may be partially due to a decrease in circulating albumins [14, 15], but intestinal Zn absorption or increased bone Zn buildup could also be affected. In experi-mental research on rats it was shown that intesti-nal absorption of Zn considerably decreased with age. It is supposed that similar changes may play
Table 1. Clinical features and sex hormones concentrations of the groups
Tabela 1. Charakterystyka kliniczna i stężenia hormonów płciowych w badanych grupach Group
(Grupa) Weight(Masa ciała) (kg)
BMI
(kg/m2) WHr rr(mm Hg)systolic rr(mm Hg)diastolic Age – years
(Wiek – lata)
FSH
(mIU/ml) E(pg/ml)2
M1
(n = 80) x 69.3± 12.0 26.03± 4.25 0.78± 0.47 138.1
a, d
± 18.4 88.3
a, d
± 11.7 50.9
a
± 2.9 82.1
a,d
± 36.9 12.4
a,d
± 9.3 SD
M2
(n = 80) x 69.4 ± 11.6 26.05 ± 4.09 0.77 ± 0.42 132.9
d
± 16.7 85.2
d
± 9.5 50.9 ± 2.9 45.8
d, e
± 26.5 48.9
d, e
± 27.1 SD
ET1
(n = 26) x 71.9
b, f
± 12.6 26.45 ± 4.56 0.79 ± 0.05 143.9
b, f, h
± 20.7 94.1
b, f, h
± 10.6 51.6
b
± 2.6 75.7
b,h
± 37.5 13.8
b, h
± 7.0 SD
ET2
(n = 26) x 71.7
g, j
± 12.4 26.39 ± 4.46 0.78 ± 0.04 136.0
h, j
± 18.5 88.4
h, j
± 10.4 51.6 ± 2.6 52.5
h, j
± 21.1 45.1
h, j
± 8.7 SD
HT1
(n = 54) x 67.7
f
± 11.5 25.75 ± 4.09 0.78 ± 0.04 131.5
f
± 15.4 83.3
f
± 10.0 50.5
c
± 3.0 87.0
c, i,
± 36.3 11.4
c, i
± 10.7 SD
HT2
(n = 54) x 67.9
g
± 10.9 25.84 ± 3.89 0.77 ± 0.04 131.1 ± 15.4 83.2 ± 8.4 50.5 ± 3.0 40.71
i,k
± 29.3 56.9
i, k
± 33.9 SD
C
(n = 40) x 67.5
b, j
± 8.6 26.23 ± 4.12 0.78 ± 0.04 130.3
a, b, j
± 14.7 82.2
a, b, j
± 9.1 48.3
a, b, c
± 2.3 7.70
a, b, c, e, j, k
± 4.56 118.6
a, b, c, e, j, k
± 66.5 SD
M1 – postmenopausal group before treatment. M1 – grupa kobiet po menopauzie przed leczeniem hormonalnym.
M2 – postmenopausal group after treatment. M2 – grupa kobiet po menopauzie po leczeniu hormonalnym.
ET1 – group with surgical menopause before ET. ET1 – grupa kobiet po menopauzie chirurgicznej przed ET.
ET2 – group with surgical menopause after ET. ET2 – grupa kobiet po menopauzie chirurgicznej po ET.
HT1 – group with natural menopause before HT. HT1 – grupa kobiet po menopauzie naturalnej przed HT.
HT2 – group with natural menopause after HT. HT2 – grupa kobiet po menopauzie naturalnej po HT.
C – control group. C – grupa kontrolna.
x – average. x – średnia.
SD – standard deviation. SD – odchylenie standardowe. Statistically significant differences between groups (p < 0.05):
Statystycznie istotne różnice między grupami (p < 0,05):
a – M1 & C b – ET1 & C c – HT1 & C d – M1 & M2 e – M2 & C f – ET1 & HT1 g – ET
2 & HT2 h – ET1 & ET2 i – HT1 & HT2 j – ET
a role in the human trace element balance in later life [20]. Many studies of menopausal women reported higher Ca and Mg serum concentrations than in healthy cycling women which were asso-ciated with higher urinary loss of these ions. The administration of HT has been reported to reverse these changes [7, 14, 21–24]. There is an analogy between Ca and Mg concentration changes and postmenopausal fluctuations of Zn concentration. The reversion of changes in Mg and Ca, as well as Zn, blood concentration and urinary excretion after HT may be partially ascribed to an estrogen-induced increase in the bone buildup process, which is crucial for preventing osteoporosis.
In own study, whole-blood and serum Se con-centrations in the M1 and M2 groups did not differ statistically significantly from those of the group of the healthy cycling controls. Serum Se concentra-tion showed only a slight tendency to be higher than in controls, whereas the whole-blood Se level appeared to be lower than in the healthy cycling women. These data on the serum Se level corre-spond with other authors’ observations. Smith et al., in a cross-sectional study of three generations of women in America, observed that the serum Se concentration in women aged 40–58 years was significantly higher than that of their daughters and mothers [25]. Another study of a Portuguese
Table 2. Whole-blood (Znb, Cub, Seb) and serum (Zns, Cus, Ses, Mns) trace metal concentrations in postmenopausal women
before and during substitution therapy and in the control group
Tabela 2. Stężenia metali we krwi pełnej (Znb, Cub, Seb) i w surowicy (Zns, Cus, Ses, Mns) u kobiet menopauzalnych przed
i w trakcie terapii hormonalnej oraz w grupie kontrolnej Group
(Grupa) (μg/ml)Znb Zn(μg/ml)s Cu(μg/ml)b (μg/ml)Cus Se(μg/ml)b Se(μg/ml)s Mn(μg/l)s M1
n = 80 x 496.4 ± 113.2 105.3
a
± 18.3 95.8± 16.2 111.8 ± 19.5 66.1 ± 10.1 57.7 ± 9.8 3.051 ± 1.362 SD
M2
n = 80 x 474.8 ± 102.7 105.0
e
± 18.0 99.7 ± 20.4 113.3 ± 20.9 69.3 ± 10.7 56.9 ± 10.4 3.096 ± 1.716 SD
ET1
n = 26 x 514.5 ± 138.5 103.9
b
± 20.9 94.8 ± 19.2 112.1 ± 22.4 68.8 ± 15.5 56.7 ± 8.9 3.172
h
± 1.487 SD
ET2
n = 26 x 487.6 ± 121.4 102.1
j
± 17.1 96.5± 27.5 114.9 ± 20.4 70.1 ± 12.6 55.8 ± 9.5 2.327
h, j
± 1.569 SD
HT1
n = 54 x 484.8 ± 93.7 106.2
c
± 16.7 96.49 ± 14.9 110.9 ± 18.1 65.1 ± 9.5 58.1 ± 9.6 2.999 ± 1.318 SD
HT2
n = 54 x 468.1 ± 81.3 106.7
k
± 18.7 101.8 ± 14.3 112.8 ± 21.1 68.5 ± 8.8 57.2 ± 11.2 3.609 ± 1.635 SD
C
n = 40 x 477.6 ± 91.4 93.2
a, b, c, e, j, k
± 16.5
98.6
± 16.4 114.0 ± 19.8 67.1 ± 10.8 56.8 ± 11.3 3.473
j
± 1.438 SD
M1 – postmenopausal group before treatment. M1 – grupa kobiet po menopauzie przed leczeniem hormonalnym.
M2 – postmenopausal group after treatment. M2 – grupa kobiet po menopauzie po leczeniu hormonalnym.
ET1 – group with surgical menopause before ET. ET1 – grupa kobiet po menopauzie chirurgicznej przed ET.
ET2 – group with surgical menopause after ET. ET2 – grupa kobiet po menopauzie chirurgicznej po ET.
HT1 – group with natural menopause before HT. HT1 – grupa kobiet po menopauzie naturalnej przed HT.
HT2 – group with natural menopause after HT. HT2 – grupa kobiet po menopauzie naturalnej po HT.
C – control group. C – grupa kontrolna.
x – average. x – średnia.
SD – standard deviation. SD – odchylenie standardowe. Statistically significant differences between groups (p < 0.05):
Statystycznie istotne różnice między grupami (p < 0,05):
a – M1 & C b – ET1 & C c – HT1 & C d – M1 & M2 e – M2 & C f – ET1 & HT1 g – ET
2 & HT2 h – ET1 & ET2 i – HT1 & HT2 j – ET
population showed an age-dependent increase in serum Se level, regardless of sex [26]; the same was found in a study of a Czech population [13]. The slightly, but not statistically significantly, higher serum Se concentration in the group of post-menopausal women in our study, who were a little bit older than the controls, agrees with the above data. Own study showed that HT did not signifi-cantly alter Se levels. It increased slightly in whole blood, whereas it rather decreased in plasma after both types of therapy. Ha et al., who observed Se fluctuation during the menstrual cycle in healthy young women, had different findings. They noted that during the estrogen peak in the periovulatory phase the serum Se concentration as well as serum and erythrocyte GPx activities were greatest com-pared with the other phases of the ovulatory cycle [27]. In own previous study on antioxidant defense in postmenopausal women the authors also found a simultaneous increase in erythrocyte GSH-Px and whole-blood Se concentration (indicating the Se erythrocyte level) during HT [8].
Ha et al. found in their investigation a posi-tive relationship between plasma estrogen and Se; a similar relationship was found by Smith et al. in a cross-sectional study of American daughters, mothers, and grandmothers [25, 27]. Own data did not confirm such a relationship.
The whole-blood and serum Cu concentra-tions in our study were slightly, but not statistical-ly significantstatistical-ly, lower than in the controls, which agrees with previous reports by other authors that the Cu concentration decreases with age in women [13]. The authors showed that the administration of estrogens and/or estroprogestins during hor-monal replacement therapy caused a tendency to increase Cu concentration to the level of the controls. These data are similar to those of the other investigators. In the study by Bureau and colleagues, hormone therapy in postmenopausal women caused a significant increase in serum cop-per level, while it remained unmodified by treat-ment in erythrocytes [14]. The recent study of a Portuguese population reported that hormonal replacement therapy does not significantly affect serum Cu concentration [26]. Other studies show that the administration of sex hormones in oral contraceptives is connected with an increase in serum copper concentration [13, 28]; similarly, it has been shown in Spanish and Polish populations that serum Cu level increases progressively during pregnancy, when estrogen levels are higher than in non-pregnant women [19, 29]. It has also been experimentally shown that estrogen deficiency leads to a decrease in copper content in rat teeth and mandible, and giving 17 beta-estradiol positively influences the content of mineral components in
these tissues [30]. The impact on Cu concentration has been ascribed to an estrogen-induced release of ceruloplasmin in the liver [28, 31]. An adequate copper status plays a crucial role in osteoporosis [30, 32]; however, the fact that in cohort studies high serum Cu levels have been associated with increased cardiovascular mortality [33–35], heart failure [36], and cardiac markers in acute coronary syndromes [37] cannot be neglected in the discus-sion. Estrogen and hormonal therapy might have some influence on increasing Cu concentration, which may be considered negative for the cardio-vascular system, but the crucial influence of estro-gens on the cardiovascular system is beneficial and depends not on trace element fluctuations, but on many positive changes in lipid profile, the func-tioning and structure of the vascular wall, inflam-matory processes, and the prooxidant-antioxidant balance [38, 39].
that higher hair Mn concentration resulting from a high intake of Mn in drinking water correlated positively with hyperactive behaviors, cognitive problems/inattention, and higher ADHD index among Canadian children [44]. Does the higher serum Mn concentration among postmenopausal women play any role in the universal menopausal syndrome, particularly consisting of concentra-tion difficulties and emoconcentra-tional hyper-reactivity? The hypothesis needs further investigation.
Trace element status in different populations of women from different countries depends largely on the geographic area of residence, diet, and the general environmental and socioeconomic condi-tions. For example, it has recently been reported that 10% of the Algerian population had plasma
zinc levels lower than 10.6 µmol/l, whereas copper and selenium status seemed to be satisfactory [45]. In New Zealand, where the soil is poor in Se, 80% of the female population of nonusers of selenium supplements had plasma selenium levels approxi-mately 10% below the mean plasma selenium level necessary for full expression of GSH-Px activity and lower serum zinc levels [46].
The authors concluded that the estrogen defi-ciency after menopause may be the cause of some small fluctuations in the serum and blood con-centrations of trace minerals. The precise impact of this deficiency and the influence of estrogen or estroprogestin therapy on trace mineral status in postmenopausal women needs further larger-pop-ulation studies.
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Address for correspondence:
Anna Jodkowska
Department of Internal Medicine, Occupational Diseases and Hypertension Wroclaw Medical University
Pasteura 4 50-367 Wrocław Poland
Tel.: +48 601 359 139
E-mail: [email protected]
Conflict of interest: None declared
