Preeclampsia Is One of the Most Common Diseases Which Occurs During the Second and Third

The Relationship between Testosterone Hormone and Lipid Profile, Proteins and Some TraceM JElements in the Sera of Patients with PreeclampsiaB

Ameera Jasem Mohamad Amen Bushra AL-Robaee* Tariq Hufdhy AL-Khayat*

*College of Medicine, University of Babylon, Hilla, Iraq.

Abstract

Preeclampsia is one of the most common diseases which occurs during the second and third trimester of pregnancy. The incidence of this disease is 2-5% among pregnant women.

The aetiology is still in debate and many theories were introduced in this field by many investigators in different countries. It is sometimes called disease of theories due to the contradictory issues concerning its causes and consequences.

In this study we tried to elucidate the relationship between testosterone and some biochemical constituents which vary during pregnancy (i.e , lipid profile, total protein, albumin and minerals (Ca & Mg).

This work was carried out on fifty five pregnant women referred to Babylon Hospital for Obstetric & Paediatrics for the period from November 2007 to May 2008 .The serum samples obtained from those patients and control groups (55 healthy pregnant) were analyzed for lipids, protein and minerals in addition to testosterone .The study group was subdivided into four subgroups as follows :

1.Group I is comprised of 25 preeclamptic patients in the second trimester of pregnancy .

2. Group II is comprised of 30 preeclamptic patients in the third trimester of pregnancy .

3.Group III includes 25 healthy pregnant women (2nd trimester) which served as control group .

4.Group IV represents 30 healthy pregnant subject in their third trimester of pregnancy

The results revealed a significant increase in serum testosterone levels in Group I and Group II compared with Group III and IV (p<0.01). These were insignificant decrease in hormone level in Group IV in comparison with GroupIII (p=0.36).

The results showed a significant increase in serum level of total cholesterol, TG, LDL, VLDL in Group I and Group II compared with those in Group III and Group IV,(p<0.001), (p<0.01) at respectively. However, there was a concomitant decrease in serum HDL level in Group I and Group II when compared with Group III and Group IV.

The results showed also a significant decrease in the levels of total protein ,albumin ,Ca and Mg in preeclamptic women compared with normotensive pregnants (p<0.05) .These changes were insignificant when the results of these component in Group IV were compared with Group III (p>0.05). There were significant correlation between serum testosterone levels and lipid profile , protein and minerals .This gives a preliminary idea about the role of testosterone in such changes. There were a positive correlation between testosterone and lipid profile except HDL-C which decrease at increase the testosterone in G1,G2 and G3 (p<0.01) and there were positive correlation between cholesterol / albumin ratio and testosterone in G1,G2 and G3 (p<0.01) but a negative correlation in G4 (p<0.01). There were inverse relationship between cholesterol and albumin (p<0.001).

الخلةصة

مرض قبل الشنج هو واحد من المراض الكثر شيوعا يحدث أثناء الحمل في فصليه الثاني والثالث ونسبة معدل وقوع هذا المرض هي 2-5% بين النساء الحوامل و أسباب هذا المرض غامضة لحد الن و العديد من النظريات طرحت في هذا المجال من قبل بعض الباحثين وفي مختلف الدول .في بعض الحيان يدعى هذا المرض بمرض النظريات بسبب تناقض الصدارات المتعلقة بأسبابه ونتائجه .

و في هذه الدراسة حاولنا ولول مرة توضيح العلقة بين هرمون الذكورة وبعض مكونات الكيمياء الحياتية التي تختلف أثناء الحمل (نطاق الدهون ,البروتين الكلي ,اللبومين , الكالسيوم , المغنيسيوم ) .

وقد انتقينا 55 امرأة مريضة حامل أحيلت إلى مستشفى بابل للولدة والطفال للفترة بين كانون الول 2007_أيار 2008 لجراء الدراسة وتم تحليل مصول من أولئك المرضى مع مجموعة السيطرة ال(55 امرأة سليمة حامل ) وفحصت الدهون والبروتينات وبعض المعادن بالضافة إلى هرمون الذكورة .

قسمت الدراسة إلى أربع مجاميع فرعية كما يأتي:

1- المجموعة الولى: تشمل 25مريضة مصابة بمرض قبل الشنج في الفصل الثاني من الحمل . 2- المجموعة الثانية: تشمل 30 مريضة مصابة بمرض قبل الشنج في الفصل الثالث من الحمل . 3- المجموعة الثالثة: تشمل 25 أمرآة سليمة حامل في الفصل الثاني من الحمل. 4- المجموعة الرابعة: تشمل 30امرآة سليمة حامل في الفصل الثالث من الحمل. وقد أظهرت النتائج زيادة معنوية في مستوى هرمون الذكورة في المجموعة الولى والثانية مقارنة بالمجموعة الثالثة والرابعة(p<0.001) وهناك نقصان غير معنوي في هرمون الذكورة في المجموعة الرابعة مقارنة بالمجموعة الثالثة (p=0.36). وبينت النتائج إن هناك زيادة معنوية في الكولسترول الكلي وتراي كليسرايد وكولسترول الليبوبروتن عالي الكثافة وكولسترول الليبوبروتين قليل الكثافة جدا في المجموعة الولى والثانية بالمقارنة مع المجموعة الثالثة والرابعة ,(p<0.001) p<0.01) ) بالتعاقب بينما هناك نقصان معنوي في كولسترول الليبوبروتين العالي الكثافة في المجموعة الولى والثانية عند المقارنة بالمجموعة الثالثة والرابعة .

كما أظهرت النتائج نقصانا معنويا في مستوى البروتين الكلي واللبومين والكالسيوم والمغنسيوم في النساء المصابات بمرض قبل الشنج بالمقارنة مع الحوامل ذوات الضغط الطبيعي (p<0.05) وهذه التغيرات كانت غير معنوية في المجموعة الثالثة والرابعة ( .(p>0.05

وقد أظهرت النتائج وجود علقة معنوية بين مستوى هرمون الذكورة في المصل و(نطاق الدهون والبروتين والمعادن).وهذا يعطي فكره حول دور هرمون الذكورة في هذه التغيرات.وتوجد علقة موجبة بين هرمون الذكورة ونطاق الدهون p<0.01) ) باستثناء كولسترول الليبوبروتين عالي الكثافة الذي يقل بزيادة هرمون الذكورة في المجموعة الولى والثانية والثالثة.وهناك علقة موجبة بين هرمون الذكورة ونسبة الكولسترول/اللبومين (p<0.01) في المجموعة الولى والثانية والثالثة ولكن العلقة موجبة في المجموعة الرابعة وبزيادة الكولسترول يقل اللبومين (p<0.001).

Introduction large body size, a family history of ypertension in pregnancy is a PET, multiple pregnancy , preexisting Hsignificant problem , if it is maternal hypertension, pregestational associated with proteinuria (which diabetes , antiphospholipid antibody indicates multisystemic disease, known syndrome , vascular or connective as preeclampsia(PET)), it will be tissue disease and advanced maternal associated with increased morbidity age (> 35 to 40 years) [4]. and mortality for both mother and fetus. It is a common problem Preeclampsia was known as the accounting one from five women after disease of theories, as the exact course 20 weeks of gestation [1]. of events that leads to the clinical syndrome have not been elucidated. Preeclampsia is divided according The first theory relates preeclampsia to to severity into mild, moderate and immunogentic factors. Numerous severe forms depending on the level of studies suggest a genetic susceptibility the blood pressure and the degree of to PET , daughters of women with PET proteinuria , mild preeclampsia are four to five times more likely to characterized by diastolic blood develop the syndrome than daughters pressure of 90 mmHg with proteinuria in law (5). How the genotype result in less than 5gm/24hr (+) to (++) and the characteristic placental lesion is not edema in feet . In severe preeclampsia , known but may involve an blood pressure is more than 110 immunological defect resulting failure mmHg and proteinuria more than to establish tolerance to the fetal 5gm/24hr (+++) to(++++) and edema allograft [5,6] . in hands and or face [2]. Symptoms and signs include sudden rise in blood The second theory relates the pressure , severe proteinuria , syndrome to the disturbance in generalized edema, excessive weight different vasoactive compounds [6]. gain , visual changes such as blurred or Disturbance of endothelial cells in PET double vision , headache , nausea , leads to alteration in the production of vomiting , epigastric pain , oliguria, several vasoactive compounds changes in liver or kidney function producing a vasoconstrictor state: tests. These are signs and symptoms of Prostacyclin (PGI2) , the predominant immenant eclampsia. If these vasodilator prostanoid is reduced while symptoms are associated with seizure, placental production of vasoconstrictor then the condition is called thromboxane A2 is increased. Plasma eclampsia .In PET an increase in the endothelin ,a potent vasoconstrictor is resistance of blood vessels may hinder also increased[5]. blood flow in many different organs The third theory which relates the like the liver, kidney, brain, uterus and disease to uteroplacental ischemia, placenta affecting their function or suggests the following:- causing placental abruption which is a premature separating of the placenta 1- Preeclampsia begins with after 20 weeks of gestation . PET can uteroplacental ischemia , which is an also lead to fetal complications increase intramural resistance in the including intrauterine growth myometerial vessels, leads to restriction (poor fetal growth) and still hightened myometerial tension birth [3]. produced by large fetus in a primipara, twins or hydramnios [6]. Major preexisting risk factors for PET include primigravida state , history of PET in previous pregnancy , Total protein , albumin, globulin and 2- The uteroplacental ischemia leads to albumin/ globulin (A/G ratio): the production of vasoconstrictor substance , which enters the The concentration of total protein circulation and produces renal in human plasma is approximately 6.2 vasoconstriction leading to increased -8.2 gm/dl , and comprises the major production of renin - angiotensin and part of the solids of the plasma [10]. aldosterone [6]. The major types of protein in the plasma are albumin , globulin and 3-The renin-angiotensin system fibrinogen . Albumin constitutes the produces a generalized major part of plasma proteins . It has vasoconstriction and aggravates further one polypeptide chain with 585 amino the uteroplacental ischemia [6]. It is acids and 17 disulfide bonds . It has followed by systemic of cytotoxic molecular weight of 69 KD . It is products that damage maternal synthesized by hepatocytes . Half life vascular endothelium [7] . of albumin is about 20 days [12]. 4- Aldosterone leads to water and A major function of albumin is to electrolyte retention and generalized provide colloid osmotic pressure in the edema[8] . plasma which prevents plasma loss from the capillaries. Another major Women with cardiovascular (CV) function of albumin is to transport risks are at increased risk for various hydrophobic substances. All preeclampsia ,and those with history of proteins have buffering capacity and preeclampsia are at increased risk for albumin may be considered as the post-pregnancy CV morbidity and transport form of essential amino acids mortality , compared with women with from liver to extrahepatic cells[12] history of normal pregnancy, This suggests that preeclampsia and CV The globulins perform a number of disease share common pathogenic enzymatic functions in the plasma , mechanism. These changes may but equally important , they are involve endothelial function deficient principally responsible for the body's in preeclampsia , as seen from reduced both natural and acquired immunity prostacyclin and / or elevated against invading organisms [13]. A/G endothelin-1 or thromboxane A2 ratio is altered or even reversed by the production [9] . reticuloendothelial system and decrease in albumin. This again leads Theca cells are the source of to edema [14] . Fibrinogen androstenedione and testosterone . polymerizes into long fibrin threads These are converted by aromatase during blood coagulation , thereby enzyme in granulosa cell to estrone forming blood clots that help repair and estradiol . Significant amounts of leaks in the circulatory system [13]. estrogens are produced by the peripheral aromatization of The total concentration of serum androgens[10]. In female , adrenal proteins decrease by about 1g/l during androgens are important substrates , pregnancy . Most of the decrease since as much as 50% of the estradiol occurs during the first trimester . The E2 produced during pregnancy comes decrease is mainly in serum albumin . from the aromatization of androgens The maternal antibody (IgG) [10]. Aromatase activity is present in component , which is the major adipose cells and also in liver, skin and immunoglobulin transferred to the other tissues [11] . fetus , falls progressively, alteration During the past 7 years , some that occurs in the levels of clotting progress has been made in the factors and plasminogen is probably prevention of preeclampsia . brought about by estrogen action on Specifically , clinical studies have the liver [15]. shown that calcium supplementation can significantly reduce the frequency Mineral homeostasis and of preeclampsia , especially in hypertension : populations with a low calcium intake. Magnesium ischemia is a term used They have suggested that in such to denote the functional impairment of the population , calcium supplementation ATP – dependent sodium /potassium and is a safe and effective measure for calcium pumps in the cell membranes and reducing the incidence of preeclampsia within the cell itself .The production of [19], as the levels of free intracellular ATP and the functioning of these pumps calcium is a major determinant of are magnesium dependent and are vascular smooth muscle tone and critically sensitive to acidosis . Zinc and consequently vascular resistance [20]. iron deficiencies may impair these pumps However ,the role of plasma and thus contribute to magnesium calcium status in normal pregnancy is ischemia as does acidosis [16] . It refers to still discussed contraversally , as well functional magnesium deficiency whether as calcium supplementation in actual or induced. It is argued that chronic preeclampsia [16]. Although acidosis is the most common inducing epidemiologic studies have suggested a factor . It can also unify clinical thinking role for calcium deficiency in the about pregnancy – induced hypertension , development of preeclampsia , the preeclampsia-eclampsia and acute fatty published information regarding liver of pregnancy. as well as the calcium metabolism in preeclampsia is coagulopathy of pregnancy . Mg can lead scanty [20] . to important predictions about perinatal morbidty and suggests that early Materials and Methods supplementation might prevent much pregnancy – induced disease [16] . On the Patients: basis of the therapeutic effects of magnesium salts and the knowledge This study was conducted in vasodilating properties of magnesium, it Babylon Maternity and Pediatrics was suggested that a deficiency of Teaching Hospital from November magnesium contributes to the 2007 to the end of May 2008. Fifty development of vasoconstriction in five pregnant women with preeclampsia [17]. preeclampsia (twenty five of them in the second trimester of pregnancy Calcium homeostasis is an while the rest of them were in the third important aspect of maternal and fetal trimester of pregnancy). physiology during gestation ,and recent evidence implicates alterations in All the patients were nonsmokers, calcium metabolism in the pathogensis have no other diseases . Detailed of hypertension during pregnancy. history and examination performed. Deficiencies in calcium intake have Pregnancy is divided into 1st trimester been linked to preeclampsia- (1-12 week), 2nd trimester (13-28 eclampsia , and hypocalciuria and week) and 3rd trimester more than 28 deviations in both 1,25 (OH)2 D3 and weeks. Depending on the gestational PTH have been shown in women with age, the patients were divided into two preeclampsia [18]. groups: Control pregnant women in the second Preeclamptics in the second trimester trimester G3: G1 :

They were twenty five healthy They were twenty five (normotensive) women in the second preeclamptics in the second trimester trimester of pregnancy. Age range 19- of pregnancy. Age range 18-37 years 35 years (mean age ± SD = 23.73 ± (mean age ± SD=26.29 ± 5.12 3.73 year). Gestational age range 20- year).Gestational age range 21-28 28 weeks (mean ± SD =23.43±3.2 weeks (mean gestational age ± SD = week).Body mass index range 21.4- 24.14 ± 3.63 week). Body mass index 50.4 kg/m2 (mean body mass index range = 24.7-50.4 kg/m2 (mean body ±SD =35.8± 11.7 kg/m2).Systolic mass index ± SD = 36.7 ± 9.87 blood pressure range 100-130 mmHg kg/m2).Systolic blood pressure range (mean Systolic blood pressure ± SD = 140-170 mmHg (mean Systolic blood 105 ± 15.1 mmHg). Diastolic blood pressure ± SD = 151.4 ± 10.7mmHg). pressure range 55-75 mmHg (mean Diastolic blood pressure range 90-120 diastolic Blood pressure ± SD = 64.3 ± mmHg (mean diastolic Blood pressure 7.9 mmHg). Proteinuria range <30 ± SD = 98.6 ± 10.3 mmHg). Mean mg/dl. proteinuria = 100 mg/dl. Control pregnant women in the third Preeclamptics in the third trimester G2: trimester G4: They were thirty preeclamptics in They were thirty healthy the third trimester of pregnancy. Age (normotensive) women in the third range 18-44 years (mean age ± SD trimester of pregnancy. Age range 19- =24.86±5.4 year). Gestational age 42 year (mean age ± SD = 26.6 ± 3.74 range 29-38 weeks (mean Gestational year). Gestational age range 29-40 age ± SD = 35.57 ± 3.21 week).Body weeks (mean ± SD = 35.3±3.99 week). mass index range 32.1-61.2 kg/m2 Body mass index range 29.5-45.1 (mean body mass index ± SD kg/m2 (mean body mass index ± SD = =46.6±1.6 kg/m2).Systolic blood 37.7 ± 5.9 kg/m2). Systolic blood pressure range 140-200 mmHg (mean pressure range 90-130 mmHg (mean Systolic blood pressure ± SD = 157.1- systolic blood pressure ± SD = 110- 13.8 mmHg). Diastolic blood pressure 14.1 mmHg). Diastolic blood pressure range 90-130 mmHg (mean diastolic range 50-80 mmHg (mean diastolic Blood pressure ± SD = 101.4 ± 10.3 Blood pressure ± SD = 62.9 ± 9.9 mmHg). Mean proteinuria = 300 mmHg). Proteinuria range <30 mg/dl mg/dl. Methods : Control:

Serum testosterone,total serum Fifty five apparently healthy cholesterol,HDL,triglecerides were pregnant women (twenty five of them measured by colorimetric assay . also were in the second trimester and thirty serum total protein of them were in the third trimester). ,albumin,globulin,S.calcium,S.magnisi Pregnant women with chronic medical um all measured by colorimetric assay. problems were excluded from this study. Depending on the gestational Calculation of body mass index(21): age, the pregnant women were divided into two groups: Results Body mass index (BMI) calculated as weight (kg)/height(m)2 , Testosterone: normal value 18.5 - 24.9 kg/m2 . Serum testosterone was Statistical analysis: significantly higher in preeclamptic groups(G1&G2) compared with The statistical analysis is based on normal pregnant women groups ANOVA test to determine the (G3&G4).Also serum testosterone was differences between groups and within significantly higher in G2 compared groups. Correlation, regression and with G1,and also shows nonsignificant correlation coefficient (r) , using SPSS decrease in G4 compared with G3 , (statistical product and service [Fig(1),Table(1),(2)] solutions) program for data

Table 1 Serum data of testosterone in preeclamptic and normal pregnant women (2nd and 3rd trimester ) (mean ± SD)

Measured parameter G1 2G G3 G4

Testosterone(ng/ml) ± SD 1.46±0.199 2.41±0.54 0.82±0.198 0.74±0.24

Testosterone

0 G4 G3 G2 G1

Figure 1 Serum data of testosterone in preeclamptic and normal pregnants women (2nd and 3rd trimester) Table 2 Significance value for testosterone in different groups

Groups P value

G1 vs G2 <0.001

G1 vs G3 <0.01

G1 vs G4 <0.001

G2 vs G3 <0.01

G2 vs G4 <0.01

G3 vs G4 =0.36

normal pregnants groups (G3&G4). Lipid profile (total cholesterol, TG, This parameters were significantly LDL-C, VLDL-C & HDL-C): higher in G2compared with G1and in G4 compared with G3,but serum Serum total cholesterol, TG, HDL-C was significantly lower in G2 LDL-C and VLDL-C were compared with G1 and G4 compared significantly higher in preeclamptic with G3 [Fig (2), Table (3) ,(4)] groups (G1&G2) compared with

Table 3 Serum data of total cholesterol, HDL-C, TG, VLDL-C, LDL-C in preeclamptic and normal pregnant women (2nd and 3rd trimester ) (mean ± SD)

Measured parameter G1 G2 G3 G4

Cholesterol(mmol/l) 5.06±0.167 5.9±0.292 4.46±0.71 5.19±0.82

HDL-C (mmol/l) 1.226±0.061 1.05±0.166 1.57±0.116 1.21±0.29

TG (mmol/l) 1.59±0.117 2.72±0.54 1.28±0.39 1.89±0.68

VLDL-C (mmol/l) 0.72±0.053 1.24±0.24 0.58±0.17 0.86±0.31 LDL-C (mmol/l) 3.117±0.18 3.62±0.24 2.31±0.65 3.12±0.82

Total cholesterol HDL-C TG VLDL-C LDL-C

3 mmol/l

0 G4 G3 G2 G1

Figure 2 Serum data of total cholesterol, HDL-C, TG, VLDL-C, LDL-C in preeclamptic and normal pregnant women (2nd and 3rd trimester )

Table 4 Significance value for lipid profile in different groups

Groups P value

G1 vs G2 <0.05

G1 vs G3 <0.001

G1 vs G4 >0.05

G2 vs G3 <0.05

G2 vs G4 <0.001

G3 vs G4 <0.05

Serum total protein and albumin Total protein, Albumin, Globulin and were significantly lower in A/G ratio: results were reversed for globulin .A/G preeclamptic groups ratio was significantly lower in G2 (G1&G2)compared with normal than G1 and nonsignificant difference pregnants groups (G3&G4), these between G3&G4 [Fig(3),Table(5),( 6), results were significantly lower in G2 (7)]. than G1 and there was insignificant decrease in G4compared to G3. The

Table 5 Serum total protein, albumin, globulin, albumin/globulin ratio in preeclamptic and normal pregnant women (2nd and 3rd trimester ) (mean ± SD)

Groups P value

G1 vs G2 <0.001

G1 vs G3 <0.01

G1 vs G4 <0.05

G2 vs G3 <0.01

G2 vs G4 <0.01

G3 vs G4 >0.127

Total protein Albumin Globulin Albumin/Gobulin ratio

0 G4 G3 G2 G1

Figure 3 Serum total protein, albumin, globulin, albumin/globulin ratio in preeclamptic and normal pregnant women (2nd and 3rd trimester ) . Measured parameter G1 G2 G3 G4

Total protein(gm/dl) 6.076±0.34 5.06±1.22 6.7±0.13 6.56±0.28

Albumin (gm/dl) 3.14 ±0.31 2.5±0.54 3.58±0.12 3.44±0.22

Globulin (gm/dl) 2.94±0.091 2.56±0.69 3.04±0.082 3.12±0.21

A/G ratio 1.109±0.1 0.999±0.11 1.112±0.049 1.112±0.153

Table 6 Significance value for total protein and albumin in different groups

Table 7 Significance value for globulin and albumin/ globulin ratio at differrent groups

Groups P value

G1 vs G2 <0.01

G1 vs G3 >0.01

G1 vs G4 >0.05

G2 vs G3 <0.01

G2 vs G4 <0.01

G3 vs G4 <0.01 compared with normal pregnants Total cholesterol/albumin ratio: groups (G3&G4). This parameter were higher in G2 compared with G1and in Serum total cholesterol/albumin G4 compared with G3.[Fig4),Table8), were significantly higher in 9)] preeclamptic groups (G1&G2)

Table 8 Total cholesterol/albumin in preeclamptic and normal pregnants women(2nd and 3rd trimester) (mean±SD). cholesterol / albumin

0 G4 G3 G2 G1

Figure 4 Total cholesterol/albumin in preeclamptic and normal pregnants women (2nd and 3rd trimester)

Table 9 Significance value for total cholesterol/albumin in different groups

Groups P value

G1 vs G2 <0.001

G1 vs G3 <0.01

G1 vs G4 >0.05

Measured parameter ± SD G1G2 vs G3 G2 <0.001G3 G4

Cholester ol/albumin ratio± SD 0.063±0.009G2 vs G4 0.096±0.028 <0.0010.048±0.009 0.059±0.0122

G3 vs G4 <0.01

Minerals: comparison with G4. The results Total calcium, corrected calcium and showed insignificant decrease of total ionized calcium calcium in normotensive pregnants at the third trimester in comparison with Total calcium, corrected calcium those of 2nd trimester.Corrected and ionized calcium were lower in calcium and ionized calcium were preeclamptic groups (G1&G2) higher in G4 than G3, non significant compared with normotensive difference [Fig(5), Table(10) , (11) , groups(G3&G4). These parameters (12)]. reversed a significant decrease in G2 in

Table 10 Serum total calcium, corrected calcium, ionized calcium in preeclamptic and normal pregnants women (2nd and 3rd trimester) (mean ± SD)

Calcium (mmol/l) 1.74±0.07 1.57±0.112 1.997±0.029 1.99±0.21

Corrected calcium (mmol/l) 1.91±0.018 1.87±0.009 2.08±0.009 2.101±0.197

Ionized calcium (mmol/l) 0.98±0.009 0.96±0.016 1.066±0.004 1.079±0.109

Calcium Corrected calcium Ionized calcium

mmol/l

0 G4 G3 G2 G1 Figure 5 Serum total calcium, corrected calcium, ionized calcium in preeclamptic and normal pregnants women (2nd and 3rd trimester)

Table 11 Significance value for calcium in different groups

Groups Value p

G1 vs G2 <0.05

G1 vs G3 <0.01

G1 vs G4 <0.01

G2 vs G3 <0.01

G2 vs G4 <0.001

G3 vs G4 =0.825

Table 12 Significance value for ionized calcium in different groups

Groups Value p

G1 vs G2 =0.375

G1 vs G3 <0.05 G1 vs G4 <0.01

G2 vs G3 <0.001

G2 vs G4 <0.001

G3 vs G4 =0.386 women Total (G1&G2)compared with normotensive pregnants women (G3&G4). These magnesium: results showed nonsignificant difference between G3&G4 and nonsignificant difference between Serum total magnesium was G1&G2[Fig(6),Table(13),(14)]. significantly lower in preeclampsia

Table 13 serum magnesium in preeclamptic and normal pregnants women (2nd and 3rd trimester) (mean ± SD).

Magnesium (mmol/l) 0.698±0.029 0.58±0.08 0.78±0.064 0.77±0.23

Magnesium

0.4 mmol/l

0 G4 G3 G2 G1 Groups Value p

G1 vs G2 =0.085

Figure 6 serum G1 vs G3 =0.024 magnesium in preeclamptic and G1 vs G4 =0.48 normal pregnants women (2nd and 3rd G2 vs G3 <0.01 trimester) G2 vs G4 <0.001

G3 vs G4 =0.694

Table14 Significance value for magnesium at different groups

syndrome in the aetiology of Correlation between serum preeclampsia [22,23,24] . testosterone and other parameters in different groups: Recent studies revealed the association between the change of Correlation between serum serum oestrogen levels and many testosterone and total cholesterol biochemical parameters during the second and third trimesters of both A significant positive normal and complicated correlations between serum total- pregnancy[25]. Other studies cholesterol and testosterone level was connected between those biochemical noticed in different groups except changes and serum changes of hCG normal pregnants in third levels in different types of trimester(G4),which reversed negative pregnancy[26] . correlation .Fig(7),( 8),( 9),( 10).

Depending on the available data, Discussion there is no study which link the Many previous studies reported the changes in testosterone levels and changes in oestrogen levels during consequent changes in lipid profile (as normal and complicated pregnancy . one of the criteria associated with Besides , there are numerous studies metabolic syndrome ). concerning the role of metabolic However, hyperinsulinemia should In this study we tried to elucidate also stimulate the production of such relationship in order to pave the adrenal androgen [28]. way for subsequent studies .

The decrease in testosterone clearance We found in our study that BMI are in normal pregnancy is intensified in increase in G1& G2 more than PET patients. This will lead to increase G3&G4 (P<0.001) but non significant in serum testosterone levels [29]. difference between G1 & G3 (p>0.05) and significant difference between G2 Our results were in good & G4 (p<0.001). agreement with the results reported by Golmahamed -Is [30] and Jasim – FG In this study, we found that ten [31]. patients out of fifty five preeclamptic patients give positive family history of The increase in serum testosterone preeclampsia (18.1%) ; five patients levels in the second trimester of had a previous history of preeclampsia normal pregnancy in comparison with (9%) (both these factors are associated those values of the 3rd trimester can be with more incidence of preeclampsia). attributed to the increase of aromatase activity with progressive course of In this study , levels of serum pregnancy (24) . testosterone were found to be significantly higher in women with A significant increase of the serum preeclampsia than in normotensive TC , TG and VLDL-C Levels in women with similar gestational age . preeclamptic women , can be Such increase in hormone level in explained in the following points : both 2nd and 3rd trimester can be attributed to : I- The endogenous female sex hormone have significant effect on Low expression of the aromatase gene serum lipid [32]. Oestrogen is due to small or impaired for the responsible for induction of TG conversion of testosterone to estrogen . synthesis [33]. There is an increase in The decrease of enzyme activity lead the hepatic lipase activity and decrease to a subsequent increase in testosterone in lipoprotein lipase activity. Hepatic level [24]. lipase is responsible for the increased synthesis of the triacylglycerols at the In the late pregnancy , when the fetal hepatic level, where the decreased adrenal gland become mature it will activity of lipoprotein lipase is result in further increment in the level responsible for the decreased of testosterone by conversion of catabolism at the adipose tissue level. DHEA to testosterone [24]. The net effect of this enzyme will be an increase in circulating Human chorionic gonadotropin triacylglycerol.The second stage of increase in PET and this will uptake of the remnant of chylomicrons stimulates the ovarian thecal cell to by the liver is delayed so it lead to synthesis androstenedione and accumulation of triacylglycerol [32]. testosterone [27]. 2-Serum VLDL increase follows Insulin stimulate the production of serum TG increase, since the former testosterone by ovarian tissue which was calculated from TG values [33]. suggests that hyperinsulinemia could The increase in triacylglycerol in be primary change that triggered the gestation is estimated mainly in the increased release of testosteron . (LCAT) reaction , is removed by VLDL, because it is synthesized in the binding to serum albumin [41]. liver and VLDL carries the endogenous triacylglycerol [34]. Our results were in good agreement with the results of Bulter- The same trend of increase in the CL [42] . levels of those constituents were reported in the studies carried out by The increase in TC, TG , VLDL- Demir-SC[35] and suzies – WJ [36] . C and LDL-C in the third trimester of uncomplicated pregnancy may be In this study , we found a attributed to the increased metabolic significant increase in LDL-C and demand of the fetus with the advancing decrease in HDL–C in preeclamptic course of pregnancy [43]. women (2nd and 3rd trimester ) These changes can be attributed to : - Our results are consistent with the results reported by Cekman-MB 1-Increased triacylglycerols play a [44] and inconsistent with those major role in decreasing HDL-C HDL reported by Tayanta–D [34]who found particles carry cholesterol from a significant decrease in the LDL-C peripheral tissues to the largest area of level in the third trimester of utilization (Liver) and this lead to pregnancy . The inconsistency can be decrease of HDL-C in serum [37] . attributed to dietary differences There is a direct correlation between between the studied groups . adipose tissue lipoprotein lipase activity and plasma HDL-C This direct In this study, we found a correlation may be responsible for low significantly decrease in serum total levels of HDL- C . protein and albumin in women with Hypertriglyceridemia , leading to low preeclampsia than in normotensive HDL-C mainly due to the actions of women with similar gestational age . cholestryl ester transfer protein (CETP)(37), which facilitates transfer This decrease in serum total protein of cholestryl ester from HDL to VLDL and albumin level in patients and , IDL and in exchange for healthy groups (2nd and 3rd trimester ) triacylglycerol , relieving product may be attributed to :- inhibition of LCAT activity in HDL-C. 1-During normal pregnancy the LCAT activity was lower in pregnancy hyperfiltration is largely due to induced hypertension [38]. profound resistance reduction in the 2-Oestrogens were shown to increase renal afferent arterioles [45]. In PET serum HDL- C levels and decrease of both glomerular filtration rate and LDL-C Levels [39]. Therefore , the renal plasma flow decrease by 30% to low level of HDL-C and a consequent 40% compared with normal pregnancy increase in LDL-C level may be of the same duration [46]. The basis attributed to hypoestrogenemia of for the hypofiltration in PET is largely preeclampsia . It may be also due to secondary to structural changes into insulin resistance in the corresponding glomerulous as opposed to constriction patients [40]. of afferent arteriolar system and depression in renal plasma flow , 3-The decrease in albumin lead to which increasing permeability of decrease in HDL- C because glomerulous to protein [47]. lysolecithin , one of the products of the lecithin cholesterol acyl transferase extracellular fluid expansion leads to a 2-The protein excretion was decrease in serum albumin [55] . approximately four fold higher than that of nonpreeclamptic women [48]. Our results were good agreement When preeclampsia is accompanied by with these reported by Salako – BL proteinuria , there is a marked fall in [56]. albumin and an increase in α2 – macroglobulin [49]. It's believed that The decrease in serum total these changes are a result of urinary calcium and magnesium in loss of the proteins of intermediate preeclamptic pregnancy compared with molecular weight, with a compensatory control group can be attributed to : unselective increased synthesis of 1-During normal Pregnancy , there are protein in the liver , and retention in many mechanism tend to promote the serum of macroglobulins , which lowering of maternal calcium are too large to pass through the concentration due to an increase in defective glomerular basement maternal estrogen production which membrane [50]. Metabolic studies blocks bone resorption and increases have shown that albumin synthesis is calcium excretion in urine [55] significantly greater in preeclampsia than in normal pregnancy , and this is 2-The haemodilution occurs during stimulated by the liver due to either the last trimester of pregnancy [57]. decrease in estrogen production or low Jord-R found that were calcium was concentration of albumin in the blood strong association between serum [51]. albumin with systolic and diastolic blood pressure [58]. Because there is a 3-The increase in urinary protein strong correlation between total and excretion in preeclampsia occurs ionized serum calcium , one would secondary to alterations in the size have to assume that the binding and / or charge selectivity of the characteristics for calcium and its glomerular filterate [52]. Loss of carrier proteins are abnormal in charge selectivity was likely the hypertension [58] . primary defect in the glomerular filtration barrier in women with 3-The prevalence of magnesium preeclampsia [47]. Preeclampsia is deficiency may be due to the associated with morphological changes difference in the dietary pattern [57]. in renal endothelial and mesangial cells The haemodilution could be another have been noted enlarged due to their factor leading to a higher prevalence of engorgement with lipid . These lipid – deficiency of magnesium [57] . induced changes have recently been named glomerular hitopathological 4-Magnesium exclusively excreted in endotheliosis [53]. urine and reabsorbed in proximal convoluted tubules by a process called 5-Proteinuria lead to hypoalbuminemia transport maximum (Tmax) its , low plasma oncotic pressure and excretion increase as a filtered load intravascular volume depletion , increase above the transport maximum, subsequent under perfusion of the in women with decrease GFR, the kidney stimulates the renin- filtered load is more excretion of angiotensin – aldosterone axis , which magnesium in urine [59] . During causes increased renal sodium and normal pregnancy, the increase in GFR volume retention which to increased causing increase in calciuria [55]. extracellular fluid[54]. The 5-Edmond-DK.Dewhurst,s text book 5-Magnesium homeostasis is linked of obstetrics & Gynecology for with calciuria [60]. Studies from the Postgraduates. 6thed. Graphicraft, first elucidated the nature of the effects Hong Kong.1999. 169. of calcium and magnesium ions at the neuromuscular junctions [61]. 6-Ficioglu-C and Kutlu-T. The role of Magnesium competes for prejunctional androgens in the aetiology and site with calcium ions , the ions pathology of preeclampsia. J Obstet competed with each other , high Gynecol.2003;23:134-137. magnesium concentration inhibit release of acetyl choline (Ach) and 7-Buhimschi-CB, Maglorri-L and high calcium concentration increases funai-E,etal. Fractional excretion of of Ach from presynaptic nerve Angiogenic factors in women with terminal . In sever preeclampsia , there severe preeclampsia. Am College is vosospasm , ischemia as well as obstet & Gynecol. 2006;107(5):1103- cellular hypoxia which may cause 11130 reperfusion injury following treatment 8-John-P. Evalution of priteinuria in [61] . pregnant women. Am J obstet & 6-Magnesium is physiologically Gynecol.2008;57:611 antagonist to calcium , it follows that 9- Takeuchi-K , Zhang-B and ideishi- in an attempt to mitigate cellular injury M , etal. Influence of age & by calcium , there will also be influx of Hypertension on the association magnesium during reperfusion . This between small artery Compliance & could explain why both calcium and coronary artery disease. Am J magnesium were reduced in the blood Hypertension. 2004;17(12);1188-1191. of preeclamptic pregnant women [62]. 10- Murray-RK, Granner-DK, Mayes- Our results are in good accordance PA and Rodwell-VW. Harper, with the results reported by Sukonpan- illusterated Biochemistry.26thed. Mc K [63] and Sanders- GT [64]. Graw-Hill, New York. 2003;440-445.s

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