Iraqi J Pharm Sci, Vol.22 (1) 2013 Hormonal changes in women with primary hypothyroidism 56 Some Hormonal Changes in Women with Primary Hypothyroidism under the Effect of Thyroid Hormone Replacement Therapy Zainab S. Jabbar* , Kassim J. Al-Shamma*,1 and Mohammad A. Taher** *Department of Clinical Pharmacy, College of Pharmacy, University of Baghdad, Baghdad, Iraq. **Department of clinical laboratory sciences, College of Pharmacy, University of Baghdad, Baghdad, Iraq. Abstract Hypothyroidism has been associated with disorders of glucose and insulin metabolism..The present study was designed to evaluate the possible change in some hormones (free testosterone, estradiol, prolactin, insulin), glucose and homeostasis model assessment of insulin resistance (HOMA-IR) in women with primary hypothyroidism under thyroid hormone replacement therapy .This cross-sectional study was carried on 62 hypothyroid patients׳ women and 22 healthy women as control group at the specialized center for endocrinology and diabetes, AL-Rasafa Directorate of Health Baghdad, with age range(15-60 years), diagnosed as having primary hypothyroidism on thyroxine replacement therapy with duration not less than four months. Each of the selected patients women and the healthy control were distributed into two groups, normal cyclic and postmenopausal. Blood samples were collected to measure thyroid stimulating hormone(TSH), total thyroxine (TT4) , total triiodothyronine (TT3), free thyroxine(fT4), free testosterone (FT), estradiol(E2) ,prolactin(PRL), insulin , fasting blood glucose( FBG), homeostasis model assessment-insulin resistance(HOMA-IR). The results showed that the majority of hypothyroid women (older than 40 years and obese) had high levels of TSH in normal cyclic and postmenopausal patients women. A significant increase in f T4 and TT4 in postmenopausal patients women when compared with postmenopausal control group f T4 and TT4. A significant increase in free testosterone and FBG and significant decrease in TT3 and E2 levels in normal cyclic patients women when compared with normal cycle control group. High prolactin levels were found in the normal cyclic patients women in comparism with control group. Higher levels of insulin were found in normal cyclic and postmenopausal patients women as compared with control groups, however insulin was not statistically different. Significant increase in HOMA-IR of normal cyclic patients women compared with control group. In conclusion, elevation of TSH levels in postmenopausal patients women were less than in normal cyclic patients women this explain the increase levels of thyroxine hormone(T4)in this group of patients as compared with both control group and normal cyclic patients women. Some hormonal changes were found in normal cyclic hypothyroid patients women as compared with control group.The alteration of these hormones disappear when euthyroid state restored, so adjustment of thyroxine therapy is required in these patients. Key words: Hypothyroidism , Thyrid replacement therapy. بعض الخغيراث الهرمىنت في النساء المصاباث بقصىر الغدة الدرقيت االبخدائي ححج حأثير عالج الهرمىن الدرقي البديل جبار زينب سخار * ، قاسم جليل الشماع *،1 و محمد عباس طاهر ** * .فشع انصٛذنت انسشٚشٚت ، كهٛت انصٛذنت ، خايؼت بغذاد ، بغذاد ، انؼشاق ** .كهٛت انصٛذنت ، خايؼت بغذاد ، بغذاد ، انؼشاق فشع انؼهٕو انًخخبشٚت انسشٚشٚت ، الخالصة صًًج ْزِ انذساست نخقٛٛى انخغٛش انًسخًم فٙ .قصٕسانغذة انذسقٛت يغ اظطشاباث فٙ انخًثٛم انغزائٙ نهدهٕكٕص ٔاألَسٕنٍٛاسحبط ،خهٕكٕصانذو نهصائى ٔ يقأيت االَسٕنٍٛ ( اسخشادإٚل، انبشٔالكخٍٛ، االَسٕنٍٛ انخسخٕسخٛشٌٔ انسش، االسخشٔخٍٛ)بؼط انٓشيَٕاث (HOMA-IR ) ْزِ انذساست انؼشظٛت .انغذة انذسقٛت االبخذائٙ حسج حأثٛشػالج انٓشيٌٕ انذسقٙ انبذٚمقصٕسنذٖ انُساءانًصاباث بًشض أيشأة سهًٛت نًدًٕػت انسٛطشة فٙ انًشكض انخخصصٙ نهغذد انصى ٔانسكش٘،دائشة 22أيشأة يصابت بقصٕس انغذة انذسقٛت ٔ 62اخشٚج ػهٗ سُت، حى حشخٛصٓى باالصابت بًشض قصٕس انغذة انذسقٛت بُاءا ػهٗ انخقٛٛى انخاسٚخٙ 60-15حخشأذ بٍٛ صست بغذاد انشصافت، باػًاس خًٛغ انُساء انًصاباث . ْٕػادة يشخص نالصابت بانًشض( TSH)إٌ صٚادة حشكٛضانٓشيٌٕ انًسفض نهغذة انذسقٛت . ٔانسشٚش٘ ٔانًخخبش٘ إٌ انُساء انًصاباث انالحٙ حى اخخٛاسٍْ ٔانُساء انسهًٛاث حى حٕصٚؼٓى انٗ يدًٕػخٍٛ .سػٕندٕا بانثاٚشٔكسٍٛ نًذة ال حقم ػٍ اسبؼت اشّ . ،رٔاث انذٔسة انطبٛؼٛت ٔيا بؼذ سٍ انٛأط 1 Corresponding author E-mail:drkassim_alshamaa@yahoo.com Received: 14/3/2012 Accepted: 16/3/2013 Iraqi J Pharm Sci, Vol.22 (1) 2013 Hormonal changes in women with primary hypothyroidism 57 انٓشيٌٕ انًسفض :انًشٚعاث ٔانسهًٛاث نقٛاط انخغٛشاث انًسخًهت نهًؤششاث انًذسٔست ٔانخٙ حخعًٍحى خًغ ػُٛاث انذو يٍ انُساء ، انبشٔالكخٍٛ، (اسخشادإٚل)انخسخٕسخٛشٌٔ انسش، االسخشٔخٍٛ ،(f T4)، انثاٚشٔكسٍٛ انسش TT4 ،TT3، انثاٚشٔكسٍٛ انكهٙ TSHنهغذة اظٓشث انُخائح اٌ اغهبٛت انُساء انًصاباث بقصٕسانغذة انذسقٛت ٍْ .(HOMA-IR)ٍٚ االَسٕنٍٛ ، خهٕكٕصانذو نهصائى ٔ يقأيت االَسٕل فٙ انُساء انًشٚعاث رٔاث انذٔسة TSHاسخُخدج انذساست ٔخٕد اسحفاع فٙ يسخٕٚاث قٛاط . سُت ٔبذُٚاث 40يًٍ حضٚذ اػًاسٍْ ػٍ ٚت فٙ انثاٚشٔكسٍٛ انكهٙ ٔانثاٚشٔكسٍٛ انسش فٙ انُساء انًشٚعاث كزنك ٔخذث صٚادة يؼُٕ. انطبٛؼٛت، ٔفٙ انُساء انًشٚعاث بؼذ سٍ انٛأط بُٛج انُخائح ٔخٕد صٚادة يؼُٕٚت . بؼذ سٍ انٛأط بانًقاسَت يغ انُساء انسهًٛاث بؼذ سٍ انٛأط نهثاٚشٔكسٍٛ انكهٙ ٔانثاٚشٔكسٍٛ انسش فٙ انُساء ( االسخشادإٚل)ٔ ْشيٌٕ االسخشٔخٍٛ TT3ٚتبانخسخٕسخٛشٌٔ انسش ٔخهٕكٕص انذو نهصائى ٔ َقصاٌ يؼُٕ٘ بٓشيٌٕ انغذة انذسق اسحفاع يسخٕٖ ْشيٌٕ انبشٔالكخٍٛ فٙ انُساء . انًشٚعاث رٔاث انذٔسة انطبٛؼٛت بانًقاسَت يغ انُساء انسهًٛاث رٔاث انذٔسةانطبٛؼٛت االَسٕنٍٛ فٙ انُساء انًشٚعاث رٔاث انذٔسة اسحفاع يسخٕٚاث ْشيٌٕ . انًشٚعاث رٔاث انذٔسة انطبٛؼٛت بانًقاسَت يغ يدًٕػتانسٛطشة صٚادة . ،ازصائٛا الٕٚخذ فشق يؼُٕ٘ فٙ يسخٕٖ االَسٕنٍٛ انطبٛؼٛت ٔ انُساء انًشٚعاث بؼذ سٍ انٛأط بانًقاسَت يغ يدًٕػاث انسٛطشة إٌ أغهبٛت ٔبزنك ًٚكٍ االسخُخاج.بانًقاسَت يغ يدًٕػت انسٛطشة يؼُٕٚت بًقأيت االَسٕنٍٛ فٙ انُساء انًشٚعاث رٔاث انذٔسة انطبٛؼٛت فٙ انُساء TSHٔخذ اٌ اسحفاع يسخٕٖ ْشيٌٕ . سُت ٔبذُٚاث 40انُساء انًصاباث بقصٕس انغذة انذسقٛت ٍْ يًٍ حضٚذ اػًاسٍْ ػٍ ْشيٌٕ انًشٚعاث بؼذ سٍ انٛأط اقم يٍ اسحفاػّ فٙ انُساء انًشٚعاث رٔاث انذٔسة انطبٛؼٛت ْٔزا ٕٚظر انضٚادة انساصهت فٙ ٔخذث بؼط . انثاٚشٔكسٍٛ فٙ ْزِ انًدًٕػت يٍ انًشٚعاث بانًقاسَت يغ يدًٕػت انسٛطشة ٔ انُساء انًشٚعاث رٔاث انذٔسة انطبٛؼٛت اٌ حغٛش ْزِ انٓشيَٕاث ٚخخفٙ ػُذ اػادة .انخغٛشاث انٓشيَٕٛت فٙ انُساء انًشٚعاث رٔاث انذٔسة انطبٛؼٛت بانًقاسَت يغ يدًٕػت انسٛطشة .انطبٛؼٛت نهذسقٛت ،نزنك ٚخطهب حُظٛى ػالج انثاٚشٔكسٍٛ نخهك انًشٚعاث انٕظٛفت .قصىر الغدة الدرقيت ، الهرمىن الدرقي البديل :الكلماث المفخاحيت Introduction Hypothyroidism has been associated with disorders of glucose and insulin metabolism, involving defective insulin secretion in response to glucose, hyperinsulinemia, altered peripheral glucose disposal, and IR (1) . The mechanisms linking hypothyroidism with IR in general and in skeletal muscles (SM) in particular are still under investigation. Insulin resistance in hypothyroidism is associated with a negative regulation of one or more intracellular enzymes involved in glucose catabolism (2) . An impaired translocation of Glucose Transporter 4 (GLUT4) on the plasma membrane has been also observed in the monocytes of subjects with clinical and subclinical hypothyroidism, in relation to a decreased Insulin-mediated glucose uptake (IMGU) (3) . An effect of thyroid hormones on insulin receptors has been suggested, but the existing data are rather conflicting, supporting either no relationship between thyroid status and the affinity of insulin receptors or diminished high affinity insulin receptors (HAIRs) in hypothyroidism (4) . In patients with primary hypothyroidism, increased levels of thyroid releasing hormone(TRH) can cause elevation of prolactin levels (5) . Many studies supported the existence of interplay between prolactin and insulin along with the influence of dopamine in the regulation of insulin secretion (6) . Hyperinsulinemia increases the production of androgens in the ovaries and of insulin-like growth factor(IGFs) in the liver (7) .The direct effect of insulin and IGF-1 is increased 17- hydroxylase activity in the ovaries, causing an excessive production of androgens, particularly androstenedione and testosterone and its precursor, 17-hydroxyprogesterone(17-OHP) (8) . Free testosterone had been found to be positively correlated with insulin resistance (9) ,as well as with components of the metabolic syndrome, including fasting plasma glucose, adiposity (10) , fasting and post challenge insulin levels (11) , insulin-to-glucose ratio (12) , and blood pressure (13) . High levels of free testosterone (11) have been shown to predict incident type 2 diabetes in women, giving the relation between androgens and insulin sensitivity. The aim of the study was to determine whether there is any change in serum levels of free testosterone, estradiol, prolactin, insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR) in women with primary hypothyroidism under thyroid hormone replacement therapy. Materials and methods This study was performed on 62 hypothyroid patient women at the specialized center for Endocrinology and diabetes, AL- Rasafa Directrate of health-Baghdad with age range(15-60 years) with mean duration of hypothyroidism of 4 months.The patients women were distributed into two groups: normal cyclic and postmenopausal. These were compared with 22 healthy women as control group with the same age range of patients, and also distributed as normal cyclic and postmenopausal.The hypothyroid women were diagnosed as hypothyroid by a senior physician through historical, clinical, and laboratory assessment. The demonsetration of an elevated TSH concentration is usually diagnostic (14) . Iraqi J Pharm Sci, Vol.22 (1) 2013 Hormonal changes in women with primary hypothyroidism 58 Table 1: Characteristics of control women and hypothyroid patients women. The data are expressed as mean ± SD. Exclusion criteria The study exclude any patient women with: secondary hypothyroidism, PCOS, inherited TBG disease, heart disease , renal disease , liver disease ,pregnancy, lactation, diabetic disease, smoking and any drugs effect thyroid function except thyroxine. Blood specimen collection and preparation Blood was taken after 12 hr fasting and at the early follicular phase (in women with normal cycle) for measurement of thyroid function tests (TSH,TT4,TT3,fT4),fasting blood glucose(FBG)levels, fasting insulin levels, free testosterone levels, estradiol levels and prolactin levels.TSH,TT4 and TT3 were measured, radioimmunoassay(RIA kits) while f T4,insulin, free testosterone, estradiol and prolactin immunoassay readymade-kits(ELISA) were had been used. Statistical analysis The following statistical data analysis approaches were done through the Statistical Package of Social Sciences (SPSS) program(version-10) and Excel application and used in order to analyze and assess the results of the study: I . Descriptive data analysis: Statistical tables (Frequencies, percents), mean value, standard deviation, standard error, (95%) confidence interval or population mean values, two extreme values (min. and max.) respondents. II- Inferential data analysis: Student t-test for equality of means coincidence testing in two independent samples. Results The results showed that an increase incidence of hypothyroidism in women with age older than 40 years old, while frequency of patients as the following : between (15-19)years old were 2(3.2%),between(20-29)years old were 7(11.3%),between (30-39)years old were 12(19.4%) , between (40-49)years old were25(40.3%) and between (50-60)years old were 16 (25.8%). The majority of hypothyroid patients were obese, in the normal cyclic patients women group were 22 (52.4%) as well as in the postmenopausal patients women were 14 (70%). The results in table(1,2,3) showed high levels of TSH were found in normal cyclic patients women (10.37±3.03, 95% C.I=4.24-16.49 µIU/ml ) and in postmenopausal patients women( 4.23±1.12, 1.89-6.57 µIU/ml)were observed. A significant increase in f T4 (14.51±0.85 , 12.72-16.30 pmol/l),and TT4 (117.8±8.34,100.31-135.23 nmol/ml ) in postmenopausal patients women when compared with postmenopausal control group f T4 (10.58±0.41, 9.64-11.52 pmol/l) and TT4 (89.71±4.19, 80.24-99.1 nmol/ml). A significant increase in the plasma free testosterone(1.65±0.26, 1.11-2.18 pg/ml) and FBG (5.36±0.13, 5.09-5.64 mmol/l)and significant decrease in TT3(1.57±0.07, 1.42-1.71 nmol/ml ) and E2(50.63±4.20, 42.15-59.11 pg/ml) levels in normal cyclic patients women when compared with normal cycle control group ,free testosterone (0.76±0.16,0.41-1.11 pg/ml), FBG(4.78±0.19, 4.36-5.20mmol/l) ,TT3 (1.90±0.06, 1.77-2.03nmol/ml )and E2(76.80±9.79, 55.25-98.35pg/ml). High prolactin levels were found in normal cyclic patients women (22.57±4.43, 13.63-31.52 ng/ml) as compared with control group(17.51±1.68, 13.82-21.20 ng/ml(. Higher levels of insulin were found in normal cyclic and postmenopausal patients women as compared with control groups ((15.86±1.47 , 12.89-18.84 versus 11.34 ±1.28, 8.52-14.16 ) , (15.47±1.92, 11.46-19.49 versus 9.90±1.41, 6.71-13.1)µIU/ml) repectively, however insulin was not statistically different. Significant increase in HOMA-IR of normal cyclic patients women (3.83±0.39,3.05-4.62) when compared with control group (2.41±0.29,1.79-3.04). variable Hypothyroid patients women(mean ±S.D) Healthy control women(mean ±S.D) Number (total) 62 22 Normal Cyclic women Age(years) BMI(kg/m²) 42 37± 9.04 31.7 ± 5.39 12 36 ± 6.68 29.9 ± 2.73 Postmenopa usal women Age(years) BMI(kg/m²) 20 52 ± 5.40 32.3 ± 5.33 10 50 ± 4.27 30.5 ± 3.03 Iraqi J Pharm Sci, Vol.22 (1) 2013 Hormonal changes in women with primary hypothyroidism 59 Table 2: Distribution of thyroid hormones levels in patients and control groups a: control(normal cycle)group, b:control(postmenopause)group, c:patients(normal cycle)group, d:patients(postmenopause)group. S: significant, NS: non-significant, HS: high significant. L.b: lower bound, u.b: upper bound. C.I: confidence interval. Parameters Groups N Mean ± Std.E. 95% C. I. for Mean Min. Max. C.S p-value L.b. U.b. TSH (µIU/ml) Control (normal cycle) a 12 1.48 ± 0.18 1.09 1.87 0.30 2.3 a×c p=0.061 NS b×d p=0.655 NS c×d p= 0.118 NS Control (postmenopause) b 10 1.75 ± 0.20 1.31 2.19 0.80 2.7 Patients (normal cycle ) c 42 10.37 ± 3.03 4.24 16.49 0.05 78.0 Patients (postmenopause) d 20 4.23 ± 1.12 1.89 6.57 0.04 17.9 fT4 (pmol/l) Control (normal cycle) a 12 11.26 ± 0.40 10.38 12.15 9.0 13.9 a×c p=0.299 NS b×d p=0.001 HS c×d p= 0.010 HS Control (postmenopause) b 10 10.58 ±0.41 9.64 11.52 8.9 12.0 Patients (normal cycle ) c 42 12.31 ± 0.50 11.29 13.33 7.2 24.6 Patients (postmenopause) d 20 14.51 ± 0.85 12.72 16.30 8.2 24.9 TT4 (nmol/ml) Control (normal cycle) a 12 88.53 ± 2.07 83.98 93.08 75.9 99.8 a×c p=0.161 NS b×d p=0.017 HS c×d p= 0.05 S Control (postmenopause) b 10 89.71 ± 4.19 80.24 99.19 71.7 113.7 Patients (normal cycle ) c 42 102.3 ± 4.92 92.32 112.20 52.3 183.5 Patients (postmenopause) d 20 117.8 ± 8.34 100.31 135.23 58.3 206.9 TT3 (nmol/ml) Control (normal cycle) a 12 1.90 ± 0.06 1.77 2.03 1.6 2.2 a×c p=0.017 HS b×d p=0.314 NS c×d p= 0.355 NS Control (postmenopause) b 10 1.62 ± 0.10 1.39 1.85 1.1 2.0 Patients (normal cycle ) c 42 1.57 ± 0.07 1.42 1.71 0.7 2.7 Patients (postmenopause) d 20 1.46 ± 0.10 1.25 1.66 0.8 2.4 Iraqi J Pharm Sci, Vol.22 (1) 2013 Hormonal changes in women with primary hypothyroidism 60 Table 3: Distribution of (free testosterone, estradiol and prolactin) hormones in patients and control groups Parameters Groups N Mean ± Std.E. 95% C. I. for Mean Min. Max. C.S P-value L.b. U.b. FT (pg/ml) Control (normal cycle) a 12 0.76 ± 0.16 0.41 1.11 0.13 2.1 a×c p=0.047 S b×d p=0.491 NS c×d p=0.044 S Control (postmenopause) b 10 1.26 ± 0.32 0.53 1.99 0.03 2.7 Patients (normal cycle ) c 42 1.65 ± 0.26 1.11 2.18 0.04 7.2 Patients (postmenopause) d 20 0.90 ± 0.16 0.57 1.23 0.01 2.6 E2 (pg/ml) Control (normal cycle) a 12 76.80 ± 9.79 55.25 98.35 32.48 137.8 a×c p=0.002 HS b×d p=0.623 NS c×d p=0.001 HS Control (postmenopause) b 10 30.76 ± 7.82 13.06 48.45 6.29 83.9 Patients (normal cycle ) c 42 50.63 ± 4.20 42.15 59.11 14.66 120.2 Patients (postmenopause) d 20 25.88 ± 3.10 19.39 32.36 7.94 52.8 PRL (ng/ml) Control (normal cycle) a 12 17.51 ± 1.68 13.82 21.20 9.59 26.7 a×c p=0.464 NS b×d p=0.287 NS c×d p=0.045 S Control (postmenopause) b 10 19.65 ± 2.55 13.88 25.42 9.93 32.4 Patients (normal cycle ) c 42 22.57 ± 4.43 13.63 31.52 3.59 163.0 Patients (postmenopause) d 20 10.91 ± 1.38 8.03 13.79 4.05 29.0 a: control(normal cycle)group, b:control(postmenopause)group, c:patients(normal cycle)group, d:patients(postmenopause)group. S: significant, NS: non-significant, HS: high significant. L.b: lower bound, u.b: upper bound. C.I: confidence interval. Iraqi J Pharm Sci, Vol.22 (1) 2013 Hormonal changes in women with primary hypothyroidism 61 Table 4: Distribution of of insulin, fasting blood glucose and HOMA-IR levels in patients and control groups. Parameters Groups N Mean ± Std.E. 95% C. I. for Mean Min. Max. C.S P-value L.b. U.b. Insulin (µIU/ml) Control (Normal cycle) a 12 11.34 ± 1.28 8.52 14.16 4.54 17.87 a×c p=0.100 NS b×d p=0.088 NS c×d p=0.863 NS Control(Postmenopausal )b 10 9.90 ± 1.41 6.71 13.10 4.05 16.83 (Normal cycle ) patients c 42 15.86 ± 1.47 12.89 18.84 3.80 44.00 Postmenopausal Patients d 20 15.47 ± 1.92 11.46 19.49 4.35 35.61 FBG (mmol/l) Control (Normal cycle) a 12 4.78 ± 0.19 4.36 5.20 3.83 5.68 a×c p=0.025 S b×d p=0.835 NS c×d p=0.764 NS Control (Postmenopausal)b 10 5.37 ± 0.21 4.90 5.83 4.45 6.52 (Normal cycle ) patients c 42 5.36 ± 0.13 5.09 5.64 4.10 8.20 Postmenopausal Patients d 20 5.43 ± 0.15 5.10 5.75 3.60 6.96 HOMA-IR Control (Normal cycle) a 12 2.41 ± 0.29 1.79 3.04 0.77 3.90 a×c p=0.05 S b×d p=0.099 NS c×d p=0.950 NS Control (Postmenopausal)b 10 2.37 ± 0.37 1.55 3.20 0.80 3.90 (Normal cycle ) patients c 42 3.83 ± 0.39 3.05 4.62 0.70 11.40 Postmenopausal Patients d 20 3.80 ± 0.52 2.70 4.89 0.89 8.60 a: control(normal cycle)group, b:control(postmenopause)group, c:patients(normal cycle)group, d:patients(postmenopause)group. S: significant, NS: non-significant, HS: high significant. L.b: lower bound, u.b: upper bound. C.I: confidence interval. Iraqi J Pharm Sci, Vol.22 (1) 2013 Hormonal changes in women with primary hypothyroidism 62 Discussion The results of an increase incident of hypothyroidism in women with age older than 40 years old were in agreement with the results of Yamada et al.(1984) (15) , who referred this to increase in the level of production of antithyroglobulin antibodies , antiperoxidase antibodies and increase level of TSH hormone ,also the mean of TRH hormone increase with advance age specially in women. Subtle elevation of TSH is associated with measurable deficiency in resting energy expenditure and increased body weight. Fox et al.(2008) (16) noted that modest increases in serum TSH concentration within the reference range may be associated with weight gain , women gained more weight than men did , although both sexes gained.the result of this study confirmed previous results that hypothyroidism and obesity frequently co-exist in varying degree of severity. Most patients in this study showed persistent elevation of TSH levels, despite they were under treatment for hypothyroidism. The elevation of TSH levels in postmenopausal patients women is less than in normal cyclic patients women, this may explained by the decreased clearance of thyroxine (T4) in postmenopausal patients women and this may confirmed by the significant higher level of thyroxin(fT4, TT4) in postmenopausal patients women when compared with both control group and normal cyclic patients women (17) . In most patients the circulating concentration of TSH serves as a reflection of thyroid hormone effect upon the pituitary and thereby as an effective marker of the adequacy of the replacement dose (18) . Triiodothyronine represented the active form of thyroid hormone for it easy separation from binding protein and easy binding to the receptors in the cells of target organ ;while T4 is the less active biologically than T3 ,and T4 represent the stored spare in the blood. This explain the presence of a significant difference in T3 level between patients women group and control group, because it is in continueous use (19) . This finding is confirmed in this study by the presence of significant decrease in T3 levels in the normal cyclic patients women in comparison with control group. There is a significant elevation of free testosterone levels in normal cycle of patients women in comparism with control group. Estrogen deficiency leads to reduced sex hormone binding globulin(SHBG) production in the liver (20) . Testosterone has a high affinity for SHBG.With decreasing SHBG concentration, less testosterone is bound to SHBG and the free testosterone in the blood increases, resulting in a relative hyperandrogenemia. The present work demonstrated that estradiol level is decreased in both groups of patients women (normal cyclic and postmenopausal) when compared with their control groups. Estradiol is produced by both the interconversion of estrone (21) and the aromatization of testosterone. The main source of estrogen in postmenopausal women appears to be the aromatization of plasma androstenedione to estrone (22) . Women with hypothyroidism had decreased metabolic clearance rates of androstenedione and oestrone and an increase in peripheral aromatization (23) . The present study showed a high levels of prolactin hormone in normal cyclic patients women as compared with control group. Hyperprolactinaemia is not seen in all patients with hypothyroidism, but it has been reported to occur in 0-40% of hypothyroid patients (24) . Prolactin hormone levels return to normal with appropriate L-thyroxine treatment. There is a significant increase in FBG levels and HOMA-IR in the normal cyclic patients women when compared with control group. Obesity is a predictor of impaired fasting glucose( IFG), and pre-diabetic state. Insulin resistance is increased by abdominal obesity, and fasting hyperinsulinemia farming a risk factor for the development of impaired fasting glucose (25) . The loss of T3 within the cells leads to increase in the level of TSH and the reduction of the activity of GLUT-4 in the insulin sensitive tissue such as skeletal muscles and adipose tissues, thus contributing to the stimulation of insulin resistance , this was observed in high percentage among obese individuals (26) .The results of the present study were in agreement with study by Singh et al.(2010) (27) . The study concluded that patients with hypothyroidism demonstrated insulin resistance as observed by the higher HOMA-IR level as compared to controls. Maratou et al.(2009) (3) ,had concluded that insulin resistance is associated with comparable HOMA-IR values in overt hypothyroidism and subclinical hypothyroidism. The study showed that insulin resistance in hypothyroidism is associated with a negative regulation of one or more intracellular enzymes involved in glucose catabolism. Conclusions The majority of hypothyroid patients women were older than 40 years old and obese. 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