Journal of Global Pharma Technology

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1 Journal of Global Pharma Technology ISSN: Available Online at RESEARCH ARTICLE Relationship between Thyroid Hormones and TSH, FSH, LH, LH/FSH Ratio, Prolactin and Testosterone Hormones in Infertile Patient Women with Hyperthyroidism in Reproductive Age Dalal Abdul Hussain Kadium 1, Methaak A Al. Shemki 2, Aseel Keamel Al.Waeli 3, Wedad Hashim 4, Zaineb Mehdi Al Saeq 5 Department of Biology, College of Girls Education Iraq. Abstract Our work involved studies for levels of thyroid hormones (Triiodothyonine T3,Thyroxin T4) and thyroid stimulating hormone (TSH),follicular stimulating hormone(fsh), luitienzing hormone(lh), prolactin(prl) and testosterone hormone LH/FSH ratio in infertile patients women with hyperthyroidism and sanitary fertile women and to find the relationship between thyroid hormones (T3,T4) and TSH, FSH, LH, PRL and testosterone hormones and LH/FSH ratio, and correlation of TSH with T3,T4, FSH, LH, PRL and testosterone hormones and LH/FSH ratio in sterile women with hyperthyroidism in reproductive age. (60) sterile women with hyperthyroidism with age (19-41) years old and body weight ( ± 0.20 kg ) who recalculated Endocrine unity of Teaching Al-Sadr hospital in Al- Najaf Al-Ashraf Governorate from 1/ 9 / 2015 to 1 / 10 / 2016, patients women group was compared with (30) fertile non- patients women with age(19-41) years old and body weight (72.35 ± 0.42 kg) as control group. The results pointed to a significant increasing(p<0.05)in levels of T3,T4, LH, PRL, testosterone and LH /FSH ratio, while a significant decreasing (P<0.05) was in TSH and FSH levels in sterile patient women with hyperthyroidism when compared with control group, and there was a positive significant (P<0.05)correlation between T3,T4 and LH,PRL, testosterone and LH/FSH ratio, while the relationship was negative significant (P<0.05)between T3,T4 and TSH and FSH in sterile patient women and the results showed a positive significant(p<0.05) relationship between TSH and FSH, while there was a negative significant(p<0.05) correlation between TSH and T3,T4, LH, PRL, testosterone and LH/FSH ratio in sterile women patients with hyperthyroidism. Key words: Thyroid hormones, Infertility, Hyperthyroidism, TSH, FSH, Prolactin. Introduction Infertility is one of principal Rum our problem of the women in reproductive age in the present time and this problem became mark ably increased during the last thirty year (1). Infertility refers to biological inability of the couple to gestate of regular sex enter course and in several countries the infertility means that failure of the couple to conceive after 12months of unprotected sexual coition (2). The infertility in human depends on different factors such as age, endocrinology, consanguinity, nutrition, scholar ships, manner of the life, economics and poignanciyes and may be due to women ( 33%) and men (33%) or both sexes and due to other unknown causes, in female the principal common cause of infertility is the troubles of ovulation which are characterized by intermittent cycles or absent cycles (3). Thyroid gland and its hormones is very important of reproductive system and productive function in different animals because the functions of thyroid hormones represent in regulation of expression of genes and metabolism, regulation of lactation, growth and sexual reproductive performance processes, fetal development and fertility in the both sexes therefore, the disorders of the hormones of thyroid gland in female several functions of the body are influenced (4; 5). These hormonal disorders of thyroid gland affect the reproductive system of female causing dysfunction of hypothalamicpituitary ovariain axis and these disorders cause the infertility whereby studies indicated a strong correlation between hypothalamic-pituitary thyroid axis and hypothalamic-pituitary ovarian axis, therefore, the disorders in the thyroid gland hormones affect the hormones of hypothalamus that cause disorders of ovarian , JGPT. All Rights Reserved 284

2 hormones (6). The thyroid disorders include hyperthyroidism and hypothyroidism and both them occur in women but the incidence of hyperthyroidism is lower than hypothyroidism that means decreased production of thyroid gland hormones, many studies showed that hypothyroidism causes anovulation, retardind in the beginning of puberty, sundry menstrual breaches and infertility(5), while hyperthyroidism is high production of thyroid hormones,the main cause of hyperthyroidism is Graves s disease but the children who were born with neonatal Graves disease did not have any defects in system of reproduction that may be correlated to Graves disease but when hyperthyroidism occur befor the puberty this causes delay the beginning of menstruations, hyperthyroidism like hypothyroidism can also lead to anovulation, infertility and disturbances of menstrual cycles including oligomenorrhea, hypomenorrhea polymenorrhoea and studies reported that regularities of menses in hyperthyroidism are about tow times more frequent than in normal women (7). Because of little studies about the relationship between the hyperthyroidism and fertility of women therefore, this study was aimed to set the correlation between thyroid hormones(t3,t4) and TSH, FSH, LH, PRL and testosterone hormones and LH/FSH ratio,and correlation of TSH with T3,T4, FSH, LH, PRL and testosterone hormones and LH/FSH ratio in sterile patients women with hyperthyroidism in reproductive age to identify reasons for these changes in display the effects of hyperthyroidism and its importance as a problem affecting women fertility. Materials and method This study was performed on (60) infertile patient women with hyperthyroidism with reproductive age (19-41) years and body weight( ± 0.20 kg) who recalculated of Endocrine glands unity\ Fertility center in Teaching AL-Sadr hospital in AL- Najaf AL- Ashraf Government from 1\6\2015 to 15\2\2016,the infertile patient women with hyperthyroidism are compared with (30) fertile health women with age (21-41) and body weight (72.35 ± 0.42 kg). Summation of Information Information are gathered from non-patient and patient women, these information were included age, weight of body, laboratory inquiries, history of obstetrical and menstruation, history of any drugs was taken,history of disease or previous surge of thyroid gland and clinical examination which is comprised many symptoms have shown on the patient women such as enlargement of thyroid gland, weakness, thinning of hair, fatigue, weight loss,increased sweating,vomiting, abnormal menstrual cycles. Samples of Blood Fasting blood samples were collected from hyperthyroidism patients and non- patients women in the morning at 9 O' clock,(5 )ml of venous blood are pulled from all contributer women during the second and third day of menstrual cycle( follicular phase),blood is put in serum tubes and after one hour, these serum tubes were centerifuged at 2500 rpm for 15 minutes to separate the serum for determination the levels of different hormones. Hormones Estimation The levels of FT3, FT4 LH, FSH, testosterone, PRL and TSH hormones were determined by specific electro chemiluminescence immunoassay (Elecsys 2010 Cobas, Roche Diagnostics, Mannheim, Germany). Statistical Analysis Results were calculated by SPSS version 17, mean and Standard deviation(mean ± SD) were calculated, statistical analysis is worken using the Student s t- test of confirmation of normal distribution.the correlation among the hormones is performed by person correlation test and p value P < 0.05 was considered statistically significant. Results Levels of Hormones in Infertile Patients with Hyperthyroidism and Control Group Results demonstrated a significant increase (P<0.05) in levels of hormone levels FT3 (5.78 ±1.23), FT4 (4.00± 0.54), LH( ±1.64), testosterone (2.52 ± 0.38), PRL (21.41±2.30) and LH/FSH ratio (3.65±0.11) in sterile patients women with hyperthyroidism comparing with control group FT3(4.88 ±0.91), FT4 (3.37±0.74), LH (6.01±1.02) testosterone(1.92 ± 0.33), PRL (16.11 ±2.07) and LH/FSH ratio(1.01±0.23), whereas a significant decrease (P<0.05) was in body weight ( ± 0.20) and hormone levels , JGPT. All Rights Reserved 285

3 TSH, FSH in infertile patients women (0.74 ±0.19, 3.35 ±0.44) respectively when compared with non- patients women (72.35 ± 0.42,1.15± 0.55,5.82 ±0.75) respectively (Table 1). The Relationship between Thyroid Hormones (FT3, FT4) and TSH, FSH, LH, PRL and Testosterone Hormones and LH/FSH Ratio in Infertile Patients Women with Hyperthyroidism The correlation of both FT3 and FT4 with TSH(P<0.05, R=0.23;0.25)and FSH(P<0.05, R= 0.17;0.03) was a significant negative in patients women(figure 1,2,3,4),while correlation of both FT3 and FT4 with LH (P<0.05, R=- 0.07;0.21), testosterone(p <0.05, R= ;--0.06), PRL ( P <0.05,R= -0.08; ) and LH/FSH ratio (P<0.05, R= ;- 0.06) was a significant positive in sterile patient women hyperthyroidism (Figure 1, 5, 6,7,8,9,10,11,12). The Relationship between TSH and FSH, LH, PRL and Testosterone Hormones and LH/FSH Ratio in Infertile Patient s Women with Hyperthyroidism There is a significant positive correlation between TSH and FSH(P<0.05, R=0.23) in infertile patients women with hyperthyroidism(figure 13), whereas there is a significant negative correlation between TSH and LH (P<0.05, R= 0.11), testosterone(p <0.05, R= ), PRL ( P <0.05,R= ) and LH/FSH ratio (P<0.05, R=- 0.28) in sterile patients women with hyperthyroidism (Figure 14,1 5, 16,17). Table 1: Levels of hormones in infertile patients with hyperthyroidism and control group Fertile health women hyperthyroidism without (control group) n= 60 In Fertile patient women with hyperthyroidism n= 114 parameters of Hormones Mean ± SD Mean ± SD ± ± 0.20 Body weight Kg 4.88 ± ±1.23 FT3 pg/ml 3.37± ± 0.54 FT4 ng/ml 6.01 ± ±1.64 LH mlu/ml 5.82 ± ± ± ± ± ± ± ± ± ± 0.38 FSH mlu/ml LH/FSH ratio P R L ng/ml TSH mlu/ml Testosterone ng/ml Figure 1, 2: Relationship T3 and T4 with TSH Figure 3, 4: Relationship T3 and T4 with FSH , JGPT. All Rights Reserved 286

4 Figure 5, 6: Relationship T3 and T4 with LH Figure 7, 8: Relationship T3 and T4 with testosterone Figure 9, 10: Relationship T3 and T4 with prolactin Figure 11, 12: Relationship T3 and T4 with LH/FSH ratio , JGPT. All Rights Reserved 287

5 Figure 13: Relationship between TSH and LH Figure 14: Relationship between TSH and FSH Figure 15: Relationship and Prolactin between TSH Figure 16: Relationship between TSH and Testosterone , JGPT. All Rights Reserved 288

6 Discussion Results showed a significant decrease (P< 0.05) in body weight in infertile patients women compared with fertile non- patients women and this reducation in body weight of sterile patients women with hyperthyroidism may back as many studies pointed to large amounts secretion of thyroid hormones in hyperthyroidism and these hormones play important and essential role in regulation and controlling of basic processes of metabolism for all body cells (4). Studies recorded that basic metabolic rate of body increase about (60-100%) when high concentrations of thyroid hormones are secreted and thyroid hormones also affect catabolic processes of different food materials especially carbohydrates and fats causing decrease in their levels and also catabolic rate of proteins is increased in the same time that protein synthetic rate is increased because food consumption for energy is largely accerlated and this leads to reduction of body weight although sometime increase of appitate of patient women with hyperthyroidism(8) and hyperthyroidism may cause increase of intestinal mortility which develops in many cases to diarrhea (9), this result agreed result of other studies in human (10) and in animals (11). Figure 17: Relationship between TSH and LH / FSH ratio hyperthyroidism is Graves disease that occurs by formation antibodies to the receptors of TSH (12). Previous researches pointed to the crest age of occurrence of Graves disease is between (20-49) while recent studies explained to augment with the age (13). The results also showed a significant increase (P< 0.05) in levels of hormone levels LH, testosterone and PRL and LH /FSH ratio, whereas a significant decrease (P<0.05) was in hormone levels FSH in sterile patients women with hyperthyroidism comparing with control group, and there was a significant(p< 0.05) negative correlation of both FT3 and FT4 with TSH and FSH while correlation of both FT3 and FT4 with LH, testosterone, PRL and LH/FSH ratio was significant(p< 0.05) positive in sterile women while there was a significant (P<0.05) positive correlation between TSH and FSH, and correlation between TSH and LH, testosterone, PRL and LH/FSH ratio was a significant (P<0.05) negative in sterile patients women with hyperthyroidism. The disorders of female reproductive hormones consist of many problems occurring by abnormal changes of hypothalamic-pituitary ovarian axis which lead to sterile (2). The results signified a significant increase (P< 0.05) in levels of hormones FT3,FT4 whereas a significant decrease (P< 0.05) was in hormone levels TSH in sterile patients women with hyperthyroidism comparing with control group, and this occurs because of the effects of thyroxine hormone that stimulates hyperthyroidism(thyrotoxicosis) because hyperthyroidism is by a high concentrations in serum T4 and T3 and a reduce concentration of TSH, the main reason of Pituitary hormones like prolactin and TSH may work synergistically with FSH and LH to stimulate the follicles to enter growth phase, FSH stimulate the development of follicles in the ovary, studies pointed to increase level of FSH causes weak development of follicles and an ovulation, whereas low FSH level causes increase secretion of prolactin, LH stimulates release the ovum from the ovaries, surge of LH occurs at about 12 day causing the ovulation , JGPT. All Rights Reserved 289

7 during 48 hours, reduced LH levels may cause increased prolactin secretion and many changes may observe in follicles in hyperthyroidism can lead to produce high prolactin concentrations that can prevent the secretion of gonadotropins (14),increased amounts of prolactin affect the fertility by weakening secretion of GnRH that interferes with ovulation and this dysfunction leads to menstrual disturbances and ovulatory disorders like anovulation, oligomenorrhea, amenorrhea and galactorrhea (15). Prolactin,thyroid hormones and TSH considered an important factors of infertility in women,the increased secretion of prolactin in different conditions stimulases inhibition of hypothalamic-pituitary gonadal axis and suppresses resistance of ovary to gonadotropin labour which causes amenorrhea and anovulation(16). In hyperthyroidism there are low levels of FSH and high levels of prolactin and these conditions are chiefly outputted by low levels of TRH stimulated by the increased negative feedback of hormones of thyroid gland at the References 1. Stephen EH, Chandra A (2000) Use of infertility services in the United States Fam. Plann. Perspect: Hammond M (1987) Evaluation of the infertile couple. Obstet. Gynecol. Clin. North America. 14(4): Fupare S, Gadhiya BM, Tambhulkar RK, Tale A (2015) Correlation of thyroid hormones with FSH, LH and prolactin in infertility in the reproductive age group women. int.j. clin -Biochem Res.,2(4): Idris MA, Idris OF, Sabhelkhier MK (2012) The effects of Induced Hyperthyroidism on plasma FSH and LH concentration in female of wistar Rats. RJ. Recent Sci. I (6): Veeresh T, Moulai D, Sarama DV (2015).A study on serum FSH, L H and prolactin levels in women with thyroid disorders. Intl. J. Sci. Res. publication. 5(3): Mc Neilly AS (1987) Prolactin and the control of gonadotrophin secretion. J. Endocrinol.115: Armada-Dias L, Carvalho J, Breitenbach M, France C, Moura E (2001) Is the level of hypothalamic-pituitary gland, increased TRH levels stimulates high secretion of both TSH and prolactin in hyperthyroidism,number and sensitivity of TRH receptors degreases in the thyrotrope and lactotrope,therefore,responses of TSH and prolactin to TRH are decreased too (17). Studies suggested that hypothalamic pituitary thyroid axis in the infertile women is more sensitive in hyperthyroidism and thyroid hormones may affect physiology of female reproductive system in different ways such as changing pituitary ovarin axis or by reducing activity of binding of sex hormone binding globulin (SHBG)causing increased level of free testosterone and estradiol or by increasing the levels of TRH causing increased the levels of prolactin or by changing pituitary ovarian axis and late response of LH to the discharge hormone of LH (18). To these causes prolactin and TSH are generally -regulated clinical examinations to assess the infertility of the women. infertility in hypothyroidism mainly due to ovarian or pituitary functional change Braz.J.Med.Biol.Res.,34 (9): Yen PM (2001) Physiological and molecular basis of thyroid hormone action.physiol. Rev Zhang J, Lazar MA (2000) The mechanism of action of thyroid hormones. Annu.Rev. physiol. 62: Pamplona R, Portero-Otin M, Ruiz C, Bellmunt MI, Requena JR, Throp JW (1999) Thyroid status modulates glycooxidative and lipooxidative modification of tissue protein.free. Radic. Bio.Med. 27: Veditti P, Balestrieri M, Di Meo, S Leo TD (1997) Effect of thyroid status on lipid peroxidation, antioxidant defences and susceptibility to oxidative stress in rat tissues. J. Endocrinal. 155: Krassas GE, pontikides N, kaltsas T, papadopou-lou P, Batrinops M (1994) Menstrual disturbancas in thyrotoxicosis. Clin Endocrinol (Oxf). 40(5): Berglund J, Christensen SB, Hallengren B (1990) Total and ege-specific incidence of , JGPT. All Rights Reserved 290

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