International Journal of Science and Research (IJSR)

ISSN: 2319-7064
SJIF (2022): 7.942

Prevalence of Subclinical Hypothyroidism in

Untreated PCOS Patients and PCOS Patients on
Metformin at a Tertiary Care Hospital of Eastern
India
Dr. Madhushree Pahari1, Dr. Mousumi Mukhopadhyay2, Dr. Sambhunath Bandopadhyay3
1MD Biochemistry, Senior Resident, Institute of Postgraduate Medical Education and Research, Kolkata
2Professor and Head, Department of Biochemistry, IPGME&R, Kolkata
3Associate Professor, Department of Gynaecology and Obstetrics, IPGME&R, Kolkata

Abstract: Background: There is increasing evidence suggesting that PCOS is linked to the increased prevalence of thyroid diseases,
especially subclinical hypothyroidism. This study aims to compare the prevalence of subclinical hypothyroidism in untreated PCOS
patients with age - matched, diagnosed PCOS patients on metformin therapy for >6 months. The aim is to establish the effect of metformin
on thyroid hormone status in patients with PCOS on metformin therapy for >6 months as compared to patients with PCOS without
metformin therapy. Aims: To compare the prevalence of subclinical hypothyroidism in untreated PCOS patients with age - matched,
diagnosed PCOS patients on metformin therapy for >6 months, in order to establish the effect of metformin on thyroid hormone status in
patients with PCOS patients on metformin therapy for >6 months. Material and Methods: Serum TSH, FT4, and FT3 of all patients were
measured. The study was conducted in the Department of Biochemistry and Department of Gynaecology in IPGME&R, Kolkata from
February 2020 to July 2021 (18 months). Results: The mean TSH level of metformin - treated PCOS was 3.29±2.73 and among untreated
was 4.15±3.28. There were no significant differences of FT4 and FT3 between the two groups. Conclusion: The metformin - treated
PCOS group had a significantly lower mean TSH level than the untreated PCOS group (t198=2.02; p=0.022).

Keywords: Polycystic Ovary Syndrome, Subclinical Hypothyroidism, Metformin

1. Introduction from 11 to 36% [16]. Over the past decades, a large number
of studies have investigated the prevalence of SCH in Since
Polycystic ovary syndrome (PCOS) is one of the most the prevalence of SCH differs from the geographic region,
common endocrine disorders characterized by anovulation, ethnicity, or age, the results of studies were inconsistent.
hyperandrogenism, and polycystic ovaries, which affect up to
15–20% of women of reproductive age [1]. These patients are PCOS and hypothyroidism both together or individually add
at risk of a range of metabolic and endocrinological the risk for infertility and menstrual irregularities. it has been
disturbances that include infertility, obesity, insulin extensively demonstrated that thyroid hormones, and
resistance, and metabolic syndrome [2–4]. In addition, there specifically T3, have insulin - antagonistic effects at the liver
is also increasing evidence suggesting that PCOS is linked to level that lead to an increased glucose hepatic output, via an
the increased prevalence of thyroid diseases [5]. Primary enhanced rate of gluconeogenesis and glycogenolysis [17].
hypothyroidism is a deficiency status in thyroid hormone For this reason, all the existing criteria used for diagnosis of
production by the thyroid gland [6] causing several PCOS necessitate exclusion of hypothyroidism at first [18,
symptoms, such as the poor ability to tolerate colds, tiredness, 19]. Insulin resistance is more likely in women who had SCH
constipation, depression, and weight gain. The severity of than in women without SCH independent of age and BMI
hypothyroidism varies significantly, from transient and [20]. compromised immune system is likely to be a cause of
subclinical forms to severe cases. Subclinical hypothyroidism the interaction between SCH and PCOS since SCH may result
(SCH), which is defined as an elevated TSH level in from autoimmune thyroiditis [21]. Normally, estrogen's
combination with normal T4 and free thyroxine (FT4) levels immune stimulatory activity is neutralized by the anti -
and lack of signs or symptoms of hypothyroidism, SCH is inflammatory actions of progesterone levels. However,
more common than overt hypothyroidism [7]. The prevalence progesterone level is near zero in PCOS because of
of SCH is affected by geographic regions, ethnicity, and age anovulatory cycles [22]. As a result, estrogen overstimulates
in the general population [8–10]. the immune system, that leads to high incidence of
autoimmune diseases [23].
Although SCH is a mild form, it also results in anovulatory
cycles, sex hormone imbalances, subfertility, and adverse Metformin may be a beneficial choice for PCOS women with
pregnancy outcomes [11–13], which are also features of SCH. Metformin is considered one of the safest
women with PCOS. In addition, patients with SCH have antihyperglycemic agents. This biguanide is an insulin
increased metabolic risk of obesity, insulin resistance, and sensitizer mainly in the liver, but also in the muscle, that
hyperlipidemia similar to those with PCOS [14, 15]. The activates AMP - activated protein kinase (AMPK), an
prevalence of SCH in women with PCOS is variable, ranging intracellular sensor of nutrient availability and regulator of

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Fully Refereed | Open Access | Double Blind Peer Reviewed Journal
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Paper ID: MR24312145447 DOI: https://dx.doi.org/10.21275/MR24312145447 833
 International Journal of Science and Research (IJSR)
ISSN: 2319-7064
SJIF (2022): 7.942
energy homeostasis. A direct effect of AMPK modulation on criteria were selected as cases and controls respectively for
thyroid function has been unraveled recently, and much of its the study.
function in the thyroid is currently unknown. The
pharmacological activation of AMPK in normal thyrocytes Method of Data Collection (including sampling procedure):
results in decreased iodide uptake counterbalancing TSH Patients’ data were collected based on a predesigned
action [24]. Activation of AMPK by metformin results in a datasheet. And findings of relevant clinical examination were
strong reduction of iodide uptake through the thyroidal recorded.10ml of venous blood sample was collected from
sodium iodide symporter. large peripheral veins, taking aseptic precaution. Samples
were collected in clot vial on day 3 of the patient’s menstrual
The present hospital - based cross - sectional observational cycle. Serum was separated by centrifugation (3500 rpm for
study aims to evaluate the prevalence of subclinical 5 minutes). And then the blood samples were analyzed for
hypothyroidism in untreated PCOS patients and PCOS serum Insulin, serum TSH, FT3and FT4, serum LH, and FSH
patients on metformin therapy. and FBS.

2. Materials and Methods Laboratory Investigation Parameters –

Serum TSH, 2. Serum FT4, 3. Serum FT3, 4. Serum LH, 5.
The study was performed after obtaining approval from the Serum FSH, 6. Serum FBS, 7. Serum Insulin
Ethics committee of the Institute of Postgraduate Medical
Education and Research. Control - 100 age - matched patients diagnosed with PCOS
according to Rotterdam criteria attending the Gynaecology
Study Setting: A cross - sectional observational Study was OPD, IPGME&R, were taken during the study period.
conducted in the Department of Biochemistry &Department
of Gynaecology, IPGME&R, Kolkata. Diagnosed untreated Schedule of Data Collection - From February 2020 to July
PCOS patients and PCOS patients on metformin therapy were 2021
selected from the Dept. of Gynaecology, IPGME&R,
Kolkata, and biochemical parameters were analyzed in the 100 patients with diagnosed PCOS untreated and 100 PCOS
Dept of Biochemistry of IPGME&R, Kolkata. The result was patients on metformin therapy for >6 months, attending the
compared with age - matched controls and data were further Gynaecology OPD, IPGME&R, during the study period, were
analyzed for clinical correlation. selected as controls and cases respectively. Informed consent
was taken. Relevant history was taken and clinical
Timelines: February 2020 to July 2021 (18 months) examination was performed. Venous blood was collected by
taking aseptic precaution. After that biochemical analysis was
Definition of the population: 100 patients with diagnosed performed in the Dept. of Biochemistry, IPGME&R.
PCOS untreated and 100 PCOS patients on metformin
therapy for >6 months, attending the Gynaecology OPD, Materials for Estimation of Study Variables
IPGME&R, during the study period. Cases were taken as per 1) Refrigerators
inclusion and exclusion criteria. 2) Laboratory Centrifuge (Remi R - 8C)
3) Micropipettes
Inclusion Criteria, Exclusion Criteria 4) Reagents and Reagent kits
5) Autoanalyzer
Inclusion criteria for cases: Patients with diagnosed PCOS
according to Rotterdam criteria, on metformin therapy >6 Estimation of Thyroid Stimulating Hormone (TSH) –
months, of age group 18 - 44 years, signed the informed
consent form. Assay Principle:
The ADVIA Centaur TSH3 - Ultra assay is a third -
Inclusion criteria for controls: Patients with diagnosed generation assay that employs anti - FITC monoclonal
PCOS according to Rotterdam criteria, untreated patients of antibody covalently bound to paramagnetic particles, an FITC
age group 18 - 44 years, signed informed consent form. - labeled anti - TSH capture monoclonal antibody, and a tracer
consisting of a proprietary acridinium ester and an anti - TSH
Exclusion criteria: mAb antibody conjugated to bovine serum albumin (BSA) for
1) Patients with diseases other than PCOS and taking any chemiluminescent detection. A direct relationship exists
other kind of medicine could have influenced the test between the amount of TSH present in the patient sample and
result. the amount of relative light units (RLUs) detected by the
2) Patients with a previous history of hypothyroidism. system.
3) PCOS patients on hormone therapy.
4) Patients on drugs affecting the thyroid profile [Lithium, Sample volume: This assay requires 100 μL of sample for a
Amiodarone], OCP, hormone replacement therapy using single determination
oral Estrogen, PPI, etc.
Estimation of serum free T4 (fT4)
Sample Size: 100 patients clinically diagnosed with PCOS on
metformin therapy>6 months and the same number of age - Assay Principle:
matched diagnosed PCOS patients according to Rotterdam The ADVIA Centaur CP FT4 assay is a competitive
immunoassay using direct chemiluminescent technology. FT4

Volume 13 Issue 3, March 2024

Fully Refereed | Open Access | Double Blind Peer Reviewed Journal
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Paper ID: MR24312145447 DOI: https://dx.doi.org/10.21275/MR24312145447 834
 International Journal of Science and Research (IJSR)
ISSN: 2319-7064
SJIF (2022): 7.942
in the patient sample competes with acridinium ester labeled 3. Result
T4 in the Lite Reagent for a limited amount of biotinylated
polyclonal rabbit anti - T antibody. Biotin - labeled anti - T4 Mean ± SD Case Control P Value
is bound to avidin that is covalently coupled to paramagnetic LH 6.29±1.91 9.81±1.48 p<0.0001
particles in the Solid Phase. Sample volume: This assay FSH 6.34±1.29 3.71±0.66 p<0.0001
requires 25 μL of sample for a single determination. TSH 3.29±2.73 4.15±3.28 p=0.022
FT4 1.08±0.25 1.04±0.20 p=0.35
Estimation of serum free T3 (FT3) – FT3 2.15±0.55 2.11±0.52 p=0.12
FBS 79.06±6.02 85.37±9.14 p<0.0001
Assay Principle: Fasting Insulin 10.56±1.32 11.44±2.80 p=0.005
The ADVIA Centaur FT3 assay is a competitive
immunoassay using direct chemiluminescent technology. Level of TSH and the patients of the two groups
FT3 in the sample competes with a T3 analog, which is TSH (in mIU/L) Case Control TOTAL
covalently coupled to paramagnetic particles in the Solid High 16 20 36
Phase for a limited amount of a combination of acridinium Row % 44.4 55.6 100
ester - labeled monoclonal mouse anti - T3 antibodies in the Col % 16 20 18
Normal 84 80 164
Lite Reagent.
Row % 51.2 48.8 100
Sample Volume - This assay requires 50 μL of sample for a
Col % 84 80 82
single determination.
TOTAL 100 100 200
Row % 50 50 100
Estimation of Luteinizing Hormone – Col % 100 100 100
Principle: IMMULITE/IMMULITE 1000 LH is a solid - Mean±s. d. 3.29±2.73 4.15±3.28
phase, two - site chemiluminescent immunometric assay. Median 2.5 2.9
Volume Required: 50 μL serum. (Sample cup must contain Range 1.1 – 15.8 1.0 – 20.9
at least 100 μL more than the total volume required.)
t - test showed that the mean level of TSH of the patients of
Estimation of Follicle Stimulating Hormone [FSH] – the controls was significantly higher than that of cases
Principle of the Procedure - IMMULITE/IMMULITE 1000 (t198=5.55; p<0.0001).
FSH is a solid - phase, two - site chemiluminescent
immunometric assay. Volume Required: 50 μL serum.
(Sample cup must contain at least 100 μL more than the total
volume required.)

Estimation of Fasting Blood Sugar [FBS] –

GOD/PAP (glucose oxidase - phenol and 4 aminophenazone)
method [Randox].

Estimation of Fasting Insulin –

Principle: IMMULITE/IMMULITE 1000 Insulin is a solid -
phase, enzyme - labeled chemiluminescent immunometric
assay.
Sample Volume: 100 μL serum or heparinized plasma.
(Sample cup must contain at least 250 μL more than the total
volume required.)

Interferences: Hemolysis, Lipemia, Jaundice, biotin

supplementation show changes in results.

Statistical Analysis
Statistical Analysis was performed with help of Epi Info (TM)
7.2.2.2 EPI INFO is a trademark of the Centers for Disease
Control and Prevention (CDC).

Descriptive statistical analysis was performed to calculate the

means with corresponding standard deviations (s. d.). Test of
proportion was used to find the Standard Normal Deviate (Z)

to compare the difference proportions and Chi - square ( )

2
test was performed to find the associations. Fisher Exact test

was applied where Chi - square (

2
) test was not applicable.
t - test was used to compare the means of any parameters of
the two groups. p<0.05 was taken to be statistically
significant.
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Level of FT4 and the patients of the two groups TOTAL 100 100 200
FT4 (in ng/mL) Case Control TOTAL Row % 50 50 100
Low 16 15 31 Col % 100 100 100
Row % 51.6 48.4 100 Mean±s. d. 6.29±1.91 9.81±1.48
Col % 16 15 15.5 Median 5.8 9.8
Normal 82 85 167 Range 3.7 - 10.0 6.8 - 11.8
Row % 49.1 50.9 100
Col % 82 85 83.5 FSH (in IU/L) Case Control TOTAL
High 2 0 2 High 100 20 120
Row % 100 0 100 Row % 83.3 16.7 100
Col % 2 0 1 Col % 100 20 60
TOTAL 100 100 200 Normal 0 80 80
Row % 50 50 100 Row % 0 100 100
Col % 100 100 100 Col % 0 80 40
Mean±s. d. 1.08±0.25 1.04±0.20 TOTAL 100 100 200
Median 1.1 1.05 Row % 50 50 100
Range 0.4 - 1.8 0.4 - 1.4 Col % 100 100 100
Mean±s. d. 6.34±1.29 3.71±0.66
t - test showed that there was no significant difference in mean Median 6.2 3.75
FT4 of the patients of the two groups (t198=1.24; p=0.21). Range 4.6 - 9.6 2.1 - 5.2

Level of fasting insulin and the patients of the two groups

Fasting insulin (in mIU/L) Case Control Total
Low 0 0 0
Row % 0 0 0
Col % 0 0 0
Normal 100 100 200
Row % 50 50 100
Col % 100 100 100
TOTAL 100 100 200
Row % 50 50 100
Col % 100 100 100
Mean±s. d. 10.56±1.32 11.44±2.80
Median 10.6 11.2
Range 8.0 - 13.6 2.0 - 18.6

t - test showed that the mean level of fasting insulin of the

controls was significantly higher than that of the cases
(t198=2.81; p=0.005).
4. Discussion
t test showed that LH: FSH ratio of controls was higher than
cases which was statistically significant (p<0.0001). Thyroid disorders and polycystic ovary syndrome (PCOS) are
LH (in IU/L) Case Control TOTAL two of the most common (and perhaps overlooked) endocrine
High 0 40 40 disorders in women of childbearing age. Genetic and
Row % 0 100 100 environmental factors are believed to contribute to thyroid
Col % 0 40 20 disorders in PCOS [1, 5]. Hypothyroidism is known to cause
Normal 100 60 160 PCOS - like ovaries and overall worsening of PCOS and
Row % 62.5 37.5 100 insulin resistance. Subclinical hypothyroidism (SCH), a mild
Col % 100 60 80 form of hypothyroidism defined as elevated TSH with normal
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ISSN: 2319-7064
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free thyroxine levels, is a common diagnosis among women significant prevalence of autoimmune thyroiditis and goiter in
of reproductive age [25]. In some, but not all, studies, it has PCOS [30] was reported. Sridhar et al reported a prevalence
been associated with infertility, an increased risk of adverse of 1.04% (2/13) of polycystic ovaries among hypothyroid
pregnancy and neonatal outcomes, and possibly with an patients.
increased risk of neurocognitive deficits in offspring. Major
contributing factors for irregular menstruation associated In our study, 14% of newly diagnosed PCOS patients had
with infertility are from local (ovarian) cause like polycystic subclinical hypothyroidism (SCH), 6% of newly diagnosed
ovarian syndrome and /or systemic cause like PCOS patients had overt hypothyroidism among case and
Hypothyroidism, Hyperprolactinemia, Hyperinsulinemia [26, among control 11% of PCOS patients on metformin therapy
27] All the above - said factors pose an individual risk for had SCH, 5% of PCOS patients on metformin had overt
anovulation. Often, they present in combination. The hypothyroidism.
compromised immune system is likely to be a cause of the
interaction between SCH and PCOS. Overall, 20% of newly diagnosed PCOS patients had thyroid
disorders, 16% of PCOS patients on metformin therapy had
Several of the early studies on metformin in PCOS were thyroid disorders. This shows that there is a correlation
compiled in a meta- analysis by Lord and colleagues [Lord et between thyroid dysfunction and PCOS which is also
al.2003]. They concluded accordingly that metformin was an supported by the findings of Maryam et al & Sridhar et al.
effective treatment to induce ovulation in PCOS patients and [30] A similar finding of hypothyroidism among PCOS
that it was justifiable to use it as a first - line treatment. women was observed by Onno E Janssen et al study (20.6%)
However, they emphasized that it should be used in [31].
conjunction with a change in lifestyle. Also, A significant
reduction in serum TSH levels was observed in patients with Again, thyroid disorders (SCH and overt hypothyroidism) are
SCH after treatment with metformin and the effect was not higher, 20% among newly diagnosed PCOS patients
related to its dose. Several mechanisms have been compared to PCOS patients on metformin, which is 16%;
hypothesized for explaining this effect: (a) a change in the Recently it has been reported that metformin is able to
affinity or number of TSH receptors; (b) an increase in the interfere with thyroid hormone profile, as shown by a
central dopaminergic tone; or (c) an interaction between decrease in the serum levels of thyrotropin (TSH) to
metformin and TSH [28]. Meanwhile, metformin also plays a subnormal levels in hypothyroid patients in stable
role in improving the ovulation rate and reproductive levothyroxine (L - T4) treatment [31, 32].
outcomes in women with PCOS [29]. In the last decade,
several studies have reported a decrease in TSH levels The most common cause of low insulin is type 1 diabetes, an
following the administration of metformin in patients with autoimmune disease in which the pancreatic cells that
polycystic ovary syndrome (PCOS). normally produce insulin are destroyed, In PCOS low level of
progesterone overstimulates the immune system that leads to
A common finding in gynaecology outpatient department is the production of autoantibodies and therefore it can be
that while treating individuals for PCOS for a period of a few labeled as an autoimmune disorder [33]. In our study, total 5
months, in some patient menstruation and ovulation is % of 100 newly diagnosed PCOS case had low fasting insulin
restored while it remains uncorrected in some individuals. On levels which is 2 uIU/mL. Among 100 case total 3 patients
further evaluation of these non - responding patients for the with SCH had low fasting insulin and 2 patients with overt
other causes of infertility / menstrual disorder, they were hypothyroidism had low fasting insulin which is as low as 2
found to have co - existing Hypothyroidism which was mostly uIU/mL. Among control, PCOS on metformin, all patients
undiagnosed and /or untreated. These individuals were found had a normal fasting insulin level.
to be mostly in subclinical status and some in overt
hypothyroid state. Screening studies help to assess the 5. Summary and Conclusion
prevalence of hypothyroidism and give insight into the
epidemiology of this disorder in the population. The study found that the mean LH was significantly higher
among controls than cases and mean FSH was significantly
A cross - sectional study comprising two comparison groups higher among cases than controls, thus LH: FSH ratio was
was conducted among 100 newly diagnosed PCOS women of higher among controls than cases.
age group 18 - 44 years and 100 diagnosed PCOS women on
metformin therapy of same age group; taken as case and It was found, the mean TSH level of controls was 4.15±3.28
control respectively, attending the Gynaecology outpatient and the mean TSH level of cases was 3.29±2.73, the mean
department for menstrual irregularity and infertility. They TSH of controls was higher than cases which was statistically
were diagnosed based on revised Rotterdam criteria, 2003. significant (t198=2.02; p=0.022).

With serum TSH level of being >5μU/L μU/L but <10 μU/L, We have identified the prevalence of subclinical
as a cutoff point with normal FT4 level to diagnose hypothyroidism among controls was14% and among cases
subclinical hypothyroidism we have identified the prevalence was 11%, where total hypothyroid (overt and subclinical)
of subclinical hypothyroidism among 100 newly diagnosed among controls was 20% and among cases was 16%.
PCOS women to be 14% and 100 diagnosed PCOS women
on metformin therapy, to be 11%. The study concluded that the control group who were not on
metformin had significantly higher BMI, mean FBS, mean
In a case - control study conducted by Maryam et al. a fasting Insulin, mean LH and LH: FSH ratio than the case
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group, thus the study concluded that metformin as one of the [9] Surks MI, Hollowell JG. Age - specific distribution of
1st line treatments for PCOS patients was significantly serum thyrotropin and antithyroid antibodies in the US
associated with long term better health outcome for treating population: implications for the prevalence of
PCOS patients. subclinical hypothyroidism. J Clin Endocrinol Metab.
(2007) 92: 4575–82.10.1210/jc.2007 - 1499 [PubMed]
As well as this study unveiled the mean TSH value [CrossRef] [Google Scholar]
significantly low among cases who were on metformin [10] Dittrich R, Kajaia N, Cupisti S, Hoffmann I, Beckmann
therapy for >6 months than the control group, the prevalence MW, Mueller A. Association of thyroid - stimulating
of subclinical hypothyroidism, as well as overt hormone with insulin resistance and androgen
hypothyroidism, were more among controls, who were not on parameters in women with PCOS. Reprod Biomed
metformin therapy. These observations lend strong support to Online (2009) 19: 319–25.10.1016/S1472 - 6483 (10)
the hypothesis that metformin, one of 1st line treatments of 60165 - 4 [PubMed] [CrossRef] [Google Scholar]
PCOS, might have a lowering effect on serum TSH level [11] Cho MK. Thyroid dysfunction and subfertility. Clin Exp
without affecting the serum FT4, FT3 among patients with Reprod Med. (2015) 42: 131–
thyroid disorders. This study suggests that screening for 5.10.5653/cerm.2015.42.4.131 [PMC free article]
hypothyroidism along with reproductive hormone profile [PubMed] [CrossRef] [Google Scholar]
should be evaluated in PCOS/infertile women for early [12] Barisic T, Mandic V, Vasilj A, Tiric D. Higher levels of
diagnosis and management. thyrotropin in pregnancy and adverse pregnancy
outcomes. J Matern Fetal Neonatal Med. (2018).1–
References 6.10.1080/14767058.2018.1451509 [PubMed]
[CrossRef] [Google Scholar]
[1] March WA, Moore VM, Willson KJ, Phillips DI, [13] Yang J, Liu Y, Liu H, Zheng H, Li X, Zhu L, et al. .
Norman RJ, Davies MJ. The prevalence of polycystic Associations of maternal iodine status and thyroid
ovary syndrome in a community sample assessed under function with adverse pregnancy outcomes in Henan
contrasting diagnostic criteria. Hum Reprod. (2010) 25: Province of China. J Trace Elem Med Biol. (2018) 47:
544–51.10.1093/humrep/dep399 [PubMed] [CrossRef] 104–10.10.1016/j. jtemb.2018.01.013 [PubMed]
[Google Scholar] [CrossRef] [Google Scholar]
[2] Morales AJ, Laughlin GA, Butzow T, Maheshwari H, [14] Ganie MA, Laway BA, Wani TA, Zargar MA, Nisar S,
Baumann G, Yen SS. Insulin, somatotropic, and Ahamed F, et al. Association of subclinical
luteinizing hormone axes in lean and obese women with hypothyroidism and phenotype, insulin resistance, and
polycystic ovary syndrome: common and distinct lipid parameters in young women with polycystic ovary
features. J Clin Endocrinol Metab. (1996) 81: 2854–64. syndrome. Fertil Steril. (2011) 95: 2039–43.10.1016/j.
[PubMed] [Google Scholar] fertnstert.2011.01.149 [PubMed] [CrossRef] [Google
[3] Carmina E, Lobo RA. Polycystic ovary syndrome Scholar]
(PCOS): arguably the most common endocrinopathy is [15] Celik C, Abali R, Tasdemir N, Guzel S, Yuksel A, Aksu
associated with significant morbidity in women. J Clin E, et al. Is subclinical hypothyroidism contributing
Endocrinol Metab. (1999) 84: 1897–9.4. dyslipidemia and insulin resistance in women with
[4] Moran LJ, Norman RJ, Teede HJ. Metabolic risk in polycystic ovary syndrome? Gynecol Endocrinol.
PCOS: phenotype and adiposity impact. Trends (2012) 28: 615–8.10.3109/09513590.2011.650765
Endocrinol Metab. (2015) 26: 136–43.10.1016/j. [PubMed] [CrossRef] [Google Scholar]
tem.2014.12.003 [PubMed] [CrossRef] [Google [16] Benetti - Pinto CL, Berini Piccolo VRS, Garmes HM,
Scholar] Teatin Juliato CR. Subclinical hypothyroidism in young
[5] Duran C, Basaran M, Kutlu O, Kucukaydin Z, Bakdik women with polycystic ovary syndrome: an analysis of
S, Burnik FS, et al. . Frequency of nodular goiter and clinical, hormonal, and metabolic parameters. Fertil
autoimmune thyroid disease in patients with polycystic Steril. (2013) 99: 588–92.10.1016/j.
ovary syndrome. Endocrine (2015) 49: 464– fertnstert.2012.10.006 [PubMed] [CrossRef] [Google
9.10.1007/s12020 - 014 - 0504 - 7 [PubMed] [CrossRef] Scholar]
[Google Scholar] [17] Nada AM. effect of treatment of overt hypothyroidism
[6] Diaz A, Lipman Diaz EG. Hypothyroidism. Pediatr on Insuline resistance. World J Diabetes.2013; 4: 157–
Rev. (2014) 35: 336–47; quiz 348–39.10.1542/pir.35 - 161. [PMC free article] [PubMed] [Google Scholar]
8 - 336 [PubMed] [CrossRef] [Google Scholar] [18] Speroff L. Clinical Gynecologic Endocrinology and
[7] Teng W, Shan Z, Patil - Sisodia K, Cooper DS. Infertility. Lippincott Williams & Wilkins; 2011.
Hypothyroidism in pregnancy. Lancet Diabetes Anovulation and the Polycystic Ovary; pp.490–531.
Endocrinol. (2013) 1: 228–37.10.1016/S2213 - 8587 [Google Scholar].
(13) 70109 - 8 [PubMed] [CrossRef] [Google Scholar] [19] Ciaraldi TP, Aroda V, Mudaliar S, Chang RJ, Henry
[8] Hollowell JG, Staehling NW, Flanders WD, Hannon RR. Polycystic ovary syndrome is associated with tissue
WH, Gunter EW, Spencer CA, et al. . Serum TSH, T specific differences in insulin resistance. J Clin
(4), and thyroid antibodies in the United States Endocrinol Metab.2009; 94: 157–163. [PMC free
population (1988 to 1994): National Health and article] [PubMed] [Google Scholar]
Nutrition Examination Survey (NHANES III). J Clin [20] Bedaiwy MA, Abdel - Rahman MY, Tan J, AbdelHafez
Endocrinol Metab. (2002) 87: 489– FF, Abdelkareem AO, Henry D, et al. . Clinical,
99.10.1210/jcem.87.2.8182 [PubMed] [CrossRef] hormonal, and metabolic parameters in women with
[Google Scholar] subclinical hypothyroidism and polycystic ovary

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ISSN: 2319-7064
SJIF (2022): 7.942
syndrome: a cross - sectional study. J Womens Health metabolic profiles in polycystic ovary syndrome
(Larchmt) (2018) 27: 659–64.10.1089/jwh.2017.6584 [published online January 9, 2018]. J Clin Endocrinol
[PubMed] [CrossRef] [Google Scholar] Metab. doi: 10.1210/jc.2017 - 01739.
[21] Effraimidis G, Wiersinga WM. Mechanisms in
endocrinology: autoimmune thyroid disease: old and
new players. Eur J Endocrinol. (2014) 170: R241–
52.10.1530/EJE - 14 - 0047 [PubMed] [CrossRef]
[Google Scholar]
[22] Petrikova J, Lazurova I, Yehuda S. Polycystic ovary
syndrome and autoimmunity. Eur J Intern Med. (2010)
21: 369–71.10.1016/j. ejim.2010.06.008 [PubMed]
[CrossRef] [Google Scholar]
[23] Angstwurm MW, Gartner R, Ziegler - Heitbrock HW.
Cyclic plasma IL - 6 levels during normal menstrual
cycle. Cytokine (1997) 9: 370–
4.10.1006/cyto.1996.0178 [PubMed] [CrossRef]
[Google Scholar]
[24] Andrade, B. M., Araujo, R. L., Perry, R. L., Souza, E.
C., Cazarin, J. M., Carvalho, D. P. and Ceddia, R. B.
(2011) A novel role for AMP - kinase in the regulation
of the Na + /I − - symporter and iodide uptake in the rat
thyroid gland. Am. J. Physiol. Cell Physiol.300, C1291–
C1297 CrossRef PubMed
[25] R. Singla, Y. Gupta, M. Khemani, and S. Aggarwal,
“Thyroid disorders and polycystic ovary syndrome: an
emerging relationship, ” Indian Journal of
Endocrinology and Metabolism, vol.19, no.1, p.25,
2015. View at: Publisher Site | Google Scholar
[26] M. A. Fritz and L. Speroff, “Chronic anovulation and
the polycystic ovary, ” in Clinical Gynecologic
Endocrinology and Infertility, pp.495–531, Lippincott
Williams & Wilkins, New York, NY, USA, 8th edition,
2011. View at: Google Scholar
[27] A. Dunaif, “Insulin resistance and the polycystic ovary
syndrome: mechanism and implications for
pathogenesis, ” Endocrine Reviews, vol.18, no.6,
pp.774–800, 1997.
[28] Rotondi M, Cappelli C, Magri F, Botta R, Dionisio R,
Iacobello C, et al. . Thyroidal effect of metformin
treatment in patients with polycystic ovary syndrome.
Clin Endocrinol. (2011) 75: 378–81.10.1111/j.1365 -
2265.2011.04042. x [PubMed] [CrossRef] [Google
Scholar]
[29] Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH.
Insulin - sensitising drugs (metformin, rosiglitazone,
pioglitazone, D - chiro - inositol) for women with
polycystic ovary syndrome, oligo amenorrhoea and
subfertility. Cochrane Database Syst Rev. (2012)
Cd003053 10.1002/14651858. CD003053. pub5
[PubMed] [CrossRef] [Google Scholar]
[30] Maryam et al. Prevalence of auto immune thyroiditis in
patients with PCOS - Archives of Gynaecology &
Obstetrics’ March 2012, vol 285. Issue 3; pg 853 - 56.
[31] OnnoJanssen OE, Mehlmauer N, Hahn S et al.
Highprevalence of autoimmune thyroiditis in patients
withpolycystic ovary syndrome. Eur J Endocrinol 2004;
150: 363 - 9.
[32] Vigersky RA, Filmore - Nassar A, Glass AR.
Thyrotropin suppression by metformin. J Clin
Endocrinol Metab 2006; 91: 225–
227CrossRefPubMedWeb of ScienceGoogle Scholar
[33] Yang PK, Hsu CY, Chen MJ, et al. The efficacy of 24 -
month metformin for improving menses, hormone and

Volume 13 Issue 3, March 2024

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Paper ID: MR24312145447 DOI: https://dx.doi.org/10.21275/MR24312145447 839