Skip to main content
Download PDF
  • Systematic Review
  • Open access
  • Published:

Prevalence of subclinical hypothyroidism in polycystic ovary syndrome and its impact on insulin resistance: a systematic review and meta-analysis

BMC Endocrine Disorders volume 25, Article number: 75 (2025) Cite this article

Abstract

Background

Although recent studies indicate a high prevalence of subclinical hypothyroidism (SCH) in women with polycystic ovary syndrome (PCOS), the reported prevalence rates vary widely. Therefore, we conducted this study to estimate the pooled prevalence of SCH among women with PCOS. Additionally, emerging evidence suggests that SCH may negatively impact insulin resistance in PCOS. Thus, we examined its effect on insulin resistance indices as our secondary objective.

Methods

We searched PubMed, Web of Science, Scopus, and Embase from their inception to February 25, 2024. Observational studies reporting the prevalence of SCH among women with PCOS were included. Joanna Briggs Institute’s (JBI) critical appraisal checklist for prevalence studies was adopted for the risk of bias assessment. The random-effects model was employed to estimate the pooled prevalence with its 95% confidence intervals (CI). The weighted mean difference (WMD) was used to compare the insulin resistance indices between PCOS patients with and without SCH.

Results

Twenty-nine studies comprising 5765 women with PCOS were included. The meta-analysis demonstrated that 19.7% (95% CI: 16.1%; 23.5%) of women with PCOS have SCH. PCOS patients with SCH had significantly higher HOMA-IR (WMD = 0.78, 95% CI: 0.34; 1.22) and fasting insulin (WMD = 2.38, 95% CI: 0.34; 4.42) levels than those without SCH. Differences in fasting plasma glucose and 2-hour postprandial glucose did not reach statistical significance.

Conclusion

This systematic review and meta-analysis found that approximately 20% of women with PCOS have SCH. This underscores the need for regular thyroid function testing in these patients. The prevalence of SCH is influenced by the TSH cut-off used for diagnosis, highlighting the need for establishing a standardized TSH cut-off value. Furthermore, SCH significantly elevates the HOMA-IR index and fasting insulin levels, highlighting its potential impact on insulin resistance. Whether these metabolic changes are clinically important and put these individuals at higher risk of developing type 2 diabetes mellitus and cardiovascular disease requires further investigation.

Systematic review registration number in PROSPERO

CRD42024510798.

Clinical trial number

Not applicable.

Peer Review reports

Introduction

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder among women of reproductive age, affecting 5 to 15% of this population [1, 2]. According to the Rotterdam criteria, a PCOS diagnosis requires at least two of the following: oligo-anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovaries on ultrasound [3]. The 2023 international evidence-based guideline for the assessment and management of PCOS now recommends that anti-Mullerian hormone (AMH) can be used as an alternative to ultrasound for diagnosis [4]. In addition to its well-known reproductive manifestations, PCOS is closely associated with metabolic disturbances, including obesity, dyslipidemia, and insulin resistance [5]. Up to 70% of women with PCOS have insulin resistance, substantially increasing their risk of type 2 diabetes mellitus (T2DM) later in life. The body’s decreased insulin sensitivity triggers compensatory hyperinsulinemia. This hyperinsulinemia leads to androgen overproduction. It also increases the amount of free androgen by lowering sex hormone-binding globulin (SHBG) levels, thereby exacerbating hyperandrogenism and PCOS symptoms [6, 7].

Subclinical hypothyroidism (SCH), a milder form of hypothyroidism, is another common endocrine disorder. It is thought to affect 4 to 10% of the adult population. As with most thyroid diseases, women are more likely to be affected [8, 9]. SCH is defined as elevated serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) within the reference range [10]. Though often asymptomatic, as the term “subclinical” suggests, research over the past decade has highlighted its potential adverse effects. Many studies have shown its negative impact on lipid profile, insulin sensitivity, and reproductive health [11,12,13]. An animal study showed that hypothyroidism leads to hyperandrogenemia and the formation of ovarian cysts, which are the main characteristics of PCOS [14]. Additionally, thyroid hormones stimulate the production of SHBG in the liver. The reduced SHBG levels in the hypothyroid state may exacerbate the vicious cycle between low SHBG, hyperandrogenemia, and hyperinsulinemia observed in PCOS [15]. Furthermore, SCH can impair insulin sensitivity by reducing intracellular glucose utilization and inhibiting GLUT4 translocation to the cell membrane [16]. Notably, it has been suggested that lower thyroid function, even in the euthyroid range, predisposes individuals to higher glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) levels [17]. Therefore, the coexistence of SCH with PCOS might have a compounding negative effect on insulin resistance and put these individuals at higher risk of T2DM and cardiovascular diseases later in life.

Three meta-analyses have explored the impact of SCH on lipid profiles and insulin resistance in women with PCOS. The most recent one, published in 2021, observed significantly higher LDL, triglyceride, and total cholesterol levels in those with both conditions, alongside a significant decrease in HDL [18]. Other reviews reported relatively similar findings except for LDL levels, which did not show a significant difference [19, 20]. However, the results concerning insulin resistance were inconclusive and somewhat contradictory. Two meta-analyses noted a significant increase in the HOMA-IR index of women with both conditions. Conversely, another meta-analysis found no difference in HOMA-IR levels between PCOS subjects with and without SCH [18,19,20].

Researchers have reported a very wide range for the prevalence of SCH among women with PCOS. Some studies reported its prevalence to be less than 10%, while others found it to be as high as 40% [21,22,23,24]. A recently published narrative review highlighted that SCH is at least two times more common in women with PCOS compared to unselected women [25]. Given the wide range of prevalence reported in original studies and the lack of a systematic review and meta-analysis on this topic, the primary objective of this study was to estimate the pooled prevalence of SCH in women with PCOS. Additionally, given the inconclusive and controversial findings of the previous meta-analyses, we aimed to elucidate its impact on insulin resistance as our secondary objective. Although this systematic review is based on observational studies, our findings could provide a basis for future clinical trials and the development of clinical guidelines to determine whether thyroid replacement therapy in women with both SCH and PCOS could lead to improved metabolic outcomes.

Methods

Protocol registration

The present systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [26]. This study was conducted following a predetermined protocol, which was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on March 2, 2024, with the registration number CRD42024510798.

Search strategy

A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Web of Science databases with a restriction to English-language publications. No publication date restriction was set (from inception until February 25, 2024). We used MeSH terms, Embase, the free-text method, and expert opinion to identify all the relevant search terms for hypothyroidism, SCH, and PCOS. Supplementary Material Table S1 outlines detailed search strategies for each database. We also hand-searched the reference lists of the included studies and relevant review articles to identify additional eligible studies.

Inclusion and exclusion criteria

Observational studies reporting SCH prevalence among individuals with PCOS were eligible to be included. Only peer-reviewed English-language studies were eligible. The exclusion criteria are as follows: (1) Conference papers, case reports, case series, animal studies, review articles, and clinical trials; (2) Studies lacking prevalence data; (3) Studies with a small sample size (fewer than 30 women with PCOS); (4) Studies that included (i) pregnant, postpartum, or lactating mothers (ii) patients with a prior history of thyroid surgery or radiotherapy to the head and neck (iii) patients who were under treatment with levothyroxine or drugs that alter thyroid function (iv) patients with central hypothyroidism (v) patients with renal or liver failure (vi) cancer cases.

Study selection

All records retrieved from the databases were imported into Endnote software. After removing the duplicate records, two reviewers (SS and MS) independently screened the studies based on their titles and abstracts. The same two reviewers then examined the remaining relevant studies in full text against the inclusion and exclusion criteria. Disagreements in the selection process were resolved through discussion. In cases of persistent disagreements, a third expert’s opinion (MF) was sought.

Data extraction

Two reviewers (MP and SS) independently extracted the following data into a predefined Excel sheet: first author, publication year, country, study design, total number of PCOS cases, mean and standard deviation (SD) of age and BMI, PCOS diagnostic criteria, number of PCOS cases diagnosed with SCH, and the normal upper limit of TSH. Additionally, the number, mean, and SD for the following variables were extracted for PCOS cases with and without SCH: HOMA-IR, fasting insulin, fasting plasma glucose (FPG), and 2-hour postprandial glucose. Any discrepancies between the reviewers were resolved through discussion. If disagreements persisted, a third expert’s (MH) opinion was sought to resolve the conflict.

Risk of bias assessment

We conducted the quality assessment of the included studies using the Joanna Briggs Institute’s (JBI) critical appraisal checklist for prevalence studies [27]. The JBI checklist consists of nine questions evaluating various aspects of methodological quality. Since the checklist does not provide a cut-off score, we categorized studies based on the following criteria: 1 to 4 indicated a high risk of bias, 5 to 6 moderate risk of bias, and 7 to 9 low risk of bias. Two authors (AS and SM-T) independently assessed the quality of the studies. Disagreements between reviewers were resolved by discussion. In cases of unresolved disagreements, a third expert’s (MH) opinion was asked.

Statistical analysis

The meta-analysis was performed using R version 4.4.0. We used the metaprop function from the meta package to calculate the pooled prevalence and its 95% confidence interval (CI) [28]. The inconsistency index (I2) was used to assess the degree of statistical heterogeneity. I2 < 25%, 25% ≤ I2 ≤ 50%, and I2 > 50% were defined as low, moderate, and high statistical heterogeneity, respectively. Given the high methodological and statistical heterogeneity across the studies, we used the random-effects model. The weighted mean difference (WMD) was chosen as the effect size to compare the insulin resistance indices between PCOS patients with and without SCH. The metacont function from the meta package employing the Hartung-Knapp adjustment method for the random-effects model was used to calculate the pooled WMD along with its 95% CI [29, 30].

We performed subgroup analyses based on the following variables (continuous variables were categorized) to investigate the potential sources of heterogeneity: study design, risk of bias, sample size, publication year, mean age of patients, mean BMI of patients, and TSH cut-off used for the diagnosis of SCH. Differences between groups were examined using the p-value of the test for subgroup differences.

Publication bias was assessed using funnel plots (for analyses including at least ten studies), as well as the Begg and Egger tests. If asymmetry was observed in the funnel plot or any of the Begg or Egger tests indicated the potential presence of publication bias, Duval and Tweedie’s trim-and-fill method was applied to assess the impact of publication bias on our findings [31,32,33]. The leave-one-out sensitivity analysis was conducted to evaluate the robustness of pooled estimates by sequentially excluding one study at a time and re-estimating outcomes. Statistical significance was defined as a p-value < 0.05 for all the statistical tests.

Results

Study selection and study characteristics

The comprehensive search across four electronic databases yielded 2371 records. After removing duplicate results, 1437 studies were screened based on their titles and abstracts. Subsequently, 108 relevant studies were eligible for full-text examination. Six studies did not have retrievable full-texts. Of the remaining 102 studies, 74 were excluded for the following reasons: 31 lacked prevalence data; 28 were reviews, conference papers, case reports, clinical trials, or animal studies; 9 met exclusion criteria; and 6 had sample sizes smaller than thirty women with PCOS. One additional study was identified from the reference lists. Ultimately, 29 observational studies were included in this systematic review and meta-analysis. The literature search results and study selection process are illustrated in detail through a PRISMA flow diagram (Fig. 1).

Fig. 1
figure 1

PRISMA flow diagram of the study selection process

Full size image

The detailed characteristics of the included studies are summarized in Table 1. Of the 29 studies, 21 were carried out in Asia, 5 in Europe, 2 in South America, and 1 in North America. Regarding study design, 20 were cross-sectional, and 9 were case-control studies. The publication dates ranged from 2009 to 2024. Since our primary objective was to assess the prevalence of SCH, all 29 studies reported its prevalence among PCOS subjects and were included in the meta-analysis. In terms of our secondary outcome, eleven studies compared the HOMA-IR index and FPG between PCOS subjects with and without SCH. Nine studies conducted this comparison for fasting insulin and six for 2-hour postprandial glucose levels.

Table 1 Main characteristics of the included studies
Full size table

Quality assessment

The average JBI score of the included studies was 4.96 ± 1.54. Five studies were classified as having a low risk of bias. Fourteen were classified as moderate, and ten as high risk of bias. Detailed quality assessment results for each study are provided in Table S2.

Meta-analysis

Primary outcome

The overall pooled prevalence of SCH across all 29 studies, with a total of 5765 PCOS subjects, was 19.7% (95% CI: 16.1%; 23.5%). The heterogeneity across studies was high (I2 = 92%). Prevalence rates varied significantly, with the lowest rate reported at 4% and the highest at 46.9%. The forest plot illustrating these findings is depicted in Fig. 2.

Subgroup analysis was performed based on the following variables: study design, risk of bias, publication year, sample size, mean age of patients, mean BMI of patients, and TSH cut-off used for diagnosing SCH. The purpose of subgroup analysis was to investigate potential sources of heterogeneity and possible causes for different prevalence rates. None of the variables were identified as sources of heterogeneity. Our subgroup analysis demonstrates that the TSH cut-off value was the only factor that could explain the wide range of prevalence across the studies. The pooled prevalence of SCH was 16.1% (95%CI: 11.9%; 20.8%) in studies with upper reference limits of 4-5.5 vs. 28.6% (95% CI: 21.6%; 36.3%) in studies with upper reference limits of 2.5-4 (P-value of test for subgroup differences = 0.003) (Fig. 3). Subgroup analysis results are presented in Table 2 and Fig. S1.

Fig. 2
figure 2

Forest plot showing the pooled prevalence of subclinical hypothyroidism

Full size image
Fig. 3
figure 3

Pooled prevalence of subclinical hypothyroidism with subgroup analysis by TSH upper limit

Full size image

Secondary outcomes

Regarding insulin resistance, the pooled WMD of 0.78 (95% CI: 0.34; 1.22) indicated a significantly higher HOMA-IR index in PCOS cases with SCH compared to those without SCH (Fig. 4). Similarly, fasting insulin levels were significantly higher in the SCH group, with a pooled WMD of 2.38 (95% CI: 0.34; 4.42) (Fig. 5). However, the pooled WMD for FPG was 1.66 (95% CI: -0.06; 3.37), which did not reach statistical significance (Supplementary Material Fig. S2). Likewise, the pooled WMD for 2-hour postprandial glucose was 10.1 (95% CI: -3.49; 23.69), also failing to reach statistical significance (Fig. S3). Table 3 provides a comparison of our results with those of previous meta-analyses.

Fig. 4
figure 4

Forest plot showing the weighted mean difference of HOMA-IR between patients with and without subclinical hypothyroidism

Full size image
Fig. 5
figure 5

Forest plot showing the weighted mean difference of fasting insulin levels between patients with and without subclinical hypothyroidism

Full size image
Table 2 Subgroup analysis
Full size table
Table 3 Comparison of findings from previous and current meta-analyses
Full size table

Publication bias and sensitivity analysis

We observed a symmetrical funnel plot for the prevalence of SCH in women with PCOS (Fig. S4). Additionally, the results of the Begg (p = 0.159) and Egger (p = 0.347) tests suggested that publication bias is unlikely to affect our findings. Similarly, the funnel plots for the WMD and its standard error for HOMA-IR and FPG (Fig. S5) also appeared symmetrical. For these secondary objectives, the Begg and Egger tests were also not significant (Table S3). The leave-one-out sensitivity analysis showed that the pooled prevalence of SCH remains stable when omitting any of the studies (Fig. S6).

Discussion

Data from the National Health and Nutrition Survey (NHANES) and the Colorado Thyroid Prevalence Study suggest that SCH affects approximately 4 to 10% of the general population [58, 59]. Our systematic review and meta-analysis, synthesizing data from 29 studies, demonstrate that 19.7% of women with PCOS have SCH, a rate considerably higher than in the general population. Supporting our findings, a systematic review and meta-analysis reported that women with PCOS are more likely to have SCH, with an odds ratio of 2.87. When limiting the analysis to studies that used a TSH cut-off of ≥ 4 mIU/L for SCH diagnosis, women with PCOS were 3.59 times more likely to have SCH compared to the control group [60]. According to existing literature, the association between PCOS and thyroid disorder goes beyond just SCH. A systematic review involving 13 studies found that autoimmune thyroiditis is nearly three times more common in women with PCOS in comparison to healthy controls [61]. Additionally, another systematic review and meta-analysis revealed that women with PCOS have a nearly threefold higher chance of having positive thyroid peroxidase antibody (TPOAb) and a twofold higher chance of positive thyroglobulin antibody compared to controls [62]. In line with these findings, another systematic review and meta-analysis demonstrated that women with PCOS are at increased risk of Hashimoto’s thyroiditis (HT), with an odds ratio of 2.28 [63]. Since HT is the primary cause of SCH and can initially present in euthyroid or SCH stages, it is plausible that some cases of SCH represent early, undiagnosed stages of HT [64].

Since SCH is defined biochemically, the upper reference limit of TSH is a critical factor to consider. The conventional threshold for TSH is around 4-5.5 mIU/L. Nevertheless, the question of whether to reduce this upper limit remains a topic of continuous debate. There are numerous arguments for and against lowering this upper limit, but they are beyond the scope of this discussion [8]. A recent study with a large sample size demonstrated that lowering the normal upper limit from 4.1 mIU/L to 2.5 mIU/L led to a threefold increase in the prevalence of SCH [65]. Based on the recommendations of the American Thyroid Association (2011) and Endocrine Society guidelines and evidence of adverse pregnancy outcomes at TSH levels above 2.5 mIU/L [66,67,68], some studies used a TSH cut-off of 2.5 mIU/L. Accordingly, we performed a subgroup analysis based on these differing cut-off values. As expected, studies using TSH upper limits of 2.5-4 mIU/L revealed a significantly higher pooled prevalence of 28.6% compared to those using the upper limits of 4-5.5 mIU/L, which had a pooled prevalence of 16.1% (p-value of test for subgroup differences = 0.003). Even with the conventional upper limit, SCH prevalence in women with PCOS is considerably higher than in women of the same age, indicating a possible association between the two conditions.

Insulin resistance, a key factor in the pathophysiology of PCOS, exacerbates the hyperandrogenism state by having direct effects on androgen production and indirect effects by suppressing SHBG production, which subsequently leads to higher free androgen levels [69]. Although the hyperinsulinemic-euglycemic clamp is the gold standard for detecting insulin resistance, its complex procedure limits its use in practice [70]. There are multiple insulin resistance indices that can be easily calculated from fasting levels of insulin and blood glucose. HOMA-IR is the most widely used index and is calculated as fasting insulin (µU/mL) × fasting glucose (mmol/L)/22.5 [71, 72]. Our study demonstrated that the HOMA-IR index is significantly higher in cases with concurrent SCH. This finding aligns with two other meta-analyses, which also reported a significant increase in the HOMA-IR of PCOS patients with SCH [18, 19]. On the contrary, another meta-analysis did not note a significant difference in HOMA-IR levels between these two groups of PCOS patients [20]. Fasting insulin was also higher in the presence of SCH. Future studies are required to confirm if this difference in HOMA-IR and fasting insulin is clinically meaningful. Our findings regarding FPG and 2-hour postprandial glucose did not reach statistical significance. Nonetheless, considering the limited number of studies and wide confidence intervals, our findings are not conclusive. Unfortunately, other insulin resistance indices, such as QUICKI and Matsuda, were underreported in the literature, precluding us from performing meta-analyses on these indices.

The primary pathophysiological mechanisms by which PCOS and SCH contribute to insulin resistance are different. In PCOS, increased serine phosphorylation of insulin receptor substrate-1 (IRS-1) inhibits PI3-K activation, impairing downstream insulin signaling pathways [73]. Hyperandrogenism, a hallmark of PCOS, can directly impair insulin signaling in skeletal muscle and adipose tissue. High androgen levels promote visceral fat accumulation, which is strongly associated with insulin resistance. It also reduces adiponectin production, which has insulin-sensitizing effects [73, 74]. In SCH, while not fully understood, impaired insulin sensitivity is primarily attributed to reduced intracellular glucose utilization, inhibition of GLUT 4 translocation, and decreased glycogen synthesis [16, 18]. Additionally, hepatic endoplasmic reticulum stress, via activation of the IRE1α/XBP-1 pathway, has been suggested to play a pivotal role in inducing insulin resistance in SCH [75]. Furthermore, TSH itself can activate the toll-like receptor 4 (TLR4)-mediated inflammatory pathway, further disrupting insulin signaling in hepatic tissue [76]. However, there are similar pathophysiological mechanisms by which both conditions promote insulin resistance. Both SCH and PCOS are associated with chronic low-grade inflammation, marked by increased levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), which can impair insulin signaling pathways [76,77,78]. Additionally, reduced SHBG levels seen in both conditions lead to higher amounts of free androgens, which is a key contributor to insulin resistance in women with PCOS [15, 55, 79]. These shared mechanisms underscore the potential synergistic adverse effect of SCH and PCOS on insulin sensitivity.

PCOS management depends on factors like symptom severity and the patient’s pregnancy plans. For most patients, combined oral contraceptives (COCs) are the first-line pharmacological therapy. When COCs are contraindicated or not preferred, metformin is considered an alternative treatment. Metformin, an insulin sensitizer, is particularly beneficial for women with PCOS who have insulin resistance, T2DM, and metabolic risk factors. It is also used as adjuvant therapy with letrozole and clomiphene citrate for ovulation induction [4, 80, 81]. In recent years, many studies have investigated metformin’s effect on thyroid function tests. Except for one study, which observed no significant difference in thyroid function tests following metformin therapy [82], other studies found that metformin significantly lowers TSH without notable changes in thyroid hormone levels [83,84,85]. Three studies, specifically on women with PCOS, observed similar TSH-lowering effects, while thyroid hormones remained unchanged [86,87,88].

SCH can be classified into mild (TSH < 10 mIU/L) or severe (TSH > 10 mIU/L). Almost all guidelines recommend thyroid replacement therapy when the serum TSH concentrations are above ten due to a higher risk of cardiovascular disease and an increased chance of progression to overt hypothyroidism [89,90,91]. However, there is no firm consensus regarding the treatment of mild SCH. Most guidelines and expert opinions do not encourage thyroid replacement therapy for most cases of mild and asymptomatic SCH. Treatment is generally considered for individuals with positive TPOAb, pregnant women or those planning to become pregnant, and patients with cardiovascular risk factors [10, 89, 91, 92]. Although PCOS is not currently recognized as an indication for treating SCH [25], many women with PCOS have obesity, dyslipidemia, and insulin resistance, which are major cardiovascular risk factors [5]. Furthermore, a systematic review and meta-analysis, including 12 randomized controlled trials, showed that treatment with levothyroxine in patients with SCH causes a significant reduction in LDL and total cholesterol. Their results remained consistent even in trials that enrolled only mild cases of SCH [93].

Similar to overt hypothyroidism, patients with SCH are at increased risk of hyperprolactinemia, a known cause of ovulatory dysfunction and infertility. It is estimated that around 20 to 30% of individuals with SCH experience hyperprolactinemia, which often resolves with thyroid replacement therapy [94, 95]. Furthermore, a recent meta-analysis found a significant increase in prolactin levels of women with concurrent PCOS and SCH compared to those with PCOS alone [18]. These findings further support the potential benefits of levothyroxine treatment for women with both conditions. Additionally, long-term use of COCs, the first-line pharmacological treatment for PCOS, is associated with a fourfold increased risk of hypothyroidism, according to a large-scale NHANES study [96]. Given these considerations, future clinical guidelines should assess whether PCOS should be recognized as an indication for treating SCH.

Another important aspect to consider is the potential impact of SCH on PCOS symptoms. Oligo-anovulation is a key component of the PCOS diagnostic criteria and one of its most important clinical features [4]. Hyperprolactinemia, commonly seen in SCH, is strongly associated with oligo-anovulation and infertility [97]. However, studies comparing menstrual irregularities in PCOS patients with and without SCH report no significant differences [13, 21, 40]. With respect to hyperandrogenism-related symptoms, namely acne and hirsutism, it is plausible that SCH may worsen these symptoms due to reduced levels of SHBG, which increase the free form of androgens [15, 55]. However, the findings of clinical research on this topic are controversial. Lu et al. reported a significantly higher Ferriman-Gallwey score among patients with both PCOS and SCH compared to those with PCOS only [23]. Conversely, another study noted a lower rate of hirsutism among those with concurrent PCOS and SCH [44]. Most studies, however, found no significant difference in the prevalence of hirsutism and acne when comparing PCOS patients with and without SCH [13, 21, 38]. Further research on this aspect is needed to draw a firm conclusion.

This study has several strengths. To our knowledge, it is the first systematic review and meta-analysis assessing the pooled prevalence of SCH in PCOS patients. The large number of included studies and extensive data extraction allowed for subgroup analyses based on seven variables. Notably, subgroup analysis demonstrated that the TSH cut-off value used for SCH diagnosis is a critical factor influencing SCH prevalence. This finding highlights the need for a standardized cut-off value to harmonize research findings and minimize over or underdiagnosis. None of the funnel plots or Begg and Egger tests indicated that our findings were influenced by publication bias. Moreover, the leave-one-out sensitivity analysis supports the robustness of our results. This study has several methodological limitations. Firstly, non-English studies were not included. Secondly, the quality assessment identified 24 studies as having a moderate or high risk of bias. Additionally, most studies had non-random sampling methods, which might have introduced selection bias by including more severe cases that sought medical care. There are also several analytical limitations. Despite conducting rigorous subgroup analyses based on seven variables, none were identified as sources of statistical heterogeneity. The observed high heterogeneity may partly stem from variations in the distribution of PCOS phenotypes among studies as well as differences in other characteristics such as ethnicity and iodine status. The use of different thyroid function test kits is likely to be another factor contributing to this high heterogeneity. The limited number of studies reporting SCH prevalence across different PCOS phenotypes prevented us from performing a meta-analysis to estimate the prevalence for each phenotype. Lastly, due to the limited number of studies and wide confidence intervals, the findings regarding 2-hour postprandial glucose and FPG are not conclusive. These limitations should be considered when interpreting our findings.

Conclusion

This study demonstrates that around 20% of women with PCOS have SCH, highlighting the importance of regular thyroid function testing in these patients. We found that the prevalence of SCH is significantly influenced by the TSH cut-off used for diagnosis. This underscores the need for a standardized TSH cut-off value to ensure consistency across studies and reduce the risk of over- or underdiagnosis. Moreover, women with both PCOS and SCH had significantly higher HOMA-IR and fasting insulin levels compared to those with PCOS alone, indicating a potential exacerbation of insulin resistance. Future cohort studies are needed to assess the long-term risks of T2DM and cardiovascular disease in these patients. Additionally, clinical trials with sufficient follow-up periods are essential to aid future guidelines in deciding whether PCOS should be considered an indication for treating SCH.

Data availability

Availability of data and materials: The dataset supporting the results of this systematic review and meta-analysis was extracted from previously published studies and is presented within the manuscript and supplementary material.

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

COCs:

Combined oral contraceptives

FPG:

Fasting plasma glucose

FT4:

Free thyroxine

HOMA-IR:

Homeostatic model assessment of insulin resistance

HT:

Hashimoto’s thyroiditis

I2 :

Inconsistency index

IL-6:

Interleukin-6

IQR:

Interquartile range

IRS-1:

Insulin receptor substrate-1

JBI:

Joanna briggs institute

NHANES:

National health and nutrition survey

NIH:

National institute of health

NR:

Not reported

PCOS:

Polycystic ovary syndrome

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

SCH:

Subclinical hypothyroidism

SD:

Standard deviation

SHBG:

Sex hormone-binding globulin

T2DM:

Type 2 diabetes mellitus

TLR4:

Toll-like receptor 4

TNF-α:

Tumor necrosis factor-α

TPOAb:

Thyroid peroxidase antibody

TSH:

Thyroid-stimulating hormone

WMD:

Weighted mean difference

References

  1. Yu O, Christ JP, Schulze-Rath R, Covey J, Kelley A, Grafton J et al. Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019. Am J Obstet Gynecol. 2023;229:39. e1-39.e12.

  2. Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37:467–520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rotterdam ESHRE, ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19–25.

    Article  Google Scholar 

  4. Teede HJ, Tay CT, Laven JJE, Dokras A, Moran LJ, Piltonen TT, et al. Recommendations from the 2023 international Evidence-based guideline for the assessment and management of polycystic ovary syndrome. J Clin Endocrinol Metab. 2023;108:2447–69.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Couto Alves A, Valcarcel B, Mäkinen V-P, Morin-Papunen L, Sebert S, Kangas AJ, et al. Metabolic profiling of polycystic ovary syndrome reveals interactions with abdominal obesity. Int J Obes (Lond). 2017;41:1331–40.

    Article  CAS  PubMed  Google Scholar 

  6. Wen Q, Hu M, Lai M, Li J, Hu Z, Quan K, et al. Effect of acupuncture and Metformin on insulin sensitivity in women with polycystic ovary syndrome and insulin resistance: a three-armed randomized controlled trial. Hum Reprod. 2021;37:542–52.

    Article  PubMed Central  Google Scholar 

  7. Anagnostis P, Tarlatzis BC, Kauffman RP. Polycystic ovarian syndrome (PCOS): Long-term metabolic consequences. Metabolism. 2018;86:33–43.

    Article  CAS  PubMed  Google Scholar 

  8. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev. 2008;29:76–131.

    Article  CAS  PubMed  Google Scholar 

  9. Darouei B, Amani-Beni R, Abhari AP, Fakhrolmobasheri M, Shafie D, Heidarpour M. Systematic review and meta-analysis of Levothyroxine effect on blood pressure in patients with subclinical hypothyroidism. Curr Probl Cardiol. 2024;49:102204.

    Article  PubMed  Google Scholar 

  10. Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: A review. JAMA. 2019;322:153–60.

    Article  CAS  PubMed  Google Scholar 

  11. Maraka S, Mwangi R, McCoy RG, Yao X, Sangaralingham LR, Singh Ospina NM, et al. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US National assessment. BMJ. 2017;356:i6865.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Urgatz B, Razvi S. Subclinical hypothyroidism, outcomes and management guidelines: a narrative review and update of recent literature. Curr Med Res Opin. 2023;39:351–65.

    Article  PubMed  Google Scholar 

  13. Dittrich R, Kajaia N, Cupisti S, Hoffmann I, Beckmann MW, Mueller A. Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS. Reprod Biomed Online. 2009;19:319–25.

    Article  CAS  PubMed  Google Scholar 

  14. Bagavandoss P, England B, Asirvatham A, Bruot BC. Transient induction of polycystic ovary-like syndrome in immature hypothyroid rats. Proc Soc Exp Biol Med. 1998;219:77–84.

    Article  CAS  PubMed  Google Scholar 

  15. Krassas GE, Poppe K, Glinoer D. Thyroid function and human reproductive health. Endocr Rev. 2010;31:702–55.

    Article  CAS  PubMed  Google Scholar 

  16. Maratou E, Hadjidakis DJ, Kollias A, Tsegka K, Peppa M, Alevizaki M, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol. 2009;160:785–90.

    Article  CAS  PubMed  Google Scholar 

  17. Garduño-Garcia J, de Alvirde-Garcia J, López-Carrasco U, Padilla Mendoza G, Mehta ME, Arellano-Campos R. TSH and free thyroxine concentrations are associated with differing metabolic markers in euthyroid subjects. Eur J Endocrinol. 2010;163:273–8.

    Article  PubMed  Google Scholar 

  18. Xing Y, Chen J, Liu J, Ma H. The impact of subclinical hypothyroidism on patients with polycystic ovary syndrome: A Meta-Analysis. Horm Metab Res. 2021;53:382–90.

    Article  CAS  PubMed  Google Scholar 

  19. Pergialiotis V, Konstantopoulos P, Prodromidou A, Florou V, Papantoniou N, Perrea DN, MANAGEMENT OF ENDOCRINE, DISEASE. The impact of subclinical hypothyroidism on anthropometric characteristics, lipid, glucose and hormonal profile of PCOS patients: a systematic review and meta-analysis. Eur J Endocrinol. 2017;176:R159–66.

    Article  CAS  PubMed  Google Scholar 

  20. de Medeiros SF, de Medeiros MAS, Ormond CM, Barbosa JS, Yamamoto MMW. Subclinical hypothyroidism impact on the characteristics of patients with polycystic ovary syndrome. A Meta-Analysis of observational studies. Gynecol Obstet Invest. 2018;83:105–15.

    Article  PubMed  Google Scholar 

  21. Trakakis E, Pergialiotis V, Hatziagelaki E, Panagopoulos P, Salloum I, Papantoniou N. Subclinical hypothyroidism does not influence the metabolic and hormonal profile of women with PCOS. Horm Mol Biol Clin Investig. 2017;31:/j/hmbci.2017.31.issue-3/hmbci-2016-0058/hmbci-2016-0058.xml

  22. Vardhan AV, Ahmed Sheikh SS, Kulkarni C, Naik K, Kamath V, STUDY OF THYROID, FUNCTION TESTS IN PATIENTS WITH PCOS AT A TERTIARY CARE CENTRE. Int J Acad Med Pharm. 2023;5:296–300.

    Google Scholar 

  23. Lu Y-H, Xia Z-L, Ma Y-Y, Chen H-J, Yan L-P, Xu H-F. Subclinical hypothyroidism is associated with metabolic syndrome and clomiphene citrate resistance in women with polycystic ovary syndrome. Gynecol Endocrinol. 2016;32:852–5.

    Article  CAS  PubMed  Google Scholar 

  24. Raj D, Pooja F, Chhabria P, Kalpana F, Lohana S, Lal K, et al. Frequency of subclinical hypothyroidism in women with polycystic ovary syndrome. Cureus. 2021;13:e17722.

    PubMed  PubMed Central  Google Scholar 

  25. Palomba S, Colombo C, Busnelli A, Caserta D, Vitale G. Polycystic ovary syndrome and thyroid disorder: a comprehensive narrative review of the literature. Front Endocrinol (Lausanne). 2023;14:1251866.

    Article  PubMed  Google Scholar 

  26. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid Based Healthc. 2015;13:147–53.

    Article  PubMed  Google Scholar 

  28. Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health. 2019;22:153–60.

    Article  PubMed  PubMed Central  Google Scholar 

  29. IntHout J, Ioannidis JPA, Borm GF. The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method. BMC Med Res Methodol. 2014;14:25.

    Article  PubMed  PubMed Central  Google Scholar 

  30. van Aert RCM, Jackson D. A new justification of the Hartung-Knapp method for random-effects meta-analysis based on weighted least squares regression. Res Synth Methods. 2019;10:515–27.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.

    Article  CAS  PubMed  Google Scholar 

  32. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56:455–63.

    Article  CAS  PubMed  Google Scholar 

  34. Anebaracy V, Naveen Kumar C, Ravi N, Rajapandian N, Association of polycystic ovary syndrome and thyroid dysfunction among reproductive women.: a cross-sectional study. Asian j pharm clin res. 2024;17:149–52.

  35. Bedaiwy MA, Abdel-Rahman MY, Tan J, AbdelHafez FF, Abdelkareem AO, Henry D, et al. Clinical, hormonal, and metabolic parameters in women with subclinical hypothyroidism and polycystic ovary syndrome: A Cross-Sectional study. J Womens Health (Larchmt). 2018;27:659–64.

    Article  PubMed  Google Scholar 

  36. Benetti-Pinto CL, Berini Piccolo VRS, Garmes HM, Teatin Juliato CR. Subclinical hypothyroidism in young women with polycystic ovary syndrome: an analysis of clinical, hormonal, and metabolic parameters. Fertil Steril. 2013;99:588–92.

    Article  CAS  PubMed  Google Scholar 

  37. Cakir I, Simsek Y. Total cholesterol/hdl cholesterol ratio and monocyte/hdl cholesterol ratio are related with subclinical hypothyroidism in polycystic ovary syndrome. Turkish J Biochem. 2022;47:65–9.

    Article  CAS  Google Scholar 

  38. Enzevaei A, Salehpour S, Tohidi M, Saharkhiz N. Subclinical hypothyroidism and insulin resistance in polycystic ovary syndrome: is there a relationship? Iran J Reprod Med. 2014;12:481–6.

    PubMed  PubMed Central  Google Scholar 

  39. Fatima M, Amjad S, Sharaf Ali H, Ahmed T, Khan S, Raza M, et al. Correlation of subclinical hypothyroidism with polycystic ovary syndrome (PCOS). Cureus. 2020;12:e8142.

    PubMed  PubMed Central  Google Scholar 

  40. Ganie MA, Laway BA, Wani TA, Zargar MA, Nisar S, Ahamed F, et al. Association of subclinical hypothyroidism and phenotype, insulin resistance, and lipid parameters in young women with polycystic ovary syndrome. Fertil Steril. 2011;95:2039–43.

    Article  CAS  PubMed  Google Scholar 

  41. Ganvir S, Sahasrabuddhe A, Pitale S. Thyroid function tests in polycystic ovarian syndrome. Natl J Physiol Pharm Pharmacol. 2017;7:1.

    Article  Google Scholar 

  42. Garelli S, Masiero S, Plebani M, Chen S, Furmaniak J, Armanini D, et al. High prevalence of chronic thyroiditis in patients with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;169:248–51.

    Article  CAS  PubMed  Google Scholar 

  43. Huang R, Zheng J, Li S, Tao T, Liu W. Subclinical hypothyroidism in patients with polycystic ovary syndrome: distribution and its association with lipid profiles. Eur J Obstet Gynecol Reprod Biol. 2014;177:52–6.

    Article  CAS  PubMed  Google Scholar 

  44. Kamrul-Hasan A, Aalpona FTZ, Selim S. Impact of subclinical hypothyroidism on reproductive and metabolic parameters in polycystic ovary Syndrome - A Cross-sectional study from Bangladesh. Eur Endocrinol. 2020;16:156–60.

    PubMed  PubMed Central  Google Scholar 

  45. Mehra T, Sharma S, Zahra T, Jangir S, Gupta B. Correlation of body mass index with anthropometric and biochemical parameters among polycystic ovary syndrome phenotypes. Indian J Clin Biochem. 2023;38:231–41.

    Article  CAS  PubMed  Google Scholar 

  46. Morgante G, Musacchio MC, Orvieto R, Massaro MG, De Leo V. Alterations in thyroid function among the different polycystic ovary syndrome phenotypes. Gynecol Endocrinol. 2013;29:967–9.

    Article  CAS  PubMed  Google Scholar 

  47. Nanda SS, Dash S, Behera A, Mishra B. Thyroid profile in polycystic ovarian syndrome. Jemds. 2014;3:9594–600.

    Article  Google Scholar 

  48. Nayak PK, Mitra S, Sahoo J, Mahapatra E, Agrawal S, Lone Z. Relationship of subclinical hypothyroidism and obesity in polycystic ovarian syndrome patients. J Family Med Prim Care. 2020;9:147–50.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Naz S, Khan KA, Umer A, Raza MT, Nasir KM, Hussain I. Frequency and pattern of thyroid dysfunction in patients with polycystic ovary syndrome. PAFMJ. 2022;72:1730–3.

    Article  Google Scholar 

  50. Novais J, de SM, Benetti-Pinto CL, Garmes HM, Jales RM, Juliato CRT. Polycystic ovary syndrome and chronic autoimmune thyroiditis. Gynecol Endocrinol. 2015;31:48–51.

    Article  CAS  PubMed  Google Scholar 

  51. Pan M, Zhang J, Zhang Q, Wang F, Qu F, Jin M. Association of serum thyroid hormone levels with androgen and metabolic parameters in Chinese women with polycystic ovary syndrome: A retrospective Cross-Sectional study. Clin Exp Obstet Gynecol. 2023;50:162.

    Article  Google Scholar 

  52. Rojhani E, Rahmati M, Firouzi F, Saei Ghare Naz M, Azizi F, Ramezani Tehrani F. Polycystic ovary syndrome, subclinical hypothyroidism, the Cut-Off value of thyroid stimulating hormone; is there a link?? Findings of a Population-Based study. Diagnostics. 2023;13:316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Saeed WM, Alsehli F. Thyroid hormones and cardiometabolic risk factors in Saudi women with polycystic ovary syndrome: A Cross-Sectional study. Int J Womens Health. 2023;15:1197–203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Sinha U, Sinharay K, Saha S, Longkumer TA, Baul SN, Pal SK. Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India. Indian J Endocrinol Metab. 2013;17:304–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Tagliaferri V, Romualdi D, Guido M, Mancini A, De Cicco S, Di Florio C, et al. The link between metabolic features and TSH levels in polycystic ovary syndrome is modulated by the body weight: an euglycaemic-hyperinsulinaemic clamp study. Eur J Endocrinol. 2016;175:433–41.

    Article  CAS  PubMed  Google Scholar 

  56. Yasar HY, Topaloglu O, Demirpence M, Ceyhan BO, Guclu F. Is subclinical hypothyroidism in patients with polycystic ovary syndrome associated with BMI? Acta Endocrinol (Buchar). 2016;12:431–6.

    Article  CAS  PubMed  Google Scholar 

  57. Yu Q, Wang J-B. Subclinical hypothyroidism in PCOS: impact on presentation, insulin resistance, and cardiovascular risk. Biomed Res Int. 2016;2016:2067087.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the united States population (1988 to 1994): National health and nutrition examination survey (NHANES III). J Clin Endocrinol Metab. 2002;87:489–99.

    Article  CAS  PubMed  Google Scholar 

  59. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526–34.

    Article  CAS  PubMed  Google Scholar 

  60. Ding X, Yang L, Wang J, Tang R, Chen Q, Pan J, et al. Subclinical hypothyroidism in polycystic ovary syndrome: A systematic review and Meta-Analysis. Front Endocrinol (Lausanne). 2018;9:700.

    Article  PubMed  Google Scholar 

  61. Romitti M, Fabris VC, Ziegelmann PK, Maia AL, Spritzer PM. Association between PCOS and autoimmune thyroid disease: a systematic review and meta-analysis. Endocr Connections. 2018;7:1158.

    Article  CAS  Google Scholar 

  62. Du D, Li X. The relationship between thyroiditis and polycystic ovary syndrome: a meta-analysis. Int J Clin Exp Med. 2013;6:880–9.

    PubMed  PubMed Central  Google Scholar 

  63. Hu X, Chen Y, Shen Y, Zhou S, Fei W, Yang Y, et al. Correlation between Hashimoto’s thyroiditis and polycystic ovary syndrome: A systematic review and meta-analysis. Front Endocrinol (Lausanne). 2022;13:1025267.

    Article  PubMed  Google Scholar 

  64. Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379:1142–54.

    Article  PubMed  Google Scholar 

  65. Arce-Sánchez L, Vitale SG, Flores-Robles CM, Godines-Enriquez MS, Noventa M, Urquia-Figueroa CM, et al. Effect of the Cut-Off level for Thyroid-Stimulating hormone on the prevalence of subclinical hypothyroidism among infertile Mexican women. Diagnostics (Basel). 2021;11:417.

    Article  PubMed  Google Scholar 

  66. Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American thyroid association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21:1081–125.

    Article  PubMed  PubMed Central  Google Scholar 

  67. De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al. Management of thyroid dysfunction during pregnancy and postpartum: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2543–65.

    Article  PubMed  Google Scholar 

  68. Blumenthal NJ, Eastman CJ. Beneficial effects on pregnancy outcomes of thyroid hormone replacement for subclinical hypothyroidism. J Thyroid Res. 2017;2017:4601365.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Azziz R. Polycystic ovary syndrome. Obstet Gynecol. 2018;132:321–36.

    Article  PubMed  Google Scholar 

  70. Tam CS, Xie W, Johnson WD, Cefalu WT, Redman LM, Ravussin E. Defining insulin resistance from hyperinsulinemic-euglycemic clamps. Diabetes Care. 2012;35:1605–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.

    Article  CAS  PubMed  Google Scholar 

  72. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294:E15–26.

    Article  CAS  PubMed  Google Scholar 

  73. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. 2012;33:981–1030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Mishra P, Mittal P, Rani A, Bharti R, Agarwal V, Suri J. Adiponectin to leptin ratio and its association with insulin resistance in women with polycystic ovarian syndrome. Indian J Endocrinol Metab. 2022;26:239–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Xu C, Zhou L, Wu K, Li Y, Xu J, Jiang D, et al. Abnormal glucose metabolism and insulin resistance are induced via the IRE1α/XBP-1 pathway in subclinical hypothyroidism. Front Endocrinol (Lausanne). 2019;10:303.

    Article  PubMed  Google Scholar 

  76. Bao S, Li F, Duan L, Li J, Jiang X. Thyroid-stimulating hormone May participate in insulin resistance by activating toll-like receptor 4 in liver tissues of subclinical hypothyroid rats. Mol Biol Rep. 2023;50:10637–50.

    Article  CAS  PubMed  Google Scholar 

  77. Xu Y, Qiao J. Association of insulin resistance and elevated androgen levels with polycystic ovarian syndrome (PCOS): A review of literature. J Healthc Eng. 2022;2022:9240569.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Türemen EE, Çetinarslan B, Şahin T, Cantürk Z, Tarkun İ. Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis. Endocr J. 2011;58:349–54.

    Article  PubMed  Google Scholar 

  79. Qu X, Donnelly R. Sex Hormone-Binding Globulin (SHBG) as an early biomarker and therapeutic target in polycystic ovary syndrome. Int J Mol Sci. 2020;21:8191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, et al. Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4565–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Heidarpour M, Mojarad M, Mazaheri-Tehrani S, Kachuei A, Najimi A, Shafie D, et al. Comparative effectiveness of antidiabetic drugs as an additional therapy to Metformin in women with polycystic ovary syndrome: A systematic review of metabolic approaches. Int J Endocrinol. 2024;2024:9900213.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Palui R, Sahoo J, Kamalanathan S, Kar SS, Sridharan K, Durgia H, et al. Effect of Metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial. J Endocrinol Invest. 2019;42:1451–8.

    Article  CAS  PubMed  Google Scholar 

  83. Dimic D, Golubovic MV, Radenkovic S, Radojkovic D, Pesic M. The effect of Metformin on TSH levels in euthyroid and hypothyroid newly diagnosed diabetes mellitus type 2 patients. Bratisl Lek Listy. 2016;117:433–5.

    CAS  PubMed  Google Scholar 

  84. Amirabadizadeh A, Amouzegar A, Mehran L, Azizi F. The effect of Metformin therapy on serum Thyrotropin and free thyroxine concentrations in patients with type 2 diabetes: a meta-analysis. Sci Rep. 2023;13:18757.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Evran M, Pire G, Güney İB. Effects of Metformin therapy on thyroid volume and functions in patients with newly diagnosed type 2 diabetes mellitus: A Single-center prospective study. Endocr Metab Immune Disord Drug Targets; 2024.

  86. Morteza Taghavi S, Rokni H, Fatemi S. Metformin decreases Thyrotropin in overweight women with polycystic ovarian syndrome and hypothyroidism. Diab Vasc Dis Res. 2011;8:47–8.

    Article  CAS  PubMed  Google Scholar 

  87. Krysiak R, Okopien B. The effect of Metformin on the hypothalamic-pituitary-thyroid axis in women with polycystic ovary syndrome and subclinical hypothyroidism. J Clin Pharmacol. 2015;55:45–9.

    Article  CAS  PubMed  Google Scholar 

  88. 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 (Oxf). 2011;75:378–81.

    Article  CAS  PubMed  Google Scholar 

  89. Sue LY, Leung AM. Levothyroxine for the treatment of subclinical hypothyroidism and cardiovascular disease. Front Endocrinol (Lausanne). 2020;11:591588.

    Article  PubMed  Google Scholar 

  90. Pearce SHS, Brabant G, Duntas LH, Monzani F, Peeters RP, Razvi S, et al. 2013 ETA guideline: management of subclinical hypothyroidism. Eur Thyroid J. 2013;2:215–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American association of clinical endocrinologists and the American thyroid association. Endocr Pract. 2012;18:988–1028.

    Article  PubMed  Google Scholar 

  92. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the American thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24:1670–751.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Li X, Wang Y, Guan Q, Zhao J, Gao L. The lipid-lowering effect of Levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta-analysis of randomized controlled trials. Clin Endocrinol (Oxf). 2017;87:1–9.

    Article  PubMed  Google Scholar 

  94. Hekimsoy Z, Kafesçiler S, Güçlü F, Ozmen B. The prevalence of hyperprolactinaemia in overt and subclinical hypothyroidism. Endocr J. 2010;57:1011–5.

    Article  CAS  PubMed  Google Scholar 

  95. Sheikhi V, Heidari Z. Increase in Thyrotropin is associated with an increase in serum prolactin in euthyroid subjects and patients with subclinical hypothyroidism. Med J Islam Repub Iran. 2021;35:167.

    PubMed  PubMed Central  Google Scholar 

  96. Qiu Y, Hu Y, Xing Z, Fu Q, Zhu J, Su A. Birth control pills and risk of hypothyroidism: a cross-sectional study of the National health and nutrition examination survey, 2007–2012. BMJ Open. 2021;11:e046607.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Sharma LK, Sharma N, Gadpayle AK, Dutta D. Prevalence and predictors of hyperprolactinemia in subclinical hypothyroidism. Eur J Intern Med. 2016;35:106–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

No funding was received.

Author information

Authors and Affiliations

  1. Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Arman Shekarian, Saba Shekarian, Melika Pourbazargan, Mahsa Setudeh & Maryam Heidarpour

  2. Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Sadegh Mazaheri-Tehrani

  3. Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

    Sadegh Mazaheri-Tehrani

  4. Heart Failure Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

    Sadegh Mazaheri-Tehrani, Amir Parsa Abhari & Mohammad Fakhrolmobasheri

Authors
  1. Arman Shekarian
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Sadegh Mazaheri-Tehrani
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Saba Shekarian
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Melika Pourbazargan
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Mahsa Setudeh
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Amir Parsa Abhari
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Mohammad Fakhrolmobasheri
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Maryam Heidarpour
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

MH and MF conceptualized and designed the study. AS and SM-T developed the search strategy. SS and MS screened the studies. MP and SS extracted the data. SM-T and AS assessed the risk of bias. MH and MF supervised the study and resolved disagreements. APA and AS conducted the statistical analysis. AS, SM-T, and APA wrote the manuscript text, and all other authors critically reviewed and revised it. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maryam Heidarpour.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shekarian, A., Mazaheri-Tehrani, S., Shekarian, S. et al. Prevalence of subclinical hypothyroidism in polycystic ovary syndrome and its impact on insulin resistance: a systematic review and meta-analysis. BMC Endocr Disord 25, 75 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12902-025-01896-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12902-025-01896-2

Keywords

BMC Endocrine Disorders

ISSN: 1472-6823

Contact us