Thyroid hormones play a pivotal role in maintaining homeostasis across various physiological systems, particularly in regulating metabolic rate and reproductive function. The influence of thyroid dysfunction extends far beyond classical endocrine symptoms and has been increasingly recognized as a contributor to gynecological and metabolic disorders in women of reproductive and post-reproductive age. Women are disproportionately affected by thyroid diseases, with hypothyroidism being up to 10 times more common in women than in men, and autoimmune thyroid disorders such as Hashimoto’s thyroiditis and Graves’ disease occurring predominantly in the female population [1,2].

The close interplay between thyroid function and female reproductive physiology is well-documented. Thyroid hormones interact with sex steroid hormones and the hypothalamic-pituitary-gonadal axis, affecting menstrual regularity, ovulation, fertility, and pregnancy outcomes [3]. Both overt and subclinical hypothyroidism have been associated with menstrual disturbances including oligomenorrhea, menorrhagia, and amenorrhea [4]. Thyroid dysfunction is also recognized as a potentially modifiable cause of infertility, and screening for thyroid abnormalities is often a routine part of infertility workups [5]. During pregnancy, maternal thyroid hormones are crucial for fetal development, especially neurocognitive development in the first trimester, when the fetus is entirely dependent on maternal T4 [6]. Thyroid dysfunction in pregnancy has been associated with adverse outcomes such as miscarriage, preeclampsia, preterm labor, and low birth weight [7]. In addition to reproductive consequences, thyroid dysfunction—particularly hypothyroidism—has profound effects on metabolic health. It contributes to weight gain, dyslipidemia, insulin resistance, and increased cardiovascular risk, all of which are components of the metabolic syndrome [8]. The mechanisms involve reduced thermogenesis, altered lipid metabolism, and changes in insulin sensitivity mediated by thyroid hormone receptors [9]. Even subclinical hypothyroidism has been linked with increased atherogenic lipid profiles and endothelial dysfunction, making it a silent contributor to long-term metabolic complications [10]. Despite known associations, the strength and direction of links between thyroid disorders and women's reproductive and metabolic health vary across studies. Clinical management of subclinical thyroid dysfunction also remains uncertain. This systematic review aims to synthesize current evidence to better understand these associations and guide informed, evidence-based clinical care.

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A predefined protocol was developed to guide the review process. The primary objective was to evaluate and synthesize existing evidence on the impact of thyroid dysfunction—including hypothyroidism, hyperthyroidism, and thyroid autoimmunity—on women's reproductive and metabolic health. Outcomes of interest included menstrual irregularities, infertility, pregnancy complications, insulin resistance, dyslipidemia, obesity, and cardiovascular risk. Eligibility criteria were defined to ensure the inclusion of high-quality, relevant studies. Peer-reviewed literature including observational studies, randomized controlled trials, systematic reviews, clinical guidelines, and expert reviews involving women aged 15–65 years with diagnosed or discussed thyroid dysfunction were included. Only English-language publications were considered. Case reports, editorials, conference abstracts, and animal studies were excluded.

A comprehensive literature search was carried out across five major databases: PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library, using a combination of MeSH terms and relevant keywords. Additional studies were identified by manual reference screening. All records were screened using Rayyan QCRI, and full texts of potentially eligible studies were reviewed independently by two reviewers. Disagreements were resolved through discussion or third-party input. Data were extracted using a standardized form, capturing study characteristics, population details, type of thyroid disorder, and reported outcomes. The Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias Tool were employed to assess study quality and risk of bias. As no new human subjects were involved, ethical approval was not required.

A total of 1,324 records were identified through database searches, and an additional 14 articles were found through manual reference screening. After removing duplicates, 1,180 unique articles were screened based on titles and abstracts. Of these, 156 full-text articles were assessed for eligibility, and 54 studies met the inclusion criteria for this systematic review. The detailed process of study selection is illustrated in the PRISMA flow diagram.

Figure 1. PRISMA Flow Diagram

Summary of reproductive outcomes by study

Thyroid dysfunction significantly affects various aspects of female reproductive health. Multiple studies have confirmed that both overt and subclinical hypothyroidism are associated with menstrual disturbances. Krassas (2000) reported common presentations such as menorrhagia, oligomenorrhea, and amenorrhea in hypothyroid women [4]. The presence of autoimmune thyroid disease has also been implicated in infertility and assisted reproductive technology (ART) failure, as outlined by Poppe & Velkeniers (2003) [3]. Pregnancy outcomes are notably impacted by thyroid status. According to Negro & Stagnaro-Green (2014) and De Groot et al. (2012), both overt and subclinical hypothyroidism are linked to complications like miscarriage, preeclampsia, preterm labor, and low birth weight [5,7]. Glinoer (2004) highlighted that iodine deficiency-induced hypothyroidism during early pregnancy can hinder fetal neurodevelopment.

Women with elevated TSH levels (>2.5 mIU/L), even within the subclinical range, demonstrated poorer ART outcomes, as shown by Velkeniers et al. (2020) [11]. Autoimmune thyroid conditions were also associated with premature ovarian failure, emphasizing a possible autoimmune basis, as discussed by van Noord et al. (2024)[12]. In line with this, Li et al. (2023) and Mirghani (2022) identified hypothyroidism as a key factor in female infertility, supporting routine thyroid screening in fertility evaluations [13,14]. Furthermore, sexual dysfunction in women with thyroid disorders was highlighted in a meta-analysis by Rastgar et al. (2024), showing reduced libido and satisfaction [15]. Kalra et al. (2022) and guidelines by the ASRM (2021) emphasized that hormonal imbalances due to thyroid dysfunction can disrupt ovulation, necessitating tailored treatment approaches in women planning conception [16,17].

Summary of Findings for Metabolic Outcomes

Thyroid dysfunction, particularly hypothyroidism, plays a significant role in metabolic disturbances. Duntas (2002) observed a clear association between hypothyroidism and dyslipidemia, notably elevated LDL and total cholesterol levels [8]. Brenta (2011) further explained that insulin resistance in hypothyroid patients is due to impaired glucose metabolism and reduced thermogenesis [9]. Rodondi et al. (2010) conducted a meta-analysis demonstrating that even subclinical hypothyroidism significantly increases the risk of coronary heart disease and all-cause mortality [10]. Similarly, Singh et al. (2015) and Meher et al. (2017) found a higher prevalence of hypothyroidism in individuals with metabolic syndrome (MetS), suggesting a synergistic interplay between thyroid dysfunction and metabolic abnormalities [18,19].

Guo et al. (2023) showed that obese women with thyroid dysfunction exhibited distinct metabolic phenotypes, reinforcing the metabolic burden imposed by thyroid disorders [20]. Additionally, Chaker et al. (2024) identified hypothyroidism as a contributing factor to metabolic dysfunction-associated steatotic liver disease (MASLD), a growing concern in endocrine hepatology [21]. Quality of life and lifestyle parameters were negatively impacted in hypothyroid women, as shown by Gierach et al. (2023), who reported increased BMI and reduced functional well-being [22]. Kalra et al. (2022) linked thyroid hormone imbalance to disrupted insulin signaling pathways, further substantiating its metabolic influence [16]. Lastly, Kitahara et al. (2023) provided evidence for a link between obesity and elevated thyroid cancer risk in women, demonstrating the oncometabolic overlap [23]. These findings collectively underscore the need for integrated screening and management strategies in women presenting with metabolic syndrome and suspected thyroid dysfunction.

Risk of Bias Assessments (Narrative)

A comprehensive evaluation of the risk of bias was performed for all included studies to ensure the reliability of findings in this systematic review. Two standardized tools were utilized: the Newcastle-Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias Tool for randomized controlled trials (RCTs). Among the 18 observational studies, most demonstrated good methodological quality. Fourteen studies achieved high scores on the NOS (7 to 9 points), indicating low risk of bias. These studies had clearly defined objectives, well-characterized populations, and used objective biomarkers such as serum TSH and FT4 for thyroid assessment. However, four studies scored moderately (5 to 6 points) due to issues such as unclear participant selection methods, inadequate adjustment for confounding variables (e.g., age, BMI, comorbidities), or self-reported outcomes that may introduce recall bias.

For the four included RCTs, three were considered low risk across most domains including random sequence generation, allocation concealment, outcome assessment, and completeness of follow-up data. One RCT was marked as moderate risk due to lack of blinding, which could potentially introduce performance and detection bias. Importantly, none of the studies—observational or RCT—were deemed high risk overall. This overall methodological assessment suggests that the evidence included in this systematic review is generally of moderate to high quality, which supports the robustness of the findings and conclusions. However, future research with consistent use of validated outcome measures and detailed reporting of confounder adjustments is warranted.

This systematic review highlights a consistent and significant association between thyroid dysfunction and adverse reproductive and metabolic outcomes in women. Reproductive health disturbances, including menstrual irregularities, infertility, premature ovarian failure, and pregnancy complications, were frequently reported in women with both overt and subclinical hypothyroidism. On the metabolic front, hypothyroidism—especially in its subclinical form—was linked with dyslipidemia, insulin resistance, metabolic syndrome, and cardiovascular risk. These findings affirm the multifaceted role of thyroid hormones in maintaining endocrine and metabolic homeostasis in women, reinforcing the need for vigilant thyroid screening in at-risk populations. The observed outcomes are in alignment with several clinical guidelines and previously published literature. The Endocrine Society and American Thyroid Association recommend screening for thyroid function in women presenting with infertility or recurrent pregnancy loss, and during early pregnancy. Studies such as those by Negro et al. (2014) and De Groot et al. (2012) emphasized the adverse effects of subclinical thyroid dysfunction on maternal-fetal outcomes, corroborating our findings [5,7]. Similarly, Brenta (2011) and Rodondi et al. (2010) documented insulin resistance and increased cardiovascular mortality in hypothyroid patients, echoing the metabolic consequences observed in our review [9,10].

This review's strengths lie in its comprehensive literature search across multiple databases, use of dual independent reviewers, and inclusion of a wide range of thyroid-related reproductive and metabolic endpoints. The use of validated tools for bias assessment ensured methodological rigor. However, certain limitations should be acknowledged. Heterogeneity in diagnostic thresholds for thyroid disorders and variations in outcome definitions across studies limited the ability to perform meta-analyses. Additionally, the exclusion of non-English language publications may have introduced language bias, and some included studies lacked sufficient adjustment for key confounders such as nutritional status or contraceptive use. Clinically, the findings underscore the necessity of integrating thyroid function assessment into routine gynecological and metabolic evaluations, especially for women with unexplained infertility, irregular menses, or features of metabolic syndrome. Identifying and managing even mild thyroid dysfunction may improve reproductive outcomes and mitigate long-term cardiometabolic risk. Future research should focus on well-powered prospective studies using standardized diagnostic criteria, particularly to determine treatment thresholds for subclinical thyroid disorders. Additionally, cost-effectiveness analyses of universal screening protocols in high-risk female populations would be valuable to guide health policy decisions.

This systematic review consolidates current evidence linking thyroid dysfunction with adverse reproductive and metabolic outcomes in women. The findings demonstrate that both overt and subclinical hypothyroidism can lead to menstrual irregularities, infertility, pregnancy complications, and sexual dysfunction. Moreover, thyroid disorders, particularly hypothyroidism, contribute significantly to metabolic disturbances such as dyslipidemia, insulin resistance, metabolic syndrome, and increased cardiovascular risk. Given the high prevalence of thyroid disorders among women and their broad systemic impact, routine thyroid screening should be considered in women presenting with reproductive or metabolic symptoms. Early detection and appropriate management of thyroid dysfunction may enhance fertility outcomes, reduce obstetric risks, and prevent long-term cardiometabolic complications. Clinicians in both gynecology and internal medicine should maintain a high index of suspicion for thyroid dysfunction in at-risk women, even in the absence of classic symptoms. Evidence-based, standardized screening and treatment protocols are essential to improve clinical outcomes. Further longitudinal and interventional research is needed to clarify the benefits of treating subclinical thyroid dysfunction and to develop cost-effective strategies for population-level screening and prevention, particularly in resource-constrained settings.

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