Thyroid status in patients with endometrial pathology

thyroid-stimulating hormone; menopause; thyroid dysfunction; thyroid peroxidase antibodies; tissue hyperplasia; reproductive age Copyright © The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (https://creativecommons.org/licenses/by/4.0/) appropriate therapy, and the prevention of complications, while also enhancing the effectiveness of comprehensive medical support for women. Among the various disorders of the female reproduc - tive system that are of interest to both clinical practice and scientific research, endometrial hyperplastic process - es warrant particular attention. Yu.V.  Strakhovetska  [1] and M. Al-Kaabi  et al. [2] examined the characteristics of Journal homepage: https://bmbr.com.ua/enDOI: 10.63341/bmbr/2.2025.49 Article’s History: Received: 03.01.2025; Revised: 21.04.2025; Accepted: 27.05.2025 Bulletin of Medical Bulletin of Medical and Biological Researchand Biological Research Vol. 7, No. 2 Vol. 7, No. 2 20252025 Thyroid status in patients with endometrial pathology 5050 Bulletin of Medical and Biological Research. 2025. Vol.7, No.2

of thyroid dysfunction in patients with en- dometrial hyperplasia gains particular importance in the context of gynaecological and oncological disease pre - vention. Given the potential for proliferative endometrial changes to undergo malignant transformation, timely cor- rection of concomitant endocrine disorders, especially thy- roid dysfunction, may serve as a valuable secondary pre - ventive strategy against oncological complications. This is especially pertinent in high-risk populations, including women in perimenopause, those with excess body weight, metabolic syndrome, or a family history of related diseas - es. D.Yu.  Beraya  [8] observed that women with infertility and various thyroid pathologies frequently present with ovarian-menstrual disorders such as dysmenorrhoea and oligomenorrhoea. In cases of infertility, the predominant contributing factor is endometriosis in patients without thyroid pathology, whereas in those with thyroid dysfunc - tion, the endocrine factor is more relevant. Endometrial hyperplastic processes are common among women of late reproductive and perimenopausal age and are associated with a high risk of recurrence and ma - lignancy. J. Huang et al. [9] have described oncological var- iants of endometrial pathology and the associated risk fac- tors. Nevertheless, the role of thyroid dysfunction in these processes remains insufficiently understood, and current clinical protocols do not mandate thyroid function assess - ment. This represents a significant scientific and practical gap, which hampers the timely identification of concomi - tant endocrine abnormalities and reduces the effectiveness of therapeutic interventions. Aim of the study: to assess the functional state of the thyroid gland in women with endo - metrial hyperplastic processes and to establish a potential pathogenetic link. Objectives of the study: to determine the prevalence of thyroid pathology among patients with endometrial hyperplastic processes; to analyse the levels of thyroid-stimulating hormone (TSH), free triiodothyro - nine (T3), free thyroxine (T4), and antibodies to thyroid peroxidase; to identify correlations between the forms of endometrial hyperplasia and thyroid function status. e MATERIALS AND METHODS During the study, 60 women aged 14 to 50 years with endo- metrial hyperplastic processes were examined. The average body weight of the patients was 65 kilograms. Two groups were formed: the second group served as the control group and comprised 30 women, also aged 14 to 50 years and weighing approximately 65 kg. The inclusion criteria were the presence of diagnosed hyperplastic changes in the en - dometrium, absence of malignant neoplasms, and informed consent to participate in the study. The exclusion criteria included severe somatic diseases, pregnancy, oncological pathology, and refusal to participate. The control group consisted of women without gynaecological pathology. All participants underwent a detailed collection of gy- naecological, reproductive, and somatic history, as well as clinical, laboratory, and instrumental examinations. The study was conducted at the Zaporizhzhia Medical Acade - my of Postgraduate Education of the Ministry of Health of Ukraine, from 1 June 2023 to 1 June 2024. All participants signed informed consent forms, which outlined the pur - pose, methods, and potential risks of the study, and guar - anteed confidentiality of personal data and medical results. endometrial hyperplastic processes in postmenopausal women, noting that the majority of patients (77%) pre - sented with climacteric syndrome during the menopausal transition. In 60% of these women, certain manifestations of the syndrome persisted into the postmenopausal period. These pathologies encompass a broad spectrum of altera - tions in the uterine mucosa, ranging from benign prolifer - ative changes to precancerous conditions and early-stage carcinoma. O.D. Leshchova [3] observed that gynaecological pathology most frequently occurred in women with simple endometrial hyperplasia without atypia, often accompanied by chronic endometritis, as well as in patients with chron - ic endometritis and reactive hyperplasia. Such cases were typically associated with urogenital infections, menstru - al irregularities, and pronounced urinary tract pathology. Despite numerous studies, the pathogenesis of endo - metrial hyperplastic processes remains complex and insuf- ficiently understood. Hormonal imbalance  – particularly oestrogen stimulation in the context of relative or absolute progesterone deficiency, frequently observed in anovula - tory cycles – plays a significant role in the development of these changes. I.K. Orishchak  et al. [4] emphasised the importance of infectious factors in the aetiology of endo - metrial hyperplastic processes. Restoration of the genital tract microbiocenosis contributes to more effective treat - ment and the prevention of relapses. Thyroid hormones participate in the regulation of the menstrual cycle, ovu - lation, endometrial development, and the maintenance of pregnancy. Thus, changes in thyroid function may direct - ly or indirectly impact the condition of the uterine lining. I.I. Kulyk & S.V. Khmil [5] noted that correcting endocrine imbalance, particularly through the use of vitamin D3 and inositol, has a positive effect on the endometrium in hor - monally dependent conditions. There is, however, a well-established association be - tween thyroid pathology and various gynaecological dis - orders, including infertility, dysfunctional uterine bleed - ing, polycystic ovary syndrome, and early menopause. The potential role of thyroid dysfunction in the pathogenesis of endometrial hyperplastic changes is of particular in - terest. Hypothyroidism – both subclinical and overt – may be accompanied by anovulation, hyperoestrogenism, and delayed secretory transformation of the endometrium, thereby creating conditions conducive to excessive prolif - eration of the uterine lining. G.  Brenta & U.  Hostalek  [6] studied comorbidities associated with hypothyroidism. Autoimmune thyroiditis, one of the most common caus - es of hypothyroidism, may also exert additional effects via systemic inflammation and impaired immune regulation. L.J. Jara  et al. [7] have explored the broader systemic im - pact of this disease in more detail. Despite the apparent pathophysiological connections, the association between thyroid status and endometrial hyperplasia remains in - consistently addressed in the literature. Some studies re - port a high frequency of thyroid abnormalities in patients with endometrial hyperplasia, while others do not identify significant differences relative to the general population. This discrepancy may be attributed to methodological var- iations across studies – such as differing designs, inclusion criteria, and classification of hyperplasia – as well as re - gional differences in thyroid disorder prevalence, iodine sufficiency, and socio-genetic factors. I. Ganzhiy and I. Sokolovska 5151 Bulletin of Medical and Biological Research. 2025. Vol.7, No. 2 The study was conducted in accordance with the ethical standards of the Declaration of Helsinki and was approved by the local ethics committee [10]. Specifically, information was gathered on the regularity of the menstrual cycle, the presence of pathological bleeding such as menorrhagia or intermenstrual bleeding, and a history of gynaecological diseases, including chronic inflammatory processes of the pelvic organs, endometrial polyps, and uterine fibroids. This information was obtained through patient interviews during the study. Additionally, data were collected on previous pregnan- cies, childbirths, abortions and any related complications, the use of contraceptives and their effect on the menstru - al cycle. Reproductive history included assessment of the number of pregnancies, deliveries, and abortions, as well as potential fertility issues or miscarriages, and the use of ovulation-stimulating medications. The presence of syn - dromes that could affect reproductive function, such as polycystic ovary syndrome, was also assessed. The somat - ic history enabled the collection of information regarding chronic diseases such as hypertension, diabetes mellitus, cardiovascular conditions, hepatic and renal disorders, as well as the presence of endocrine abnormalities, particu - larly hypothyroidism or autoimmune thyroid diseases. Data concerning body weight, obesity, and lifestyle fac - tors  – including nutrition, physical activity, and harmful habits such as smoking or alcohol consumption – were also recorded. In addition, the patients underwent a clinical ex- amination, which included a general physical assessment, blood pressure measurement, and evaluation of the genital organs via gynaecological examination, abdominal palpa - tion, and cervical inspection. Laboratory testing was conducted once, in the early morning hours (07:00-08:00), on an empty stomach, tak - ing into account diurnal hormonal fluctuations. Levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), and antibodies to thyroid peroxidase, as well as oestrogens, progesterone, follicle-stimulating hor - mone (FSH), and luteinising hormone (LH), were measured using enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassay on the Cobas e411 auto - matic analyser (Roche Diagnostics, Switzerland). A complete blood count and urinalysis were carried out using haematological and automatic biochemical analys - ers, respectively. Blood glucose levels were determined using the glucose oxidase reaction method. To detect po - tential infectious agents influencing endometrial status, bacteriological cultures and cytological smear examina - tions were performed. Instrumental diagnostics included pelvic ultrasound to assess the condition of the uterus and ovaries, and to identify any tumorous formations or anom- alies. For more detailed endometrial assessment, hyster - oscopy was employed, and where necessary, endometrial biopsy was performed for histological tissue analysis. This comprehensive approach enabled evaluation not only of gynaecological status but also of thyroid function, and fa - cilitated the detection of comorbidities potentially influ - encing the course of endometrial hyperplastic processes. Morphological findings were interpreted according to the World Health Organization (WHO) classification [11]. The detection of antibodies to thyroid peroxidase suggested a possible autoimmune origin of the disorders, which is particularly relevant in patients with gynaecolog- ical pathology. Measurement of thyroglobulin levels fur - ther contributed to the evaluation of thyroid function and structure, especially when destructive thyroid processes were suspected. This methodology allowed for the iden - tification of both hypo- and hyperthyroid states, which is essential for understanding the role of thyroid dysfunction in the development of endometrial proliferative processes. Statistical data analysis was performed using variational statistics in the Excel software package. Differences were considered statistically significant at p  < 0.05. Descriptive statistics, expressed as mean ± standard deviation, were ap- plied to characterise both parametric and non-parametric data appropriately. e RESULTS AND DISCUSSION During the survey, it was established that the vast majority of patients – 90% – resided in urban areas, and approxi - mately half (53.33%) were employed in the service sector or engaged in intellectual work (i.e. white-collar occupations) (Fig. 1). Only one patient (3.33%) reported exposure to oc- cupational hazards in the workplace. Figure 1. Distribution of examined patients by employment status Source: created by the authors Based on the data presented in Figure 1, it can be not- ed that the majority of women were white-collar work - ers, indicating a predominance of individuals engaged in sedentary or office-based occupations. Housewives and those involved in physical or other forms of active labour comprised a smaller proportion. This distribution may be relevant when analysing risk factors associated with life - style and levels of physical activity. Analysis of menstrual function revealed that the average age at menarche among patients was 12.27   ±  1.04 years. At the time of examina - tion, only 4 women (13.33%) had regular menstrual cycles, while the majority of patients (80%) experienced heavy menstrual bleeding. Within the gynaecological history of women with endometrial hyperplastic processes, the most frequently associated diagnosis was uterine leiomyoma, observed in 63.33% of cases (Fig. 2). Figure  2 illustrated the structure of concomitant gy - naecological diseases in women with endometrial hyper - plastic processes. The most prevalent pathology was sal - pingo-oophoritis, diagnosed in over 30% of cases. This was followed in frequency by endometrial hyperplasia, adeno - myosis, cervical or uterine corpus pathology, and dysfunc- tional uterine bleeding. Ovarian cysts were less commonly observed. These findings highlighted a high incidence of chronic inflammatory and proliferative changes within the reproductive system among the study group. It is note - worthy that the average duration of uterine leiomyoma in 30 16.67 53.33 Housemakers Workers Employees Thyroid status in patients with endometrial pathology 5252 Bulletin of Medical and Biological Research. 2025. Vol.7, No.2 patients was 3.61 ± 0.75 years, while endometrial hyperpla- sia had been diagnosed in five women approximately three years prior to the current assessment. Menometrorrhagia (prolonged and heavy menstrual bleeding) was reported to have begun, on average, 2.32  ± 0.16 years before the study (range: 0.5 to 8 years). The most frequently performed sur- gical intervention on the reproductive system among those examined was separate diagnostic curettage of the uterine cavity, which had been undertaken in 23.33% of women. Two patients had previously undergone adnexectomy, and one had undergone cystectomy. J.G.  Kruthica  et al.   [12] identified in their study that mutations in the MED12, HMGA2, COL4A5, FN1, TGFB3, and KLF6 genes were as - sociated with the formation of leiomyomas. Among these, mutations in the MED12 gene were found to be the most common cause of leiomyomas across different populations. 35 33.33 Disease30 25 20 16.67 13.33 13.33 13.3315 10 10 5 0 Cysts Thyroid Salpingoophoritis Endometrial hyperplasia Adenomyosis Dysfunctional pathology uterine bleeding % Figure 2. Prevalence of gynecological pathologies in the history of examined women Source: created by the authors The results of the histological examination of the re - moved endometrium are presented in Figure 3. The most frequent morphological form identified was simple atyp - ical endometrial hyperplasia, which was diagnosed in 19 women. In six cases, an endometrial sample could not be obtained, most likely due to the prolonged nature of the bleeding, which resulted in either the absence or signifi - cant thinning of the uterine mucosa, rendering morpho - logical analysis unfeasible. Figure 3. Structure of the results of histological examination of the endometrium Source: created by the authors 4.17 79.17 8.33 8.33 Glandular-fibrous hyperplasia Simple, atypical hyperplasia Micropolyposis Mixed hyperplasia Half of the examined women (15 individuals) had a history of childbirth, while every fourth participant (8 women or 26.67%) reported having undergone a medical termination of pregnancy. Spontaneous abortions were noted in 5 women (16.67%). The average number of preg - nancies was 1.58  ± 0.14, deliveries – 1.24 ± 0.22, and abor- tions – 1.29 ± 0.09. It is notable that the maximum number of deliveries did not exceed two, induced abortions – three, and spontaneous abortions – one. Within the structure of somatic pathology, arterial hypertension was the most fre- quently observed condition, recorded in 4 women (13.33%). Isolated cases of diabetes mellitus, liver disease, and renal disorders were also noted. A history of thyroid pathology was found in 12 women (40%), of whom half (6 patients, or 20% of the total cohort) had hypothyroidism. Thyroid nod- ules were identified in 5 women (16.67%), one woman had thyrotoxicosis, and another had undergone bilateral thy - roid lobe resection. The average duration of thyroid disease was 7.46 ± 1.03 years. Ultrasound examination of the thyroid gland revealed no abnormalities in only one patient. Nodular formations were visualised in 15 women (50%), diffuse parenchymal changes in 8 women (26.67%), follicular formations in 2 cases, and isolated cases of hyperplasia, thyroiditis, atro - phy, or post-resection changes were also observed. The average volume of the thyroid gland was 10.78  ± 1.05 cm3, with the right lobe measuring 6.57   ±  0.24  cm3 and the left lobe 6.31  ± 0.17 cm3. The average volume of the nod - ules was 0.86   ±  0.04  cm3. Ultrasound measurements of the uterus and ovaries were consistent with age-relat - ed norms. However, the M-echo thickness on days 5-7 of the menstrual cycle was 10.06  ± 1.17  mm (range: 3.2  mm to 18.5 mm), exceeding physiological parameters and sug - gesting the presence of endometrial hyperplasia. Thyroid function assessment revealed the following hormone lev - els: thyroid-stimulating hormone (TSH) – 3.55 mIU/L, free thyroxine (T4)  – 16.03  pmol/L, triiodothyronine (T3)  – 3.94 pmol/L, antibodies to thyroid peroxidase – 97.28 IU/ mL, and thyroglobulin – 21.72 ng/mL. These findings indi- cate that the TSH level approached the upper limit of the normal range, T3 was below normal, while other indicators remained within reference values. During the study, it was found that 60% of patients with endometrial pathology had thyroid dysfunction. Sub- clinical hypothyroidism was most frequently diagnosed, accounting for 20% of cases, while clinical hypothyroidism and thyrotoxicosis were each observed in 10% of cases. Additionally, a euthyroid state with elevated antibodies to thyroid peroxidase was recorded in 20% of patients, indi - cating autoimmune thyroid pathology without overt clin - ical manifestations. A. Muzafar Jafaar & M.Q. Meena [13] reported that most cases of hypothyroidism in their study were attributable to autoimmune thyroid disease, support- ed by the presence of goitre and elevated levels of both an- ti-thyroid antibodies. I. Ganzhiy and I. Sokolovska 5353 Bulletin of Medical and Biological Research. 2025. Vol.7, No. 2 endometrial hyperplasia in that study had hypothyroidism. These data underscore the importance of assessing thyroid function in women with menstrual irregularities to ensure timely diagnosis and effective treatment. A similar view - point is presented by R.A. Safonov et al. [16], who reported that significant abnormalities in steroid hormone levels in women with thyroid dysfunction support the existence of a relationship between endometrial proliferative processes and thyroid function. Their findings, like the current study, demonstrated a close association between thyroid dys - function and abnormal uterine bleeding. As part of this research, patients were stratified into age groups to assess the influence of age on the frequency of thyroid dysfunction in the context of endometrial pa - thology. The highest frequency of thyroid dysfunction was recorded in women aged 36-45 years, at 66.7% (10 out of 15). In the younger cohort (20-35 years; 9 patients), the rate was 55.6% (5 women), and among those over 45 years (6 patients), it was 50% (3 women). These results indicate a heightened vulnerability to endocrine dysregulation among women of mid-reproductive age, likely due to the combined influence of hormonal fluctuations, stress, and metabolic changes. F.  Memon  et al.   [17] also noted that thyroid fibrosis was most prevalent (36%) in middle-aged patients, while the thickness of the basement membrane was lowest in younger patients (12%) and highest in older patients (31%), which supports the reliability of the pres - ent data. The relationship between body mass index (BMI) and thyroid function was also examined. Among the 19 overweight patients (BMI >25), thyroid dysfunction was observed in 73.7% (14 women). In contrast, among the 11 patients with normal weight (BMI ≤25), only 36.4% (4 wom- en) had thyroid dysfunction. Furthermore, of the 12 women with confirmed hypothyroidism, 83.3% (10 patients) had a BMI over 25. This finding points to a close association be - tween reduced thyroid function and metabolic disturbanc- es, including obesity. E.M. Milewska-Kobos  et al. [18] and F. Torre et al. [19] have similarly indicated a connection be- tween increased body weight and thyroid status. Excessive obesity and adipose tissue dysfunction may contribute to the development of thyroid disorders such as autoimmun - ity, thyroid nodules, and thyroid cancer. The prevalence of thyroid disease is significantly higher among obese indi - viduals than in those with normal weight, particularly in the presence of unhealthy obesity phenotypes. Among the eight women diagnosed with autoimmune thyroiditis, three (37.5%) also exhibited ultrasound signs of polycystic ovary syndrome (PCOS). These patients ex - perienced prolonged anovulatory cycles and menstrual irregularities, which were associated with hyperplastic processes in the endometrium. It was found that five out of eight (62.5%) patients with autoimmune thyroiditis and chronic anovulation had complex forms of endometrial hyperplasia, including cases with proliferative and atypical changes. This underscores the importance of thyroid func- tion in regulating the endocrine axis – hypothalamus-pi - tuitary-ovarian – and its influence on the endometrium. A retrospective analysis of reproductive history revealed that out of 30 patients, nine women (30%) had a history of miscarriage or infertility. Among these, seven (77.8%) had thyroid dysfunction, suggesting a potential role in the on - set or persistence of reproductive disorders. Specifically, Analysis of the types of endometrial pathology re - vealed that the highest proportion of patients with thyroid dysfunction had endometrial hyperplasia  – comprising 40% of the cohort. Among these, 70% had coexisting thy - roid dysfunction. In the subgroup with endometrial polyps, thyroid dysfunction was identified in 50% of cases. In pa - tients with atypical hyperplasia, observed in three indi - viduals, the incidence of thyroid pathology reached 30%, suggesting a potential impact of thyroid hormone imbal - ance on the development of more severe forms of endome- trial hyperplasia. The relationship between thyroid-stim - ulating hormone (TSH) levels and endometrial thickness was also examined. In patients with elevated TSH levels (above 4 mIU/L), the average endometrial thickness was 12.3 ± 2.1 mm, compared to 9.6 ± 1.7 mm in those with nor- mal TSH levels (p  < 0.01). This finding suggests a possible role of hypothyroidism in promoting proliferative changes in the endometrium. B. Gautam et al. [14] analysed patients who tested positive for anti-TPO antibodies, including 59 women. A significant positive correlation was observed be- tween TSH and anti-TPO levels, along with a negative cor- relation between free T3, T4 and anti-TPO. These findings underscore the value of anti-TPO level determination for the early detection and confirmation of autoimmune thy - roid disease.Elevated levels of antibodies to thyroid perox- idase were found in 30% of the total cohort. Among these, 60% also exhibited menstrual irregularities, such as ano - vulatory bleeding or secondary amenorrhoea. This further supports the association between autoimmune thyroiditis and disrupted endometrial function. Ultrasound examination of the thyroid gland revealed structural changes in 40% of the participants. The most common findings included signs of diffuse thyroiditis and the presence of nodules (20%). Nodular goitre was more frequently observed in patients with endometrial polyps, whereas diffuse changes predominated in the group with endometrial hyperplasia. Additionally, among women with elevated thyroid-stimulating hormone (TSH) levels and re- duced concentrations of free T4, 80% reported symptoms such as excess weight, increased fatigue, and dry skin, indi- cating the systemic nature of hypothyroidism. In this sub - group, delayed menstruation (60%) and anovulation were also more common, suggesting that these endocrine dis - turbances may have contributed to the structural chang - es in the endometrium. Particular attention was given to patients with recurrent endometrial hyperplasia following hormonal therapy. In 60% of these cases, previously undi - agnosed or latent hypothyroidism was identified. This find- ing suggests that untreated thyroid dysfunction may reduce the effectiveness of treatment for endometrial pathologies. Comparison of treatment outcomes showed that patients whose thyroid function was normalised (via levothyroxine or antithyroid therapy) demonstrated better clinical out - comes, including reduced endometrial thickness, regular - isation of the menstrual cycle, and a lower recurrence rate of hyperplasia. A. Nayak [15] conducted a study investigat- ing the relationship between thyroid dysfunction and ab - normal menstrual bleeding, reporting that 32.6% of partic- ipants had hypothyroidism and 2.5% had hyperthyroidism. Hypothyroidism was most common among women with menorrhagia and metrorrhagia, as well as in cases of pu - bertal menorrhagia. Furthermore, 17.6% of patients with Thyroid status in patients with endometrial pathology 5454 Bulletin of Medical and Biological Research. 2025. Vol.7, No.2 three cases involved hypothyroidism, while two patients exhibited elevated titres of antibodies to thyroid peroxi - dase despite maintaining a euthyroid state. Such immune activity could interfere with implantation or early embry - onic development. A.  Beadini  et al.   [20] also identified a link between autoimmune thyroiditis and PCOS, report - ing that among women with PCOS, 26.03% had markers of autoimmune thyroiditis (elevated anti-TPO or anti-Tg levels), compared to only 9.72% in the control group. This suggests a significantly higher risk of developing auto - immune thyroiditis in women with PCOS, irrespective of geographic location or diagnostic criteria. Addition - al analysis of clinical symptoms associated with thyroid dysfunction demonstrated a relationship with the type of endometrial changes. Among the 12 patients with hypo - thyroidism, the most commonly reported symptoms were fatigue (83.3%, 10 women), facial or limb swelling (58.3%, 7 women), dry skin (66.7%, 8 women), and menstrual ir - regularities (91.7%, 11 women). In contrast, among the 12 patients without thyroid pathology, these symptoms were significantly less frequent: fatigue (33.3%), swell - ing (16.7%), dry skin (25%), and menstrual irregularities (41.7%). Statistical analysis confirmed a significant dif - ference in the prevalence of these symptoms between the two groups (p   <  0.05), highlighting the clinical relevance of thyroid dysfunction in the development of endome - trial disorders. Evaluation of the relationship between thyroid-stimulating hormone (TSH) levels and the type of endometrial pathology revealed that the highest mean TSH values were observed in patients with atypical hyper - plasia (5.1 ± 1.3 mIU/L). In those with simple hyperplasia, the average TSH level was 4.2  ± 1.1 mIU/L, while patients with polyps had a mean TSH of 3.4 ± 1.2 mIU/L. By compar- ison, women without thyroid pathology had a significantly lower mean TSH level of 2.1   ±  0.7  mIU/L. These findings suggest a potential progression of endometrial patholo - gy with increasing thyroid dysfunction. S.S.  Bahreiny  et al.  [21] similarly reported that in women with abnormal uterine bleeding, the most common histopathological findings included proliferative endometrium, hyperplasia without atypia, and secretory endometrium. Hyperplastic endometrial changes were more prevalent in patients with hypothyroidism, further supporting the role of thyroid dysfunction in endometrial pathology. Additionally, endo- metrial thickness as measured by ultrasound was found to correlate with histopathological findings: patients diag - nosed with endometrial hyperplasia had greater endome - trial thickness than those in other groups. The study analysed the effect of thyroid gland treat - ment on the endometrium. Among six patients who re - ceived levothyroxine replacement therapy for hypothy - roidism for at least six months, four (66.7%) demonstrated positive dynamics  – namely, a decrease in endometrial thickness (by an average of 2.4 mm), normalisation of the menstrual cycle, and the disappearance or reduction of menorrhagia. These findings indicate the effectiveness of correcting thyroid insufficiency as a key component in the management of concomitant gynaecological pathology. Another important aspect was the assessment of free T4 levels in relation to endometrial pathology. Patients with atypical hyperplasia had statistically lower free T4 levels than those in other groups – 9.7  ± 1.4 pmol/L compared to 12.2 ± 1.5 pmol/L in women with endometrial polyps. This correlation may reflect the duration and severity of hy - pothyroidism as a contributing factor in the progression of endometrial pathology. The level of prolactin was also measured separately in patients with menstrual disorders and concurrent hypothyroidism. In six out of twelve such women (50%), a moderate increase in prolactin levels was detected (mean value – 33.4  ± 4.5 ng/mL). This was likely due to the stimulatory effect of elevated thyroid-stimulat- ing hormone on prolactin production, which could nega - tively impact ovulatory function and contribute to chronic anovulation. The overall analysis of the study findings en- abled the identification of the most significant risk factors for the development of thyroid dysfunction in women with endometrial pathology. More detailed information is pre - sented in Table 1. Risk factor Frequency of occurrence Note Overweight (BMI>25 kg/m2) 63.6% Mostly associated with hypothyroidism Age 36-45 years 66.7% The highest incidence of thyroid dysfunction Atypical or recurrent endometrial hyperplasia 75% Accompanied by thyroid dysfunction Autoimmune thyroiditis 80% Often accompanied by menstrual irregularities Reproductive losses (miscarriage, infertility, premature birth, fetal growth retardation) 77.8% In most cases – hypothyroidism or antibodies to thyroid peroxidase Table 1. Risk factors for thyroid pathology Source: created by the authors In order to further analyse the relationship between the functional state of the thyroid gland and the mor - phological structure of the endometrium, the results of histological examination were assessed. In patients with hypothyroidism, proliferative changes predominated: sim- ple or complex hyperplasia without atypia was identified in 66.7% (8 out of 12) of cases, and atypical hyperplasia in 25% (3 women). In only one case (8.3%) was secreto - ry endometrium observed without pathological chang - es. In the group of women with normal thyroid function, pathological changes were less pronounced: endometrial hyperplasia was detected in 33.3% of cases (4 out of 12), and no atypical changes were observed. Furthermore, based on the evaluation of the morphofunctional state of the endo - metrium in patients with varying levels of thyroid-stimu - lating hormone (TSH), it was noted that the higher the TSH level, the greater the likelihood of persistent endometrial thickening, regardless of the phase of the menstrual cycle. In 70% of patients with TSH >4.5  mIU/L, an endometrial thickness exceeding 11 mm was recorded, which is consid- ered a pathological indicator for women of reproductive age, particularly in the luteal phase. In contrast, among I. Ganzhiy and I. Sokolovska 5555 Bulletin of Medical and Biological Research. 2025. Vol.7, No. 2 patients with TSH <2.5 mIU/L, such thickness was observed in only 16.7% of cases. These findings suggest that disrup- tion of thyroid homeostasis may lead to increased stimula- tion of endometrial growth, potentially due to altered lev - els of gonadotropins or the influence of thyroid hormones on the oestrogen-progesterone balance. In this context, it is important to highlight that the study found a statisti - cally significant correlation between TSH levels and the frequency of hyperplastic processes in the endometrium. Another important clinical consideration was the in - vestigation of anaemic syndrome in patients with con - current endometrial and thyroid pathology. In nine wom - en (30% of the sample), haemoglobin levels were below 110 g/L; in all these cases, both heavy menstrual bleeding and concomitant hypothyroidism or thyroiditis were pres - ent. This supports the hypothesis of an indirect effect of hy- pothyroidism on the intensity of uterine bleeding, possibly via destabilisation of the endometrial layer. An additional examination of inflammatory markers, particularly C-reac- tive protein (CRP), revealed that among patients with auto- immune thyroid changes (elevated anti-thyroid peroxidase antibodies), CRP levels were raised in 54.5% of cases (6 out of 11), indicating possible systemic immune activation. This finding suggests a potential role for immune mechanisms in the pathogenesis of endometrial changes, especially in the context of autoimmune thyroiditis as a systemic con - dition. Analysis of lifestyle and associated factors demon - strated that 10 patients (33.3%) experienced chronic stress or psycho-emotional exhaustion. Within this subgroup, thyroid pathology was identified in 70% of cases (7 women). It was also recorded that six patients (20%) were tak - ing combined oral contraceptives at the time of examina - tion. Among them, only one woman was diagnosed with hypothyroidism, while the remainder had thyroid function within normal limits. This provided grounds to assume that hormonal contraception may stabilise the hormonal back - ground to some extent, but does not influence autoimmune processes. It should also be noted that comorbid pathology was identified in five patients: arterial hypertension (three cases) and insulin resistance (two cases). All these women had concomitant hypothyroidism, suggesting the presence of a general metabolic syndrome in which thyroid insuffi - ciency plays a significant role. Thus, the results obtained demonstrate the multifactorial influence of the thyroid gland on the condition of the endometrium. Dysfunction of this organ is associated not only with morphological chang- es in the endometrium, but also with general somatic and metabolic disorders, significantly complicating the clinical picture. This once again highlights the need for an individ- ualised approach to the examination and treatment of such patients, with mandatory consideration of thyroid status in each case. H.D. Sahu et al. [22] analysed the relationship between hormonal oral contraceptives and thyroid func - tion. Oral contraceptives containing oestrogens increase the level of thyroxine-binding globulin, which leads to a rise in the total serum levels of T4 and T3, while the levels of free hormones remain stable. This may complicate the interpretation of thyroid function test results, especially in women receiving levothyroxine replacement therapy, as an increase in thyroxine-binding globulin may reduce the bioavailability of free T4, necessitating an adjustment in the levothyroxine dose. In addition, in women with subclinical hypothyroidism or those on levothyroxine ther- apy, oral contraceptives may increase the risk of thrombo- embolic and cardiovascular complications. Therefore, when prescribing oral contraceptives to women with thyroid dys- function, it is essential to consider potential changes in the hormonal profile and adjust therapy accordingly. The investigation into the relationship between the level of antibodies to thyroid peroxidase and the type of endometrial pathology deserves particular attention. An - tibodies to thyroid peroxidase were detected in 11 patients (36.7%), of whom nine had morphologically confirmed en- dometrial hyperplasia (81.8%). In five cases (45.5%), the hyperplasia was atypical, indicating the potential role of autoimmune inflammation in the development of prolif - erative processes in the endometrium. Notably, atypical hyperplasia was not observed in women without elevated levels of antibodies to thyroid peroxidase. This pattern suggests that autoimmune processes in the thyroid gland may exert systemic effects and contribute to destructive changes in the endometrium. The study also assessed the influence of reproductive history on the likelihood of de - veloping thyroid dysfunction. Among infertile patients (six women), hypothyroidism of varying degrees or elevat- ed antibodies to thyroid peroxidase were identified in five cases (83.3%). All these women also exhibited hyperplastic changes in the endometrium, further supporting the hy - pothesis that thyroid dysfunction is involved in impaired implantation processes and the development of chronic anovulation. By contrast, among patients with at least one previous normal pregnancy, thyroid pathology was detect- ed in only 33.3% of cases (six out of 18 women). A. Muzafar Jafaar & M.Q. Meena [13] demonstrated in their study that most cases of hypothyroidism are associated with autoim - mune processes, as evidenced by the high frequency of An- ti-TPO and Anti-Tg antibodies and the presence of goitre in patients. These findings underscore the importance of accounting for the autoimmune component in the diagno- sis and treatment of hypothyroidism. Similarly, a study by I. Upadhyay et al. [23] found that most patients with thyroid disease tested positive for thyroid peroxidase antibodies, confirming the autoimmune nature of these conditions. The detection of diffuse hypoechogenicity on ultrasound closely correlated with the presence of Anti-TPO antibod - ies, highlighting the value of ultrasound diagnostics as a non-invasive, safe, and cost-effective method for the de - tection and prognosis of autoimmune thyroid diseases. The influence of seasonal factors was also examined. Among the 30 patients assessed, 18 were evaluated during the autumn-winter period. Of these, 11 women (61.1%) exhibited signs of thyroid dysfunction, compared to 6 of 12 patients (50%) examined in the spring-summer period. Although the difference was not statistically significant, it may suggest seasonal fluctuations in thyroid function, particularly in regions characterised by low insolation or iodine deficiency. In several cases (three patients), hypo - thyroidism was found in combination with other autoim - mune conditions  – specifically, one case of rheumatoid arthritis and two cases of subclinical gastritis with pos - itive antibodies to parietal cells. These findings support the systemic nature of the autoimmune process, which extends beyond the thyroid gland and may potentially re - sult in multiorgan involvement, including disruption of Thyroid status in patients with endometrial pathology 5656 Bulletin of Medical and Biological Research. 2025. Vol.7, No.2 endometrial structure. Overall, the detection rate of sub - clinical hypothyroidism was slightly higher (13.3%) than that of clinical hypothyroidism (10%), reinforcing the importance of screening for thyroid function even in the absence of overt symptoms. Most patients with subclini - cal hypothyroidism had elevated thyroid-stimulating hor - mone (TSH) levels with normal free T4 levels; however, even at this stage, they already presented with menstru - al irregularities, increased endometrial thickness, and a heightened risk of hyperplastic processes. A comprehen - sive evaluation of the effectiveness of an interdisciplinary approach to managing patients with endometrial pathol - ogy and concurrent thyroid dysfunction was undertaken. It was found that, when an endocrinologist participat - ed in correcting thyroid status, positive outcomes were achieved in 10 out of 13 such cases (76.9%), both in terms of reproductive function (normalisation of the menstrual cycle, onset of ovulation) and in the morphological con - dition of the endometrium (reduction in hyperplasia, re - gression of polyps). A.S. Vishen et al. [24] also determined that seasonal changes affect the histochemical properties of the thyroid gland. Specifically, during winter, the gland demonstrates increased functional activity, possibly as an adaptive response to decreased ambient temperature. I. Domuschiev [25], in studying the impact of global warm- ing on the thyroid gland, found that elevated ambient tem- peratures may lead to hormonal imbalance, increasing the risk of thyroid disease. Climate change may also affect the availability of iodine in food, which is crucial for thyroid hormone synthesis. Another significant area of investigation was the im - pact of body weight and body mass index (BMI) on the functional state of the thyroid gland and the nature of endometrial pathology. Among the 30 patients, 16 wom - en (53.3%) were overweight or obese (BMI >25 kg/m 2), of whom 11 (68.8%) exhibited signs of thyroid dysfunction, primarily subclinical or overt hypothyroidism. Conversely, among women with normal body weight (14 individuals), thyroid dysfunction was detected in only 4 cases (28.6%). This disparity indicates a strong association between met- abolic disorders and thyroid function. Overweight patients also more frequently exhibited hyperplastic changes in the endometrium – 75% of cases (12 out of 16) – includ - ing both simple and atypical hyperplasia. This underscores that excess body weight may act not only as an independ - ent risk factor for endometrial hyperplasia but also as an amplifying factor in the adverse effects of thyroid dysfunc- tion on hormonal homeostasis. An analysis of the study by S.B. Kaur et al. [26] confirmed that the group with elevated BMI had a greater mean endometrial thickness and a high- er incidence of atypical endometrial hyperplasia. Notably, the frequency of atypical endometrial hyperplasia was sig- nificantly higher among women with increased BMI. It is important to note that among all the examined women, 10 cases (33.3%) exhibited anovulatory or irregu - lar menstrual cycles, and thyroid pathology was detected in 8 of these cases. In three women, the menstrual cycle exceeded 45 days, indicating a marked disruption of ovu - lation. Following correction of thyroid-stimulating hor - mone (TSH) levels and normalisation of T4 and T3 con - centrations over a period of 3-6 months, normalisation of the menstrual cycle was achieved. In two cases, pregnancy occurred within one year following comprehensive treat - ment, further supporting the role of thyroid dysfunction in fertility disorders. H.I. Aliu-Ayo  et al. [27] similarly found that menstrual disorders, such as oligomenorrhoea and amenorrhoea, were more prevalent among infertile women with thyroid dysfunction. A significant correlation was also observed between thyroid hormone levels and different types of menstrual cycles. To assess the emotional state of the patients, a sur - vey was conducted. In 12 women (40%), mild or moderate depressive syndrome was recorded, of whom nine exhibit - ed signs of hypothyroidism. This finding corroborates the well-documented clinical association between thyroid in - sufficiency and depressive states. It also highlights the ne- cessity of considering the psycho-emotional component in the management of such patients, particularly when plan - ning hormone therapy. Among the 30 patients, only three women (10%) presented a normal histological picture of the endometrium despite clinical evidence of thyroid dys - function. In these instances, it may be assumed that thy - roid pathology had not yet progressed sufficiently to induce morphological changes, or that compensatory mechanisms had temporarily offset its effects. I.I. Rodrigues da Cunha et al. [28] demonstrated that even minor alterations in thy - roid hormone levels can influence brain function and con- tribute to the development of depression. Specifically, thy- roid dysfunction may result in reduced levels of serotonin and noradrenaline in the central nervous system, both of which are characteristic of depressive states. This finding further underscores the importance of early diagnosis and intervention, even in the presence of minimal symptoms. Similar conclusions were drawn in the studies by K. Gökçe & D. Doğan [29] and J. Fedorko et al. [30]. The results of ultrasound examination of the thyroid gland were also included in the analysis. Diffuse changes characteristic of thyroiditis was identified in 14 women (46.7%), including hypoechogenicity, structural heteroge - neity, and increased vascularisation. Of these, 11 women had positive titres of antibodies to thyroid peroxidase, con- firming the autoimmune nature of the thyroid pathology. Thyroid nodules were detected in five patients (16.7%), although only two of these were associated with hormo - nal activity. No cases of malignant lesions were identified. While this suggests a relatively low oncological risk within the sample, it highlights the importance of regular ultra - sound monitoring in women presenting with both hyper - plastic changes in the endometrium and nodular altera - tions in the thyroid gland. In summary, the study results confirmed not only the statistical, but also the clinical significance of thyroid dysfunction in patients with endo - metrial pathology. Particular attention should be given to women with hypothyroidism, positive autoimmune mark - ers, excess body weight, and irregular menstrual cycles. These factors significantly increase the risk of developing proliferative changes in the endometrium and, in some instances, may contribute to the development of atypical forms of hyperplasia. The ultrasound findings, when considered alongside laboratory indicators, enabled a more comprehensive char- acterisation of the structural and functional state of the thyroid gland in women with endometrial pathology. The observed diffuse changes, nodular formations, and signs of I. Ganzhiy and I. Sokolovska 5757 Bulletin of Medical and Biological Research. 2025. Vol.7, No. 2 autoimmune processes confirm the close interrelationship between the endocrine and reproductive systems. This di - agnostic approach facilitates not only the timely identifi - cation of co-existing pathologies but also the development of individualised monitoring and treatment plans. Such an approach is particularly crucial for the prevention of hyper- plastic and atypical changes in the endometrium. Thus, the findings of the study provide a foundation for the formu - lation of practical recommendations and evidence-based conclusions. e CONCLUSIONS The study revealed a significant association between thy - roid pathology and endometrial changes in patients with various forms of endometrial disease. Among the 30 pa - tients included in the study, 60% were found to have thy - roid dysfunction. Specifically, overt hypothyroidism was present in 10% of cases, subclinical hypothyroidism in 13.3%, and elevated levels of antibodies to thyroid per - oxidase – indicative of autoimmune thyroid disease – in 36.7%. Simultaneously, 73.3% of patients were diagnosed with endometrial hyperplasia. Among these, 36.4% had simple hyperplasia without atypia, 18.2% had complex hy- perplasia, and 45.5% had atypical hyperplasia, reflecting a substantial proportion of patients at increased oncological risk. This distribution of morphological types of hyperpla - sia is clinically significant for patient assessment and fur - ther management, particularly in the context of concomi - tant endocrine disorders. Special attention should be directed toward over - weight patients, as thyroid dysfunction was observed in 68.8% of such cases, and endometrial hyperplasia in 75%. An even higher prevalence of thyroid disorders – 80% – was noted in patients with anovulatory cycles. The correction of thyroid status was shown to have a beneficial effect on menstrual cycle regulation and the restoration of ovula - tion in some patients. In several instances, treatment led to normalisation of endometrial thickness and improved reproductive function, underscoring the importance of early diagnosis and intervention in thyroid pathology. The findings support the necessity of routine screening for thy- roid function in patients with endometrial pathology. Early identification of dysfunction allows for timely intervention to prevent the progression of hyperplastic endometrial changes. Including ultrasound examination of the thyroid gland in the standard diagnostic protocol for women with endometrial disorders is both appropriate and advisable in clinical practice. Thus, the results of this study underscore the impor - tance of comprehensive diagnostic and therapeutic ap - proaches in managing patients with endometrial pathol - ogy. This includes not only the treatment of endometrial abnormalities but also the correction of thyroid dysfunc - tion, which significantly improves clinical outcomes and reproductive potential. A key strength of this study lies in the integrated analysis of morphological variants of endo - metrial hyperplasia alongside types of thyroid dysfunction, enabling a deeper exploration of the pathogenetic links between endocrine and gynaecological disorders. This con- trasts with most previous studies, which have tended to examine these conditions in isolation. One of the prima - ry limitations of the present study is the relatively small sample size, which affects the statistical power and limits the generalisability of the findings. Future research should aim to expand the study population, adopt a multicentre approach, and incorporate long-term dynamic observation with consideration of therapeutic interventions. e ACKNOWLEDGEMENTS None. e FUNDING None. e CONFLICT OF INTEREST None. e REFERENCES [1] Strakhovetska YuV. The women of postmenopausal age have features of hyperplastic processes of endometrium. Perinatol Reproductol Res Pract. 2024;4(3-1):91–8. 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J Endocr Soc. 2024;8(1):bvae163.1841. DOI: 10.1210/jendso/ bvae163.1841 I. Ganzhiy and I. Sokolovska 5959 Bulletin of Medical and Biological Research. 2025. Vol.7, No. 2 Стан щитоподібної залози у пацієнтів з патологією ендометрію Ірина Ганжий Доктор медичних наук, професор Запорізький державний медико-фармацевтичний університет 69035, бульв. Марії Примаченко, 26, м. Запоріжжя, Україна https://orcid.org/0009-0008-2490-5222 Ірина Соколовська Кандидат медичних наук, асистент Запорізький державний медико-фармацевтичний університет 69035, бульв. Марії Примаченко, 26, м. Запоріжжя, Україна https://orcid.org/0009-0008-2487-1675 Анотація. Метою цього дослідження було вивчення функціонального стану щитовидної залози у жінок із гіперпластичними процесами ендометрію, з огляду на зростаючий інтерес до ролі тиреоїдної дисфункції в етіопатогенезі проліферативних змін слизової оболонки матки. У дослідження було включено 30 жінок пізнього репродуктивного та перименопаузального віку, а саме 14-50 років, у яких діагностовано різні форми гіперпластичної патології ендометрію, на базі Запорізької медичної академії післядипломної освіти Міністерства охорони здоров'я України. Методологія дослідження передбачала клініко-лабораторне обстеження пацієнток, включаючи ультразвукову діагностику органів малого таза, гістологічне дослідження ендометрію, а також визначення рівнів тиреотропного гормону, вільних фракцій тироксину і трийодтироніну, антитіл до тиреоїдної пероксидази. Основні результати дослідження показали, що жінки із гіперплазією ендометрію мали супутні порушення функції щитовидної залози, серед яких спостерігався субклінічний або явний гіпотиреоз. Виявлено зростання рівня тиреотропного гормону (3,8   ±  1,2  мМО/л) у пацієнток з гіперплазією ендометрію порівняно з контрольною групою, а також збільшення концентрації антитіл до тиреоїдної пероксидази, що свідчить про автоімунний характер порушень. Аналіз отриманих даних дозволив виявити взаємозв’язок між вираженістю тиреоїдної дисфункції та морфологічним варіантом гіперпластичних змін ендометрію: у жінок з атиповою гіперплазією діагностували клінічно значимі порушення функції щитоподібної залози. Отримані результати свідчать про доцільність рутинного скринінгу тиреоїдної функції у жінок з гіперплазією ендометрію для виявлення прихованих форм тиреоїдної патології, яка може бути як фоновим, так і тригерним чинником проліферативних змін ендометрію. Таким чином, результати дослідження підтверджують важливість інтегрованого підходу до діагностики та лікування гіперпластичних процесів ендометрію з урахуванням стану щитоподібної залози та ендокринної системи вцілому Ключові слова: тиреотропні гормони; менопауза; тиреоїдна дисфункція; антитіла до тиреоїдної пероксидази; гіперплазія тканини; репродуктивний вік