European Journal of Cardiovascular Medicine

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 6 – 7% of premenopausal women. ^[1] PCOS is clinically diagnosed by hyperandrogenism and chronic anovulation; however, its morbidity includes insulin resistance, type 2 diabetes mellitus, hypertension, cardiovascular disease, and infertility. ^[2]

Female reproductive health concerns include organ mutilations controlled by estrogen, hormonal irregularities and diseases like endometriosis, polycystic ovary syndrome (PCOS), fibroids, and cancers affect women due to increased exposure to endocrine toxicants. PCOS, a common endocrine disorder, often goes undiagnosed initially. Its prevalence ranges from 5 to 25 %, and leading to infertility and various clinical and metabolic disorders, posing an economic burden on healthcare. The symptom varies from mild presentation in some to severe disturbance of reproductive, endocrine and metabolic function in others. ^[3] PCOS features are divided into three categories: clinical, metabolic and endocrine. The clinical features are menstrual abnormalities, hirsutism, acne, alopecia, anovulatory, infertility and recurrent miscarriages. Thus, PCOS is a syndrome, has got multiple components including reproductive, metabolic and hormonal with long term health concerns that cross the life span. ^[4]

PCOS involves an imbalance in sex hormones, leading to cyst formation in the ovaries. Elevated luteinizing hormone (LH) levels and a decreased follicle-stimulating hormone (FSH) level result in a higher LH/FSH ratio, which is often associated with an abnormal BMI in PCOS women. The dominant follicle compensates for the loss of FSH stimulation, resulting in luteinizing hormone surge and subsequent ovulation. PCOS impacts the ovarian stroma, making it more rigid and less conducive to follicular growth. Abnormal growth during the early stages of follicular development contributes to the ovarian characteristics seen in PCOS. PCOS involves an imbalance in sex hormones, leading to cyst formation in the ovaries. Elevated luteinizing hormones (LH) levels and a decreased follicle-stimulating hormones (FSH) level result in a higher LH/FSH ratio, which is often associated with an abnormal BMI in PCOS women. Excess androgen secretion inside the ovary is a significant factor in PCOS development caused by hyperinsulinemia and altered steroidgenesis. ^[5]

Thyroid hormone is crucial for the regulation of female hypothalamic-pituitary gonadal axis, thus the correlation between thyroid function and PCOS have been extensively studied. A prospective study indicated that the incidence of PCOS is higher in patients with Hashimoto’s thyroiditis (HT) compared with people without HT.^[6] Thyroid disorder may also cause menstrual dysfunction, infertility and metabolic disorders, and are extremely common in females.^{[7 – 9]}  Although data on thyroid function/dysfunction in women with PCOS are spare and confusing growing evidence suggest a potential link between these disease.^{[10 – 11]}

Increased autoimmunity in PCOS with higher secretion of TRAb antibodies could increase the risk for Grave’s disease and higher activity of the inflammatory system could increase the risk of thyroiditis. Some authors suggested that higher LH levels in PCOS could stimulate thyroid growth and increase the risk of goiter. ^[12]

STUDY DESIGN

The study was conducted in the Index Medical Hospital and Department of Biochemistry, Index Medical College and Hospital, Indore (M. P).The subjects with PCOS women visited Gynaecology and Endocrinology OPD, Index Hospital, Indore. Study was approved by the ethical committee of the institute.

PARTICIPANTS

A Total number of 90 patients diagnosed with PCOS (mean age 27.62 ± 6.25 years) as case group and 90 healthy women (mean age 28.84 ± 5.04 years) as control group was enrolled from 5th June 2023 to 28th August 2024. To diagnosed and confirm PCOS patients aged between 20 to 40yrs by revised Rotterdam’s criteria such as excess androgen level, ovulatory dysfunction and ultrasonography showing polycystic ovaries. Informed consent was obtained according to institutional guidelines. Exclusion criteria were hyperprolactemia, pregnancy status, patients on hormonal therapy, use of drugs that affect the hyperthalamic – Ovarian axis, any chronic disease, smoker, alcohol consumption and diagnosed with pituitary disease, benign pituitary tumor, other pituitary disease, craniopharyngeoma acromegaly, Cushing’s syndrome, adrenogenital syndrome, and Turner syndrome were excluded from the study.

SAMPLE COLLECTION

Venous blood sample from all subjects were collected under aseptic condition and drawn from median cubital vein. 5 ml blood sample was collected from each participant in SST vial tube and send them to laboratory for further investigations. The tube was centrifuged at 3000 to 4000 rpm for 15-20 minutes. Serum or plasma collected carefully and stored in sterile aliquots and freeze at -20⁰ C to -80⁰ C until ready for assay.

DETERMINATION OF ASSAY

PCOS patient were screened and examined by revised Rotterdam criteria for their eligibility as study participant. Gonadotropin level (LH and FSH) and Thyroid profile (T₃, T₄ and TSH) was measured by Chemiluminescent Immunoassay technique. These results can be useful as diagnostic and therapeutic finding for the PCOS patients.

STATISTICAL ANALYSIS

The present study will prospective observational case control study and the method of sampling will be random - purposive. Correlations will be calculated by Pearson’s Correlation Coefficient (two-tailed). The said calculations will be made on SPSS software version 30.0. P value less than 0.05 was considered as statistically significant.

The study was included a total of 180 diagnosed patients with PCOS. The main demographic characteristics of the two groups (cases and healthy controls) are represented in table no.1. The result shows correlation between the Gonadotropin level (LH, FSH and LH /FSH ratio) and Thyroid Profile in PCOS patients were compared with healthy controls.

Table no.1: Association between the Gonadotropin level and Thyroid profile in PCOS patients were compared with healthy controls.

Note: The results are expressed as mean and Standard Deviation (S.D) with the range value with 95% confidence intervals. P values < 0.05 were considered as statistically significant.

The result shows no significant difference in age of PCOS women (27.62 ± 6.25) as compared to healthy women (28.84 ± 5.04). When the healthy control and PCOS women were compared in terms of clinical features and laboratory finding, the Body Mass Index (BMI),

Luteinizing hormone (LH) and thyroid stimulating hormone (TSH) were found to be statistically significant in PCOS group. There was a significant difference between in both groups in term of LH / FSH ratio and other parameters such as Follicular stimulating hormone (FSH), T₃ and T₄ were not significant in PCOS group as compare with healthy control.

In this study, we compared the Gonadotropin level and thyroid level in patients with PCOS and healthy women. We found that the alteration in gonadotropin level and thyroid levels. Similar to these finding several studies revealed that patients with PCOS had been increased LH, LH / FSH ratio and low FSH levels. A study conducted by Moran C et. al., (2015) and Tock L et. al., (2014) have shown that LH levels and the LH/FSH ratio are significantly higher in lean PCOS as compare with without PCOS. These findings suggest that neuroendocrine disturbances may be the most crucial mechanism in PCOS women. ^{[13, 14]}

The abnormal gonadotropin secretion pattern in PCOS is characterized by increased LH levels and LH/FSH ratio. ^[15] This pattern is related to increases in both the amplitude and frequency of LH secretion secondary t increased pulse frequency of hypothalamic gonadotropin – releasing hormone. ^{[16, 17]} increased frequency of GnRH secretion favors transcription of the β – subunit of LH over the β – subunit of FSH, which cause the increase in the LH/FSH ratio in PCOS patients. ^[16]

As the prevalence of these endocrine dysfunctions increases, the association of polycystic ovary syndrome (PCOS) and autoimmune thyroid disease is increasingly being recognised. There is enough literature support to argue that prevalence of subclinical hypothyroidism/thyroid autoimmunity is increased in women with PCOS patients. Studies conducted by Singh R et. al., (2015) and Shanmugham D et. al., (2018), shown that the rate of thyroid disease was significantly and substantially higher in women with PCOS compared to controls. Our finding’s supported that the prevalence of subclinical hypothyroidism / thyroid autoimmunity is increased in women with PCOS.  ^{[18, 19]}

The risk of development of thyroid disease was significantly higher in PCOS with hypothyroidism as the most prevalent diagnosis. Our data support that screening for thyroid diseases are relevant not only at diagnosis of PCOS, but also during follow up and especially before and during pregnancy. Recent studies by D Glintborg et. al., (2019) and Khatri et. al., (2022), concluded that the strong association of hypothyroidism in women with PCOS when compared with women without PCOS. ^{[20, 21]}

STUDY LIMITATIONS

Recognizing the limits of our research, particularly the comparatively limited number of participants, is crucial. Further investigations involving large no. of patients are important to enhance the dependability of these measures. However, we have not found many studies in the literature examining the relationship between Gonadotropin levels and thyroid dysfunction in PCOS. Conducting research on this subject is among the strengths of the study.

The study is conducted to elucidate the relationship between Gonadotropin levels and thyroid levels in the affected women with PCOS. Our results concluded that the alteration in levels of Gonadotropin and thyroid are strongly associated with severity of PCOS in affected women. Our results concluded that the women suffered with PCOS had slightly low or normal FSH level, higher LH, LH/FSH ratio and higher TSH level as compare to women without PCOS. The findings of the study are expected to enhance to understanding of the pathophysiological mechanisms linking these parameters and severity of PCOS disease. The study seeks to identify their potential as prognostic indicators of PCOS and could lead to the development of targeted therapeutic interventions that help to cure the disease, and improving overall patient outcomes in this vulnerable population.

CONFLICT OF INTEREST

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004; 89:2745 – 9.
2. Lobo RA, Carmina E. The importance of diagnosing the polycystic ovary syndrome. Ann Intern Med. 2000; 132: 989 – 93.
3. Adam Balen MD. The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Obstetrics and Gynaecology. Oct 2004; 18(5): 685 – 706.
4. Krishnan A, Muthusami S. Hormonal alteration in PCOS and its influence on bone metabolism. Journal of Endocrinology.2017; 232: 99 – 113.
5. Franks, S., Stark, J., Hardy, K. Follicle dynamics and anovulation in polycystic ovary syndrome. Reprod. Update. 2008;14 (4), 367–378.
6. Obermayer-Pietsch B, Klaritsch P, Pregartner G, Herzog SA, Lerchbaum E, et al. Impact of thyroid function on pregnancy and neonatal outcome in women with and without Pcos. (2022) 10:750. doi: 10.3390/biomedicines10040750
7. Garmendia Madariage A, Santos Palacions S, Gullien-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014; 99-923-31. Doi: 10.1210/jc.2013-2409.
8. Mu C, Ming X, Tian Y, Liu Y, Yao M, Ni Y, et al. Mapping global epidemiology of thyroid nodules among general population: a systematic review and meta-analysis. Front Oncol. 2022; 12:1029926. Doi 10.3389/fonc. 2022.1029926.
9. Hu X, Chen Y, Shen Y, Tian R Sheng Y, Que H. Global prevalence and epidemiological trends of Hashimoto’s thyroiditis in adults: a systematic review and meta-analysis. Front public Health. 2022; 10:1020709. Doi 10.3389. 2022.1020709.
10. Gaberscek S, Zaletel K, Schwetez V, Pieber T, Obermayer-Pietsch B, Lerchbaum E, Mechanisms in endocrinology thyroid and polycystic ovary syndrome. Eur J Endocrinol. 2015; 172:R9-21. Doi:10.1530/EJE-14-0295.
11. Kowalczyk K, Franik G, Kowalczyk D, Pulta D, Blukacz L, Madej P. Thyroid disorders in polycystic ovary syndrome. Eur Rev Med Pharmacol Sci. 2017; 21:346-60.
12. Cakir E, Sahin M, Cakal E, Ozbek M & Delibasi T. Medical hypothesis: can gonadotropins influence thyroid volume in women with PCOS? Thyroid Research. 2012; 5:17.
13. Moran, C.,Arriaga, M., Arechavaleta-Velasco, F. & Moran, S. Adrenal androgen excess and body mass index in polycystic ovary syndrome. Clin. Endocrinol. Metab. 2015, 100(3), 942-950.
14. Tock, L., Carneiro, G., Pereira, A. Z., Tufik, S. & Zanella, M. T. Adrenocortical production is associated with higher levels of luteinizing hormone in nonobese women with polycystic ovary syndrome. J. Endocrinol. 2014.
15. Fritz MA, Speroff L. Clinical Gynecological endocrinology and infertility. 8^th Philadelphia (PA): Lippincott Williams and Wilkins; 2011. P: 501 – 518.
16. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005; 352:1223-1236. PMID: 15788499.
17. Waldstreicher J, SantoroNF, Hall JE, Filicori M, Crowley WF Jr. Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab. 1988;66:165-172. PMID:2961784.
18. Singh R, Gupta Y, Khemani M, Aggarwal S. Thyroid disorder and polycystic ovary syndrome: An emerging relationship. Indian Journal of Endocrinology and Metabolism. 2015; 19(1):25 – 29.
19. Shanmughum D, Natrajan S, Karthik A. Prevalence of thyroid dysfunction with polycystic ovarian syndrome: a cross sectional study. International Journal of Reproductive, Contraception, Obstetrics and Gynecology. Aug 2018; 7(8): 3055 – 3059.
20. Glintborg D, Rubin KH, Nybo M, Abrahamsen Bo, Anderson M. Increased risk of thyroid disease in Danish women with polycystic ovary syndrome; a cohort study. Endocrine Connections. 2019; 8(10): 1405 – 1415.
21. Khatri G, Bika S, Singh M, Saxena M, Joshi K, Yadav P. To determine the association between polycystic ovarian syndrome and thyroid function in a tertiary care hospital in western Rajasthan. International Journal of Pharmaceutical and Clinical Reseach. 2022;15(3): 729 – 737.