Abstract

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Polycystic ovarian syndrome (PCOS) is associated with a derangement in reproductive hormones and its clinical features resemble those with thyroid insufficiency. Therefore, this study was conducted on 50 newly diagnosed patients of PCOS and their serum samples were analysed for follicle stimulating hormone (FSH), leutinizing hormone (LH), estradiol, progesterone, testosterone, thyroid stimulating hormone (TSH), free and total T₃ and T₄. The patients of PCOS were found to be suffering form hypothyroidism as was evident by increased TSH and decsreased free and tolal T₃ and T₄ levels. Thus, thyroid profile analysis may help in providing a better insight into symptomatology and treatment of PCOS.

Introduction

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Polycystic ovarian syndrome (PCOS) is a disorder characterized by oligomenorrhoea or amenorrhea with clinical or laboratory evidence of hyperandrogenemia (1). Polycystic ovaries are defined as the presence of twelve or more follicles in each ovary measuring 2-9 mm and /or increased ovarian volume greater than 10 mL. Most cycles fail to lead to the emergence of dominant follicle that releases an oocyte on a monthly basis. Although follicle development occasionally proceeds to ovulation in affected patients, development of the follicle to only its initial growth stage is common. The hyperandrogenemic state is believed to be a cause of incomplete follicular development (2). PCOS is a common endocrinopathy in reproductive age group and is commonly associated with obesity, menstrual irregularity, insulin resistance and infertility (3). Various therapeutic modalities for PCOS include lifestyle modification, combined oral contraceptive pills, androgen receptor antagonists and insulin-lowering medications (4,5). Thyroid gland dysfunction leading to hypothyroidism is a common disorder affecting women more often than men. The clinical features of hypothyroidism also include weight gain, menstual irregularities and infertility (6). An association has been reported between PCOS and hypothyroidism. Most of the times hypothyroidism is subclinical and diagnosed first time during evaluation of PCOS (7,8). Tri-iodothyronine (T₃) and thyroxine (T₄) circulate in blood bound to carrier proteins which are T₄ binding globulin (TBG), T₄ binding prealbumin (TBPA) and albumin. Approximately 99.97% of T₄ and 99.7 % of T₃ is in bound form and only a small fraction of these hormones circulate unbound and is free for biological activity (9). Thus, to reach the actual diagnosis and to assess the thyroid function, free fraction of these hormones is essential. Therefore, this study was planned to estimate total and free T₃ and T₄ and thyroid stimulating hormone (TSH) in patients of PCOS.

Methods

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This study was conducted on 50 newly diagnosed patients of PCOS according to Rotterdam consensus diagnostic criteria before starting any treatment. Only infertile patients in an age group of 18-35 years and presenting with other features of PCOS were enrolled for the study. Patients presenting with two or more of the following features were selected:
1. Oligomenorrhoea and/ or anovulation
2. Clinical and/ or biochemical signs of hyperandrogenism
3. Polycystic ovaries

Patients of any other chronic illness or thyroid disorders or on any hormonal medication were excluded. Fifty age matched healthy females were taken as controls. The selected patients were subjected to detailed clinical history including menstrual history and thorough clinical examination. After obtaining the informed consent, venous blood samples of these patients were collected on the second day of menstrual cycle under all aseptic conditions. Serum was separated and analysed for leutinising hormone (LH), follicle stimulating hormone (FSH), Testosterone, estradiol, progesterone, free T4 (FT4), free T3 (FT3) and TSH on chemiluminometer (Advia Centaur CP, Siemens) and total T3 and T4 using radioimmunoassay technique. Body mass index (body weight in Kg/ height in meter squared) was also calculated for all the subjects.
The results were statistically compared using SPSS version 17.0 and expressed as mean ±standard deviation.

Results

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Out of 50 patients, 20 patients were in the age group of 18-25 years, 20 patients were in 26-30 years, 10 were in the age group of 31-35 years. The mean age of PCOS patients was 27.48±4.22 years and that for controls was 28.28±3.55 years. The serum levels of various hormones and BMI are shown in table1.

Discussion

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The present study shows a state of hypothyroidism in the patients of PCOS which is obvious by raised levels of TSH and decreased levels of total and free T3 and T4 as compared to healthy females (p<0.001). PCOS patients were found to have increased levels of LH, FSH, estradiol and testosterone though the increase in the levels of FSH was not statistically significant (p>0.05). The levels of progesterone were significantly decreased in these patients (p<0.001)
Exposure of ovaries to high LH concentration during the phase of follicular growth is deleterious to the developing oocyte. LH penetrates the follicle and causes premature completion of the oocyte maturation and reduces its chances of fertilization and implantation. Estimation of FSH is also a direct method to assess ovarian reserve which is an indicator of reproductive potential (10,11). TSH is the most sensitive indicator of hypothyroidism. The prevalence of hypothyroidism in reproductive age group is upto 4 % and it is associated with a broad spectrum of reproductive disorders ranging from menstrual irregularities to infertilty and abortions (12). Thyroid responsivity by the ovaries could be explained by the presence of the thyroid hormone receptors on human oocytes. TSH also affects estrogen metabolism and decreases production of sex hormone binding globulin (8,9,13). Serum testosterone levels were found to be increased in PCOS patients with hypothyroidism. This may be explained as hypothyroidism reduces sex hormone binding globulin and increases free testosterone. This free testosterone is responsible for most of the features of PCOS like hirsutism, infertility, polycystic ovaries, acne etc (14,15). PCOS patients were found to have increased estrogen levels as compared to controls. This increased estrogen dominance may increase the levels of TBG and may mask the activity of free thyroid hormones. Thus, there may be associated clinical features of hypothyroidism which generally overlap with features of PCOS (16). Levels of progesterone were found to be decreased in patients of PCOS. Low progesterone levels produce a stimulatory effect of estrogen on the immune system (16). The hypothyroidism associated with PCOS is generally found to be due to Hashimoto’s thyroiditis, an autoimune disease of the thyroid gland (7).

Conclusion(s)

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Thus, a variety of disturbance in reproductive hormone profile is found to be associated with a state of hypothyroidism. As the features of both PCOS and hypothyroidism are overlapping and an association between these two disease states is not uncommon, therefore, thyroid profile should be analysed along with the reproductive hormonal profile which may help in better understanding of the etiology and management of PCOS.

References

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Source(s) of Funding

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None

Competing Interests

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None

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