Thyroid Dysfunction in Patient with Abnormal Uterine Bleeding in a Tertiary Hospital of Eastern Nepal: A Descriptive Cross-sectional Study

ABSTRACT Introduction: Thyroid hormone is known to affect reproductive biology. Abnormal uterine bleeding is one of the common presentations in gynaecology outpatient departments and thyroid dysfunction is known to affect its progression. This study aims to find the prevalence of thyroid dysfunction in diagnosed cases of abnormal uterine bleeding in patients in a tertiary hospital of eastern Nepal. Methods: A descriptive cross-sectional study was conducted in patients diagnosed with abnormal uterine bleeding in a tertiary care hospital of eastern Nepal from April 2019-March 2020 after taking ethical clearance from the Institutional Review Committee. On basis of inclusion and exclusion criteria, 95 cases of abnormal uterine bleeding were included in the study. A blood sample was taken and a thyroid function test was done by chemiluminescence assay on an automated analyzer. Convenient sampling method was used for sample collection. Statistical analysis was done using Statistical Package for the Social Sciences version 16. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. Results: Out of the total cases of abnormal uterine bleeding, 15 (15.79%) (8.46-23.12 at 95% Confidence Interval) had thyroid dysfunction. Among total cases, 80 (84.21%) were euthyroid. The mean age of the patients was 33±8 years. Among thyroid dysfunction, 9 (60.0%) were hypothyroid, 4 (26.66 %) were subclinical hypothyroid, and 2 (13.33 %) were hyperthyroid. Conclusions: Thyroid dysfunction was common among patients with abnormal uterine bleeding, with hypothyroidism being the most common type.


INTRODUCTION
The impact of thyroid hormone on reproductive biology has been studied. 1 Due to similarity of Thyroid Stimulating Hormone (TSH) to gonadotropins -Follicle Stimulating Hormone (FSH) and, Leutinizing Hormone (LH) and, presence of thyroid hormone receptors on ovaries, thyroid hormones can affect menstrual cycle by direct impact on ovaries or through impact on sex hormone binding globulin (SHBG), prolactin and gonadotropin releasing hormone (GnRH). 1,2 Abnormal uterine bleeding (AUB) is known to affect 10-15% women of reproductive age globally, with prevalence of 6.2% in Nepal. 3,4 Hypothyroidism has been found to cause menorrhagia and hyperthyroidism to cause oligomenorrhoea and amenorrhoea. 1 Most cases of anovulatory bleeding can be treated by hormonal and non-hormonal medicines, thus avoiding surgeries. 5 Treating thyroid function has shown to improve the menstrual abnormalities. 6,7 This study aims to find the prevalence of thyroid dysfunction in women of reproductive age with abnormal uterine bleeding in a tertiary hospital of eastern Nepal. The sample size was calculated was 76. Adding a 10% non-response rate, the sample size was calculated as 83. We have collected data from 95 participants.

METHODS
A complete history of age, parity, menstrual history, onset and duration of menstrual problems, volume of blood flow and any other relevant complaints was taken. After case history and clinical examination, urine pregnancy test followed by bleeding time, clotting time, ultrasonography of abdomen and pelvis was done. After all the exclusion criteria ruled out and diagnosis confirmed, patient was prepared for Thyroid function test (TFT).
Approximately 3ml venous blood sample was collected in a yellow capped plain vial, from antecubital vein under strict aseptic conditions following the universal precautions. Centrifugation was done at 3000rpm for 10 minutes and separated serum was stored at -20°C until analysis. Serum triiodothyronine (T3), Thyroxine (T4) and thyroid stimulating hormone (TSH) level were measured by chemiluminescence assay on Advia centaur XP immunoassay analyzer. Normal range for T3, T4 and TSH was respectively 2.5-4.16pg/ml, 0.89-1.76ng/dl and 0.34-5.12IU/ml and thyroid function was interpreted as:

DISCUSSION
Abnormal uterine bleeding is one of the common finding among females of reproductive age. Among the wide spectrum of causes, from structural causes like polyps, leiomyoma etc. to non-structural causes, thyroid dysfunction is found as occult cause which may be readily missed out. Thyroid dysfunction, since being common in women 8 and has been known to affect all events right from menarche to menopause, cannot be overlooked while treating any forms of menstrual disturbances. 9 Our study consisted mainly of women from age group 25-34 (37.9%) and age group 35-44 (32.6%). In this study, 15.79% of total cases of AUB had thyroid dysfunction. Rest 84.21% of total cases of AUB were euthyroid. Out of cases with thyroid dysfunction, hypothyroid was most common followed by subclinical hypothyroid and hyperthyroid. Hypothyroidism is generally known to cause heavy and irregular menstrual bleeding and hyperthyroidism is generally associated with hypo, oligo and amenorrhoea. 1 Our finding is similar to studies done in Nepal and India where researchers also found majority of AUB cases associated with euthyroidism followed by hypothyroidism, Subedi, et al. 10 found 89.3% cases were euthyroid and 9.3% hypothyroid; Thakur, et al. 11 found 84.9% as euthyroid and 13.9% hypothyroid; Kattel, et al. 4 found 80% cases euthyroid and 11.1% as subclinical hypothyroid; Bhavani, et al. 12 found 81% cases as euthyroid and 10% as subclinical hypothyroid; Gowri M, et al. 13 found 77.6% cases as euthyroid and 17.6% cases as hypothyroid. In contrast according to Ajmani, et al. 14 44% of the patients with menstrual disorder had thyroid disorders.
The most common pattern of AUB was found to be menorrhagia was most common 45 (47.37%) followed by metrorrhagia 20 (21.05%), polymenorrhoea 13 (13.68%), menometrorrhagia 8 (8.42%), hypomenorrhoea 6 (6.31%), and oligomenorrhoea 3 (3.15%). This is similar to study done by Kattel,et al. 4 where menorrhagia (36.7%) was most common complaint among AUB. Bhavani, et al. 12 found the incidence of menorrhagia to be 54%. Recent similar study in Nepal by Thakur,et al. 11 also showed menorrhagia to be present among 40.5% cases of AUB. Second most common finding was metrorrhagia in our case which is similar to study done by Muzaffer, et al. (35.4 %). 15 This is in contrast to study by Thakur,et al. 11 in which polymenorrhoea was second most common finding.
Observing individual types of AUB, menorrhagia was mostly associated with overt hypothyroidism (15.5%) followed by subclinical hypothyroidism (4.5%). Menorrhagia has been reported to occur in 32-56% of cases of myxedema. 16 Polymenorrhoea was associated with subclinical hypothyroidism only (15.4%). Oligomenorrhoea and hypomenorrhoea were associated with hyperthyroidism. This finding is similar to study done by Kattel, et al. 4 Subedi, et al. 11 and Byna,et al. 17 Free Full Text Articles are Available at www.jnma.com.np TSH can be used as a screening test for every patient visiting gynaecology department with complaint of menstrual disorder. This will provide less financial burden to the patients rather than opting for whole thyroid function test. Median TSH in our study was found to be 2.12IU/L (1.12-3.60) which is in accordance with study done by Khatiwada,et al. 18 in eastern Nepal who found median TSH to be 2 IU/L (1.0-4.0). Brayshaw, et al. 19 also reported majority of premenstrual syndrome (35 out of 54 cases) on basis of abnormal TSH test.
This study is a cross sectional study so the cause-andeffect relation of thyroid dysfunction and AUB cannot be elaborated and thus this result cannot be generalized to all patients in our country. Random sampling with more representative sample followed by rigorous study design adjusting the confounding factor would be required in future to further put light on the topic.

CONCLUSIONS
Our study found substantial patients with AUB suffering from thyroid dysfunction which was similar to previous studies done in similar setting. Hypothyroidism was most common finding in menorrhagia and metrorrhagia and hyperthyroidism was found in oligomenorrhoea and hypomenorrhoea.