Thyroid Dysfunction in Iranian Patients with Premature Ovarian Failure

Elham Neisani Samani(1), Masoumeh Fallahian(2), Reza Salmanyazdi(3), Ali AM
Ghazi(4), Ladan Ajori(5)

1. Resident of obstetrics and gynecology, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
2. Professor, Infertility & Reproductive Health Research Center (IRHRC), Shaheed Beheshti University of Medical Science, Tehran, Iran.
3. Pathologist, The Head of Laboratory, Royan Research Institute, Tehran, Iran.
4. Professor , Endocrine Research center, Shaheed Beheshti University of
   Medical Sciences, Tehran, Iran.
5. Associate professor, Obstetrics and Gynecology Department, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
   

Correspondence:
Elham Neisani Samani,MD,
Resident of obstetrics and gynecology,
Obstetrics & Gynecology Department,
Ayat - al- lah Taleghani Hospital,
Shaheed Beheshti University of Medical Sciences,
Evin Ave, Velenjak Street, Tehran, Iran.
Tel : +9821-22432574
Fax:+ 9821-88844304
E-mail: eneisani@yahoo.com

INTRODUCTION

Premature ovarian failure (POF) is a heterogenous syndrome defined as hypoestrogenic hypergonadotropic secondary amenorrhea that occurs in women under the age of 40 years. It is characterized by loss of oocytes, lack of folliculogenesis and ovarian estrogen production, and infertility. The incidence rate of POF is approximately 1%^(1,2). It is usually permanent, but resumption of ovarian activity and fertility has been documented in over 50 percent of women based upon hormonal measurements^(2-5), pelvic ultrasonography^(6,7), or conception⁽⁸⁾. 5 - 10% of patients with POF, may subsequently experience spontaneous ovulation⁽¹⁾.

The clinical picture of POF was first described in detail in 1950 by Atria⁽³⁾ and De Moraes-Ruehsen and Jones in 1967 described it as non physiological cessation of menses before the age of 40 yr⁽¹⁾.

The association of POF with hypothyroidism, Addison disease, vitiligo, myasthenia gravis, Graves' disease, Sjogren syndrome, systemic lupus erythematosus , hypoparathyroidism, recurrent mucocutaneous candidiasis, celiac disease, type 1 diabetes, and rheumatoid arthritis, have been previously reported^(1-7).

Gokmen and Shah showed that thyroid dysfunction can be associated with POF. In a study done by Weyermann and his colleagues, they found that autoimmune thyroid disorder is the most common endocrine disease in their patients with POF⁽¹⁵⁾. While
there were no studies on POF in our country, we conducted present study to shed more light to the problem in an Iranian population.

METHODOLOGY

This study was approved by the Institutional Review Board at Medical Science University. All women signed consent forms before participation

It has been done on 46 patients with POF who were referred to the hospital. The POF status was defined as the cessation of ovarian function for a period of > 6 months, before the age of 40 years, and Follicular Stimulating Hormone (FSH) concentration greater than 20 IU/ml detected on two different occasions. The exclusion criteria were:

1. History of ovarian surgery, radiation or chemotherapy, autoimmune diseases or metabolic disorders,
   
2. History of thyroid disorders or abnormal thyroid function tests,
   
3. Usage of drugs which may affect thyroid hormone metabolism in the past 6 months.

The controls had been picked at random, and included 46 normal cycling women attending a family planning clinic for contraception methods of intra uterine device (IUD) or tubal ligation. All the women gave written informed consent. Demographic questionnaires on age of menarche and early menopause, family history of POF, etc were completed.

Samples were saved at -20°C and done in one run. Thyroxine (T4), tri-Iodothyronine (T3), T3 resin uptake (T3RUP), and thyroid stimulating Hormone (TSH) and FSH were evaluated by using commercial radioimmunoassay kits (RIA, Pouyesh Tashkhis, Tehran, Iran). Anti TPO and Anti Tg antibodies were assessed by using commercial enzyme linked immunosorbent assay kits.(ELISA, GENESIS, Cambridge Shire, CB6 ISE, UK).

SPSS Statistical programs(SPSS, software 11.0, Chicago, USA) were used to analyze results. Exact Fisher test and Chi square test were used for the comparison. P value less than 0.05 was considered statistically significant.

RESULTS

Table 1 shows the demographic data of both groups.

Table 1. Demographic data in POF and control groups

All subjects were euthyroid. T4, T3, T3RUP and TSH levels were not significantly different between patients with POF and controls. The mean level of T4 , T3, T3RUP and TSH were 9.40±2.29 (µg/dl), 1.2±0.34 (ng/ml), 28.41±1.33(%) and 2.07±1.66( m IU/ l) respectively in patients with POF. The mean level of T4, T3, T3RUP and TSH were 7.9±1.48(µg/dl), 1.2±0.32(ng/ml), 28.27±4.68(%) and 1.52±1.14( m IU/l) respectively in the controls. Anti TPO antibodies were positive in 14 out of 46 (30.4%) patients with POF, compared to 4 out of 46 (8.6%) controls. Anti Tg antibodies were positive in 22 out of 46 (48%) of patients with POF, compared to 9 out of 46 (19.5%) controls. Anti TPO and Anti Tg levels were significantly high in patients with POF compared to controls. (P value = 0.02 and P value = 0.01, respectively) (Table2).

Table 2. Positive Anti thyroid antibodies in POF and control groups

* Confidence Interval(95%)

DISCUSSIONS

We found a higher frequency of anti TPO and anti Tg antibodies in patients with POF in comparison to controls. This study showed that premature ovarian failure can be associated with presence of anti-thyroid peroxidase and anti thyroglobulin antibodies.

There were no cases of hypo or hyperthyroidism in patients with POF. These findings are in favour of autoimmunity as a possible mechanism in pathogenesis of POF. The association between premature ovarian failure and thyroid dysfunction has been discussed before, but in our study presence of anti thyroid antibodies happened in patients who were euthyroid.

Gokmen et al showed significant difference in TSH levels between his patients and control groups⁽¹²⁾, that is different from our findings, but they had not excluded all the known thyroid dysfunction cases. Betterle et al, in a descriptive study showed that 10% of patients with POF had anti thyroid antibodies. However, that study didn't have any control group⁽¹³⁾.

Goswami supported our results by showing higher frequency of anti TPO antibodies in patients with POF in comparison to controls⁽⁷⁾. Shah and colleagues studied 37 Indian patients with POF, and reported 22% prevalence of thyroid dysfunction. They reported that hypothyroidism was the most common coexistent thyroid disorder in patients with POF⁽¹⁴⁾.

In a study which was done by Weyermann and colleagues, they found that autoimmune thyroid disorder is the most common endocrine disease in their patients and they recommended measurement of TSH as a screening test for thyroid dysfunction in patients with POF⁽¹⁵⁾.

According to our study, we advise measurement of thyroid function tests in patients with POF. Accepting the concept that POF is a heterogeneous disorder in which some of the idiopathic forms are based on an abnormal self-recognition by the immune system will lead to new approaches in the treatment of reproductive problems and infertility in these patients.

ACKNOWLEDGEMENTS

The authors wish to thank staff of Endocrine and Metabolism Research Center in Shaheed Beheshti University of Iran for storage and cryo preservation of the sera, and also Royan Institute for doing laboratory tests, and Dr Fakhrolmolook Yasaee and Azadeh Akbari Sene for editing the issue. We extend our appreciation to all the patients for their cooperation in this study.

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