Introduction 

Certain conditions can sneak up on us, masked behind symptoms we tend to overlook. Thyroid disorders top the list when it comes to these conditions. The thyroid is a small, unassuming, and hormone-producing gland located in front of the neck. This butterfly-shaped gland coordinates various metabolic processes in your body. Thus, disruption in its function can elicit a cascade of metabolic consequences, which includes fertility. 

Notably, thyroid dysfunction can impact fertility in both people assigned male at birth (AMAB) and people assigned female at birth (AFAB). However, thyroid conditions disproportionately affect AFAB in comparison to AMAB. This article unveils the indisputable connection between thyroid health and fertility. 

Understanding the thyroid gland and its functions

The thyroid gland is a vital endocrine gland that produces and secretes thyroid hormones, triiodothyronine (T3) and thyroxine (T4).¹ This butterfly-shaped gland is found in front of the neck (just below the larynx or voice box) and is made up of two cells: follicular and parafollicular cells. The former produces thyroid hormones, while the latter (also known as C-cells) is responsible for the secretion of calcitonin, which regulates calcium levels in the body.¹ 

A feedback system involving the hypothalamus, pituitary gland, and thyroid gland known as the HPT axis controls the production of thyroid hormones. The following summarises the steps involved in the synthesis of thyroid hormones.²

Thyroid hormones perform a wide spectrum of functions in the body, which involve the brain, bones, nervous system, lungs, and heart. 

• The hormones are essential for aerobic mitochondrial function (energy production) in the heart and blood vessels
• The hormones prevent lactic acid buildup in the blood and regulate bone formation and resorption
• Thyroid hormones promote cell differentiation, growth, and maturation
• Essential in early foetal life for normal growth and brain development³ 

Thus, given their effects, thyroid hormones are critical for the survival and optimal functioning of the human body.³

The connection between thyroid health and fertility explained 

A healthy and well-functioning thyroid is crucial for fertility because:⁴

• The thyroid hormones influence fertility in AFAB
• Directly stimulate the maturation of oocytes (immature eggs)
• Regulate the concentration of prolactin and sex-hormone binding globulin (SHBG) 

Therefore, undiagnosed or untreated thyroid disorders or conditions can lead to infertility due to high prolactin levels, lack of ovulation, and defects in the luteal phase and sex hormones.⁵

However, most of the problems in the female reproductive system stem from a dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis.⁶ The HPO axis is a major regulator of oestrogen and progesterone, which are the female reproductive hormones.

The hypothalamus releases gonadotrophin-releasing hormones once AFAB reaches puberty. This induces the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. LH and FSH bind to ovarian receptors and elicit the release of oestrogen and progesterone.⁶ Fluctuating concentrations of oestrogen and progesterone are released throughout the menstrual cycle, resulting in the follicular phase (i.e., low oestrogen) and luteal phase (i.e., high oestrogen).⁶ 

Thyroid hormones work in coordination with FSH and stimulate the differentiation of granulosa cells. Differentiated granulosa cells promote normal follicle development, which is necessary for ovulation and corpus luteum formation.⁷ Therefore, adequate levels of thyroid hormones are essential for the induction of ovulation.

Thyroid abnormalities, i.e., hypothyroidism and hyperthyroidism, can lead to infertility, miscarriage, stillbirth, menstrual irregularities, and menorrhagia.⁸ Hypothyroidism can cause ovulation and menstrual problems.⁷ Hypothyroidism in particular is associated with menstrual disorders.

Contrarily, hyperthyroidism may cause irregular menses such as hypomenorrhoea (light periods) and polymenorrhoea (irregular periods). Fertility problems in AFAB with hyperthyroidism occur with a frequency of 5.8% to 50%, while the prevalence of hypothyroidism in AFAB of reproductive age is 2% to 4%.⁹

Studies have also reported that hormonal abnormalities in oestrogen and progesterone levels can significantly affect thyroid function, causing hyperthyroidism, hypothyroidism, and hyperprolactinemia.⁸

How thyroid health affects male fertility

The two most common types of thyroid disorders, hypothyroidism and hyperthyroidism, can also affect male fertility. The human testes have two major functions: the production of mature sperm (spermatogenesis) and the production of androgens. The main cells of the testes responsible for reproductive functions are the Leydig cells and the Sertoli cells.¹⁰ The former produces testosterone alongside other androgens and is vital for the development of male sex characteristics, while the latter is essential for spermatogenesis.¹⁰

Thyroid hormone receptors are found in the testis and have an effect on Sertoli cells, Leydig cells, and spermatogenesis. The hormones regulate various cells through the regulation of gene transcription, protein synthesis, differentiation, and proliferation.¹¹ 

Thyroid dysfunction can affect male fertility and sexual dysfunction in various ways:¹¹

• Hypothyroidism can cause changes in sperm morphology
• Hypothyroidism adversely affects the quality of semen by compromising semen volume and progressive sperm motility and morphology
• Hypothyroidism can also decrease the total sperm number and lead to an impairment in mitochondrial activity
• Thyroid abnormalities affect levels of sex hormones by influencing the pathways of the central and peripheral nerves and malfunctioning of the autonomic nervous system
• AMAB with hypothyroidism experience delayed ejaculation, while hyperthyroidism can induce premature ejaculation¹²

How autoimmune thyroid disorders affect fertility

Apart from hypothyroidism and hyperthyroidism, autoimmune disorders that target the thyroid gland can impact fertility in the form of two conditions: Hashimoto’s thyroiditis and Graves’ disease.¹³ These autoimmune conditions affect fertility in the following ways:

Hashimoto’s thyroiditis

This is a chronic autoimmune thyroid disease that causes primary hypothyroidism due to the destruction of the thyroid by infiltration of lymphocytes.¹³ This condition affects about 5% to 15% of AFAB of reproductive age and 20% to 30% of the general population. However,it is more prevalent in AFAB.¹³

The risk factors include genetic conditions (such as Down syndrome and Turner syndrome), stress, family history, gender, high iodine diet, etc. Hashimoto’s thyroiditis affects fertility due to the changes in the levels and metabolism of thyroid hormones. This occurs as a result of an increase in the titer levels of antibodies against thyroid peroxidase (TPO) and thyroglobulin (TG).¹³

Hashimoto’s thyroiditis can interfere with ovulation, affecting fertility. If an AFAB becomes pregnant, it can lead to pregnancy losses or negatively impact the health of the foetus.¹³

Graves’ disease

This is a common cause of hyperthyroidism caused by autoimmunity. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Graves’ disease occurs when the body secretes thyroid-stimulating immunoglobulin (TSI), which can be mistaken for TSH in the body.

Consequently, your body starts producing excessive amounts of thyroid hormones, i.e., T3 and T4. Due to the variety of functions of T3 and T4, this condition leads to the following signs and symptoms due to the excessive production of thyroid hormones: bulging eyeballs (in some cases), weight loss, trouble sleeping, goiter, irritability, etc.

Since Graves’ disease is a common cause of hyperthyroidism, it can affect fertility by causing irregular periods, premature menopause, and early pregnancy loss. Graves' disease (GD) affects about 1% of the population, while Hashimoto's thyroiditis (HT) affects around 3%.⁹

Treatment and management of thyroid disorders to improve fertility

Hyperthyroidism and hypothyroidism are more prevalent in AFAB of reproductive age than in AMAB. Thus, measurement of the levels of T3, T4, and TSH should be carefully monitored when AFAB are pregnant. However, the treatment of hyperthyroidism is determined by the age of the individual, the size of the goitre, and whether there are any coexisting health conditions.¹⁴

The most commonly used antithyroid drug in the United Kingdom is carbimazole (which is almost completely converted to methimazole in your body), and less commonly, propylthiouracil. The treatment of choice for people with Graves’ disease (a form of hyperthyroidism) is radioiodine. This is used for patients who relapse after long-term use of antithyroid drugs and experience severe thyrocardiac disease.¹⁴ It is, however, not used during pregnancy or breastfeeding. 

Treatment of hyperthyroidism in pregnancy

It is vital to note that hyperthyroidism can cause pregnancy complications and may lead to increased foetal loss.¹⁴ Therefore, treatment should be initiated with the smallest dose and strict monitoring of antithyroid drugs.

Propylthiouracil is usually preferred over methimazole because it has been studied to have lower transplacental passage. Additionally, pregnant patients and AFAB who have adverse reactions to propylthiouracil can be advised to undergo subtotal thyroidectomy. It is also an appropriate therapy for patients with large goitres that can extend and lead to compressive manifestations and for patients with thyroid carcinoma.¹⁴ 

Hypothyroidism is usually treated with thyroid replacement therapy or levothyroxine. The dosage of levothyroxine may have to be increased when its metabolic disposition is accelerated by pregnancy or by certain drugs such as rifampin, phenytoin, or carbamazepine.¹⁴ For AMAB with thyroid dysfunction, the same treatment strategies apply and can include hormone replacement therapy to regulate thyroid levels, restore the quality of semen, and improve overall fertility.¹⁴

Dietary interventions can also support thyroid health. These include nutrients, such as iodine, zinc, and selenium, which can improve thyroid function. However, excessive iodine intake can worsen thyroid disorders. Therefore, accurate diagnosis is essential before treatment is commenced, especially with antithyroid medications. 

Summary 

• The thyroid is a vital endocrine gland that produces thyroid-stimulating hormones and carries out numerous functions in the body
• Thyroid hormones play an essential role in the reproductive system by coordinating the development of the ovarian, uterine, and placental tissues and sperm production and motility in AMAB. 
• The risk factors for the development of thyroid-related disorders include gender, autoimmune disease, iodine deficiency, radiation therapy, and damage to the pituitary gland
• Thyroid health affects male and female fertility by triggering changes in the function and metabolism of thyroid hormone as a result of hyperthyroidism and hyperthyroidism
• Treatment of hyperthyroidism and hypothyroidism involves the use of antithyroid drugs, thyroid replacement therapy, levothyroxine and subtotal thyroidectomy
• It is imperative to manage your thyroid health through dietary intervention and appropriate medical attention when needed

FAQs

How are thyroid disorders diagnosed?

Thyroid disorders can be diagnosed through a physical examination by a medical professional, which entails checking the neck for any abnormalities. This can be combined with a blood test to measure levels of TSH and thyroid hormones like T3 and T4. High levels of TSH usually indicate an underactive thyroid (hypothyroidism), while low TSH levels imply an overactive thyroid (hyperthyroidism).

What causes thyroid dysfunction?

Thyroid dysfunction can be triggered by different factors such as iodine deficiency, autoimmune disease, unhealthy eating habits, genetics, pregnancy, etc. 

Can thyroid dysfunction be prevented? 

Generally, thyroid dysfunction cannot be prevented. However, you can improve your thyroid health by managing your stress levels, exercising regularly, eating healthily, quitting smoking, and having regular check-ups. This will help reduce the risk of developing a thyroid disorder, which can significantly impact your daily life.