What is hypothyroidism?

The thyroid is a small gland located in the front of the neck that produces the two thyroid gland hormones: thyroxine (T4) and triiodothyronine (T3).ⁱ The thyroid hormones (together, referred to as “thyroid hormone”) control the body's metabolism and act on virtually every cell in the body, particularly ones that produce proteins and increase the oxygen usage of cells.ⁱⁱ They also have many downstream effects on other body functions:ⁱⁱⁱ

• Fertility
• Hair and skin health
• Growth
• The rate calories are burned and food is digested
• Heart rate

Hypothyroidism, also called underactive thyroid, is one of the many conditions that can affect the thyroid. There are two types:^iv

• ‍^‍Primary hypothyroidism: In this instance, there is an issue with the thyroid gland itself, leading to high levels of thyroid stimulating hormone (TSH), which stimulates the thyroid gland.
• ‍Secondary hypothyroidism: Much rarer than primary hypothyroidism, it is caused by a problem with the part of the brain that makes TSH. In this case, TSH levels are lower than normal.

In both cases, the levels of thyroid hormone T3 and T4 are lower than normal.^v

How common is hypothyroidism?

In parts of the world where people consume sufficient iodine, approximately 0.3 to 1 percent of people have overt hypothyroidism, meaning low levels of the thyroid hormone T3 and T4.^vi A larger percentage — 2 to 10 percent — have subclinical hypothyroidism or a condition where the TSH is high, but levels of T3 and T4 are normal.^vii

Hypothyroidism is more common in females (3 percent prevalence, 10x more common in females than males), older individuals (5x greater odds of hypothyroidism in patients older than 80 years), and in patients who have been treated for hyperthyroidism.^viii  

An iodine deficiency can increase a person's risk as well. Iodine is essential to the thyroid’s ability to create thyroid hormone, and insufficient iodine intake can cause birth defects and lead to growth retardation in children. Therefore, in the U.S., Canada, and much of the rest of the world, salt is fortified with iodine to ensure there are high enough levels in people’s diets. In countries where iodine is not included in the diet, iodine deficiency is the most common cause of both hypo- and hyperthyroidism.^ix

Hypothyroidism vs. hyperthyroidism

Hypothyroidism is caused by insufficient thyroid hormone production, while hyperthyroidism is caused by too much thyroid hormone.^x The normal value for a thyroid stimulating hormone is typically between 0.4 and 4 mIU/L; however, different laboratories may have slightly different reference ranges depending on the assay used for the test.

• ‍Underactive thyroid gland or primary overt hypothyroidism: TSH value higher than the upper limit of normal with a low free T4^xi‍
• Overactive thyroid gland or hyperthyroidism: TSH value of less than the lower limit of normal with a high free T4^xii

What causes hypothyroidism?

When an individual experiences reduced thyroid hormone production, it is generally caused by a problem within the thyroid gland itself.^xiii

Hashimoto’s thyroiditis

In areas of the world such as the U.S. where iodine is sufficiently available in the diet, Hashimoto’s thyroiditis is the most common of hypothyroidism. It is a chronic autoimmune disease where the patient’s immune system develops antibodies that attack and destroy their own thyroid gland cells. This condition — as with many autoimmune diseases — is most common in females.^xiv

Medical treatments

Another common cause of hypothyroidism is treatment for hyperthyroidism or thyroid cancer, which can include thyroid surgery, medications, radiation, or radioiodine therapy.^xv These treatments remove or shrink part or all of the thyroid gland, thereby reducing the amount of thyroid hormone production. After these treatments, patients typically require lifelong thyroid hormone supplementation.

In addition, hypothyroidism can result from medications such as lithium (psychiatric), amiodarone (heart), and certain immune treatments for cancer.^xvi

Inflammation

Sometimes, inflammation of the thyroid gland can first cause hyperthyroidism and then, over time, transition to hypothyroidism. This process can occur in females immediately after pregnancy, as part of a condition called postpartum thyroiditis. Females with postpartum thyroiditis have hyperthyroidism for a period of time, after which the thyroid gland “burns out," and the patient develops hypothyroidism. In most cases, these changes are temporary and improve with time or resolve on their own.^xvii

However, there is a high risk for this condition to recur following future pregnancies and these patients are more likely to develop hypothyroidism in the future. Therefore, it is recommended that patients with postpartum thyroiditis have TSH screened annually following their initial recovery.^xviii

Secondary hypothyroidism

It is rare for hypothyroidism to stem from any other part of the body besides the thyroid. However, in less than 1 percent of patients with hypothyroidism, it can be caused by a problem in the part of the brain secreting TSH, the hormone that stimulates thyroid hormone production. In this case, called secondary hypothyroidism, the brain does not produce enough TSH.^xix

What are the symptoms of hypothyroidism?

Only a healthcare provider can provide a definitive diagnosis because symptoms can mimic those of other conditions. Patients with hypothyroidism may present with a variety of concerns:^xx

• Fatigue
• Weight gain despite no change in diet or activity
• Body temperature issues, intolerance to cold
• Constipation
• Muscle aches
• Dry/flaky skin
• Swelling of the legs
• Swelling around the eyes
• Irregular menstrual cycles
• Thinning hair
• Heavy menstrual bleeding

Because many patients have non-specific symptoms, a delayed diagnosis is common.

How is hypothyroidism diagnosed?

If an individual has symptoms of hypothyroidism or has had multiple miscarriages, their doctor may initiate a work-up. In general, hypothyroidism can be diagnosed by a simple blood test measuring the level of thyroid stimulatory hormone (TSH). In patients with primary hypothyroidism, the TSH value is typically high because the thyroid is not producing enough thyroid hormone; therefore, the brain secretes more TSH to encourage the thyroid to ramp up production.^xxi

When a blood test discovers elevated TSH, free T4 must be measured. If the free T4 is low, this confirms the diagnosis of overt hypothyroidism. If the free T4 is normal, this indicates subclinical hypothyroidism.

What hypothyroidism treatments exist and how successful are they?

Hypothyroidism is quite treatable, though not curable. Treatment involves supplementation with the thyroid hormone levothyroxine (e.g., Synthroid (R), Levothroid (R), or Tirosint (R)). After being treated with levothyroxine, 15 percent of patients do not achieve normal T3 and T4 despite TSH being in a normal range, and sometimes different dosages or formulations of medication are required. About 5 percent of patients have persistent symptoms of hypothyroidism despite normalization of thyroid hormone levels with treatment.^xxii

What should my TSH level be if I am trying to conceive or considering assisted reproduction or IVF?

Patients diagnosed with overt hypothyroidism should have their physician test the dose of their thyroid hormone supplementation to ensure that their TSH lab values return to the normal reference range. Reaching this range often requires increasing or decreasing the amount of medication being used, which is true for all non-pregnant patients, including individuals who are trying to conceive.

For pregnant females, the normal TSH level is lower than in non-pregnant patients. The reason is that pregnancy hormone (hCG) can bind TSH receptors and lead to lower TSH levels while maintaining a normal level of thyroid hormone. Therefore, the ideal TSH reference range decreases when someone is pregnant.

For females with subclinical hypothyroidism who are trying to conceive, there is evidence that a TSH level above 4.0 mIU/L with a normal free T4 is associated with increased risk of miscarriage in infertile and non-infertile patients. Further, TSH values greater than 4.0 mIU/L have been associated with decreased pregnancy rates after embryo transfer among infertile patients. Therefore, females with subclinical hypothyroidism defined as a TSH greater than 4.0 mIU/L should be treated when trying to conceive.^xxiii

A more controversial topic is how to manage a TSH level between 2.5 to 4.0 mIU/L in females trying to conceive. There is insufficient evidence that a TSH level in this range is associated with infertility or miscarriage. However, some doctors recommend treating this group of patients, especially if infertile, because 2.5mIU/L is often used as the upper limit of normal in the first trimester. On the other hand, TSH is expected to decrease in most females as hCG rises in pregnancy, so a TSH above 2.5 mIU/L prior to conception may naturally fall below this threshold once a pregnancy is achieved.^xxiv

The American Society for Reproductive Medicine (ASRM) states that, due to the limited data for pre-conception TSH levels in the 2.5 to 4.0 mIU/L range, reasonable management options include either monitoring and treating if the level increases above 4.0 mIU/L, or treating the patient to maintain a TSH less than 2.5 mIU/L.^xxv

However, many other endocrinologists, as well as the guidelines from the American Thyroid Association (ATA), do not support this cut-off value of 2.5mIU/L for females trying to conceive. A 2017 review notes that there is not enough evidence to routinely recommend treatment with levothyroxine for TSH levels 2.5 to 4.0 mIU/L.^xxvi

Who should be tested for hypothyroidism?

Often, hypothyroidism develops slowly, and the typical symptoms of a problematic thyroid may not appear until severe hypothyroidism is evident. While anyone with actual symptoms of hypothyroidism should be tested, a physician may also recommend thyroid testing for couples struggling with recurrent pregnancy losses or females who do not ovulate or who have irregular or absent menstrual cycles.^xxvii Even if there is no history of infertility, a doctor may suggest a quick TSH test prior to starting attempts at conception.

In addition, individuals with a family history of thyroid disease should have their TSH levels checked.^xxviii

How does hypothyroidism impact fertility and pregnancy?

There are several ways that hypothyroidism can impact fertility and pregnancy. A female with hypothyroidism may be able to get pregnant and have a healthy pregnancy, but it may require medical intervention (and that intervention may not be successful).

Miscarriage and fetal birth defects

Maternal thyroid hormone is essential to the growth and maturation of the fetal brain because the fetal thyroid does not produce its own thyroid hormone until the 10^th week of pregnancy. If the mother’s thyroid gland does not produce enough thyroid hormone, it can lead to spontaneous miscarriages or fetal birth defects.^xxix

Furthermore, hypothyroidism leads to changes in other hormones — such as estrogen, testosterone, prolactin, luteinizing hormone (LH), and gonadotropin releasing hormone (GnRH) — that support fertility and pregnancy. These hormonal changes may also affect fertility and maintenance of pregnancy.^xxx

Menstruation

Thyroid issues can also affect menstruation. In females with hypothyroidism, 16 percent have light periods or the complete absence of menstruation, while 7 percent have heavy menstrual bleeding.^xxxi

Hypothyroidism in males

As in females, hypothyroidism in males can change the levels of important hormones such as testosterone and prolactin. It may affect testicular function and is also associated with low libido, erectile dysfunction, and delayed ejaculation, which can secondarily affect the ability to conceive.^xxxii

Can IVF drugs cause thyroid problems?

While there is some evidence that fertility treatments can lead to an increase in TSH and asymptomatic (sub-clinical) hypothyroidism, these effects will typically resolve on their own and it is unclear what effect this has on the success of IVF.^xxxiii There may be a small increased risk of thyroid cancer in females treated with clomiphene or progesterone for infertility.^xxxiv

What are the other hypothyroidism risks or complications?

Untreated hypothyroidism can lead to weight gain/obesity, shortness of breath or fatigue on exertion, or muscle weakness.^xxxv A hypothyroid individual could also experience confusion or difficulty with memory, tingling in the extremities, constipation, changes in vision or taste, bleeding, changes in hair and skin, or kidney damage.^xxxvi

Conclusion

Hypothyroidism can take a toll on a female’s overall health and affect her fertility and ability to sustain a pregnancy. Anyone who suspects they are having thyroid issues should talk with their physician to check thyroid levels and determine a treatment course to alleviate both short- and long-term repercussions.