Can a Transgender Transition Trigger Hypothyroidism?

In this article

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The intersection of transgender health and endocrinology is a complex and evolving field. Among the various health considerations that arise during transgender transition, the potential impact on thyroid function is an area of growing interest and research. A recent study estimated the prevalence of hypothyroidism in the gender-diverse population to be almost 9%. This level is higher than in the general population. This statistic raises an important question: Can gender-affirming hormonal therapy for transgender transition trigger hypothyroidism or Hashimoto’s thyroiditis? Let’s look at the scientific evidence and clinical observations.

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Hypothyroidism is a condition characterized by an underactive thyroid gland, which results in insufficient production of thyroid hormones. Symptoms can include fatigue, weight gain, cold intolerance, depression, and more. The most common cause of hypothyroidism in the United States is Hashimoto’s thyroiditis.

Hashimoto’s thyroiditis is an autoimmune disorder where the immune system mistakenly attacks the thyroid gland. This attack leads to chronic inflammation and an immune response. Over time, thyroid tissue is gradually destroyed, leading to a decrease in thyroid hormone production. This autoimmune condition is more prevalent in women and is often associated with other autoimmune diseases.

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Transgender individuals may undergo various medical interventions to align their physical characteristics with their gender identity. This process can include hormone replacement therapy (HRT), surgeries, and other treatments.

• For transgender women (male to female): HRT typically involves feminizing hormonal treatment with estrogen and testosterone-lowering (anti-androgens) medications.
• For transgender men (female to male): HRT generally involves masculinizing hormonal treatment with testosterone.

These hormonal treatments are designed to induce physical changes that align with the individual’s gender identity, such as breast development in transgender women or facial hair growth in transgender men.

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The hypothalamus-pituitary axis (HPA) is a feedback control system. It connects our central nervous system with the endocrine system. Your hypothalamus, located in your brain, receives information about hormone levels in your body. In response, it signals your pituitary gland, also in your brain, to increase or decrease the release of stimulating hormones.

Stimulating hormones cause their target gland to release more hormones. Types of stimulating hormones include:

• Thyroid-stimulating hormone (TSH) tells your thyroid gland to release thyroid hormone.
• Adrenocorticotropin hormone (ACH) signals your adrenal gland to release steroid hormones (cortisol and androgens).
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) increase production of the sex hormones estrogen and testosterone in the ovaries and testes.

 Most of the time, your hypothalamus-pituitary axis can adjust hormone production to keep hormones balanced and ensure normal thyroid function. But this balance is affected by:

• Certain medications and hormonal treatments, including estrogen and testosterone hormone therapy
• Autoimmune thyroid diseases like Hashimoto’s thyroiditis or Graves’ disease
• Nutritional deficiencies
• Stress

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Sex hormones like estrogen and progesterone influence normal thyroid function by affecting binding globulins. Binding globulins are proteins that bind to specific hormones. Since your body can’t use bound hormones, hormone production usually increases.

High estrogen levels in the body have been shown to increase thyroid-binding globulin (TBG) levels, a protein that binds thyroid hormones in the blood. Thyroxine binding globulin (TBG) then attaches to thyroid hormone. As more thyroid hormone binds to TBG, thyroid hormone levels drop. This triggers the release of TSH. In response, the thyroid gland releases more thyroid hormone.

On the other hand, androgen therapy, such as testosterone, decreases the amount of TBG, increasing the levels of thyroid hormone but with less impact than estrogen. However, it can influence overall metabolism and might affect thyroid hormone metabolism indirectly. The exact mechanisms and effects of testosterone on thyroid function are still under investigation. 

At the same time, another binding protein – sex hormone-binding globulin (SHBG) – binds to testosterone and the estradiol form of estrogen. Once bound, these hormones become inactive. In response, the body makes more sex hormones to make sure your body has enough available.

Thyroid hormone plays a role in how much SHBG your liver makes. As thyroid hormone production increases, your liver produces more SHBG. In fact, taking thyroid hormone replacement medication increases your SHBG levels.

Estrogen is the main hormonal treatment in transgender women. It lowers thyroid levels -- and can increase the risk of developing hypothyroidism.

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Does gender-affirming HRT trigger autoimmune responses that lead to conditions like Hashimoto’s thyroiditis? Estrogen does appear to play a role in autoimmunity, and the incidence of autoimmune disease is significantly higher in women compared to men because estrogen can cause a heightened immune response. In some cases, this increased immune response leads to an increased risk of autoimmune diseases. 

Experts have theorized that the estrogen’s effect on the immune response may also affect transgender women receiving estrogen therapy. However, current research doesn’t support this theory. 

In a study published in late 2023 in the Journal of the Endocrine Society, 2830 trans women and 1854 trans men were studied. All study group participants were taking gender-affirming hormones. Interestingly, this large study found that the risk of developing autoimmune diseases in trans women who used gender-affirming hormones was similar to the risk in cis (cisgender) men. (Cisgender refers to people whose gender identity matches the sex they were assigned at birth.) Trans men had a similar risk as cis women of developing autoimmune diseases. The study findings suggest that gender-affirming hormone therapy does not influence the risk of developing autoimmune diseases.

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Taking estrogen or testosterone can affect TBG concentrations. To account for these changes, in non-transgender women and non-transgender men, the thyroid gland adjusts the production of thyroid hormone and TSH. However, research shows that people receiving gender-affirming therapy may need an increase in their previously prescribed dose of thyroid medication.

During gender-affirming therapy, SHBG levels change based on the treatment. Estrogen therapy causes an increase in SHBG, while testosterone causes a decrease. These changes in SHBG levels may also affect thyroid hormone levels.

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The current body of research indicates a possible connection between HRT and thyroid function, but more comprehensive studies are needed to establish definitive links. More research is needed, including:

• Long-term studies following transgender individuals through their transition and beyond to provide more insights into how HRT affects thyroid function over time.
• Studies investigating the biological mechanisms by which sex hormones influence thyroid function and autoimmunity to help clarify potential causal pathways.
• Research involving diverse populations can help understand how factors like age, genetics, and pre-existing conditions interact with HRT and thyroid health.

For transgender individuals considering or undergoing HRT, awareness and proactive management of thyroid health are crucial. Practical steps include:

• Baseline thyroid function tests: Before starting gender-affirming HRT, it’s advisable to have baseline thyroid function tests. This helps identify any pre-existing thyroid conditions.
• Regular monitoring: Periodic thyroid function tests during HRT can help detect changes early and allow timely intervention and management.
• Symptom awareness: Being aware of the symptoms of hypothyroidism and Hashimoto’s thyroiditis enables individuals to seek medical advice if they notice any changes.
• Collaborative care: Working with healthcare providers knowledgeable about thyroid health ensures comprehensive and tailored care.

Based on recent research, experts recommend that transgender women who have had orchiectomy surgery (removal of the testicles) or who are taking androgen-blocking medications consider using dehydroepiandrosterone (DHEA) supplementation because research shows that it may mitigate the shift towards autoimmunity. 

Finally, experts also counsel that transgender women with autoimmune disorders be aware that their condition may worsen once they start feminizing therapy. Hormone dosing should begin at a low level and be gradually increased, with careful monitoring for any worsening of autoimmune symptoms.

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The relationship between transgender transition, hormone replacement therapy, and thyroid disorders such as hypothyroidism and Hashimoto’s thyroiditis is a complex and multifaceted issue. While there is some evidence suggesting that HRT can influence thyroid function and potentially trigger or exacerbate hypothyroidism, more research is needed to establish clear causal links.

Thyroid testing before and during gender-affirming hormone treatment is an integral part of ensuring thyroid health throughout the process. Frequent monitoring of thyroid levels can be convenient and easy with Paloma’s home Thyroid Test Kit. This test kit accurately measures Thyroid Stimulating Hormone (TSH), Free Thyroxine (Free T4), and Free Triiodothyronine (Free T3). Thyroid Peroxidase Antibodies (TPOAb) are also included in the panel to help identify autoimmune thyroid disease. 

Getting an accurate diagnosis and effective hypothyroidism treatment is also made easy with Paloma’s team of knowledgeable thyroid doctors. Our thyroid-savvy healthcare providers can guide you toward successful treatment options and put you on the path to healthy living.

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