How Testosterone Therapy Can Protect You From Autoimmunity

Testosterone and thyroid hormones have a bidirectional relationship — each influences the production and function of the other through shared hormonal pathways governed by the hypothalamus. Thyroid hormone is required for optimal testosterone production — hypothyroidism is associated with reduced testosterone output because thyroid hormone supports the Leydig cell function in the testes that produces testosterone, and it regulates sex hormone-binding globulin (SHBG) levels that determine how much testosterone is biologically available. In the other direction, testosterone influences thyroid hormone metabolism and may have a protective effect on thyroid tissue, particularly against the autoimmune attack that underlies Hashimoto’s thyroiditis. Because both the hypothalamic-pituitary-thyroid axis and the hypothalamic-pituitary-gonadal axis are regulated by the same master structure, dysfunction in one consistently produces downstream effects in the other.

Research suggests that testosterone may have a protective effect against autoimmune thyroiditis — the underlying mechanism in Hashimoto’s disease, the most common autoimmune condition in women. The proposed mechanism involves testosterone’s immunomodulatory properties: testosterone suppresses Th1-mediated immune responses, which are the dominant pattern in autoimmune thyroid disease. Th1 immune activation drives the production of thyroid antibodies (TPO and thyroglobulin antibodies) that progressively destroy thyroid tissue in Hashimoto’s. By dampening this Th1 response, testosterone may reduce the intensity of the autoimmune attack on the thyroid. Studies examining testosterone therapy in transgender men have observed changes in thyroid size and function consistent with a protective or modulatory effect, though research in this area is still developing and findings are not yet definitive enough to recommend testosterone therapy as an autoimmune thyroid treatment

Autoimmune thyroiditis — most commonly Hashimoto’s thyroiditis — is a condition in which the immune system produces antibodies that attack the thyroid gland, causing progressive inflammation and destruction of thyroid tissue and leading to hypothyroidism. It is the most common autoimmune disease and the most common cause of hypothyroidism in developed countries. Women are seven to ten times more likely than men to develop Hashimoto’s — a disparity driven largely by sex hormone differences. Estrogen tends to upregulate immune activity and promote Th1 and Th2 immune responses, making the immune system more reactive and more prone to mounting attacks on the body’s own tissues. Testosterone, by contrast, has immune-dampening effects that suppress autoimmune reactivity. The dramatically higher rates of autoimmune disease in women compared to men reflect this fundamental hormonal influence on immune regulation.

Hypothyroidism reduces testosterone availability through two distinct mechanisms. First, thyroid hormone is required for the normal function of Leydig cells in the testes, which are responsible for producing testosterone. When thyroid hormone is insufficient, Leydig cell activity declines and testosterone production falls. Second, hypothyroidism alters sex hormone-binding globulin (SHBG) levels — the protein that binds testosterone in the bloodstream and renders it biologically inactive. Low thyroid function lowers SHBG, which sounds beneficial but actually disrupts the normal balance between bound and free testosterone, contributing to irregular testosterone metabolism. The combined effect of reduced production and altered binding means that men and women with untreated hypothyroidism frequently experience symptoms of testosterone insufficiency — including fatigue, reduced libido, mood changes, and reduced muscle strength — even when their total testosterone readings appear normal.

Research in transgender men receiving exogenous testosterone has found that testosterone administration is associated with increases in thyroid gland volume. The proposed explanation relates to the metabolic demands of a testosterone-dominant hormonal environment — male metabolism is generally more active than female metabolism, requiring greater thyroid hormone output to sustain. As testosterone shifts the metabolic rate upward, the thyroid gland adapts by increasing its mass to produce more thyroid hormone to meet this elevated demand. This finding illustrates the deep interconnection between sex hormone levels and thyroid function — the thyroid is not operating independently but is continuously calibrating its output in response to the overall hormonal environment, particularly the sex hormone signals that the hypothalamus is also regulating.