BACKGROUND
Hypothyroidism is common and affects many more women than men. Many symptoms of hypothyroidism are nonspecific and, while most patients note improvement in their symptoms once started on thyroid hormone replacement, most commonly levothyroxine, as many as 10% of hypothyroid patients continue to have symptoms. For example, some hypothyroid patients treated with levothyroxine report persistent cognitive symptoms such as “brain fog” and difficulty concentrating despite normal TSH blood levels. This has led to the discussion of alternative treatment options for hypothyroidism (combination T4/T3 therapy, desiccated thyroid extract).

Similar cognitive symptoms can be seen during menopause. The menopause transition occurs on average at the age of 51, and estrogen levels decrease during this time. The Study of Women’s Health Across the Nation (SWAN) is a longitudinal study tracking health outcomes in women through midlife. This study aimed to investigate whether levothyroxine-treated hypothyroidism is associated with a more significant decline in cognitive function in women during the menopausal transition.

THE FULL ARTICLE TITLE
Ettleson MD et al. The association between hypothyroidism and cognitive function change in women across the menopause transition: the study of women’s health across the nation. Thyroid 2024;34(10):1205-1213; doi: 10.1089/thy.2024.0358. PMID: 39225158.

SUMMARY OF THE STUDY
Data was gathered from the SWAN by following the patients from the beginning and comparing cognitive testing to other patients with similar characteristics (age, race, education level, menopausal status, and other health conditions) except the presence of thyroid disease. Of the 2,033 patients followed, 227 had hypothyroidism treated with levothyroxine, and 1,806 had no thyroid disease. Women with a history of thyroid cancer, other thyroid disease without the use of levothyroxine, or the use of other thyroid hormone replacement such as liothyronine or desiccated thyroid extract were not included in the study.

At several points throughout the 15 years, the women were tested on processing speed, working memory, and episodic memory and were asked to fill out a survey at the end about how well they were able to concentrate.

Although not different enough to be significant, the processing speed and working memory of women taking levothyroxine were better at the initial assessment. Over the entire 15-year time, there was no difference in processing speed, working memory, or episodic memory between the women on levothyroxine and those not on levothyroxine. This finding held true even when they took into consideration abnormal TSH blood levels in both groups. There was also no difference in the ability to concentrate reported between the two groups on the survey conducted at the end.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study suggests that cognitive functioning in hypothyroid women taking levothyroxine during menopause is the same as in women who are not hypothyroid. Interestingly, hypothyroid women taking levothyroxine appeared to be slightly better in the processing speed and working memory of women than those without hypothyroidism, although the differences were not significant. These results also suggest that, despite some persistent symptoms in concentrating, actual cognitive function is normal. Finally, this study suggests that levothyroxine is sufficient for treatment of hypothyroidism and its cognitive symptoms in the menopausal female population. To help sort out causes and treatment of persistent cognitive symptoms in hypothyroid women, future studies might be able to incorporate more ways of testing concentration, documentation of whether the patient has antibodies against his/her thyroid gland, and the differences in patients’ response to levothyroxine medication.

— Pinar Smith, MD

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