Benefits and Harms of Levothyroxine/L-Triiodothyronine Versus Levothyroxine Monotherapy for Adult Patients with Hypothyroidism: Systematic Review and Meta-Analysis

Combined T4 + T3 therapy versus T4 monotherapy effect on psychological health in hypothyroidism: A systematic review and meta‐analysis

“…Compared with the various uncertainties of the combination therapy, the advantages of T4 monotherapy are obvious: long halflife, low cost, convenient monitoring, T4 conversion outside the thyroid gland to T3 provides continuous T3 production, and the once daily dose is sufficient. 4 However, consistent with the previous study, 6 our results showed that patients preferred the combination therapy. Given the double-blind process applied in the included studies, it is difficult to attribute this phenomenon to the influence of external environment rather than subjective feelings.…”

“…Compared with monotherapy, combination therapy was more commonly preferred by the patients and did not increase the risk of cardiovascular side effects. The results further confirmed the conclusions of previous metaanalyses [6][7][8] and provided sufficient evidence that T4 monotherapy should be viewed as the first choice for patients with overt hypothyroidism. This is because whether the combination therapy has objective advantages remains to be evaluated.…”

“…The clinical trial by Bunevicius et al 15 showed a significant improvement in the psychological health of patients receiving the combination therapy. However, most follow‐up clinical trials and meta‐analyses, 6–8 including the present meta‐analysis, could not replicate this result. The reasons for this difference may be as follows: first, the awareness of a chronic disease requiring lifelong treatment and follow‐up may affect patients' moods 31 .…”

“…4 However, some patients experience hypothyroid symptoms despite having normal TSH levels, and adjusting the dose of LT4 slightly helped in improving psychological health. 4,5 Although most previous studies and metaanalysis [6][7][8] showed disappointing results of the combination therapy in improving psychological health, patients' preference for combination therapy is evident. 9 We speculate that the methodological heterogeneity of included clinical studies in previous meta-analysis may have obscured the subtle advantages of combination therapy.…”

Triiodothyronine alongside levothyroxine in the management of hypothyroidism?

“…Although patients preferred the combination in some studies, this was not explained necessarily by improvements in symptoms related to hypothyroidism, as described above. Recent (2018 50 and 2021 51 ) systematic review/meta-analyses concluded that the addition of T3 to LT4 therapy had little benefit in terms of objective improvements in such outcomes (the more recent review also concluded that LT4 + T3 and LT4 monotherapy were tolerated similarly). However, these trials were conducted in relatively broad populations of patients with hypothyroidism, did not consistently use disease-specific instruments for measuring patientreported outcomes, and therefore cannot exclude a potential benefit in subgroups of patients with hypothyroidism: these issues are discussed in greater detail below.…”