Age-specific TSH reference limits and early levothyroxine effects in postmenopausal women with subclinical hypothyroidism: a prospective cohort study in Vietnam

Subclinical hypothyroidism (SCH) in postmenopausal women is challenging to diagnose due to age-related shifts in thyroid-stimulating hormone (TSH) and a lack of population-specific reference limits. Evidence on levothyroxine responsiveness in this group is also limited. This study aimed to establish age-specific TSH reference limits in postmenopausal women and to evaluate the six-month effects of low-dose levothyroxine on thyroid-related quality of life and thyroid function. Age-specific TSH reference limits were derived from 754 euthyroid postmenopausal women. A separate cohort of 27 women with subclinical hypothyroidism was prospectively followed for six months during levothyroxine therapy initiated with conservative dosing and adjusted according to TSH response. Thyroid function and ThyPRO scores were assessed at baseline, 3 months, and 6 months. The 97·5th percentile upper TSH limits were 3.43 mU/L (ages 50–64) and 3.57 mU/L (≥65 years), both lower than values reported in international cohorts. Levothyroxine therapy produced a clinically meaningful 6.5-point improvement in ThyPRO scores. Median TSH decreased from 7.30 mU/L (IQR 5.56–12.21) at baseline to 2.14 mU/L (IQR 1.43–2.92) at 6 months, with modest increases in free thyroxine. Anthropometric and cardiometabolic parameters did not show meaningful changes over the 6-month follow-up. Postmenopausal women in this population exhibited lower age-specific TSH limits than those reported internationally, supporting a ≥ 4.5 mU/L diagnostic threshold for subclinical hypothyroidism. Low-dose levothyroxine improved thyroid-related quality of life without short-term metabolic effects. Not applicable.