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Background: Subclinical hypothyroidism (SH) is more frequent in females than males, with a female to male ratio ranging from 1.5 to 5 in the general population. The aim of this study was to evaluate for the first time the association of reproductive factors, particularly age at menarche, with SH risk. Materials and methods: In a cross-sectional study, reproductive factors such as age at menarche, at menopause and at first birth, lactation, parity, full-term pregnancies, reproductive years, use of oral contraceptives and hormonal replacement therapy, somatometric data and insulin resistance parameters were recorded in 72 consecutive female patients with SH and 72 healthy female controls matched on age (±5 years) and date of diagnosis (±1 month). Results: SH cases exhibited significantly younger age at menarche than controls (12.6 ± 1.2 vs. 13.3 ± 0.8 years, respectively, p < 0.001). Cases presented later age at first pregnancy with a lower number of full-term pregnancies (p = 0.04). Early age at menarche was independently associated with SH risk, above and beyond thyroid autoimmunity, body mass index (BMI), hip circumference (HC), homeostatic model assessment of insulin resistance and alcohol consumption [odds ratio (OR): 0.22, 95% confidence interval (CI): 0.11–0.44; p < 0.001]. Conclusions: It is possible that an interplay of early exposure to estrogens, as expressed by early menarche, and induction of thyroid autoimmunity may be associated with SH risk. More prospective studies shedding light on the role of estrogens in SH are required to confirm these findings. [ABSTRACT FROM AUTHOR]