Subclinical Hypothyroidism Is Associated with Lower Ovarian Reserve in Women Aged 35 Years or Older

Background: Overt thyroid diseases have been identified as risk factors for female infertility. However, it remains largely unclear whether subclinical hypothyroidism (SCH), a very common thyroid disorder, is associated with female infertility. This study aimed to investigate the potential association between SCH and the ovarian reserve in women seeking infertility treatment. Methods: This retrospective study included 2568 women with normal thyroid function (n = 2279) or SCH (n = 289) who visited our clinic for infertility treatment. Ovarian reserve markers, including follicle-stimulating hormone (FSH) concentrations on days 2-4, the antral follicle count (AFC), and anti-Müllerian hormone (AMH) concentration, were compared between euthyroid women and those with SCH. Multiple linear and Poisson regression analyses were used to estimate the associations of SCH with ovarian reserve markers. These analyses were repeated separately in women aged <35 (n = 1349) and ≥35 years (n = 1219). Results: In the total study population, women with SCH had significantly lower AMH concentrations (median: 2.05 vs. 2.51 ng/mL, p = 0.015) and AFCs (median: 10.0 vs. 11.0, p = 0.013), compared with euthyroid women. In linear and Poisson regression analyses, SCH was significantly associated with a higher basal FSH concentration (mean difference = 1.13 mIU/mL [95% confidence interval (CI) 0.97 to 1.29 mIU/mL], p < 0.001), lower AMH concentration (mean difference = -0.27 ng/mL [CI -0.43 to -0.12 ng/mL], p = 0.001), and lower AFC (mean difference = -0.7 [CI -1.3 to -0.2], p = 0.005). In women aged ≥35 years, SCH was significantly associated with FSH (mean difference = 1.74 mIU/mL, p < 0.001) and AMH concentrations (mean difference = -0.40 mg/mL, p < 0.001) and AFC (mean difference = -0.8, p < 0.001). In women <35 years old, SCH was significantly associated with a higher FSH concentration (mean difference = 0.30 mIU/mL, p < 0.001), but not with AMH or AFC concentrations (p = 0.84 and 0.06, respectively). Thyroperoxidase antibody (TPOAb) positivity was not associated with measures of ovarian reserve. Conclusions: The data suggest that SCH is associated with decreased ovarian reserve during later reproductive age. TPOAb positivity was not associated with ovarian reserve. Future research is necessary to investigate the underlying molecular mechanisms regulating the diminished ovarian reserve in women with SCH and to evaluate whether levothyroxine supplementation may improve the ovarian function of women with SCH.