The association between high levels of luteinizing hormone and proliferative retinopathy of prematurity in female preterm infants

BACKGROUND Luteinizing hormone (LH) and human chorionic gonadotropin (hCG), generally considered reproductive hormones, have potent proangiogenic properties. Both of these hormones and their joint receptor (CG/LH receptor) are found in the human eye. We hypothesized that an excess of these hormones is associated with proliferative retinopathy of prematurity (P-ROP). METHODS Dried blood spots (DBS) were used to perform a cross-sectional study of infants (gestational age of <26 weeks) with and without P-ROP, born in Michigan between August 1, 2012, and March 15, 2015. The DBS were collected at 1 week and 4 weeks of age from 45 preterm infants (27 no-ROP and 18 P-ROP). The DBS were linked to hospital records and then deidentified. ICD-9 codes were used to identify P-ROP cases. Hormones levels were measured via electrochemiluminescence assays on the Meso Scale Discovery platform. Associations between hormone levels at 1 and 4 weeks of age and the presence or absence of P-ROP were assessed. RESULTS In female infants, we noted a trend toward higher LH levels in ROP cases at week 1 (P = 0.11) and significantly higher LH levels in cases at week 4 (P = 0.03). In male infants, no ROP-related differences in LH levels were found at either time point. For hCG levels, no associations with P-ROP were found in either sex at either time point. CONCLUSIONS The association of high LH with P-ROP in female but not male infants raises the possibility that there are sex-specific hormonal determinants of aberrant retinal angiogenesis.