Association of the Salivary Progesterone-to-Estradiol Ratio with Threatened Miscarriage

Objective: To evaluate the association of salivary progesterone and estradiol levels and the progesterone-to-estradiol ratio (P4/E2 ratio) in early pregnancy with threatened miscarriage and pregnancy outcome. Methods: This single-center prospective cohort study was conducted at the Department of Obstetrics and Gynecology, Ankara Atatürk Sanatorium Training and Research Hospital, between 10 January 2025 and 10 January 2026. Primigravid women with a confirmed live intrauterine pregnancy were included. Saliva samples were collected at 6-7 and 8-9 weeks of gestation; in pregnancies remaining viable to 12 weeks, salivary estradiol was also measured at week 12. Progesterone and estradiol levels were measured by immunoassay, and the P4/E2 ratio was calculated. Participants were classified as healthy ongoing pregnancies to 12 weeks (n = 102), threatened miscarriage with viability preserved to 12 weeks after progesterone treatment (n = 63), and miscarriage (n = 29). Group comparisons were performed using the Kruskal-Wallis test, one-way ANOVA, Mann-Whitney U test, and paired-samples t-test, as appropriate. Results: At both 6-7 and 8-9 weeks, progesterone, estradiol, and the P4/E2 ratio differed significantly among groups. Values were highest in uncomplicated ongoing pregnancies, lowest in pregnancies ending in miscarriage, and generally intermediate in progesterone-treated threatened miscarriage with preserved viability. The progesterone-to-estradiol ratio increased significantly from 6-7 to 8-9 weeks in uncomplicated ongoing pregnancies (p = 0.005), whereas no significant longitudinal change was observed in the threatened miscarriage group. Among pregnancies viable at 12 weeks, estradiol levels at week 12 remained significantly lower in women with prior vaginal bleeding (p < 0.001). Conclusions: Salivary progesterone, estradiol, and the progesterone-to-estradiol ratio were significantly associated with early pregnancy outcome in this prospective cohort. These findings suggest that salivary hormonal assessment may provide a non-invasive adjunct for characterizing early hormonal patterns in threatened miscarriage; however, it should not be interpreted as a stand-alone prognostic tool without further validation in larger cohorts.