Abstract

Background: Progesterone is widely used in obstetric practice to avert preterm labor and miscarriage. Yet, its potential for endocrine disruption during fetal development is an understudied phenomenon. This research aims to analyze the long-term impact of prenatal exposure to progesterone on the endocrine and metabolic systems of female progeny.
Methods: This study employed a retrospective cohort design on 209 female offspring (average age 21.19 ± 2.64 years) whose mothers were on supplemental progesterone during gestation. The study analyzed the data to determine the incidence of features of Polycystic Ovary Syndrome (PCOS), metabolic syndrome, and the outcomes of different management methods. Statistical analyses, including Pearson Chi-square tests and multivariable logistic regression, were employed to identify significant correlations.
Results: Daughters who had prenatal exposure to progesterone during the first trimester had a statistically significant likelihood of having polycystic ovarian (PCO) morphology (p = 0.002). Additionally, the daughters of exposed mothers had a higher incidence of amenorrhea (p = 0.015), hirsutism (p = 0.042), and metabolic syndrome (p = 0.005) than the daughters of unexposed mothers. The daughters of mothers with gestational diabetes comorbidity had metabolic disturbances (p = 0.016). Concerning treatment, the protective effect of inositol therapy, whether with Metformin or by itself, was significant for the development of insulin resistance (p < 0.001). Use of Metformin without inositol therapy was associated with higher baseline metabolic risk.
Conclusion: There is a considerable risk of long-term reproductive and metabolic illnesses, including PCO morphology and metabolic syndrome, associated with prenatal exposure to progesterone. This illuminates the possibility that during pregnancy, the hypothalamic-pituitary-ovarian axis and metabolic circuitry of the fetus are permanently altered. Therefore, the clinical utility of progesterone should be used cautiously, and exposed children should be monitored endocrinologically.