Cesarean delivery modifies the association between prenatal exogenous progesterone and cryptorchidism: a case-control...

This study investigated the association between prenatal exogenous progesterone exposure and cryptorchidism, and whether delivery mode modifies this association. We conducted a retrospective case-control study of 610 cryptorchidism cases and 610 controls from pediatric surgical admissions between April 2016 and October 2021. Data on prenatal exogenous progesterone exposure, delivery mode, and relevant covariates were extracted from medical records. Multivariable logistic regression assessed associations and interactions. Prenatal exogenous progesterone exposure was associated with increased odds of cryptorchidism (aOR = 1.85; 95% CI = 1.42-2.40; P < .001). This association was significantly modified by delivery mode (interaction P = .001). In the cesarean delivery subgroup, progesterone exposure was linked to a higher incidence of cryptorchidism (65.6% vs. 41.9%; P < .001) and substantially increased odds (aOR = 3.27; 95% CI = 2.15-4.98; P < .001), whereas the association was attenuated and not statistically significant following vaginal delivery (aOR = 1.28; 95% CI = 0.90-1.81). Within the cesarean subgroup, progesterone-exposed infants also had higher rates of preterm birth (13.8% vs. 7.3%; P = .018) and low birth weight (17.5% vs. 9.9%; P = .014), whereas maternal age was comparable between groups (P = .409).

Our findings support that prenatal exogenous progesterone exposure was associated with increased odds of cryptorchidism, with a stronger association among cesarean deliveries. The higher prevalence of preterm birth and low birth weight in progesterone-exposed cesarean deliveries is consistent with case-mix differences and may reflect them. Clinicians should remain cautious, and further confirmation from prospective studies is warranted.

• Cryptorchidism is common; etiology is multifactorial and incompletely understood. • Perinatal factors (e.g., prematurity, LBW) and endocrine disruption have been implicated.

• Prenatal exogenous progesterone exposure is associated with higher odds of cryptorchidism. • Cesarean delivery modifies this association, resulting in a stronger association in exposed infants.