Hypoxia is common with preterm birth and may lead to long‐term effects on the adult hypothalamic–pituitary–adrenal (HPA) axis that are sexually dimorphic due to neonatal androgens. Although the adult rat adrenal does not express appreciable CYP17 activity, the neonatal rat adrenal may synthesize androgens that could be a critical local factor in the development of adrenal function. We evaluated these phenomena by pretreating the neonatal rats on postnatal days (PD) 1, 6, 13, 20 with flutamide (a nonsteroidal androgen receptor antagonist) at a standard or a high dose (10 mg/kg or 50 mg/kg) compared to vehicle control. One day later, neonatal rats were exposed to acute hypoxia and blood was sampled. We found that (a) in PD2 pups, flutamide augmented corticosterone responses in a sexually dimorphic pattern and without an increase in ACTH, (b) PD7 and PD14 pups had the smallest corticosterone response to hypoxia (c) PD21 pups had an adult‐like corticosterone response to hypoxia that was sexually dimorphic, (d) flutamide attenuated ACTH responses in PD7 hypoxic pups, and (e) high‐dose flutamide suppressed the HPA axis, FSH, and estradiol. Flutamide demonstrated mixed antagonist and agonist effects that changed during the first three weeks of neonatal life. We conclude that the use of flutamide in neonatal rats to evaluate androgen‐induced programming of subsequent adult behavior is not optimal. However, our studies suggest neonatal androgens play a role in regulation of adrenal function that is sexually dimorphic and changes during early development.

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Objective: Small abdominal aortic aneurysm (AAA) surveillance intervals remain controversial and difficult to standardize. Current Society for Vascular Surgery guidelines lack quality evidence. The objective of this study was to examine patients observed in a high-volume noninvasive vascular laboratory, to determine whether current guidelines are fitting in clinical practice, and to attempt to further identify risk factors for growth.Methods: A retrospective analysis was conducted of patients who underwent at least two ultrasound examinations for AAA in the vascular laboratory during 2008 to 2018 with baseline diameter <5.0 cm. Patients' demographics were collected. Groups were created for comparison using size criteria according to Society for Vascular Surgery guidelines. We also compared overall growth rates, specifically rapid growth (rate of at least 1.0 cm/y and size change of at least 0.5 cm), expected growth (any growth <1.0 cm/y and at least 0.5 cm from baseline), and no growth.Results: There were 1581 patients (1232 male, 349 female) identified, with a total of 5945 ultrasound examinations. The median age was 73 years, and mean follow-up was 27.8 months. Baseline AAA size was 3.0 to 3.9 cm in 986 patients and 4.0 to 4.9 cm in 595 patients. The average maximum growth rate was 0.18 cm/y for AAAs 3.0 to 3.9 cm and 0.36 cm/y for AAAs 4.0 to 4.9 cm (P < .001). Patients with AAA 4.0 to 4.9 cm at baseline were more likely to be white, male, and hypertensive and to have chronic kidney disease (P < .05). There were 1078 patients (68.2%) who demonstrated no growth during the time period, with 342 patients (21.6%) demonstrating expected growth and 161 (10.2%) rapid growth. Male sex and baseline AAA 4.0 to 4.9 cm were more likely to demonstrate rapid growth (P ¼ .002) and eventual repair (P < .001). Female sex was associated with less rapid growth (P < .05). Metformin use was more common in the AAA group with no growth (P < .05). Freedom from rapid growth and repair indication at 2 years were significantly lower in patients with baseline AAAs 3.0 to 3.9 cm (P < .001).Conclusions: The low rate of events in small AAAs supports continued surveillance every 3 years for AAAs between 3.0 and 3.9 cm and yearly for 4.0 to 4.9 cm. Female sex may have less rapid growth, and metformin may abrogate aneurysmal growth. A subset of patients exhibit rapid growth of their small AAAs, and further study is required to further classify these patients.