The effect of polycystic ovary syndrome history on neonatal anogenital distance: a prospective study in Turkish population

Abstract

Aim: Embryonic anogenital length depends on fetal sex and testosterone. Children of women with a history of polycystic ovary syndrome (PCOS) who became pregnant may have different anogenital lengths due to hyperandrogenemia. Therefore, the aim of this study was to compare the anogenital lengths of male and female newborns of women with and without a history of PCOS.
Material and Method: The study was designed prospectively. Pregnant women with PCOS and control group who gave birth at term (≥37-42 weeks) between March 2019 and March 2020 in University of Health Sciences, Tepecik Training and Research Hospital, Department of Obstetrics and Gynecology were included in this study.
Results: A total of 119 patients, including 21 mothers with PCOS and female newborns, 35 mothers with female newborns in the control group, 21 mothers with PCOS and male newborns and 42 mothers with male newborns in the control group, were included in this prospective study. Anogenital distance-anus fourchette (AGD-AF) measurement was significantly higher in the female newborns from mother with PCOS than in the female newborns from control group (18.1±2.5 vs. 14.1±1.6, p=0.046). Also, AGD-AF was 20.3±3.5 in the PCOS with hirsutism group and 15.2±1.5 in the PCOS without hirsutism group, and the difference between them was statistically significant (p=0.041).
Conclusion: The anogenital distance may change in female newborns in the presence of maternal PCOS. Considering that AGD reflects fetal testosterone exposure, the findings may reflect increased testosterone exposure in female fetuses of pregnant women with PCOS. The results pave the way for new studies.

Keywords

• Anogenital distance
• polycystic ovary syndrome
• fetus
• newborn
• testosterone

References

1. Sajjad Y. Development of the genital ducts and external genitalia in the early human embryo. J Obstet Gynaecol Res 2010; 36: 929–37.
2. Cunha GR, Liu G, Sinclair A, et al. Androgen-independent events in penile development in humans and animals. Differentiation 2020; 111: 98–114.
3. Salazar-Martinez E, Romano-Riquer P, Yanez-Marquez E, Longnecker MP, Hernandez-Avila M. Anogenital distance in human male and female newborns: a descriptive, cross-sectional study. Environ Health Glob Access Sci Source 2004; 3: 8.
4. Demirtaş A, Pişkin İ. Memelilerde cinsiyet gelişimi ve hormonal kontrolü. Vet Hekimler Derneği Derg 2009; 80: 23–8.
5. Deswal R, Narwal V, Dang A, Pundir CS. The prevalence of polycystic ovary syndrome: a brief systematic review. J Hum Reprod Sci 2020; 13: 261–71.
6. Ndefo UA, Eaton A, Green MR. Polycystic ovary syndrome. Pharm Ther 2013; 38: 336–55.
7. Swan SH, Main KM, Liu F, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 2005; 113: 1056–61.
8. Simsir C, Kuru Pekcan M, Aksoy R, et al. The ratio of anterior anogenital distance to posterior anogenital distance: A novel biomarker for polycystic ovary syndrome. J Chin Med Assoc 2019; 82: 1.

9. Barrett ES, Hoeger KM, Sathyanarayana S, et al. Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure. J Dev Orig Health Dis 2018; 9: 307–14.
10. Glintborg D, Jensen RC, Schmedes AV, et al. Anogenital distance in children born of mothers with polycystic ovary syndrome: the Odense Child Cohort. Hum Reprod 2019; 34: 2061–70.
11. Thankamony A, Pasterski V, Ong KK, Acerini CL, Hughes IA. Anogenital distance as a marker of androgen exposure in humans. Andrology 2016; 4: 616–25.
12. Nelson W, Liu D-Y, Yang Y, Zhong Z-H, Wang Y-X, Ding Y. In utero exposure to persistent and nonpersistent endocrine-disrupting chemicals and anogenital distance. A systematic review of epidemiological studies†. Biol Reprod 2020; 102: 276–91.
13. Barrett ES, Parlett LE, Sathyanarayana S, et al. Prenatal exposure to stressful life events is associated with masculinized anogenital distance (AGD) in female infants. Physiol Behav 2013; 114–115: 14–20.
14. Hotchkiss AK, Lambright CS, Ostby JS, Parks-Saldutti L, Vandenbergh JG, Gray LE Jr. Prenatal testosterone exposure permanently masculinizes anogenital distance, nipple development, and reproductive tract morphology in female sprague-dawley rats. Toxicol Sci 2007; 96: 335–45.
15. McCoy SJ, Shirley BA. Effects of prenatal administration of testosterone and cortisone on the reproductive system of the female rat. Life Sci 1992; 50: 621–8.
16. Fischer MB, Ljubicic ML, Hagen CP, et al. Anogenital distance in healthy ınfants: method-, age- and sex-related reference ranges. J Clin Endocrinol Metab 2020; 105: 2996–3004.
17. Fowler PA, Bhattacharya S, Flannigan S, Drake AJ, O’Shaughnessy PJ. Maternal cigarette smoking and effects on androgen action in male offspring: unexpected effects on second-trimester anogenital distance. J Clin Endocrinol Metab 2011; 96: E1502-1506.
18. Sathyanarayana S, Grady R, Redmon JB, et al. Anogenital distance and penile width measurements in The Infant Development and the Environment Study (TIDES): methods and predictors. J Pediatr Urol 2015; 11: 76.e1–6.
19. Park JY, Lim G, Oh KW, et al. Penile length, digit length, and anogenital distance according to birth weight in newborn male infants. Korean J Urol 2015; 56: 248–53.
20. Thankamony A, Ong KK, Dunger DB, Acerini CL, Hughes IA. Anogenital distance from birth to 2 years: a population study. Environ Health Perspect 2009; 117: 1786–90.