Anogenital distance

Anogenital distance (AGD) is the distance from the midpoint of the anus to the genitalia, the underside of the vagina, the clitoris or the scrotum. It is considered medically significant for a number of reasons, in both humans and other animals, including sex determination and as a marker of endocrine disruptor exposure.[1] It is regulated by dihydrotestosterone, which can be disrupted by phthalates common in plastics.

Anogenital distance of human female and male

The anogenital index (AGI) is an index used to compare the AGD relative to a model based on body weight.[2] It is computed as the AGD divided by weight [AGI = AGD/weight (mm/kg)].[3]

Measurement

The AGD is usually measured as follows: from the center of the anus to the posterior convergence of the fourchette (where the vestibule begins) in females (AGD-AF); and from the center of the anus to the junction of the smooth perineal skin with the rugate skin of the scrotum in males (AGD-AS).[4] An alternative measurement, AGD-AC, defined only in females, is measured from the anus to the clitoris.[5]

In humans

Early studies showed that the human perineum was half as long in females as in males, but it has since been found to be three quarters the male distance in females,[6] although males have more variance. Measuring the anogenital distance in neonatal humans has been suggested as a noninvasive method to determine male feminisation and female virilization and thereby predict neonatal and adult reproductive disorders.[7]

A study by Swan et al. determined that the AGD is linked to fertility in males, and penis size.[3] Males with a short AGD (lower than the median around 52 mm (2 in)) have seven times the chance of being sub-fertile as those with a longer AGD. It is linked to both semen volume and sperm count.[8] A lower than median AGD also increases the likelihood of undescended testes, and lowered sperm counts and testicular tumors in adulthood. Babies with high total exposure to phthalates were ninety times more likely to have a short AGD, despite not every type of the nine phthalates tested being correlated with shorter AGD.[3]

Swan et al. report that the levels of phthalates associated with significant AGD reductions are found in approximately one-quarter of Americans tested by the Centers for Disease Control and Prevention (CDC) for phthalate body burdens.[3]

Women who had high levels of phthalates in their urine during pregnancy gave birth to sons who were ten times more likely to have shorter than expected AGDs.[9]

A 2018 study by Barrett et al. found that infant girls born to women with polycystic ovary syndrome (PCOS) had longer AGD, suggesting higher fetal testosterone exposure, than girls born to women without PCOS.[10]

Conditions

Hypospadias and cryptorchidism are conditions which may be induced in males with short AGD.[11][12] Other problems in males include risk of testicular dysgenesis syndrome.[2]

In other animals

There have been extensive studies of AGD effects on animals. In some animals it is routinely measured to determine health.

Experiments have demonstrated that in rodent studies this distance is shortened when the mother is exposed to chemicals that are anti-androgenic, such as dibutyl phthalate (DBP) or benzyl butyl phthalate (BBzP).

Bisphenol A in certain doses increases the AGD of both genders of a study on mice.[13]

In 2017, Gobikrushanth et al. studied the relationship between AGD (the distance from the center of the anus to the base of the vagina and the clitoris) and fertility in Canadian Holstein cows. They found that in first and second parity cows an increase in AGD has an inverse correlation with pregnancy success after first artificial insemination. This correlation was not found in third+ parity cows.[14]

See also

References
  1. Mammadov, E; Uncu, M; Dalkan, C (1 March 2018). "High Prenatal Exposure to Bisphenol A Reduces Anogenital Distance in Healthy Male Newborns". Journal of Clinical Research in Pediatric Endocrinology. 10 (1): 25–29. doi:10.4274/jcrpe.4817. PMC 5838369. PMID 28825590.
  2. Hood, Ernie (October 2005). "Are EDCs Blurring Issues of Gender?". Environmental Health Perspectives. 113 (10): A670–A677. doi:10.1289/ehp.113-a670. PMC 1281309. PMID 16203228.
  3. Swan, Shanna H.; et al. (August 2005). "Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure". Environmental Health Perspectives. 113 (8): 1056–1061. doi:10.1289/ehp.8100. PMC 1280349. PMID 16079079.
  4. Salazar-Martinez, Eduardo; Romano-Riquer, Patricia; Yanez-Marquez, Edith; Longnecker, Matthew P.; Hernandez-Avila, Mauricio (2004-09-13). "Anogenital distance in human male and female newborns: a descriptive, cross-sectional study". Environmental Health. 3 (1): 8. doi:10.1186/1476-069X-3-8. ISSN 1476-069X. PMC 521084. PMID 15363098.
  5. Crestani, A; Arfi, A; Ploteau, S; Breban, M; Boudy, A-S; Bendifallah, S; Ferrier, C; Darai, E (2020-06-06). "Anogenital distance in adult women is a strong marker of endometriosis: results of a prospective study with laparoscopic and histological findings". Human Reproduction Open. 2020 (3): hoaa023. doi:10.1093/hropen/hoaa023. ISSN 2399-3529. PMC 7275635. PMID 32529050.
  6. McEwen, GN; Renner, G (January 2006). "Validity of anogenital distance as a marker of in utero phthalate exposure". Environmental Health Perspectives. 114 (1): A19–20. doi:10.1289/ehp.114-a19b. PMC 1332693. PMID 16393642.
  7. Welsh, Michelle; et al. (13 March 2008). "Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism". Journal of Clinical Investigation. 118 (4): 1479–1490. doi:10.1172/JCI34241. PMC 2267017. PMID 18340380.
  8. Zabarenko, Deborah (4 April 2011). "Key genital measurement linked to male fertility". Reuters. Retrieved 2011-08-24.
  9. Swan SH, Sathyanarayana S, Barrett ES, Janssen S, Liu F, Nguyen RH, Redmon JB, TIDES Study Team (April 2015). "First trimester phthalate exposure and anogenital distance in newborns". Human Reproduction. 30 (4): 963–972. doi:10.1093/humrep/deu363. PMC 4359397. PMID 25697839.
  10. Barrett, E. S.; Hoeger, K. M.; Sathyanarayana, S.; Abbott, D. H.; Redmon, J. B.; Nguyen, R. H. N.; Swan, S. H. (January 2018). "Anogenital distance in newborn daughters of women with polycystic ovary syndrome indicates fetal testosterone exposure". Journal of Developmental Origins of Health and Disease. 9 (3): 307–314. doi:10.1017/S2040174417001118. ISSN 2040-1744. PMC 5997496. PMID 29310733.
  11. Hsieh MH, Breyer BN, Eisenberg ML, Baskin LS (March 2008). "Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption". Current Urology Reports. 9 (2): 137–142. doi:10.1007/s11934-008-0025-0. PMID 18419998. S2CID 11807854.
  12. Jain VG, Singal AK (September 2013). "Shorter anogenital distance correlates with undescended testis: a detailed genital anthropometric analysis in human newborns". Human Reproduction. 28 (9): 2343–9. doi:10.1093/humrep/det286. PMID 23838161.
  13. Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe H, Iguchi T (2002). "Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction". Reproductive Toxicology. 16 (2): 117–22. doi:10.1016/S0890-6238(02)00006-0. PMID 11955942.
  14. Gobikrushanth M, Bruinje TC, Colazo MG, Butler ST, Ambrose DJ (2017). "Characterization of anogenital distance and its relationship to fertility in lactating Holstein cows". Journal of Dairy Science. 100 (12): 9815–9823. doi:10.3168/jds.2017-13033. hdl:11019/1690. PMID 28941819.
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