This Key Event Relationship is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.
Relationship: 3628
Title
Androgen receptor activation, increased leads to Anogenital distance (AGD), increased
Upstream event
Downstream event
Key Event Relationship Overview
AOPs Referencing Relationship
| AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|---|---|
| Androgen receptor agonism leading to long anogenital distance (AGD) in female offspring | adjacent | High | Low | Johanna Zilliacus (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Sex Applicability
| Sex | Evidence |
|---|---|
| Female | High |
Life Stage Applicability
| Term | Evidence |
|---|---|
| Fetal | High |
Key Event Relationship Description
This KER describes how increased androgen receptor (AR) activation in females during fetal development can lead to an increased AGD. The AR is a member of the steroid hormone receptor family and mediates the biological effects of androgens. Increased AR activation can occur either through AR agonism (i.e., activation of the receptor by a compound) or through elevated levels of endogenous hormones such as testosterone or dihydrotestosterone (DHT) (Dalton & Gao, 2010; Davey & Grossmann, 2016; Luetjens & Weinbauer, 2012; Naamneh Elzenaty et al., 2022; Sutinen et al., 2017).
Anogenital distance (AGD) refers to the distance between the anus and the external genitalia. In both rodents and humans, female AGD is approximately half the length of male AGD (Liu et al., 2014; Salazar-Martinez et al, 2004; Schwartz et al., 2019; Sharpe, 2020; Thankamony at al., 2016; Wise, 2024). This difference is due to androgen-dependent regulation of perineal growth during fetal development in males, whereas in females, the absence of androgens limits this growth (Ipulan at al., 2016; Schwartz at al., 2019; Sharpe, 2020; Welsh at al., 2008).
It should be noted that the upstream Key Event (KE) ‘increase, androgen receptor activation’ (KE-2274) specifically focuses on increased activation of the androgen receptor in vivo, while most methods that can be used to measure AR activity are carried out in vitro. Indirect information about this KE may for example be provided from assays showing in vitro AR agonism, increased in vitro or in vivo testosterone production/levels or increased in vitro or in vivo dihydrotestosterone (DHT) production/levels.
Evidence Collection Strategy
A systematic weight of evidence approach was applied to collect, evaluate, extract and integrate evidence for the KER.
Literature search
First, a scoping literature search was performed in PubMed to identify relevant model substances using the search string: (anogenital distance OR AGD) AND (androgen receptor OR testosterone OR dihydrotestosterone) AND female. This search was performed on January 10, 2025. Additionally, results from a previous literature search conducted for the development of KER 2820 were reviewed (Holmer at., 2024).
Based on these findings, the following model substances were selected for developing the KER: methyl testosterone, testosterone, testosterone propionate and trenbolone.
A targeted literature search was performed on January 28, 2025, in PubMed and Web of Science using the following search strings:
PubMed: ("testosterone propionate"[Title/Abstract] OR "Testosterone Propionate"[MeSH Terms] OR "trenbolone"[Title/Abstract] OR "Trenbolone Acetate"[MeSH Terms] OR "methyl testosterone"[Title/Abstract] OR "Methyltestosterone"[MeSH Terms]) AND ("anogenital distance"[Title/Abstract] OR "AGD"[Title/Abstract])
Web of Science, Core Collection: (("testosterone propionate" OR "trenbolone" OR "methyl testosterone") AND ("anogenital distance*" OR "AGD"))
The retrieved publications were imported into Rayyan (https://www.rayyan.ai), and duplicates were removed, resulting in 40 unique publications. Screening was performed in two stages—titles and abstracts, followed by full-text review—using the following criteria:
Inclusion criteria:
- Primary literature on prenatal exposure to testosterone, testosterone propionate, trenbolone or methyl testosterone in rat or mouse measuring anogenital distance in female offspring as an outcome
- Reviews on anogenital distance
Exclusion criteria:
- Not in English
- Not full text
After screening of titles and abstract 33 publications were retained for full-text review. Of these, 14 original studies and 1 review met the inclusion criteria. Screening of reference lists identified two additional publications.
An additional literature search was conducted on August 16, 2025, in PubMed to identify reviews on AGD using the search string:
("anogenital distance"[Title/Abstract] OR "AGD"[Title/Abstract]) AND (review[Filter] OR systematicreview[Filter]).
This search identified 10 relevant reviews, which were analysed for supplementary evidence.
Data extraction and study quality assessment
Data was extracted from the publications into an Excel template and divided into datasets based on administered doses, exposure timepoint and measurement timepoint.
Study reliability was assessed using the Science in Risk Assessment and Policy (SciRAP) tools for in vivo studies (http://www.scirap.org). The SciRAP criteria, including considerations for each criterion and identification of key criteria, are summarized in Table 1. The SciRAP assessment for each dataset was then translated into a reliability category based on predefined principles (Table 2). The overall confidence in the evidence for each model substance was categorized as strong, moderate, or weak, based on reliability and consistency (Table 3). All data extraction, SciRAP assessments, and categorizations were performed by one reviewer and verified by a second reviewer, with disagreements resolved through discussion.
Evidence Supporting this KER
Biological Plausibility
The biological plausibility for this KER is judged to be high based on the following:
- During the masculinization programming window of fetal development, androgens drive the masculinization process in males, including growth of the perineum, which can be measured as anogenital distance (AGD), the distance between the anus and the genitalia. In female fetuses, lower androgen levels limit this growth, resulting in male AGD being approximately twice as long as female AGD (Liu et al., 2014; Salazar-Martinez et al, 2004; Schwartz at al., 2019; Sharpe, 2020; Thankamony at al., 2016; Welsh at al., 2008; Wise, 2024).
- Studies in androgen receptor (AR) knockout mice demonstrate that AR is essential for a longer AGD, as male AR knockout mice exhibit AGD lengths comparable to female wild-type mice (Yeh et al., 2002, Sato et al., 2004).
- The mechanism underlying androgen regulation of perineal growth likely involves androgen-mediated development of the levator ani and bulbocavernosus (LABC) muscle complex in the perineum. AR knockout in non-myocytic cells of the LABC leads to defective muscle formation and reduced AGD (Ipulan et al., 2016). Furthermore, differential gene expression profiles have been observed in the perineum of male and female rats (Schwartz et al., 2019)
- An association between higher testosterone levels in young women and longer AGD has been reported in a cross-sectional study (Mira-Escolano at al., 2014).
- Epidemiological studies of women with polycystic ovary syndrome (PCOS) indicate that elevated androgen levels are associated with increased AGD. Women with PCOS produce higher androgen levels (Yang & Chen, 2024), and several studies have shown longer AGD in women with PCOS (Pan at al., 2021; Zamani at al., 2023). Evidence regarding AGD in daughters of women with PCOS is mixed: Barrett at al. (2018) reported an association, whereas Glintborg at al. (2019) did not. Additionally, one study found that fetuses of women with PCOS exhibited longer AGD (Perlman et al., 2020).
Empirical Evidence
The empirical evidence for this KER is judged to be high based on the following: .
The empirical evidence is based on four model substances: methyl testosterone, testosterone, testosterone propionate and trenbolone. Evidence for the upstream KE (androgen receptor activation, increased) is derived from in vitro assays assessing AR agonism, as well as in vivo Hershberger assays that measure androgenic effects. Evidence for the downstream KE (Anogenital distance, increased) is based on prenatal in vivo studies measuring AGD. To date, no in vivo studies have measured both KEs within the same experiment.
Evidence for the upstream KE
Methyl testosterone
Methyl testosterone is synthetic androgen previously used as a pharmaceutical. It binds to AR and acts as an AR agonist in vitro (Kleinstreuer et al., 2018; Judson et al., 2020) and show androgen activity in vivo in Hershberger assays (Browne et al., 2018).
Testosterone
Testosterone is an endogenous androgen that binds to AR and acts as an AR agonist.
Testosterone propionate
Testosterone propionate is synthetic androgen formerly used as a pharmaceutical. It binds to AR and acts as an AR agonist in vitro (Kleinstreuer et al., 2018; Judson et al., 2020) and show androgen activity in vivo in Hershberger assays (Browne et al., 2018).
Trenbolone
Trenbolone is synthetic androgen used in veterinary medicine. It binds to AR and acts as an AR agonist in vitro(Kleinstreuer et al., 2018; Judson et al., 2020) and show androgen activity in vivo in Hershberger assays (Browne et al., 2018).
Evidence for the downstream KE
Methyl testosterone
Overall confidence in the data for methyl testosterone is weak. 2 publications including 3 datasets were analysed. Increased AGD in females was observed in all three datasets, but the datasets were classified as not reliable (Table 4).
Testosterone
Overall confidence in the data for testosterone is weak. 3 publications including 16 datasets were analysed. All datasets were classified as not reliable. Increased AGD in females was observed in 12 out of 16 datasets. The conflicting results in four datasets, i.e. no effect on AGD in females, could possibly be explained by that exposure was only during one of the days GD19, 20, 21 or 22, which is at the end of the male programming window GD16-20. Effect was observed in the same study for exposure during GD16, 17 or 18 (Table 4).
Testosterone propionate
Overall confidence in the data for testosterone propionate is moderate. 9 publications including 22 datasets were analysed. Increased AGD in females was observed in eight out of twelve datasets classified as reliable without restriction and in both datasets classified as reliable with restriction. The conflicting results, i.e. no effect on AGD in females, could possibly be explained in three of the datasets (testosterone-propionate-3B, testosterone-propionate-8B and testosterone-propionate-8C) by that AGD was measured at later timepoint (PND24, at puberty, PND75), since an effect was observed in the same studies when AGD was measured at earlier timepoints (PND2, PND1). The conflicting result, i.e. no effect on AGD in females, in the fourth dataset (testosterone-propionate-7) cannot be explained by differences in study design. Increased AGD in females was also observed in seven out of eight datasets classified as non-reliable. The dataset, testosterone-propionate-2B, showed increased AGD but the authors report that it was not significant (Table 4).
Trenbolone
Overall confidence in the data for trenbolone is strong. 2 publications including 2 datasets were analysed. Increased AGD in females was observed in two datasets classified as reliable (Table 4).
Uncertainties and Inconsistencies
For the model substances, there were some inconsistencies in the empirical evidence, but they could mostly be explained by differences in study design.
Known modulating factors
No known modulating factors have been identified for this KER.
| Modulating Factor (MF) | MF Specification | Effect(s) on the KER | Reference(s) |
|---|---|---|---|
Quantitative Understanding of the Linkage
The quantitative understanding of the KER is low. This is a consequence of it not being possible to measure the upstream and the downstream event in the same study.
Response-response Relationship
No specific evidence for response-response relationships has been identified for this KER.
Time-scale
In a prenatal in vivo study, exposure to a substance that acts on the upstream KE (androgen receptor activation) for five to six days during the masculinization window (around GD16-20 in rats) can lead to a measurable effect on the downstream KE (increased anogenital distance) at PND2 (Hotchkiss et al., 2007; Wilson et al., 2002; Wolf et al., 2004).
Known Feedforward/Feedback loops influencing this KER
No specific evidence for feedforward or feedback loops has been identified for this KER.
Domain of Applicability
Taxonomic Applicability
The biologically plausible taxonomic applicability domain is mammals, as fetal masculinization is regulated by androgens across all mammalian species (Welsh, 2014). The empirical taxonomic applicability domain is based on rat, supported by prenatal studies demonstrating that androgen receptor activation leads to a measurable increase in female AGD (Armoskus et al., 2014; Guerra et al., 2014; Hotchkiss et al., 2007; Sathishkumar et al., 2011; Welsh et al., 2009; Wilson et al., 2002; Wolf et al., 2002; Wolf et al., 2004). Additionally, epidemiological studies suggest that elevated androgen levels in women are associated with increased AGD (Mira-Escolano et al., 2014; Pan et al., 2021; Zamani et al., 2023).
Sex applicability
This KER focuses on effects on AGD in females, supported by empirical evidence from prenatal studies in rats (Armoskus et al., 2014; Guerra et al., 2014; Hotchkiss et al., 2007; Sathishkumar et al., 2011; Welsh et al., 2009; Wilson et al., 2002; Wolf et al., 2002; Wolf et al., 2004).
Life Stage Applicability
Growth of AGD in rats is regulated by androgens during the masculinization programming window, which occurs during fetal development around GD16-20 (MacLeod et al., 2010; Welsh et al., 2008).
References
Armoskus, C., Mota, T., Moreira, D., & Tsai, H.-W. (2014). Effects of Prenatal Testosterone Exposure on Sexually Dimorphic Gene Expression in the Neonatal Mouse Cortex and Hippocampus. Journal of Steroids & Hormonal Science, 5(3), 1000139.
Barrett, E. S., Hoeger, K. M., Sathyanarayana, S., Abbott, D. H., Redmon, J. B., Nguyen, R. H. N., & Swan, S. H. (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. https://doi.org/10.1017/S2040174417001118
Browne, P., Kleinstreuer, N. C., Ceger, P., Deisenroth, C., Baker, N., Markey, K., Thomas, R. S., Judson, R. J., & Casey, W. (2018). Development of a curated Hershberger database. Reproductive Toxicology, 81, 259–271. https://doi.org/10.1016/j.reprotox.2018.08.016
Dalton, J. T., & Gao, W. (2010). Androgen Receptor. In C. M. Bunce & M. J. Campbell (Eds), Nuclear Receptors (pp. 143–182). Springer Netherlands. https://doi.org/10.1007/978-90-481-3303-1_6
Davey, R.A., Grossmann, M. (2016). Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin Biochem Rev. Feb;37(1):3-15.
Glintborg, D., Jensen, R. C., Schmedes, A. V., Brandslund, I., Kyhl, H. B., Jensen, T. K., & Andersen, M. S. (2019). Anogenital distance in children born of mothers with polycystic ovary syndrome: The Odense Child Cohort. Human Reproduction, 34(10), 2061–2070. https://doi.org/10.1093/humrep/dez122
Guerra, M., Silva, R., Luchiari, H., Sanabria, M., & Kempinas, W. (2014). Perinatal Androgenic Exposure and Reproductive Health Effects Female Rat Offspring. Journal of Toxicology and Environmental Health-Part A-Current Issues, 77(7), 375–389. https://doi.org/10.1080/15287394.2013.874881
Hotchkiss, A. K., Lambright, C. S., Ostby, J. S., Parks-Saldutti, L., Vandenbergh, J. G., & Gray, L. E. J. (2007). Prenatal testosterone exposure permanently masculinizes anogenital distance, nipple development, and reproductive tract morphology in female Sprague-Dawley rats. Toxicological Sciences : An Official Journal of the Society of Toxicology, 96(2), 335–345. https://doi.org/10.1093/toxsci/kfm002
Ipulan, L. A., Raga, D., Suzuki, K., Murashima, A., Matsumaru, D., Cunha, G., & Yamada, G. (2016). Investigation of sexual dimorphisms through mouse models and hormone/hormone-disruptor treatments. Differentiation; Research in Biological Diversity, 91(4–5), 78–89. https://doi.org/10.1016/j.diff.2015.11.001
Juárez, J., Corsi-Cabrera, M., & del Río-Portilla, I. (1995). Effects of prenatal testosterone treatment on sex differences in the EEG activity of the rat. Brain Research, 694(1–2), 21–28. https://doi.org/10.1016/0006-8993(95)00725-6
Judson, R., Houck, K., Paul Friedman, K., Brown, J., Browne, P., Johnston, P. A., Close, D. A., Mansouri, K., & Kleinstreuer, N. (2020). Selecting a minimal set of androgen receptor assays for screening chemicals. Regulatory Toxicology and Pharmacology, 117, 104764. https://doi.org/10.1016/j.yrtph.2020.104764
Kato, S., Matsumoto, T., Kawano, H., Sato, T., & Takeyama, K. (2004). Function of androgen receptor in gene regulations. The Journal of Steroid Biochemistry and Molecular Biology, 89–90, 627–633. https://doi.org/10.1016/j.jsbmb.2004.03.099
Kawashima, K., Nakaura, S., Nagao, S., Tanaka, S., & Kuwamura, T. (1975). Quantitative evaluation of virilizing activity of steroids by measuring morphological changes in uro-genital region of rats. Endocrinologia Japonica, 22(5), 439–444. https://doi.org/10.1507/endocrj1954.22.439
Kawashima, K., Nakaura, S., Nagao, S., Tanaka, S., Kuwamura, T., & Omori, Y. (1978). Virilizing effect of methyltestosterone on female descendants in the rat. Endocrinologia Japonica, 25(1), 1–6. https://doi.org/10.1507/endocrj1954.25.1
Kleinstreuer, N. C., Browne, P., Chang, X., Judson, R., Casey, W., Ceger, P., Deisenroth, C., Baker, N., Markey, K., & Thomas, R. S. (2018). Evaluation of androgen assay results using a curated Hershberger database. Reproductive Toxicology, 81, 272–280. https://doi.org/10.1016/j.reprotox.2018.08.017
Liu, C., Xu, X., & Huo, X. (2014). Anogenital distance and its application in environmental health research. Environmental Science and Pollution Research International, 21(8), 5457–5464. https://doi.org/10.1007/s11356-014-2570-z
Luetjens, C. M., & Weinbauer, G. F. (2012). Testosterone: Biosynthesis, transport, metabolism and (non-genomic) actions. In E. Nieschlag, H. M. Behre, & S. Nieschlag (Eds), Testosterone (4th edn, pp. 15–32). Cambridge University Press. https://doi.org/10.1017/CBO9781139003353.003
MacLeod, D. J., Sharpe, R. M., Welsh, M., Fisken, M., Scott, H. M., Hutchison, G. R., Drake, A. J., & Van Den Driesche, S. (2010). Androgen action in the masculinization programming window and development of male reproductive organs. International Journal of Andrology, 33(2), 279–287. https://doi.org/10.1111/j.1365-2605.2009.01005.x
McCoy, S. J., & Shirley, B. A. (1992). Effects of prenatal administration of testosterone and cortisone on the reproductive system of the female rat. Life Sciences, 50(9), 621–628. https://doi.org/10.1016/0024-3205(92)90248-n
Mira-Escolano, M., Mendiola, J., Mínguez-Alarcón, L., Roca, M., Cutillas-Tolín, A., López-Espín, J., & Torres-Cantero, A. (2014). Anogenital distance of women in relation to their mother’s gynaecological characteristics before or during pregnancy. Reproductive Biomedicine Online, 28(2), 209–215. https://doi.org/10.1016/j.rbmo.2013.09.026
Naamneh Elzenaty, R., Du Toit, T., & Flück, C. E. (2022). Basics of androgen synthesis and action. Best Practice & Research Clinical Endocrinology & Metabolism, 36(4), 101665. https://doi.org/10.1016/j.beem.2022.101665
Pan, Z., Zhu, F., & Zhou, K. (2021). A Systematic Review of Anogenital Distance and Gynecological Disorders: Endometriosis and Polycystic Ovary Syndrome. Frontiers in Endocrinology, 12, 696879. https://doi.org/10.3389/fendo.2021.696879
Perlman, S., Toledano, Y., Kivilevitch, Z., Halevy, N., Rubin, E., & Gilboa, Y. (2020). Foetal Sonographic Anogenital Distance Is Longer in Polycystic Ovary Syndrome Mothers. Journal of Clinical Medicine, 9(9), 2863. https://doi.org/10.3390/jcm9092863
Rhees, R. W., Kirk, B. A., Sephton, S., & Lephart, E. D. (1997). Effects of Prenatal Testosterone on Sexual Behavior, Reproductive Morphology and LH Secretion in the Female Rat. Developmental Neuroscience, 19(5), 430–437. https://doi.org/10.1159/000111240
Salazar-Martinez, E., Romano-Riquer, P., Yanez-Marquez, E., Longnecker, M. P., & Hernandez-Avila, M. (2004). Anogenital distance in human male and female newborns: A descriptive, cross-sectional study. Environmental Health, 3(1), 8. https://doi.org/10.1186/1476-069X-3-8
Sathishkumar, K., Elkins, R., Chinnathambi, V., Gao, H., Hankins, G., & Yallampalli, C. (2011). Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport. Reproductive Biology and Endocrinology, Aug 3;9:110. https://doi.org/10.1186/1477-7827-9-110
Sato, T., Matsumoto, T., Kawano, H., Watanabe, T., Uematsu, Y., Sekine, K., Fukuda, T., Aihara, K., Krust, A., Yamada, T., Nakamichi, Y., Yamamoto, Y., Nakamura, T., Yoshimura, K., Yoshizawa, T., Metzger, D., Chambon, P., & Kato, S. (2004). Brain masculinization requires androgen receptor function. Proceedings of the National Academy of Sciences, 101(6), 1673–1678. https://doi.org/10.1073/pnas.0305303101
Schwartz, C. L., Christiansen, S., Vinggaard, A. M., Axelstad, M., Hass, U., & Svingen, T. (2019). Anogenital distance as a toxicological or clinical marker for fetal androgen action and risk for reproductive disorders. Archives of Toxicology, 93(2), 253–272. https://doi.org/10.1007/s00204-018-2350-5
Sharpe, R. M. (2020). Androgens and the masculinization programming window: Human-rodent differences. Biochemical Society Transactions, 48(4), 1725–1735. https://doi.org/10.1042/BST20200200
Sutinen, P., Malinen, M., & Palvimo, J. J. (2017). Androgen Receptor. In M. Simoni & I. T. Huhtaniemi (Eds), Endocrinology of the Testis and Male Reproduction (pp. 395–416). Springer International Publishing. https://doi.org/10.1007/978-3-319-44441-3_12
Tehrani, F., Noroozzadeh, M., Zahediasl, S., Piryaei, A., Hashemi, S., & Azizi, F. (2014). The Time of Prenatal Androgen Exposure Affects Development of Polycystic Ovary Syndrome-Like Phenotype in Adulthood in Female Rats. International Journal of Endocrinology and Metabolism, 12(2). https://doi.org/10.5812/ijem.16502
Thankamony, A., Pasterski, V., Ong, K. K., Acerini, C. L., & Hughes, I. A. (2016). Anogenital distance as a marker of androgen exposure in humans. Andrology, 4(4), 616–625. https://doi.org/10.1111/andr.12156
Welsh, M., Saunders, P. T. K., Fisken, M., Scott, H. M., Hutchison, G. R., Smith, L. B., & Sharpe, R. M. (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. https://doi.org/10.1172/JCI34241
Welsh, M., Sharpe, R., Walker, M., Smith, L., & Saunders, P. (2009). New Insights into the Role of Androgens in Wolffian Duct Stabilization in Male and Female Rodents. Endocrinology, 150(5), 2472–2480. https://doi.org/10.1210/en.2008-0529
Welsh, M., Suzuki, H., & Yamada, G. (2014). The Masculinization Programming Window. In O. Hiort & S. F. Ahmed (Eds), Endocrine Development (Vol. 27, pp. 17–27). S. Karger AG. https://doi.org/10.1159/000363609
Wilson, V. S., Lambright, C., Ostby, J., & Gray, L. E. J. (2002). In vitro and in vivo effects of 17beta-trenbolone: A feedlot effluent contaminant. Toxicological Sciences : An Official Journal of the Society of Toxicology, 70(2), 202–211. https://doi.org/10.1093/toxsci/70.2.202
Wise, L. D. (2024). Rodent anogenital distance recommendations. Birth Defects Research, 116(6), e2347. https://doi.org/10.1002/bdr2.2347
Wolf, C. J., Hotchkiss, A., Ostby, J. S., LeBlanc, G. A., & Gray, L. E. J. (2002). Effects of prenatal testosterone propionate on the sexual development of male and female rats: A dose-response study. Toxicological Sciences : An Official Journal of the Society of Toxicology, 65(1), 71–86. https://doi.org/10.1093/toxsci/65.1.71
Wolf, C. J., LeBlanc, G. A., & Gray, L. E. J. (2004). Interactive effects of vinclozolin and testosterone propionate on pregnancy and sexual differentiation of the male and female SD rat. Toxicological Sciences : An Official Journal of the Society of Toxicology, 78(1), 135–143. https://doi.org/10.1093/toxsci/kfh018
Wu, X.-Y., Li, Z.-L., Wu, C.-Y., Liu, Y.-M., Lin, H., Wang, S.-H., & Xiao, W.-F. (2010). Endocrine Traits of Polycystic Ovary Syndrome in Prenatally Androgenized Female Sprague-Dawley Rats. Endocrine Journal, 57(3), 201–209. https://doi.org/10.1507/endocrj.K09E-205
Yang, J., & Chen, C. (2024). Hormonal changes in PCOS. Journal of Endocrinology, 261(1), e230342. https://doi.org/10.1530/JOE-23-0342
Yeh, S., Tsai, M.-Y., Xu, Q., Mu, X.-M., Lardy, H., Huang, K.-E., Lin, H., Yeh, S.-D., Yeh, S., Tsai, M.-Y., Xu, Q., Mu, X.-M., Lardy, H., Huang, K.-E., Lin, H., Yeh, S.-D., Altuwaijri, S., Zhou, X., Xing, L., Boyce, B. F., Hung, M.-C., Zhang, S., Gan, L., & Chang, C. (2002). Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues. Proceedings of the National Academy of Sciences of the United States of America, 99(21), 13498–13503. https://doi.org/10.1073/pnas.212474399
Zamani, P., Hemati, Z., Kelishadi, R., Kolahdozan, S., Dianatinasab, M., & Keikha, M. (2023). Association between anogenital distance as a noninvasive index in the diagnosis and prognosis of reproductive disorder: A systematic review. International Journal of Reproductive Biomedicine, 21(8), 599–618. https://doi.org/10.18502/ijrm.v21i8.14016