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Cited by 152Ovarian function and disordersSexual Differentiation and DisordersReproductive Biology and Fertility

Is foetal hyperexposure to androgens a cause of PCOS?

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Filippou, Panagiota, Homburg, Roy·2017·Human Reproduction Update
DOI 10.1093/humupd/dmx013
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Abstract

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive-aged women. The pathophysiology of this syndrome is still not completely understood but recent evidence suggests that the intra-uterine environment may be a key factor in the pathogenesis of PCOS, in particular, hyperexposure of the foetus to androgens. High concentrations of maternal serum testosterone during pregnancy have been shown to influence behaviour during childhood, the prevalence of autism disorders and anti-Mullerian hormone (AMH) concentrations in adolescence. They are also thought to re-programme the female reproductive axis to induce the features of PCOS in later life: oligo/anovulation, polycystic ovaries, hyperandrogenism and insulin resistance (IR). Support for this developmental theory for the aetiology of PCOS is gathering momentum, following results from first animal studies and now human data, which lend credence to many aspects of this hypothesis. OBJECTIVE AND RATIONALE: In this review the recent available evidence is presented to support the hypothesis that hyperandrogenic changes in the intra-uterine environment could play a major part in the aetiological basis of PCOS. SEARCH METHODS: An extensive PubMED and MEDline database search was conducted. Relevant studies were identified using a combination of search terms: 'polycystic ovary syndrome', 'PCOS', 'aetiology', 'anti-Mullerian hormone', 'AMH', 'pathogenesis', 'kisspeptin', 'hyperandrogenism', 'insulin resistance', 'metabolic factors', 'placenta', 'developmental hypothesis', 'genetic and epigenetic origins'. OUTCOMES: A total of 82 studies were finally included in this review. There is robust evidence that a hyperandrogenic intra-uterine environment 'programmes' the genes concerned with ovarian steroidogenesis, insulin metabolism, gonadotrophin secretion and ovarian follicle development resulting in the development of PCOS in adult life. WIDER IMPLICATIONS: Once the evidence supporting this hypothesis has been expanded by additional studies, the door would be open to find innovative treatments and preventative measures for this very prevalent condition. Such measures could considerably ease the human and economic burden that PCOS creates.

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  • Elevated prenatal testosterone is a well-established cause of PCOS.

    “Whereas elevated prenatal testosterone is a well‐established cause of PCOS (Abbott et al., 2019; Filippou & Homburg, 2017), understanding endometriosis as a developmental disorder involving reduced prenatal testosterone exposure is a novel contribution with diverse clinical, research, and theoretical implications.”

    From Endometriosis and polycystic ovary syndrome are diametric disorders (2021) · cites this paper as Filippou & Homburg, 2017

    The Conclusion says high prenatal androgen exposure may predispose to PCOS and cites rhesus-monkey studies as the strongest evidence for that theory. But it also says the origin of PCOS remains unclear, so the source does not support calling elevated prenatal testosterone a well-established cause in humans. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Fetal exposure to high levels of testosterone during an early, critical window of embryological development biases the HPG axis toward increased testosterone production that continues throughout postnatal life.

    “Fetal exposure to high levels of testosterone during an early, critical window of embryological development biases the HPG axis toward increased testosterone production that continues throughout postnatal life (Abbott et al., 2002, 2019; Filippou & Homburg, 2017; Walters et al., 2018).”

    From Endometriosis and polycystic ovary syndrome are diametric disorders (2021) · cites this paper as Filippou & Homburg, 2017

    The ‘Prenatal exposure to androgens’ section (page unavailable) proposes that fetal testosterone exposure can affect GnRH pulsatility and ovarian steroid production, and reports elevated LH after puberty in prenatally exposed monkeys. It also suggests a critical window of susceptibility, but does not establish that early exposure programs the HPG axis to produce more testosterone continuously throughout postnatal life. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Women with PCOS have significantly longer AGDs than unaffected controls.

    “Women with PCOS have significantly longer AGDs than unaffected controls (Table 1), supporting the hypothesis that PCOS involves elevated prenatal exposure to testosterone (Filippou & Homburg, 2017).”

    From Endometriosis and polycystic ovary syndrome are diametric disorders (2021) · cites this paper as Filippou & Homburg, 2017

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Cited by

Sorted by citations

Authors
Filippou, P., & Homburg, R.
Affiliations
Homerton University Hospital (GB)
ORCID
Homburg, Roy
Venue
Human Reproduction Update
Publisher
Oxford University Press (OUP)
Published
2017-05-20
Volume
23
Issue
4
Pages
421-432
ISSN
  • 1355-4786 (ISSN-L)
  • 1460-2369
DOI
10.1093/humupd/dmx013
OpenAlex
W2615036945
Cited by
152
References
18
Citations by year
2026: 10 · 2025: 7 · 2024: 11 · 2023: 25 · 2022: 14 · 2021: 23 · 2020: 24 · 2019: 23 · 2018: 11 · 2017: 3 · 2016: 1
FWCI
2.74
Type
journal article
Language
en
Open access
Locations
  • Human Reproduction Update (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords
polycystic ovary syndrome, developmental origins of health and disease, anti-Müllerian hormone, kisspeptin, insulin resistance, hyperandrogenism, ovarian steroidogenesis, epigenetic programming, placenta, ovarian follicle development
MeSH terms
Androgens, Animals, Female, Humans, Insulin Resistance, Polycystic Ovary Syndrome, Pregnancy, Prenatal Exposure Delayed Effects, Risk, Testosterone, Hyperandrogenism, Maternal Exposure, Anti-Mullerian Hormone

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