The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome
Abstract
Polycystic ovary syndrome (PCOS) is a common clinical disorder characterized by ovulatory dysfunction and hyperandrogenaemia. A neuroendocrine hallmark of PCOS is persistently rapid LH (GnRH) pulsatility, which favours pituitary synthesis of LH over that of FSH and contributes to the increased LH concentrations and LH : FSH ratios typical of PCOS. Inadequate FSH levels contribute to impaired follicular development, whereas elevated LH levels augment ovarian androgen production. Whereas luteal phase elevations in progesterone normally slow GnRH pulse frequency, women with PCOS do not experience normal progesterone-mediated slowing, due in part to impaired hypothalamic progesterone sensitivity. This reduction in hypothalamic progesterone sensitivity appears to be mediated by elevated androgens because sensitivity can be restored with the androgen receptor blocker flutamide. The ovulatory and hormonal abnormalities associated with PCOS generally present during puberty, typically associated with hyperandrogenaemia. Along with elevated LH concentration and pulsatility, some girls with hyperandrogenaemia have impaired hypothalamic progesterone sensitivity similar to that seen in adult women with PCOS. We propose that peripubertal hyperandrogenaemia may lead to persistently rapid GnRH pulse frequency via impaired hypothalamic feedback inhibition. The subsequent abnormalities in gonadotropin secretion, androgen production and ovulatory function may support progression towards the adult PCOS phenotype.
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Androgen excess disturbs the hypothalamic-pituitary-ovarian axis, hindering cyclic production of estradiol and progesterone, causing oligomenorrhea and ovulatory dysfunction.
“Favoring LH over FSH synthesis in the pituitary gland, this disturbance of the hypothalamic–pituitary–ovarian axis by androgen excess hinders cyclic production of estradiol and progesterone, causing oligomenorrhea and ovulatory dysfunction [197, 240].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [240]
Free T positively correlates with LH and the LH/FSH ratio, independent of BMI.
“Additionally, free T positively correlated with LH as well as the LH/follicle stimulating hormone (FSH)-ratio, independent of BMI.”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [240]
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- Authors
- Blank, S. K., McCartney, C. R., & Marshall, J. C.
- Affiliations
- University of Virginia Health System (US)
- Corresponding author
- Blank, S.K.
- ORCID
- Marshall, J.C.
- Venue
- Human Reproduction Update
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-05-02
- Volume
- 12
- Issue
- 4
- Pages
- 351-361
- ISSN
- 1355-4786 (ISSN-L)
- 1460-2369
- OpenAlex
- W2155530831
- Cited by
- 301
- References
- 14
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 10 · 2023: 17 · 2022: 19 · 2021: 16 · 2020: 15 · 2019: 12 · 2018: 16 · 2017: 12 · 2016: 15 · 2015: 14 · 2014: 15 · 2013: 25 · 2012: 9
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction Update (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Institutes of Health (28934, 5r01hd034179-03, 5k23hd044742-05)
- National Institute of Child Health and Human Development (T32-HD)
- National Center for Research Resources (5 M01 RR00847, M01RR000847)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (1K23 HD 044742, R01 HD 34179, R01HD033039, R01 HD33039, T32HD007382, T32 HD07382, U54HD028934, U54-HD-28934)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- polycystic ovary syndrome, neuroendocrine function, LH pulsatility, GnRH pulsatility, LH/FSH ratio, FSH deficiency, hyperandrogenemia, androgen receptor, flutamide, ovulatory dysfunction, ovarian androgen production, puberty
- MeSH terms
- Adolescent, Androgens, Estrogens, Female, Follicle Stimulating Hormone, Humans, Insulin, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Neurosecretory Systems, Ovulation, Polycystic Ovary Syndrome, Progesterone, Puberty, Reference Values, Hyperandrogenism
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