Reflections on inositol(s) for PCOS therapy: steps toward success
Abstract
In polycystic ovary syndrome (PCOS) pathogenesis, both the insulin resistance and the related compensatory hyperinsulinemia are involved. Despite their similarities, Myo-inositol (MI) and d-chiro-inositol (DCI) play different roles in PCOS etiology and therapy. Indeed, in tissue such as the liver both molecules are involved in the insulin signaling, i.e. MI promotes glucose uptake and DCI glycogen synthesis. In reproductive tissue such as the ovary, MI regulates glucose uptake and follicle stimulating hormone (FSH) signaling, whereas DCI is devoted to the insulin-mediated androgen production. The new hypothesis on "DCI paradox" in the ovary has provided the key for a better understanding. Unlike other tissues, ovary is not insulin resistant, indeed because the epimerase enzyme, which converts MI to DCI, is insulin dependent, the "DCI paradox" hypothesis suggests that in the ovary of PCOS women, an increased epimerase activity leads to a DCI overproduction and MI depletion. This imbalance could be the cause of the poor oocyte quality and the impairment in the FSH signaling. Owing to this situation, the focal point is the administration of both MI and DCI in a proper ratio for treating PCOS. This topic, with several other "hot" issues, was the driving thread in the discussion between the two scientists.
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DCI stimulates glycogen production and facilitates additional uptake of glucose through mobilization of glucose transporter type 4 transporters.
“which stimulates glycogen production and facilitates additional uptake of glucose through mobilization of glucose transporter type 4 transporters (11).”
From Inositol for Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis to Inform the 2023 Update of the International Evidence-based PCOS Guidelines (2024) · cites this paper as [11]
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“Insulin stimulates unidirectional conversion of MI to D-chiro-inositol (DCI) (10), which stimulates glycogen production and facilitates additional uptake of glucose through mobilization of glucose transporter type 4 transporters (11).”
BackgroundPharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS
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- Authors
- Nestler, J. E., & Unfer, V.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Nestler, John E.
- ORCID
- Unfer, Vittorio
- Venue
- Gynecological Endocrinology
- Publisher
- Informa UK Limited
- Published
- 2015-07-03
- Volume
- 31
- Issue
- 7
- Pages
- 501-505
- ISSN
- 0951-3590 (ISSN-L)
- 1473-0766
- OpenAlex
- W2201373703
- Cited by
- 106
- References
- 37
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 14 · 2022: 10 · 2021: 16 · 2020: 20 · 2019: 7 · 2018: 10 · 2017: 5 · 2016: 11
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecological Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- polycystic ovary syndrome, myo-inositol, D-chiro-inositol, insulin resistance, hyperinsulinemia, insulin signaling, epimerase, androgen production, oocyte quality, insulin-sensitizing therapy
- MeSH terms
- Female, Humans, Inositol, Polycystic Ovary Syndrome
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