Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 May 21:19:4183-4199.
doi: 10.2147/DDDT.S524718. eCollection 2025.

PCOS and Inositols - Advances and Lessons We are Learning. A Narrative Review

Guglielmo Lentini  1 , Alessandro Querqui  1 , Noemi Monti  1 , Mariano Bizzarri  1
Affiliations
Review

PCOS and Inositols - Advances and Lessons We are Learning. A Narrative Review

Guglielmo Lentini et al. Drug Des Devel Ther. .

Abstract

Introduction: This Expert Opinion covers recent updates in the use of Inositol in polycystic ovary syndrome (PCOS), highlighting the specific effects triggered upon ovarian steroidogenesis.

Areas covered: An impressive body of evidence, obtained from molecular, animal and clinical studies, demonstrated the striking association between PCOS and the metabolism of myo-Inositol (myo-Ins) and its isomer D-Chiro-Inositol (DCI). Early investigations focused primarily on the metabolic consequences of inositol in modulating insulin transduction. However, recent advances disclosed that Inositols trigger direct effects on steroidogenesis. High DCI levels exacerbate androgen synthesis, and downregulate aromatase expression. Myo-Ins modulates insulin effects too, but exerts opposite actions on steroidogenesis, by increasing aromatase and FSH receptor expression. Clinical studies demonstrated myo-Ins efficacy, suggesting that an appropriate ratio in between myo-Ins/DCI (40:1) improves the reproductive function in PCOS women, even in absence of insulin resistance.

Expert opinion: Inositol-based treatments in PCOS are gaining momentum, demonstrating safety and efficacy greater than those obtained with other pharmacological agents. The efficacy depends not only on the modulation of insulin sensitivity but also on the direct, steroidogenic effects upon the ovaries. Adequate adsorption of Inositol is a critical issue, and the association of α-Lactalbumin can significantly overcome this problem. However, if a treatment based on inositol could be equally effective on different phenotypes of PCOS needs a specific assessment.

Keywords: (polycystic ovary syndrome); D-chiro-inositol; PCOS; aromatase; hyperandrogenism; insulin resistance; myo-Inositol.

Plain language summary

Myo-inositol (myo-Ins) and D-chiro-inositol (DCI) are two isomers of inositol playing a key role in insulin signaling throughout the body, mainly through their phosphoglycan derivatives. They act as important regulators of hormone production within the ovaries, modulating steroidogenesis.Molecular and clinical studies showed that myo-Ins enhances FSH and aromatase activity, while DCI stimulates androgenesis in the theca. These isomers seem to have opposite, yet complementary, actions upon ovarian function. In the last decades, inositols have emerged to treat Polycystic Ovary Syndrome (PCOS), one of the most common benign ovarian disorders affecting young, fertile women.Myo-Ins/DCI ratio in the blood averages 40:1, and this parameter has been used as a basis for establishing a pharmacological formula. Treatments based according to this ratio showed to be successful in the management of several symptoms and signs of PCOS. This is particularly evident in obese patients, whereby the low doses of DCI help in counteracting insulin resistance.Further extensive research, both at the molecular and clinical levels, is needed to better understand inositol biology in mammals. In particular, it should be clarified how myo-inositol modulates the nuclear steroidogenic factor-1 (SF-1) and other key enzymes involved in steroid production. This could be done through epigenetic modifications.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The Hypothalamic-Pituitary-Gonadal axis. The HPG is subject to a set of regulatory rules, involving many levels, from the central nervous system to the local factor produced by the ovaries. The integrated network includes also stimulatory/inhibitory cues provided by the environment and the metabolism.
Figure 2
Figure 2
Ovarian steroidogenesis. Steroidogenesis in the ovary encompasses two principal phases. First, LH (in association with insulin (IN) promotes androgens synthesis and androgen receptors (AR) expression, mostly by up-regulating CYP17A1. IGF-1, AMH, and Inhibin-B progressively increase, amplifying LH-induced stimulation, meanwhile blocking CYP19A1 activation. PI3K overexpression/hyperactivation is required. Correspondently, the primordial follicle progresses to reach the small antral stage. This phase is largely gonadotropin-independent. The bifurcation point occurs when, under the increase of FSH (and of its receptor), aromatase becomes activated. Aromatase levels increase and trigger the synthesis of estrogens, quickly followed by a parallel increase in progesterone (P4), and Activin that contributes in enhancing oocyte’s maturation. The follicle progresses until reaching the pre-ovulatory condition. This secondary phase is considered gonadotropin-dependent.
Figure 3
Figure 3
Mio-Inositol effects in the ovarian cell. The picture shows schematically the principal effects related to myo-Inositol treatment. Myo-Ins modulate insulin transduction (mostly through the epimerase-dependent conversion into DCI; participate in CSK remodelling; modulate the ratio between PIP2 and PIP3; antagonize oxidative and inflammatory processes. Overall, those mechanisms contribute in modulating the ovarian steroidogenesis. Myo-Ins up-regulate CYP19A1 and FSHr expression, while inhibiting some androgenic enzymes. AT the opposite, DCI favor androgenesis and downregulates CYP19A1 expression.
See this image and copyright information in PMC

References

    1. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol. 1935;29(2):181–191. doi:10.1016/S0002-9378(15)30642-6 - DOI
    1. Dennett CC, Simon J. The Role of Polycystic Ovary Syndrome in Reproductive and Metabolic Health: overview and Approaches for Treatment. Diabetes Spectr. 2015;28(2):116–120. doi:10.2337/diaspect.28.2.116 - DOI - PMC - PubMed
    1. Coyle C, Campbell RE. Pathological pulses in PCOS. Mol Cell Endocrinol. 2019;498:110561. doi:10.1016/j.mce.2019.110561 - DOI - PubMed
    1. Yu O, Christ JP, Schulze-Rath R, et al. Incidence, prevalence, and trends in polycystic ovary syndrome diagnosis: a United States population-based study from 2006 to 2019. Am J Clin Exp Obstet Gynecol. 2023;229(1):39.e1–39.e12. doi:10.1016/j.ajog.2023.04.010 - DOI - PubMed
    1. Miazgowski T, Martopullo I, Widecka J, Miazgowski B, Brodowska A. National and regional trends in the prevalence of polycystic ovary syndrome since 1990 within Europe: the modeled estimates from the Global Burden of Disease Study 2016. Arch Med Sci. 2021;17(2):343–351. doi:10.5114/aoms.2019.87112 - DOI - PMC - PubMed

LinkOut - more resources