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Endocrinology

Cite as: Archiv EuroMedica. 2026. 16; 4. DOI 10.35630/2026/16/Iss.4.15

Received 29 May 2026;
Accepted 16 July 2026;
Published 2 August 2026

INOSITOLS AS A MULTIDIMENSIONAL THERAPEUTIC APPROACH TO PCOS/PMOS: EFFECTS ON METABOLIC, HORMONAL, AND REPRODUCTIVE OUTCOMES

Izabela Staszczyk1 email orcid id logo, Magdalena Warchoł1 orcid id logo,
Roksana Hashemi2 orcid id logo, Magdalena Korba3 orcid id logo

1 J. Gromkowski Provincial Specialist Hospital, Wroclaw, Poland
2 Provincial Specialist Hospital, Wroclaw, Poland
3 St. Anne's Hospital in Miechów, Poland

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  izastaszczyk99@gmail.com

ABSTRACT

Background

Polycystic ovary syndrome (PCOS), recently renamed Polyendocrine Metabolic Ovarian Syndrome (PMOS), is one of the most common endocrine disorders affecting women of reproductive age, characterized by metabolic, hormonal, and reproductive disturbances. Current therapies mainly address symptoms and may be associated with adverse effects, highlighting the need for better tolerated treatment strategies. Inositols may represent a promising adjunctive therapeutic approach.

Aims

This narrative review provides an updated overview of the role of myo-inositol (MYO) and D-chiro-inositol (DCI) in the management of PCOS, focusing on metabolic, hormonal, reproductive and safety outcomes, while highlighting the potential relevance of individualized therapeutic approaches.

Methods

A narrative literature review was conducted using the PubMed database. Clinical studies evaluating the effects of MYO and/or DCI in women with PCOS were identified using predefined keyword combinations.

Results

Available evidence suggests that MYO, alone or combined with DCI, may improve metabolic, hormonal, and reproductive outcomes in selected women with PCOS. Benefits include improvements in insulin sensitivity, hormonal profile, menstrual regularity, ovulatory function, and fertility outcomes, together with reductions in HOMA-IR and androgen levels. MYO and DCI were generally well tolerated. However, considerable heterogeneity among studies limits the strength of the available evidence.

Conclusions

MYO, alone or in combination with DCI, may be considered as an adjunctive therapeutic option for selected women with PCOS. Further large-scale randomized controlled trials are required to establish optimal treatment regimens and identify patients most likely to benefit.

Keywords: Polycystic Ovary Syndrome; Inositol; Myo-inositol; D-chiro-inositol; Infertility; Reproductive Techniques, Assisted; Insulin Resistance; Hormones.

INTRODUCTION

Polycystic ovary syndrome (PCOS) has been identified as the most prevalent endocrine disorder among women of reproductive age on a global scale [1].

In May 2026, an international expert consensus established Polyendocrine Metabolic Ovarian Syndrome (PMOS) as a new nomenclature for PCOS to better reflect the complex metabolic, endocrine, and multisystem nature of the disorder and to avoid the potentially misleading reference to ovarian cysts [2]. However, as most of the studies included in this review, as well as current clinical guidelines, continue to use the term PCOS, this terminology is used throughout the present review.

The most common clinical manifestations of PCOS include menstrual irregularities, oligo- or anovulation, infertility, and hyperandrogenism, which may present with hirsutism, acne, and weight gain. The syndrome is characterized by considerable phenotypic heterogeneity, encompassing various combinations of clinical, biochemical, and metabolic features [3]. According to the Rotterdam criteria, PCOS is classified into four phenotypes based on different combinations of hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology [4]. Table 1 summarizes the Rotterdam diagnostic criteria used to classify these four PCOS phenotypes.

Table 1. Diagnostic phenotypes of PCOS according to the Rotterdam criteria [4]

Diagnostic feature Phenotype A Phenotype B Phenotype C Phenotype D
Biochemical/clinical hyperandrogenism Present Present Present Absent
Chronic anovulation Present Present Absent Present
Polycystic ovaries Present Absent Present Present

Despite this classification, considerable differences in clinical presentation and response to treatment remain among individual phenotypes and continue to be the subject of ongoing research [5]. PCOS is associated with an increased risk of developing metabolic and cardiovascular complications, such as insulin resistance, type 2 diabetes, hypertension and heart disease [6]. Insulin resistance is the main mechanism linking PCOS to its metabolic and cardiovascular complications, making the improvement of insulin sensitivity a key element of therapeutic strategies in these patients [7]. Among the available insulin-sensitizing agents, increasing attention has been paid to inositols, particularly myo-inositol (MYO) and D-chiro-inositol (DCI), which play important roles in insulin signaling and ovarian function and have shown beneficial effects on metabolic, hormonal, and reproductive outcomes in women with PCOS [8-12].

Relevance and Novelty

Although several reviews have evaluated the use of MYO and DCI in women with PCOS, new clinical studies published in recent years have substantially expanded the available evidence. These studies provide additional data regarding metabolic, hormonal, reproductive, and assisted reproductive technology (ART) outcomes, as well as the safety and tolerability of inositol supplementation. The novelty of the present review lies in the integration of these recent findings within a single narrative framework. In addition to summarizing the available evidence on MYO and DCI therapy, this review discusses their potential role within current therapeutic strategies for PCOS, highlights the relevance of individualized therapeutic approaches according to the predominant clinical features of the syndrome and identifies areas requiring further research.

AIM

The aim of this narrative review is to summarize current evidence regarding the use of MYO and DCI in women with PCOS, with particular emphasis on metabolic, hormonal, and reproductive outcomes including assisted reproductive technology (ART), as well as their safety and tolerability. In addition, the review discusses the potential role of MYO and DCI within current therapeutic strategies for PCOS and highlights areas requiring further clinical research.

MATERIALS AND METHOD

This article is a narrative review based primarily on publications identified in the PubMed database. The literature search was conducted during manuscript preparation between October 2025 and May 2026, with the final PubMed search performed on 15 May 2026. The search strategy consisted of complementary PubMed searches using combinations of the following terms with Boolean operators (AND/OR): ("Polycystic Ovary Syndrome" OR "PCOS") AND ("Inositol" OR "Myo-inositol" OR "D-chiro-inositol"), combined separately with "Insulin resistance", "Infertility", "Reproductive Techniques, Assisted", and "Hormones".

Publications published between 2016 and 2026 were considered for the main analytical section of the review. This time frame was selected to reflect the most recent evidence regarding the use of inositols in women with PCOS. Earlier publications were included only where necessary to reference original diagnostic criteria or provide essential clinical background.

The initial search yielded 174 records. After removing 105 duplicate records, 69 publications remained for screening. Many of the publications identified during the screening process did not directly evaluate the clinical effects of MYO and/or DCI supplementation in women with PCOS. Therefore, they were not included in the main analytical section of the review.

To provide the necessary clinical background and context, additional PubMed searches were performed to identify publications concerning the pathophysiology, diagnosis, and current management of PCOS, including international clinical guidelines, meta-analyses, and selected review articles.

Inclusion criteria for the main analytical section comprised studies published between 2016 and 2026 evaluating the effects of MYO and/or DCI in women with PCOS. Eligible publications included randomized controlled trials (RCTs), clinical trials, and prospective studies reporting metabolic, hormonal, reproductive, or assisted reproductive technology (ART) outcomes in women with PCOS.

Exclusion criteria for the main analytical section included studies published before 2016, duplicate records, articles unrelated to PCOS or inositol therapy, and studies lacking clinically relevant outcome data. Animal studies were generally excluded from the primary clinical analysis; however, one experimental study using a mouse model of PCOS was included because of its important contribution to understanding the molecular mechanisms and steroidogenic effects of inositols.

Additionally, a recently published global consensus statement in The Lancet on 12 May 2026 regarding the renaming of PCOS to Polyendocrine Metabolic Ovarian Syndrome (PMOS) was included separately from the primary PubMed-based literature search because it became available during the final stage of manuscript preparation. The publication was included due to its significant clinical and nomenclature relevance.

Based on the above selection process, the final review comprised 46 publications.

CURRENT CLINICAL MANAGEMENT OF PCOS

Today, PCOS is viewed as a condition with a multifactorial etiology, in which disorders of the hypothalamic-pituitary-ovarian axis, excess androgens, and insulin resistance play a key role [13]. PCOS is currently diagnosed based on the modified Rotterdam criteria, which require the fulfillment of at least two of three main conditions: ovulatory dysfunction, the presence of hyperandrogenism in either clinical or biochemical form, and the detection of a polycystic ovarian structure on ultrasound examination [14]. The mainstay of PCOS treatment is lifestyle changes, including both dietary modifications and increased physical activity [15]. In patients with PCOS who experience menstrual cycle disorders and symptoms of hyperandrogenism, combined oral contraceptives (COCP) are most commonly used. Systematic reviews indicate that their use helps regulate menstrual cycles and alleviates symptoms associated with excess androgens [16]. At the same time, the literature notes that the long-term impact of COCPs in patients with PCOS is not yet fully understood and requires further studies [17]. Another drug used in the treatment of PCOS is metformin. In clinical practice, it is also used in women with PCOS due to its ability to improve insulin sensitivity. Data from meta-analyses suggest that this drug reduces hepatic glucose production, increases its utilization in peripheral tissues, and activates the AMPK pathway, which has a beneficial effect on the body's energy balance. Consequently, in many patients, especially those who are overweight and insulin-resistant, a reduction in insulin and androgen levels, regularization of menstrual cycles, and improved fertility outcomes are observed [18]. Nevertheless, the clinical response to metformin appears to be heterogeneous, and the most pronounced metabolic benefits are generally observed in women presenting with significant insulin resistance [19]. Infertility in women with PCOS is primarily due to anovulation; therefore, the main goal of therapy in such cases is the pharmacological induction of ovulation [20]. Currently, the first-line agent for ovulation induction in patients with PCOS is the aromatase inhibitor letrozole. In clinical trials, it has demonstrated improvements in ovulation rates, clinical pregnancies, and live births compared to clomiphene citrate, which was previously the primary standard of care [21]. In situations where oral medications used for ovulation induction are ineffective, the next stage of treatment involves more intensive protocols. These include gonadotropins administered via injection. Their mechanism of action involves stimulating the growth of ovarian follicles [22]. In women with PCOS and anovulatory infertility, IVF (with or without Intracytoplasmic Sperm Injection (ICSI)) can be considered as a third-line treatment option if initial ovulation induction therapies are unsuccessful [23]. Currently, MYO is increasingly recognized as a potential therapeutic option for PCOS, particularly in patients with insulin resistance and menstrual irregularities [24]. In clinical practice, MYO may represent an alternative to metformin, particularly in women with poor tolerance to standard antidiabetic medications [25]. PCOS is a heterogeneous syndrome with diverse clinical and metabolic phenotypes, representing a clinical challenge that requires individualized management [26].

RESULTS

The available evidence regarding the use of MYO and DCI in women with PCOS is presented in the following sections, beginning with their mechanisms of action and followed by the available clinical evidence on metabolic, hormonal, reproductive, and safety outcomes.

Mechanisms of Action of MYO and DCI

Inositols play a vital role as structural components of cell membranes, including in the form of phosphatidylinositol, and are involved in hormonal signaling, for example via inositol triphosphate [9]. Of these, MYO and DCI are of the greatest physiological and clinical significance [10]. MYO is the most abundant form in the human body [9]. It increases the expression of aromatase and the FSH receptor, thereby supporting the normal function of granulosa cells [11]. DCI acts via two distinct biological mechanisms. At the metabolic level, it improves insulin signaling, contributing to the normalisation of insulin levels in individuals with insulin resistance. At the cellular level, however, this compound reduces the expression of aromatase, a key enzyme in steroidogenesis responsible for the conversion of androgens to estrogens [12]. Consequently, it increases androgen synthesis in theca cells. Experimental studies have shown that both MYO and DCI are essential for proper insulin signal transduction and other molecular processes. These mechanisms contribute to improved glucose metabolism in the citric acid cycle, particularly in tissues with high glucose requirements, such as the ovaries [11].

Role of Inositols in Metabolic Regulation

Insulin resistance is recognized as a key pathophysiological feature of PCOS and represents an important therapeutic target. Consequently, considerable attention has been focused on the effects of MYO supplementation, either alone or in combination with DCI, on carbohydrate metabolism. Evidence from clinical studies suggests that MYO may improve insulin sensitivity and positively influence metabolic parameters in women with PCOS [27]. The efficacy of MYO in improving metabolic parameters has been confirmed, among others, in clinical trials conducted by Vyas et al., which demonstrated a significant reduction in serum insulin levels, the HOMA-IR index, and body weight, as well as an improvement in the lipid profile [28]. In the context of comparing MYO with standard treatment, studies comparing its efficacy with that of metformin are particularly important. In the study by Gudović et al., MYO demonstrated comparable efficacy to metformin in improving insulin sensitivity. However, the authors emphasized that metformin was more frequently associated with adverse effects, which negatively impacted patients' adherence to therapy, whereas MYO was better tolerated; consequently, the authors suggest the possibility of using MYO as a first-line alternative in selected patients with PCOS [29]. Similar conclusions were presented in the study by Ozay et al., which compared MYO/DCI supplementation (40:1) with metformin. Both groups showed significant improvement in metabolic parameters, while the MYO/DCI group exhibited a more pronounced reduction in asprosin levels, an adipokine associated with insulin resistance, which may indicate an additional mechanism of action for this therapy [30]. When evaluating MYO in a broader therapeutic context, Mishra et al. compared the efficacy of berberine, metformin, and MYO in a randomized trial. All interventions led to significant improvements in anthropometric, metabolic, hormonal, and lipid parameters, with MYO showing a particularly beneficial effect on insulin sensitivity, berberine on the lipid profile and body weight, while metformin affected a broad spectrum of indicators. These results highlight the possibility of individualized therapy selection in PCOS depending on the predominant metabolic disorders and suggest that MYO may be the preferred option in patients with marked insulin resistance [31]. In the context of seeking an optimal supplementation strategy, particular importance is attributed to combined MYO/DCI therapy in a 40:1 ratio, considered physiological. Benelli et al. demonstrated that only the combination of both isomers in this ratio led to a significant improvement in insulin sensitivity compared to placebo, indicating a synergistic effect of both forms of inositol [32]. Similar observations were reported by Pustotin et al., who noted a significant reduction in BMI and the HOMA-IR index following MYO/DCI supplementation in a 40:1 ratio in women with the A phenotype of PCOS. Changes in fasting blood glucose were minor, suggesting that the primary effect of the therapy involves improved insulin sensitivity rather than a direct reduction in serum glucose levels [33].

Effects of Inositol on Hormonal Regulation

Numerous studies indicate that inositol supplementation has a beneficial effect on hormonal balance, particularly in women with PCOS [33–35]. The study by Pustotin et al. mentioned above also demonstrated that the use of a MYO/DCI 40:1 combination in women with the A phenotype of PCOS improved not only the metabolic profile but also the hormonal profile. This resulted in a reduction in total and free testosterone, the free androgen index (FAI) and luteinising hormone (LH), whilst simultaneously increasing the concentrations of SHBG and estradiol. It is worth noting that the concentration of inositol used was lower than in previous studies [33]. Similar findings have also been reported in animal studies. Valeria Fedeli et al. used a mouse model of PCOS induced by continuous light exposure for 10 weeks. After the induction period, both healthy mice and mice with PCOS received supplementation with myo-inositol (MYO) and D-chiro-inositol (DCI) in a 40:1 ratio. The treatment improved impaired ovarian steroidogenesis and reduced PCOS-related symptoms. In addition, the authors observed increased expression of the Cyp19a1 and Fshr genes, which are associated with aromatase activity and the follicle-stimulating hormone receptor, respectively, together with a decrease in excessive androgen production by ovarian thecal cells [36]. The impact of inositol-based therapies on ovarian function has also been explored in combination treatments targeting metabolic pathways. In a pilot study, women with PCOS received MYO (1.75 g/day), DCI (0.25 g/day), and glucomannan (4 g/day) over three months. This intervention was associated with improved menstrual regularity, along with reductions in both antral follicle count and ovarian volume compared to controls [34]. Further scientific reports also point to the benefits of combination therapy with MYO and DCI in a 3,6:1 ratio. A study comparing this combination with combined hormonal contraception in young Indian women with PCOS demonstrated the normalisation of menstrual cycles and an improvement in carbohydrate metabolism parameters, including glucose profile [35]. Similar effects on androgen reduction were observed in the study by Nuria Mendoza et al., in which combined MYO and DCI supplementation was administered to women with PCOS undergoing ICSI treatment [37]. The available clinical trials have examined both the efficacy of MYO as monotherapy [38] and MYO/DCI combination therapy, with the aim of determining the optimal treatment strategy for hormonal disorders in women with PCOS [32]. MYO alone, as monotherapy, has a beneficial effect on the hormonal profile of patients with PCOS, as demonstrated in a study by Minthami Sharon P. et al., where oral administration of MYO at a dose of 1 g twice daily for 6 months was associated with the normalisation of menstrual cycles, a significant reduction in LH levels and a reduction in the LH/FSH ratio, with good tolerability and a low incidence of adverse effects [38]. In contrast, Benelli et al. demonstrated that in young women who were overweight and had PCOS, presenting with ovulatory dysfunction, hyperandrogenism and insulin resistance, a marked clinical improvement was observed only when a combination of MYO and DCI in a 40:1 ratio was used. This therapy reduced concentrations of LH and free testosterone, whilst simultaneously increasing levels of 17-β-estradiol, whereas no comparable changes were observed in the placebo group [32].

The Impact of Inositols on Ovulation, Fertility, and the Effectiveness of Assisted Reproductive Technologies

A mounting body of research suggests that inositols may have a substantial role in restoring ovulation, enhancing fertility, and optimizing outcomes of ART treatments in women diagnosed with PCOS [39–40]. In a 2020 randomized controlled clinical trial involving infertile women diagnosed with PCOS, the efficacy of MYO monotherapy (4 g/day) was compared with combination therapy of metformin (1500 mg/day) combined with MYO (4 g/day). The women were advised to attempt spontaneous conception for a period of three months. In patients who did not achieve pregnancy after this period, three cycles of ovulation induction were subsequently performed. Following a six-month period of observation, the pregnancy rate was found to be 42% in the group that received metformin in combination with MYO, while the rate was 45.5% in the group treated with MYO alone. The live birth rate and the incidence of gestational diabetes were comparable in both groups. However, it is noteworthy that adverse effects were observed with greater frequency in patients undergoing combination therapy [41]. In another study, A. Agrawal et al. posited in their study that women with PCOS undergoing ovulation induction experienced benefits from the synergistic effect of the combination of metformin (500 mg) and MYO (600 mg), administered three times daily. The utilization of this combination resulted in a higher live birth rate than metformin alone [42]. Noteworthy are reports indicating that the use of MYO therapy prior to intrauterine insemination (IUI) in patients with PCOS is associated with a higher pregnancy rate compared to IUI alone (18.6% vs. 12.2%). Additionally, MYO therapy has been shown to reduce the duration of ovulation induction and permit the utilization of reduced doses of recombinant FSH. This phenomenon may be attributed to the role of MYO in modulating calcium-dependent signaling pathways, thereby promoting enhanced oocyte maturation [43]. An improvement in oocyte quality was also observed in another study, which demonstrated that supplementation with a higher dose of DCI (150 mg) combined with a fixed dose of 550 mg MYO, administered twice daily, was more effective in improving oocyte quality markers than a regimen containing a lower dose of DCI (13.8 mg) at the same MYO dose and identical administration frequency. The administration of a higher dose of DCI resulted in a significant improvement in cytoplasm quality, plasma membrane elasticity, and the visibility of the injection cone [37]. Furthermore, Rajasekaran et al. demonstrated that in patients diagnosed with PCOS undergoing gonadotropin-releasing hormone (GnRH) antagonist protocols, the administration of MYO supplementation for a period of three months prior to in vitro fertilization (IVF) exhibited a comparable efficacy in reducing the risk of ovarian hyperstimulation syndrome (OHSS) when compared to metformin [44]. The role of MYO in the treatment of women with PCOS is significant; however, a group of patients remains resistant to treatment with this substance. A particular study observed that among patients diagnosed with PCOS who were administered MYO therapy and did not undergo ovulation, there was no notable increase in plasma MYO levels. Oliva et al. concluded in their study that the problem may be inadequate absorption of MYO. In their study, the researchers elected to assess a combination of MYO with alpha-lactalbumin (alpha-LA). Alpha-LA is a milk protein designed to facilitate the passage of MYO molecules through biological barriers. The administration of MYO (2 g) in conjunction with alpha-LA (50 mg) twice daily for a period of three months led to a substantial increase in plasma MYO concentration and the occurrence of ovulation in 86% of patients who were resistant to treatment with MYO alone [45]. As posited by another study, the enhanced absorption of MYO may be a consequence of the favorable impact of alpha-LA on the gut microbiota [46].

Tolerability and Safety

An important aspect of MYO therapy is its safety profile. In a study by Lila Vyas et al., the therapy was well tolerated, and adverse effects were minimal [28]. Similarly, Gudović et al. highlighted the better tolerability of MYO compared to metformin [29]. The good safety and tolerability of MYO as monotherapy align with observations from other studies on MYO/DCI combination therapy, underscoring its potential as a long-term therapeutic strategy [38].

Summary of Key Clinical Studies

The principal clinical studies included in the analytical section of this review are summarized in Table 2, which provides an overview of their design, treatment protocols, and main findings. Overall, the included studies most consistently reported improvements in metabolic and hormonal parameters, with additional beneficial effects observed for reproductive outcomes and a generally favorable tolerability profile.

Table 2. Selected key clinical studies evaluating the effects of MYO and DCI supplementation in women with PCOS

Study Patients Therapy (dose) Duration Comparator Key findings Limitations
Benelli et al., 2016 (RCT) [32] PCOS, obesity (n=46) MYO/DCI (40:1) 550/13.8 mg BID 6 mo Placebo ↓ fasting insulin; ↓ HOMA-IR; ↓ LH; ↓ free testosterone; improved endocrine and metabolic profile Small sample; short follow-up; limited generalizability
Gudović et al., 2024 (RCT) [29] PCOS + IR (n=60) MYO 4 g/day 6 mo Metformin ≈ metformin; ↓ insulin AUC during OGTT; ↑ menstrual regularity; ↓ hyperandrogenism; good tolerability Single centre; small sample
Mishra et al., 2022 (RCT) [31] PCOS (n=20) MYO 2 g/day 3 mo Metformin/Berberine ↑ insulin sensitivity; ↓ glucose and insulin; ↓ testosterone/FAI; improved lipid profile; ≈ comparators Small sample; short follow-up
Özay et al., 2025 (Randomized comparative study) [30] PCOS (n=30) MYO/DCI (40:1) 550/13.8 mg + α-lactalbumin 14.1 mg + folic acid 200 μg BID. 12–16 wk Metformin ↓ asprosin; improved metabolic parameters Pilot study; short duration
Pustotin et al., 2024 (Prospective open-label study) [33] Phenotype A PCOS (n=34) MYO/DCI (40:1) 2200/55 mg/day 3 mo No control group ↓ BMI; ↓ HOMA-IR; ↓ LH; ↓ testosterone; ↓ FAI; ↑ SHBG Open-label; no control; small sample
Sharon et al., 2024 (Prospective single-arm study) [38] PCOS (n=90) MYO 1 g BID 6 mo No control group ↑ menstrual regularity; ↓ LH; ↓ LH/FSH ratio; ↓ fasting insulin; ↓ HOMA-IR Single arm; no control
Troisi et al., 2019 (Pilot clinical study) [34] PCOS + controls (n=15+15) MYO/DCI (7:1) 1.75 g/0.25 g/day + glucomannan 3 mo Healthy controls ↓ BMI; improved metabolic and ovarian profile; improved glucose/lipid metabolomic profile Pilot; small sample; no RCT
Kachhawa et al., 2021 (Open-label clinical study) [35] Young PCOS (n=70) MYO/DCI (3.6:1) 1100/300 mg/day 6 mo COC ↑ cycle regularity; ↓ cycle length; improved insulin resistance parameters Young population; open-label
Prabhakar et al., 2021 (RCT) [41] Infertile PCOS (n=116) MYO 4 g/day + metformin 1500 mg/day 6 mo MYO ≈ pregnancy/metabolic outcomes; ↓ GI adverse effects with MYO Infertile population only
Agrawal et al., 2019 (RCT) [42] Infertile PCOS (n=120) MYO 1.8 g/day + metformin 1500 mg/day 3 mo (before ovulation induction) Metformin ↑ live birth; ↑ menstrual outcomes Short treatment; infertile population
Mendoza et al., 2020 (RCT (pilot study)) [37] PCOS undergoing ICSI (n=11) MYO/DCI 550/300 mg/day 12 wk Low-dose DCI ↑ oocyte quality; ↑ oocyte morphology; ↑ insulin sensitivity markers Very small sample; pilot
Rajasekaran et al., 2021 (RCT) [44] PCOS undergoing IVF (n=102) MYO 4 g/day 3 mo Metformin ≈ OHSS prevention; improved pregnancy outcomes and embryo quality Single centre
Oliva et al., 2018 (non-randomized clinical study) [45] MYO-resistant PCOS (n=14) MYO 4 g/day + α-lactalbumin 100 mg/day 3 mo MYO ↑ MYO absorption; ↑ ovulation; improved hormonal/metabolic profile Small selected subgroup; non-randomized

Abbreviations: ART – assisted reproductive technology; AUC – area under the curve; BID – twice daily; BMI – body mass index; COC – combined oral contraceptive; DCI – D-chiro-inositol; FAI – free androgen index; FSH – follicle-stimulating hormone; GI – gastrointestinal; HOMA-IR – homeostatic model assessment of insulin resistance; ICSI – intracytoplasmic sperm injection; IR – insulin resistance; IVF – in vitro fertilization; LH – luteinizing hormone; MYO – myo-inositol; OGTT – oral glucose tolerance test; OHSS – ovarian hyperstimulation syndrome; PCOS – polycystic ovary syndrome; RCT – randomized controlled trial; SHBG – sex hormone-binding globulin.

DISCUSSION

The findings of this review highlight considerable heterogeneity across the included studies in terms of dosage regimens, treatment duration, and therapeutic combinations. Most of the analyzed clinical trials applied different doses of MYO, either as monotherapy or in combination with other agents such as DCI, metformin, or additional supplements. This variability reflects the evolving and still non-standardized nature of therapeutic strategies in PCOS management; however, it also limits direct comparability between studies and complicates the development of unified clinical recommendations.

Despite these differences, the available evidence suggests beneficial effects of inositols on metabolic, hormonal, and reproductive outcomes in women with PCOS [28-45].

MYO appears to improve insulin sensitivity and reduce HOMA-IR [28–33], while favorable effects on lipid profile have also been reported in some clinical studies [28,31]. These metabolic improvements are often accompanied by normalization of hormonal parameters, including reductions in androgen concentrations [32,33], improvements in the LH levels and LH/FSH ratio [32,38], and increased SHBG levels [33], ultimately contributing to improved menstrual regularity [35,38].

Importantly, the reproductive benefits of inositol supplementation are also supported by multiple clinical studies. MYO, alone or in combination with DCI, has been associated with improved ovulatory function, oocyte quality, pregnancy outcomes, particularly in women undergoing ovulation induction or ART [37, 41-45].

Additionally, MYO supplementation may reduce the required doses of gonadotropins and lower the risk of OHSS, suggesting a potential role in optimizing fertility treatment protocols; however, these findings are based on a limited number of studies and should be interpreted with caution [43,44].

The clinical significance of inositol supplementation appears to depend on the characteristics of the treated population. The available evidence suggests that the most consistent metabolic benefits are observed in women with insulin resistance, whereas reproductive benefits have primarily been reported in infertile women undergoing ovulation induction or ART. Moreover, the included studies enrolled patients with different PCOS phenotypes, BMI, age, and reproductive goals, which may partly explain the variability of the reported outcomes. Therefore, MYO and DCI should not be considered equally applicable to all women with PCOS, and treatment decisions should be individualized according to the predominant clinical features of the syndrome.

Current evidence supports lifestyle modification as the cornerstone of PCOS management [18,19], while metformin, hormonal contraception, and ovulation induction therapies remain established treatment options depending on the patient's clinical presentation [18–20]. Although several clinical studies have demonstrated comparable efficacy of MYO-based therapy to metformin for selected metabolic and reproductive outcomes [29,30,41], the available evidence is still insufficient to support replacing these therapies with MYO or DCI in routine clinical practice.

Instead, inositols may be considered as adjunctive or alternative therapeutic options in selected patients, particularly in women with insulin resistance, menstrual irregularities, anovulation, or poor tolerance to metformin.

The existence of MYO-resistant patients further supports the need for personalized therapeutic approaches [45], as well as the exploration of strategies aimed at improving bioavailability, such as co-administration with alpha-lactalbumin [45,46].

A key issue emerging from this review is the lack of standardized dosing regimens and optimal MYO:DCI ratios across studies. Although the 40:1 ratio is generally regarded as physiological and has demonstrated beneficial effects in several clinical studies [30,32,33], the currently available evidence does not establish this ratio as the optimal regimen for all PCOS phenotypes or clinical situations. Alternative MYO:DCI ratios have also demonstrated beneficial effects in selected patient populations [35,37], indicating that a "one-size-fits-all" approach may not be appropriate and that further comparative studies are required.

Another important consideration is the safety profile of inositol supplementation. Overall, the available clinical studies reported good tolerability of MYO, with fewer adverse effects than metformin in comparative trials [29,41]. However, evidence regarding long-term safety remains limited, as most studies had relatively short follow-up periods. Similarly, although MYO has been investigated in women planning pregnancy and those undergoing ART, additional high-quality studies are needed to establish its long-term safety and optimal use in these clinical settings.

Taken together, the available evidence suggests that MYO and DCI may represent promising adjunctive therapeutic options in selected women with PCOS. However, their clinical use should be individualized and interpreted in the context of the heterogeneous nature of the syndrome and the currently available evidence. Future research should focus on stratifying patients according to dominant clinical features and tailoring treatment protocols accordingly. Well-designed, large-scale randomized controlled trials are needed to establish optimal dosing strategies for different PCOS phenotypes.

Limitations

The findings of this review should be interpreted in light of several limitations of the currently available evidence. Considerable heterogeneity exists among the included studies with respect to study design, patient populations, MYO and DCI dosages, MYO:DCI ratios, treatment duration, and evaluated clinical outcomes, limiting direct comparisons between studies. Many of the included studies also involved relatively small sample sizes, further limiting the robustness and generalizability of the available evidence. Furthermore, the studies included women with different PCOS phenotypes, metabolic characteristics, and reproductive goals, which may have influenced treatment response and reduced the generalizability of the findings. Evidence regarding the long-term safety of inositol supplementation remains limited, as most clinical trials had relatively short follow-up periods. In addition, although improvements in metabolic, hormonal, and reproductive parameters have been reported, data on clinically important outcomes, particularly live birth rates, remain insufficient. Therefore, further large-scale, well-designed randomized controlled trials using standardized treatment protocols are required.

CONCLUSIONS

MYO, either alone or in combination with DCI, may be considered as a useful adjunctive therapeutic option for selected women with PCOS, particularly those presenting with insulin resistance, menstrual irregularities, anovulation, or poor tolerance to metformin. Current evidence suggests potential benefits with respect to metabolic, hormonal, and reproductive outcomes, while generally demonstrating good tolerability. The considerable heterogeneity among the available studies highlights the need for further large-scale, well-designed randomized controlled trials to establish the optimal MYO and DCI doses, MYO:DCI ratio, treatment duration, long-term safety, and the patient groups most likely to benefit from this therapy.

Finally, the recently proposed PMOS nomenclature reflects the evolving understanding of the syndrome and its multisystem nature.

DISCLOSURE

Author Contributions

Conceptualization: Izabela Staszczyk, Magdalena Warchoł, Roksana Hashemi.

Methodology: Roksana Hashemi, Magdalena Korba.

Investigation and data collection: Magdalena Warchoł, Magdalena Korba.

Formal analysis: Izabela Staszczyk, Magdalena Warchoł, Roksana Hashemi.

Writing – original draft preparation: Izabela Staszczyk, Magdalena Warchoł, Roksana Hashemi, Magdalena Korba.

Writing – review and editing: Roksana Hashemi, Izabela Staszczyk, Magdalena Warchoł, Magdalena Korba.

All authors read and approved the final version of the manuscript and agree to be accountable for all aspects of the work.

Funding

The article did not receive any funding.

Conflict of Interest

The authors declare no conflict of interest.

Use of Artificial Intelligence

The authors used artificial intelligence tools to assist with language editing and structural refinement of the manuscript. All AI-generated content was carefully reviewed and revised by the authors to ensure accuracy and that it did not affect the scientific integrity or substantive content of the work.

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