Inositol, PCOS/PMOS and ovulation: What does the evidence tell us?

Inositol, PCOS/PMOS and Ovulation: What Does the Evidence Tell Us?

Ovulation depends on a carefully coordinated relationship between metabolic and reproductive signalling. For many women this occurs quietly in the background each month, but in polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome (PCOS), parts of this relationship can become disrupted.

Insulin is one of the metabolic signals woven into this ovulatory sequence.

When the body's tissues become less responsive to insulin, the pancreas does not simply stop trying to maintain glucose regulation. Instead, it can respond by producing more insulin. This compensation means that blood glucose may remain within the expected range, while considerably more insulin is required to keep it there. Insulin resistance and this accompanying rise in circulating insulin, known as compensatory hyperinsulinaemia, are common in PMOS, although they are not present to the same degree in every woman with the condition (Zhao et al., 2023).

And those higher insulin concentrations do not remain confined to glucose metabolism.

The ovary is responsive to insulin too. Higher circulating insulin can act alongside reproductive hormones to encourage androgen production by the ovarian theca cells (the cells within the developing follicle that produce androgen precursors). At the same time, hyperinsulinaemia can reduce the liver's production of sex hormone-binding globulin, leaving a greater proportion of circulating androgens biologically available. For a woman already susceptible to androgen excess, this facilitates a change in the hormonal environment in which follicles are trying to grow and mature. Follicular development can become disrupted, the selection and maturation of a dominant follicle may not proceed normally, and the carefully coordinated sequence leading towards ovulation can become less predictable (Zhao et al., 2023).

It is within this relationship between metabolic signalling and ovarian function that inositol has attracted increasing interest.

Inositol is involved in cellular signalling, including pathways that participate in insulin action. This has led to its use in PMOS with the hope that improving aspects of insulin signalling may extend beyond glucose and insulin metabolism to the hormonal environment surrounding follicular development and ovulation (Fitz et al., 2024).

The biological rationale is certainly interesting. But it also raises a more clinically useful question. If insulin resistance and hyperinsulinaemia are not present to the same degree in every woman with PMOS, would we expect an intervention targeting these pathways to have the same effect in everyone?

That question becomes particularly important when we begin looking at the different PMOS phenotypes, and at what the inositol studies actually show.

PCOS/PMOS does not look the same in every woman

One of the difficulties with talking about PMOS as a single condition is just how differently it can present.

Under the Rotterdam criteria, diagnosis has traditionally involved the presence of at least two of three features: ovulatory dysfunction, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology, once other relevant causes have been excluded. Different combinations of these features may give rise to four different phenotypes, although these phenotype classifications are not necessarily used routinely in every clinical setting (Teede et al., 2023).

What this means in practice is that two women can meet the diagnostic criteria for the same condition while experiencing quite different symptoms and reproductive presentations. One may have irregular or absent ovulation alongside clear biochemical or clinical signs of androgen excess. Another may experience ovulatory dysfunction and polycystic ovarian morphology without the same degree of hyperandrogenism. Others may continue to ovulate relatively regularly despite having other features of the condition.

And the differences do not end with the reproductive presentation.

The metabolic environment sitting underneath PMOS can vary considerably as well. Insulin resistance can occur across different presentations and is not confined to women living in larger bodies. Higher body weight and central adiposity can, however, contribute additional metabolic pressure through their relationship with insulin resistance and compensatory hyperinsulinaemia. So a woman may have quite marked hyperinsulinaemia alongside disrupted ovulation, while another woman with the same diagnosis may experience irregular or absent ovulation without the same degree of metabolic dysfunction (Zhao et al., 2023).

It is here that the rationale for inositol becomes more complicated.

If improving insulin signalling is one of the proposed pathways through which inositol might influence ovarian function, it would seem reasonable to wonder whether the women with the greatest degree of insulin resistance or hyperinsulinaemia might also be the women most likely to respond.

The research has not given us such a neat answer.

Tienforti et al. (2026) explored this question by examining whether metabolic phenotype influenced biochemical responses to inositol supplementation in women with PMOS. Interestingly, the more consistent improvements in biochemical hyperandrogenism were observed among women with a BMI below 25 kg/m², while the presence of insulin resistance did not identify a subgroup with a consistently significant response. These were exploratory subgroup findings rather than evidence that women with a lower BMI respond better to inositol, and the authors highlighted the need for trials specifically designed to determine whether metabolic phenotype influences clinically meaningful outcomes such as ovulation (Tienforti et al., 2026).

And this is where we need to be careful about what we ask of the evidence. A change in insulin, HOMA-IR or circulating androgens can tell us something useful about what may be happening metabolically. It does not yet tell us whether a woman is ovulating more regularly, whether conception occurs sooner, or whether the likelihood of a successful pregnancy has changed.

Where do body weight and metabolic change fit into the reproductive story?

Total body weight adds another layer to this discussion because body weight, metabolic health and ovulatory function can intersect in PCOS/PMOS without being interchangeable.

For women with PCOS/PMOS who are living with overweight or obesity, weight reduction may be accompanied by improvements in insulin sensitivity, menstrual function and ovulation. Yet when dietary intake and physical activity change, body weight is rarely the only thing changing. Glucose regulation, insulin sensitivity, dietary quality, physical fitness and other metabolic parameters can shift alongside it. The number on the scales therefore captures only one part of a much broader physiological change (Teede et al., 2023).

There are some encouraging signals when we follow these changes through to pregnancy. Fernandes et al. (2025) examined 37 randomised controlled trials involving 2,061 women with PCOS/PMOS and a BMI of 25 kg/m² or above. In the trial that specifically examined pregnancy as a primary outcome, pregnancy rates were higher following the lifestyle intervention, at 23.3–26.7%, compared with 16.7% with standard care. Four of another five studies that recorded pregnancy as an additional outcome also reported higher pregnancy rates in the intervention groups. However, the overall evidence remained limited, and a clear improvement in time to conception or live birth was not established (Fernandes et al., 2025).

This is useful context when we return to inositol. If an intervention improves insulin sensitivity, androgen concentrations or another metabolic marker, that change may still be clinically valuable. If menstrual regularity or ovulatory function subsequently improves, we have another potentially meaningful reproductive change. What we cannot assume is that an improvement at one point will inevitably continue through every reproductive outcome that follows.

This distinction becomes particularly important when we move into assisted reproduction. During IVF, there are even more points along the reproductive journey that can be measured, from ovarian stimulation and oocyte retrieval through to embryo development, pregnancy and live birth.

What about inositol during IVF?

If the desired end result of improving ovulation is pregnancy and ultimately live birth, then it makes sense to follow the evidence beyond changes in menstrual regularity and ovulatory function.

IVF gives us an interesting opportunity to do this because there are many more points along the reproductive journey that can be measured. We can look at the amount of gonadotrophin medication required during ovarian stimulation, the number and maturity of oocytes retrieved, fertilisation, embryo development, clinical pregnancy and, eventually, live birth.

There are some encouraging signals for the use of inositol within this setting. Myo-inositol also has a generally favourable safety and tolerability profile and, in the United States, is recognised as Generally Recognized as Safe (GRAS) for specified food uses, including use as a nutrient supplement (Wdowiak et al., 2025).

A 2025 position statement reviewing the clinical use of myo-inositol before IVF found potential benefits across several stages of treatment, including reduced gonadotrophin requirements and possible improvements in oocyte and embryo quality, fertilisation and clinical pregnancy. The studies it reviewed commonly provided myo-inositol for around two to three months before ovarian stimulation, although treatment duration varied between studies. The expert group recommended considering myo-inositol as a pretreatment strategy before ovarian stimulation, while also recognising that the available studies were often small and sometimes combined myo-inositol with folic acid, metformin or other interventions (Wdowiak et al., 2025).

More recent pooled evidence specifically in women with PCOS/PMOS is encouraging too. Akbari Sene et al. (2025) included 17 intervention studies and found that myo-inositol/D-chiro-inositol supplementation was associated with a higher clinical pregnancy rate (RR 1.64, 95% CI 1.25–2.15) and a modestly higher proportion of top-grade embryos (RR 1.12, 95% CI 1.02–1.23). The variation between studies was relatively low for clinical pregnancy, although considerably greater for some of the other outcomes measured.

This gives us a more encouraging picture than looking at ovulation alone. There are signals that inositol may influence several stages of assisted reproduction and, importantly, newer pooled evidence suggests that some of these benefits may extend as far as clinical pregnancy. What remains less certain is whether those improvements consistently continue through to live birth

Does the type or ratio of inositol matter?

Myo-inositol (MI) and D-chiro-inositol (DCI) are both naturally present in the human body and participate in insulin signalling, although they have somewhat different physiological roles. Their relative concentrations also vary between tissues rather than existing in one fixed ratio throughout the body. This physiology has led to considerable interest in whether supplementing the two forms together, and in a particular ratio, might offer additional benefit in PCOS/PMOS (Fitz et al., 2024).

The 40:1 MI:DCI ratio has received particular attention and is now commonly found in commercial formulations. There is some biological rationale behind exploring this relationship, and studies using 40:1 have reported encouraging metabolic, hormonal and menstrual outcomes (Lete et al., 2024; Pustotina et al., 2024).

But 40:1 is not the only formulation in which benefits have been observed. Trials of MI alone have reported improvements in some metabolic and hormonal measures, while DCI alone has also demonstrated benefits for some metabolic outcomes and possible benefit for ovulation. When MI and DCI combinations have been compared directly with MI alone, the evidence has not consistently demonstrated that the combination produces superior outcomes. In the systematic review by Fitz et al. (2024), these comparisons were generally based on small studies and the certainty of the evidence was very low.

Even the evidence comparing different MI:DCI ratios remains quite limited. Fitz et al. (2024) identified only two trials directly comparing different ratios. One small study reported some favourable outcomes with 40:1, including menstrual regularity, but the overall certainty of this evidence was again considered very low.

This is also an area where critical appraisal becomes particularly important. Some of the literature examining specific inositol formulations and ratios has involved commercial funding or potential conflicts of interest. This does not mean that positive findings should be dismissed, but they should be considered alongside study size and design, independent replication and the wider evidence base.

For now, the physiological rationale behind 40:1 remains interesting, but the weight of evidence simply does not establish that this particular ratio is superior. The international guideline reflects this uncertainty and does not currently recommend a specific type, dose or combination of inositol because there is insufficient quality evidence to determine that one approach is superior (Teede et al., 2023; Fitz et al., 2024).

So, what does the evidence tell us about inositol, ovulation and PCOS/PMOS?

When we bring the different pieces of evidence together, there is reasonable weight behind considering inositol as part of the nutritional management of PCOS/PMOS. Its involvement in insulin signalling provides a plausible physiological pathway, particularly where insulin resistance and compensatory hyperinsulinaemia are contributing to the metabolic and hormonal environment surrounding ovarian function. Clinical research has also reported improvements across a number of metabolic and hormonal outcomes, including insulin-related measures and biochemical markers of hyperandrogenism, alongside encouraging findings for menstrual regulation and aspects of reproductive function (Fitz et al., 2024; Tienforti et al., 2026; Wdowiak et al., 2025).

There are encouraging signals for ovulation too. Individual trials have reported improvements in ovulatory function, while the systematic review by Fitz et al. (2024) identified potential benefit for ovulation within parts of the evidence base. At the same time, the overall evidence has not yet reached the level of certainty needed to suggest that inositol will be appropriate for every woman with PCOS/PMOS experiencing altered or absent ovulation. This caution largely reflects the quality of the research available: many studies have been small, some have important risks of bias, interventions and comparators have varied, and relatively few trials have provided sufficiently precise estimates for outcomes such as ovulation, pregnancy and live birth (Fitz et al., 2024; Teede et al., 2023).

There are further encouraging signals as we follow the evidence along the reproductive journey. During assisted reproduction, inositol has been associated with improvements in several intermediate outcomes, while newer pooled evidence in women with PCOS/PMOS found a higher clinical pregnancy rate and a greater proportion of high-quality embryos following MI/DCI supplementation (Akbari Sene et al., 2025). This is important because achieving pregnancy is ultimately one of the outcomes we hope improvements in ovulatory and ovarian function will help support.

Inositol also has a generally favourable safety and tolerability profile, adding to the interest surrounding its use within nutrition and reproductive care (Wdowiak et al., 2025). Questions remain around the optimal formulation, dose and ratio, but there is now a body of evidence extending beyond biochemical rationale alone. We have measurable metabolic and hormonal effects, encouraging signals for ovulatory function and emerging evidence around clinically meaningful reproductive outcomes (Fitz et al., 2024; Akbari Sene et al., 2025; Wdowiak et al., 2025).

PCOS/PMOS, however, does not present in exactly the same way in every woman. Metabolic phenotype may influence some biochemical responses to inositol, although we are not yet able to reliably predict who will experience the greatest reproductive benefit (Tienforti et al., 2026). Whether insulin resistance or hyperinsulinaemia is present, whether ovulation is occurring, metabolic health, dietary intake, body composition where relevant, other contributors to infertility and whether conception is being attempted naturally or through assisted reproduction all form part of that individual picture.

So perhaps the answer to our original question is not simply whether inositol “works”. The evidence suggests that inositol can have a useful place in PCOS/PMOS care, with the weight of evidence stronger for some outcomes than others. The more useful question is what we are hoping to change for the individual woman in front of us, and whether inositol has an appropriate place within the wider nutritional and fertility strategy being used to help her get there.

For some women, it may. And where supplementation is appropriate, it can sit alongside nutrition, movement, metabolic care and medical fertility treatment as one part of supporting the journey from metabolic and ovarian health towards ovulation, conception and, ultimately, the outcome everyone is working towards: a healthy live birth.

References

Akbari Sene, A., Saeedzarandi, M., Yazdizadeh, M., Ghaffari, S. R., Amjadi, F., Zandieh, Z., & Moradi, Y. (2025). The effect of myo-inositol on assisted reproductive technology outcomes in women with polycystic ovarian syndrome: A systematic review and meta-analysis of randomized clinical trial studies. International Journal of Reproductive BioMedicine, 23(5), 353–376. https://doi.org/10.18502/ijrm.v23i5.19260

Fernandes, A., Gordon, A., & Sweeting, A. (2025). Pre-conception weight loss interventions in women with polycystic ovary syndrome and the effect on perinatal outcomes: A quantitative synthesis of surrogate outcomes. Diabetes, Obesity and Metabolism, 27(12), 7158–7179. https://doi.org/10.1111/dom.70116

Fitz, V., Graca, S., Mahalingaiah, S., Liu, J., Lai, L., Butt, A., Armour, M., Rao, V., Naidoo, D., Maunder, A., Yang, G., Vaddiparthi, V., Witchel, S. F., Pena, A., Spritzer, P. M., Li, R., Tay, C., Mousa, A., Teede, H., & Ee, C. (2024). Inositol for polycystic ovary syndrome: A systematic review and meta-analysis to inform the 2023 update of the international evidence-based PCOS guidelines. The Journal of Clinical Endocrinology & Metabolism, 109(6), 1630–1655. https://doi.org/10.1210/clinem/dgad762

Lete, I., Martínez, A., Lasaga, I., Centurión, E., & Vesga, A. (2024). Update on the combination of myo-inositol/D-chiro-inositol for the treatment of polycystic ovary syndrome. Gynecological Endocrinology, 40(1), 2301554. https://doi.org/10.1080/09513590.2023.2301554

Pustotina, O., Myers, S. H., Unfer, V., & Rasulova, I. (2024). The effects of myo-inositol and D-chiro-inositol in a ratio 40:1 on hormonal and metabolic profile in women with polycystic ovary syndrome classified as phenotype A by the Rotterdam criteria and EMS-type 1 by the EGOI criteria. Gynecologic and Obstetric Investigation, 89(2), 131–139. https://doi.org/10.1159/000536163

Teede, H. J., Tay, C. T., Laven, J., Dokras, A., Moran, L. J., Piltonen, T. T., Costello, M. F., Boivin, J., Redman, L. M., Boyle, J. A., Norman, R. J., Mousa, A., & Joham, A. E. (2023). Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertility and Sterility, 120(4), 767–793. https://doi.org/10.1016/j.fertnstert.2023.07.025

Tienforti, D., Puocci, G., Venditti, C., Gizzi, V., Pisanò, C., Cocci, E., Perfetto, E., D'Alessandro, F., Spagnolo, L., Baroni, M. G., & Barbonetti, A. (2026). Metabolic phenotype predicts biochemical response to inositol supplementation in polycystic ovary syndrome: A systematic review and meta-analysis. Clinical Endocrinology, 105(2), 237–244. https://doi.org/10.1111/cen.70140

Wdowiak, A., Bakalczuk, S., Filip, M., Laganà, A. S., & Unfer, V. (2025). The clinical use of myo-inositol in IVF-ET: A position statement from the Experts Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), the Polish Society of Andrology, and the International Scientific Association for the Support and Development of Medical Technologies. Journal of Clinical Medicine, 14(2), 558. https://doi.org/10.3390/jcm14020558

Zhao, H., Zhang, J., Cheng, X., Nie, X., & He, B. (2023). Insulin resistance in polycystic ovary syndrome across various tissues: An updated review of pathogenesis, evaluation, and treatment. Journal of Ovarian Research, 16, 9. https://doi.org/10.1186/s13048-022-01091-0

Last reviewed: 23/09/2026