Understanding Iron Metabolism in PCOS/PMOS and the Role of Lactoferrin

For many women with polycystic ovary syndrome, or PCOS, the condition is first associated with irregular periods, androgen excess, difficulty with ovulation and fertility. But there is much more going on beneath the surface. PCOS can also involve insulin resistance, inflammation and changes in metabolic health, and researchers are increasingly interested in how these different parts of the condition might connect.

 

In 2026, PCOS has also been referred to by the proposed name polyendocrine metabolic ovarian syndrome (PMOS), reflecting this broader understanding of the condition. The terminology is currently transitioning, however, and PCOS remains widely used throughout the medical literature.

 

One reason PCOS can be so difficult to understand is that it does not look the same in everyone. Two women can both have PCOS while experiencing completely different symptoms and metabolic features. This is why researchers are looking beyond hormones alone and exploring what else might be happening in the body, including inflammation, oxidative stress and, increasingly, iron metabolism.

 

This does not mean that PCOS is an iron disorder, or that everyone with PCOS has an iron imbalance. Instead, studies have started to uncover differences in some iron-related markers in people with PCOS. The interesting question is whether these changes are simply another feature of the condition, or whether iron regulation could be connected to some of the hormonal and metabolic changes happening at the same time.

 

Why is iron relevant to PCOS?

 

We tend to think of iron simply as something we need to avoid becoming deficient in, but its role in the body is much more complicated than that. Iron is essential for oxygen transport, energy production, DNA synthesis and countless enzymatic reactions. We need it every day, but the body also has to be very careful about how much free or reactive iron is available.

 

Too little iron can impair normal cellular function, while poorly controlled reactive iron can contribute to the formation of reactive oxygen species. When these molecules build up faster than the body's antioxidant systems can deal with them, oxidative stress can occur.

 

This is why the body has a whole system dedicated to keeping iron in check. Ferritin helps store it, transferrin transports it through the bloodstream, and proteins such as lactoferrin can bind it in different biological environments.

 

Researchers have started to notice that some of these iron-related markers look different in people with PCOS. A recent meta-analysis of 22 studies found that, on average, people with PCOS had higher ferritin, serum iron and transferrin saturation and lower hepcidin than control groups. However, the results varied considerably between studies, particularly for ferritin, serum iron and hepcidin, so these findings do not mean that everyone with PCOS has the same iron profile.

 

There are plenty of reasons why iron markers might differ between individuals. Ferritin, for example, is commonly used as a marker of stored iron, but it can also rise with inflammation, obesity and liver disease. Period patterns matter too. Someone who has infrequent periods may lose less iron over time, whereas prolonged or heavy bleeding can increase the risk of iron deficiency.

 

So the story is not simply that PCOS means having “too much iron” or “too little iron”. It is more interesting than that. Researchers are asking whether the way the body regulates iron may be part of the wider metabolic picture in some people with PCOS.

 

Hepcidin: the body's iron traffic controller

 

One of the most important characters in this story is hepcidin, a hormone produced mainly by the liver. Its job is to help decide how much iron should make its way into the bloodstream.

 

Hepcidin does this by controlling a protein called ferroportin, which moves iron out of intestinal cells and cells involved in storing and recycling iron. When hepcidin binds to ferroportin, ferroportin is removed from the cell surface and less iron is released into circulation. When hepcidin signalling is lower, more ferroportin remains available, potentially allowing more iron into the bloodstream. Think of it as the body's iron traffic controller, helping to decide when the gates should be opened and when they should be closed.

 

Some studies in PCOS have found lower hepcidin, while others have reported no difference or even higher levels. A recent meta-analysis found lower average hepcidin in PCOS, but the differences between the studies were very large. So, while hepcidin is clearly an interesting piece of the puzzle, we cannot yet say that there is one typical hepcidin pattern in PCOS.

 

What researchers are really trying to understand is why these differences occur and what they mean. Could changes in iron regulation contribute to the condition? Could they be a consequence of metabolic changes that are already happening? Or could both be influenced by another underlying process? At the moment, we do not have a definitive answer.

 

When iron meets oxidative stress

 

This brings us to another part of the story: oxidative stress. Our cells naturally produce reactive oxygen species as they go about their everyday work. Normally, the body has antioxidant systems that keep these molecules under control. Problems can arise when their production starts to outweigh the body's ability to manage them.

 

Oxidative stress is already being studied in PCOS because of its potential links with inflammation, insulin resistance and ovarian function. Now researchers are also asking whether iron itself could be involved in some of these processes.

 

One particularly interesting area is ferroptosis, a form of regulated cell death that depends on iron and involves oxidative damage to the fats that make up cell membranes.

 

Early laboratory and animal research has raised questions about whether ferroptosis-related pathways could affect ovarian granulosa cells, the cells that support developing follicles and eggs. This creates an interesting connection between iron regulation, oxidative stress and ovarian biology.

 

But this is still an emerging area of research. We cannot currently say that ferroptosis causes infertility in women with PCOS. Much of the evidence comes from laboratory studies, animal models and specific pregnancy-related research, so these findings are better thought of as clues that are helping scientists decide where to look next.

 

And then there is insulin resistance

 

Insulin resistance is another important part of the PCOS story. It affects many, although not everyone, with PCOS and can influence both metabolic health and ovarian hormone production. When cells become less responsive to insulin, the body may compensate by producing more of it. Higher insulin levels can then contribute to increased ovarian androgen production and problems with ovulation in some women.

 

The interesting thing is that insulin resistance, inflammation, oxidative stress and iron regulation do not necessarily exist in separate little boxes. They can influence one another, creating a much more complicated metabolic environment inside the body.

 

So, where does lactoferrin come in?

 

Lactoferrin is a naturally occurring protein from the transferrin family. It is found in milk and other bodily secretions and is also produced by certain immune cells. It has two characteristics that make it particularly relevant to this conversation: it can bind iron, and it plays a role in the body's innate immune defence.

 

The iron-binding part is especially interesting. Lactoferrin can hold onto iron and influence how much is available in different biological environments. But it is not as simple as saying that lactoferrin “removes iron”. Its role is more about how iron is handled and made available, depending on what is happening around it.

 

Researchers have also been studying lactoferrin in relation to the hepcidin-ferroportin system, inflammation and oxidative stress. This is important because these are all areas that have started to attract attention in PCOS research.

 

Lactoferrin has also been investigated in relation to glucose metabolism and insulin signalling, with experimental findings suggesting that it may influence some of the pathways involved in metabolic regulation. Most of this research has been carried out in laboratory and animal models, so we cannot yet say that taking lactoferrin improves insulin resistance in women with PCOS.

 

Taken together, these findings help explain why lactoferrin is attracting interest in the PCOS space. Lactoferrin is involved in iron handling, innate immune defence and inflammatory signalling, while PCOS research is increasingly exploring the connections between iron, inflammation, oxidative stress and metabolic health. This overlap gives lactoferrin a particularly interesting role to explore as research into PCOS continues.

 

What does this mean for PCOS?

 

 

The research is still developing, but it is painting a more connected picture of PCOS, with growing interest in how iron regulation, oxidative stress, inflammation and metabolic health interact. Lactoferrin is particularly interesting because its roles in iron handling, innate immune defence and inflammatory pathways overlap with several of these areas.

 

Direct clinical research in people with PCOS is still needed before we can say that lactoferrin treats the condition, improves fertility or corrects PCOS-related changes in iron metabolism. However, its biology gives researchers a strong reason to keep exploring its potential role.

 

PCOS is complex, and lactoferrin is unlikely to be a single answer. What makes it interesting is that it sits at the intersection of several systems already being investigated, making it an ingredient worth watching as the science develops.

 

Where Leapfrog Remedies fits in

 

 

This is where DAILY and IMMUNE fit naturally. DAILY provides 100 mg of lactoferrin alongside vitamin C, D3, E, K2 and zinc, making it a broader everyday nutritional formula for anyone who wants to incorporate lactoferrin alongside other key nutrients. IMMUNE provides a higher 250 mg dose of lactoferrin alongside vitamin C and zinc, with a stronger focus on everyday immune defence, reflecting one of lactoferrin's best-established biological roles.

 

For someone interested in lactoferrin specifically, DAILY offers a broader everyday approach, while IMMUNE provides a more focused lactoferrin option alongside nutrients involved in normal immune function. Neither is a treatment for PCOS or PMOS, but lactoferrin's increasingly interesting role in iron handling, immune defence and inflammatory pathways makes it an ingredient worth paying attention to as the science develops.

 

As always, individual iron status is important. Anyone with suspected iron deficiency, raised ferritin, liver disease or possible iron overload should have appropriate medical assessment rather than trying to manage these issues through supplementation alone.

 

Reference list

 

Diamanti-Kandarakis, E. and Dunaif, A. (2012). Insulin resistance and the polycystic ovary syndrome revisited: An update on mechanisms and implications. Endocrine Reviews, 33(6), pp.981–1030. doi:10.1210/er.2011-1034.

 

Du, Y., Li, D., Chen, J., Li, Y.-H., Zhang, Z., Hidayat, K., Wan, Z., Xu, J.-Y. and Qin, L.-Q. (2022). Lactoferrin improves hepatic insulin resistance and pancreatic dysfunction in high-fat diet and streptozotocin-induced diabetic mice. Nutrition Research, 103, pp.47–58. doi:10.1016/j.nutres.2022.03.011.

 

Escobar-Morreale, H.F., Luque-Ramírez, M., Álvarez-Blasco, F. and Alpañés, M. (2011). Role of decreased circulating hepcidin concentrations in the iron excess of women with the polycystic ovary syndrome. The Journal of Clinical Endocrinology & Metabolism, 96(3), pp.846–852. doi:10.1210/jc.2010-2211.

 

Ianiro, G., Rosa, L., Bonaccorsi di Patti, M.C., Valenti, P., Musci, G. and Cutone, A. (2023). Lactoferrin: From the structure to the functional orchestration of iron homeostasis. BioMetals, 36(3), pp.391–416. doi:10.1007/s10534-022-00453-x.

 

Kim, J.W., Kang, K.M., Yoon, T.K., Shim, S.H. and Lee, W.S. (2014). Study of circulating hepcidin in association with iron excess, metabolic syndrome, and BMP-6 expression in granulosa cells in women with polycystic ovary syndrome. Fertility and Sterility, 102(2), pp.548–554.e2. doi:10.1016/j.fertnstert.2014.04.031.

 

Li, X., Lin, Y., Cheng, X., Yao, G., Yao, J., Hu, S., Zhu, Q., Wang, Y., Ding, Y., Lu, Y., Qi, J., Zhao, H., Bian, X., Du, Y., Sun, K., Vankelecom, H. and Sun, Y. (2024). Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS. Human Reproduction Open. doi:10.1093/hropen/hoae013.

 

Mayeur, S., Veilleux, A., Pouliot, Y., Lamarche, B., Beaulieu, J.-F., Hould, F.S., Richard, D., Tchernof, A. and Levy, E. (2016). Plasma lactoferrin levels positively correlate with insulin resistance despite an inverse association with total adiposity in lean and severely obese patients. PLOS ONE, 11(11), p.e0166138. doi:10.1371/journal.pone.0166138.

 

Nong, J., Li, H., Yang, Y., Lu, Q., Sun, Y., Yin, Q. and He, H. (2024). Low serum hepcidin levels in women with polycystic ovary syndrome: Evidence from meta-analysis. Gynecological Endocrinology, 40(1). doi:10.1080/09513590.2024.2375568.

 

Rudnicka, E., Duszewska, A.M., Kucharski, M., Tyczyński, P. and Smolarczyk, R. (2022). Oxidative stress in polycystic ovary syndrome (PCOS). Reproduction, 164(6). doi:10.1530/rep-22-0152.

 

Stockwell, B.R., Friedmann Angeli, J.P., Bayir, H., Bush, A.I., Conrad, M., Dixon, S.J., Fulda, S., Gascón, S., Hatzios, S.K., Kagan, V.E., Noel, K., Jiang, X., Linkermann, A., Murphy, M.E., Overholtzer, M., Oyagi, A., Pagnussat, G.C., Park, J., Ran, Q., Rosenfeld, C.S., Salnikow, K., Tang, D., Torti, F.M., Torti, S.V., Toyokuni, S., Woerpel, K.A. and Zhang, D.D. (2017). Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell, [online] 171(2), pp.273–285. doi:10.1016/j.cell.2017.09.021.

 

Teede, H., Chau Thien Tay, Joop S.E. Laven, Anuja Dokras, Moran, L.J., Terhi Piltonen, Costello, M., Boivin, J., Redman, L.M., Boyle, J., Norman, R.J., Mousa, A. and Joham, A.E. (2023). Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Human Reproduction, 38(9), pp.1655–1679. doi:10.1093/humrep/dead156.

 

Teede, H.J., Mahnaz Bahri Khomami, Morman, R., Laven, J.S.E., Joham, A.E., Costello, M.F., Patil, M., Rees, D.A., Berry, L., Cree, M.G., Zhao, H., Norman, R.J., Anuja Dokras and Terhi Piltonen (2026). Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: A multistep global consensus process. The Lancet, [online] 0(0). doi:10.1016/S0140-6736(26)00717-8.

 

Tiongco, R.E., Rivera, N., Clemente, B., Dizon, D., Salita, C. and Pineda-Cortel, M.R. (2019). Serum ferritin as a candidate diagnostic biomarker of polycystic ovarian syndrome: A meta-analysis. Biomarkers, 24(5), pp.484–491. doi:10.1080/1354750x.2019.1620335.

 

Wang, T., Hu, W., Zhou, J., Fu, L., Xie, N., Yun, F., Piao, J., Lin, J., Chen, D., Qu, F. and Wang, F. (2025). Dysregulated iron metabolism related to ferroptosis in polycystic ovary syndrome: A meta-analysis and a case-control study in pregnant women. BMC Endocrine Disorders, 26(1). doi:10.1186/s12902-025-02113-w.

 

Zong, X., Wang, Y., Chen, Y., Fang, P. and Zhang, Y. (2025). Role of lactoferrin and its derived peptides in metabolic syndrome treatment. Frontiers in Endocrinology, 16. doi:10.3389/fendo.2025.1562653.