News About Polycystic Ovary Syndrome (PCOS) - Recently Renamed Polyendocrine Metabolic Ovarian Syndrome (PMOS)
Today’s posting addresses recently published articles and papers about polycystic ovary syndrome (PCOS), which has now been officially renamed polyendocrine metabolic ovarian syndrome (PMOS). From management of infertility in obese PCOS patients to defining adolescent lean PCOS to questions about whether pain is a characteristic of PCOS, it’s clear that there’s still a lot to learn about this condition, which affects millions of women around the world. As always, we are welcoming comments from our readers.
The CHR’s Editorial Staff
Already Used to the New Name – PMOS – for PCOS?
To be frank, we haven’t completely gotten used to it yet, and, therefore, we still use both terms together for a transition period; but we are trying to get there.
The discussion about the name change has, indeed, heated up: As we have already opined, we are certainly not enamored as much by the name change as many of our more “politically” oriented colleagues apparently are because we would rather have put more emphasis on improvements in study designs and clinical practice. A name change alone will, of course, not do either.
We therefore were pleased to see in a recent Medscape article that we are not the only ones who are skeptical about the name change from Polycystic Ovary Syndrome (PCOS) to Polyendocrine Metabolic Ovarian Syndrome (PMOS).1 We were especially pleased that Andrea E. Dunaif, MD, Head of the Medical Endocrine program at the Mount Sinai System, for many years worldwide recognized as a leading authority on PCOS/PMOS, was critical. As we repeatedly before noted, the results her genomics laboratory obtained in defining PCOS/PMOS phenotypes largely overlapped with the CHR’s clinical research on PCOS/PMOS phenotypes. Her laboratory was, indeed, the first to report genomic analyses of these distinct biological subtypes of PCOS/PMOS.
Interestingly – and, in our opinion, also correctly – Dunaif et al. not only criticized the absence of any recognition of these now genomically (and by the CHR clinically2) defined biological subtypes of PCOS/PMOS, but also the lack of recognition that this disorder now has also been identified in men and, therefore, represents a metabolic disorder across sexes. And she voiced her discontent, as the Medscape article described, with “Shakespearean flourish,” when introducing her talk to the consortium by announcing her intent “not to praise but to bury the term PMOS.”
Other prominent figures had other reasons to oppose the renaming, among those David A. Ehrmann, MD, professor emeritus and expert on PCOS at the University of Chicago, and Ellen W. Seely, MD, director of clinical research in the division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital in Boston. Meanwhile, China announced that it will continue using PCOS as the clinical term, while trying to introduce PMOS as a possible academic term (whatever that is supposed to mean).
We frankly don’t understand all the fuss in lay media about the name change – and also felt that supporting articles about the name change in Nature Metabolism, Nature Medicine, The Lancet, The Lancet Child & Adolescent Health, Obstetrics, Gynecology & Women’s Health were just too much marketing and too little science and more of a self-aggrandizement by the “political” leadership that had pushed for the name change (and, of course, also authored the papers). Like in most aspects of life, medical practice too, is usually dictated by medical “politicians” and not the medical “scientists.”
REFERENCES
Gleicher et al., Biomedicines. 2022;10(7):1505
Managing Infertility in Obese PCOS Patients
Two recent papers addressed this issue: In a first, Canadian authors investigated whether lifestyle interventions before and during fertility treatments in obese and overweight women with PCOS/PMOS made any difference.1 The study’s conclusion was that comparing lifestyle interventions alone for 6 months – and then followed by infertility treatments – in comparison to usual care (without any interventions) within 18 months did not lead to an increase in live births following fertility treatment, but significantly increased spontaneous pregnancy rates, potentially leading them to avoid costly infertility treatments.
This paper is very difficult to evaluate since this randomized study – without question – has considerable shortcomings, starting with the fact that it included obese women as well as simply overweight women with PCOS/PMOS, - and some PCOS/PMOS patients were included with slightly lower BMIs as they allegedly “exhibit metabolic consequences already at lower BMIs.” Moreover, the trial “was planned” in 2011. Study consistency, therefore, of course, is a major issue because IVF practice has radically changed since then. And we could go on and on with study design criticisms.
However, this paper does offer at least one important point for consideration that especially applies in consideration of the above-noted name change from PCOS to PMOS: Why is it that the very important and very basic question whether – and by which methods – lifestyle interventions potentially can positively affect spontaneous conception rates and/or fertility treatment success has not yet been resolved? And then there is, of course, the point we have been making by now for literally decades, - why are PCOS studies almost uniformly of unacceptably poor quality?
A second paper – this time from U.S. investigators – was much simpler in its design and, therefore, also much easier to judge. Here, the goal was to determine whether time-restricted eating (TRE) was a successful strategy in reducing body weight in women with PCOS/PMOS. The efficiency of TRE for weight management in PCOS is not well understood. The authors, therefore, evaluated the effectiveness of TRE compared with standard care [daily calorie restriction (CR)] and a no-intervention control in women with PCOS.
The study involved only 76 participants who randomly were assigned for 6 months to one out of three study subgroups: (i) a 6-hour TRE regimen (all meals consumed between 1 p.m. and 7 p.m., without calorie tracking): (ii) a CR plan (25% daily energy restriction); and (iii) a control group with no dietary changes. Endpoint of the study was the percent change in body weight at 6 months.
And by month 6, body weight had indeed significantly decreased in TRE (-4.32% (95% CI, -6.20, -2.44), P < 0.01) as well as CR groups (-4.66% (95% CI, -7.13, -2.19), P < 0.01), relative to controls and there was, therefore, no difference between the TRE and CR groups (0.34% (95% CI, -2.15, 2.83), P = 0.79). In short, TRE and CR had similar effects, thereby – at least to a degree – rebutting the first here-discussed study.
Though clearly a much better-quality study than the first study, it is important to note that the definition of PCOS/PMOS in this study – like in practically almost all studies of this condition – was all-encompassing and not – as should be the case – broken out ideally by genomic and/or clinical sub-types or at least standard old-fashioned phenotypes under Rotterdam criteria. And since by now it is undeniable that lean and obese PCOS/PMOS patients present with distinct clinical-biological as well as genomic characteristics, including lean patients indiscriminately into the large majority of obese patients risks selection biases dependent on the distribution of these two distinct patient groups within the complete study population. In a study as small in size as the here-discussed paper, even small changes in distribution can make statistically significant changes.
This is, of course, a very significant shortcoming of this paper, and we, therefore, were somewhat surprised by its acceptance by Nature Medicine.
Defining Adolescent Lean PCOS
A very interesting paper for us was recently published by Boston-based investigators in The Journal of Clinical Endocrinology and Metabolism3 because – to the best of our knowledge – the concept of a hyperandrogenic “lean” PCOS phenotype in adolescence has never before been reported, - except for one paper from NIH investigators several years ago, which described a group of such adolescents who exhibited what the authors described as microgranular adrenal hyperplasia.4
We have since suspected that this microgranular pattern of adrenal hyperplasia in teens likely is what under Rotterdam criteria was described as the only non-hyper-androgenic and lean PCOS/PMOS phenotype-D and demonstrated that this group of young women, indeed, like all other women in the postmenarchal period, are hyperandrogenic (therefore, the suspected association with micronodular adrenal hyperplasia). They, however, at very young ages, develop increasing insufficiency in adrenal androgen production and by approximately age 25 have become normo-androgenic. Because ca. 90% of PCOS/PMOS diagnoses are made between ages 25-35 years, Rotterdam erroneously considered these women, therefore, as non-hyperandrogenic!5
Because of our interest in lean PCOS/PMOS, this new paper about lean adolescent PCOS patients immediately attracted our attention even though the principal issue the paper investigated – metabolic findings (insulin resistance and adipokine profiles) – are not issues we considered particularly relevant for this group of young women. The authors recruited pregnant women at their initial prenatal visit between 1999-2002. In-person study visits occurred during infancy, early and mid-childhood, and early and mid-teen years. Between visits, participants received annual mailed or online questionnaires. Only 51 participants met the study’s criteria for a PCOS/PMOS diagnosis and among those with normally low BMI were only 27.
Somewhat surprisingly, we need to acknowledge, the study demonstrated that even these young women with apparently lean PCOS/PMOS demonstrated altered adipokine profiles suggestive of adipose tissue dysfunction. In other words, - even in the absence of obesity, this dysfunction exists. This is interesting because – after having doubts whether our lean PCOS/PMOS patients who after age 35 usually become hypo-androgenic and who, in contrast to all other PCOS/PMOS patients, usually do not develop metabolic syndrome, - instead demonstrating a very high association with hyperactive immune system activity (and, therefore, miscarriage risk) really should still be viewed as PCOS/PMOS patients, these findings would support keeping them within this designation. It also supports the notion that if PCOS/PMOS really is genomically and biologically made up of in principle only two biological subgroups (or phenotypes), there likely exists a third one that demonstrates overlapping characteristics from both main types at different proportions. Considering the obvious polygenic etiology of PCOS/PMOS, such a conclusion, of course, makes sense.
The Immune System in PCOS/PMOS
And since we are already talking about the immune system, a recent paper from the University of Wisconsin in Madison reported on a single cell analysis of follicular fluid in PCOS/PMOS, suggesting dysregulation of immune function in PCOS/PMOS patients undergoing ovarian stimulation.6 As the authors noted in their paper, since PCOS/PMOS has been known for some time to be characterized by an inflammatory cytokine and leukocyte bias, this association has been made for all of PCOS/PMOS. It was, indeed, only the CHR’s research that isolated this association with a hyperactive immune system primarily to the lean PCOS/PMOS phenotype under Rotterdam called the D-phenotype. But assuming again overlapping characteristics in some patients, it should not surprise anyone that these immune abnormalities were attributed to all PCOS/PMOS patients.
How these immune abnormalities, however, affect ovaries is not well understood and was, therefore, the subject of this investigation. And even though this study once again – like most PCOS/PMOS studies – did not define individual sub-groupings of the condition in their study population, the study’s results were interesting, and the authors hypothesize that the ovarian follicular immune environment in these patients is uniquely dysregulated.
Using single-cell RNA and surface protein analysis of peripheral blood and follicular fluid from patients undergoing IVF, they then discovered that follicles in general - both in PCOS/PMOS as well as in controls - were immunologically distinct from what happened in the circulation. At the systemic level, they found that ovulation induction in PCOS/PMOS women may alleviate systemic inflammation, while healthy control ovaries experienced acute immune-directed ovulatory signaling. PCOS/PMOS follicles were deficient in key pro-ovulatory cell to cell communications and displayed instead a chronic low-grade inflammatory state with fibrotic features.
It now, of course, would be more than interesting to determine whether these characteristics are mostly concentrated in lean PCOS/PMOS patients, but that would be, indeed, what we would expect, considering that the lean PCOS/PMOS patient population demonstrates evidence of a hyperactive immune system (autoimmunity, inflammation allergies) in over 85%.5
Is Pain a Characteristic of PCOS/PMOS?
This is what a preprint in eLife recently suggested, which in the journal’s editorial assessment “presented valuable findings on the high prevalence of pain in women with PCOS/PMOS.7 The journal’s assessment also concluded that “the evidence supporting the conclusions is compelling, utilizing a massive global dataset and rigorous propensity score matching to identify pain as a critical, yet underexplored, clinical marker.”
We acknowledge surprise about this association. Conducted in January 2026, using data from 120 Health Care Organizations within the TriNetX Global Network, the study involved 103,675,738 women from diverse racial backgrounds. The analysis focused on the prevalence of pain among women with PCOS/PMOS, both overall and in those prescribed PCOS-related medications. The study found that 20.67% of women with PCOS/PMOS experienced pain, with the highest prevalence among Black or African American (32.70%) and White (30.78%) populations. Both the PCOS/PMOS and PCOS/PMOS and pain cohorts exhibited increased relative risk for various health conditions, with significant differences noted across racial groups for infertility, ovarian cysts, obesity, and respiratory diseases. Additionally, women with PCOS/PMOS who were treated with PCOS/PMOS-related medications showed a decrease in pain diagnoses following treatment. In conclusion, this study highlights the critical need to address pain in the diagnosis and management of PCOS/PMOS due to its significant impact on patient health outcomes.
After reading this preprint, we must say we are unconvinced and – if anything – even more skeptical, - at least how the paper is presented. The data – we agree – are believable and, of course, gigantic in numbers of patients. But where is the evidence that any of the pain symptoms described in these PCOS/PMOS patients have anything to do with their PCOS/PMOS? Or even more surprising, considering the laudatory editorial assessment of this paper by eLife, where is the evidence that we are really dealing with PCOS/PMOS patients, considering how inaccurate a diagnosis this is (as already noted here) and has been for decades? If this paper had already completed peer review and been published, it definitely would have deserved even stronger criticism from us. But because it still is a preprint, we will withhold final judgment.
REFERENCES
Belan et al., J Clin Endocrinol Metab. 2026;111:e1643-e1652.
Corapi et al., Nat Med 2026;32:2155-2163
Whooten et al., J Clin Endocrinol Metab 2026;111:e1364-1372
Gourgari et al., J Clin Endocrinol Metab 2016;101(9):3353-3360
Gleicher et al., Biomedicines. 2022;10(7):1505
Wgrzynowicz et al., Biol Reprod 2026;114(5):1736-1746
Cherlin et al., eLife, Reviewed Preprint. June 9, 2026. https://elifesciences.org/reviewed-preprints/103875