The findings arrive at a moment when the scientific community is increasingly aware that polycystic ovary syndrome, or PCOS, is not a single disease but a spectrum of overlapping phenotypes. Affecting an estimated five to ten percent of women of reproductive age, the syndrome is defined by the 2003 Rotterdam ESHRE/ASRM criteria, which require two of three features: oligo-ovulation or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound. That broad definition captures women whose experiences of the disorder can differ dramatically. Some struggle primarily with irregular cycles and fertility; others are marked by the visible stigmata of androgen excess, including coarse terminal hair growth on the face and body, a condition known as hirsutism, along with acne and androgenic alopecia. Understanding which biological signals distinguish these phenotypes has become a central goal of reproductive endocrinology.

The rationale for studying PSA in this context rests on a surprising body of evidence accumulated over nearly three decades. Although PSA, encoded by the KLK3 gene, is produced abundantly by prostatic epithelial cells, immunoreactive PSA has also been detected in female tissues, including the breast, the salivary glands, and the endometrium, and measurable amounts circulate in the blood of healthy women at concentrations far below those seen in men. Crucially, early work by Melegos, Diamandis and colleagues in 1997 demonstrated that female serum PSA rises in conditions of androgen excess, and subsequent studies showed that antiandrogen drugs lower PSA levels in hirsute women, providing pharmacological evidence that the protein functions as a downstream readout of androgen action in female tissues. In other words, PSA in women is not a prostate marker at all; it is a marker of what androgens are actually doing to target tissues.

This biological logic made PSA an attractive candidate for the Turkish research team, led by Seyma Donmez Sahip and Batuhan Turgay of the University of Health Sciences at Ankara Bilkent City Hospital, with Turgay also affiliated with Ankara University’s Reproductive Health center. Their hypothesis was straightforward: if PSA reflects androgen activity, and if hirsute women with PCOS experience more intense androgenic stimulation of hair follicles and sebaceous glands than their non-hirsute counterparts, then hirsute patients should display higher serum concentrations of both total and free PSA. To test this, the investigators enrolled ninety women diagnosed with PCOS by Rotterdam criteria between May 2022 and January 2023, stratifying them into hirsute and non-hirsute groups using the modified Ferriman-Gallwey score, the standard clinical instrument for visually grading terminal hair growth across nine androgen-sensitive body areas.

The methodology reflects careful attention to the confounders that plague hormonal research. Venous blood samples were drawn on cycle days two or three, when baseline reproductive hormones are most reliably interpreted, and the panel included total and free PSA alongside total and free testosterone, DHEA-S, luteinizing hormone, and metabolic parameters. Insulin resistance was quantified using the homeostatic model assessment, HOMA-IR, a calculation derived from fasting glucose and insulin that estimates how hard the pancreas must work to maintain normal blood sugar. This detail matters because insulin resistance is not merely a metabolic side effect of PCOS; it is widely regarded as a central driver of the syndrome, amplifying ovarian and adrenal androgen production while suppressing hepatic synthesis of sex hormone-binding globulin, the carrier protein that keeps circulating testosterone biologically inert.

When the two phenotypic groups were compared directly, the results partially confirmed expectations. Hirsute women had significantly higher body mass index, with a p-value of 0.044, higher acne prevalence at p equal to 0.032, and higher free testosterone at p equal to 0.014, painting a coherent picture of a phenotype in which androgenic and metabolic disturbances cluster together. Interestingly, menstrual disturbance ran in the opposite direction: amenorrhea and oligomenorrhea were more frequent among non-hirsute women, a reminder that the severity of ovulatory dysfunction and the intensity of cutaneous androgen effects do not march in lockstep. Ovarian morphology and alopecia showed no significant differences between the groups, and, contrary to the primary hypothesis, neither total nor free PSA concentrations differed significantly between hirsute and non-hirsute patients, with all such comparisons yielding p-values above 0.05.

But the story changed when the researchers abandoned group comparisons in favor of correlation analysis across the whole cohort. Using Spearman rank correlation, a non-parametric method appropriate for biological variables that do not follow normal distributions, the team uncovered strikingly strong positive associations. PSA correlated with the Ferriman-Gallwey hirsutism score at a rank correlation coefficient of 0.896, with total testosterone at 0.779, with HOMA-IR at 0.838, with DHEA-S at 0.807, and with luteinizing hormone at 0.804, all with p-values below 0.001. In clinical research, correlation coefficients of this magnitude are rare; values approaching 0.9 indicate that two variables rise and fall together almost in lockstep across the study population. The implication is that PSA behaves as a continuous integrator of androgenic and metabolic load, even if the binary split into hirsute and non-hirsute categories is too coarse to reveal differences in group means.

This distinction between categorical and continuous analysis carries real methodological weight. Phenotypic classification by Ferriman-Gallwey score necessarily dichotomizes a graded biological variable, and thresholds for hirsutism vary by ethnicity and remain imperfectly standardized. A molecule whose expression is driven by tissue-level androgen action may respond smoothly to the full range of androgen exposure, so that averaging PSA values across a threshold-defined group obscures the very dose-response relationship that correlation analysis exposes. The strong PSA-HOMA-IR correlation adds a further layer, suggesting that PSA may capture the intertwined androgen-insulin axis that many investigators consider the engine of PCOS pathophysiology, in which hyperinsulinemia potentiates luteinizing hormone-driven ovarian theca cell androgen synthesis and reduces binding-protein-mediated sequestration of free testosterone.

The new findings also sit within a contested literature. Prior studies of PSA in PCOS have produced mixed results: some reported elevated PSA in affected women compared with controls, a 2019 systematic review and meta-analysis in Hormone and Metabolic Research found overall differences supporting PSA as a potential androgen-excess marker, and work in adolescent girls explored its diagnostic value, while other investigations failed to replicate clear group-level differences. The Ankara study’s design differs from much of this literature in that it compared PSA across PCOS phenotypes rather than between PCOS and healthy controls, asking a subtler question about within-syndrome heterogeneity. The answer, that PSA does not separate hirsute from non-hirsute patients but correlates powerfully with hirsutism severity, androgen concentrations, and insulin resistance, suggests that PSA’s utility may lie not as a diagnostic classifier but as a quantitative index of androgenic-metabolic activity.

For patients and clinicians, the practical implications remain preliminary. PSA is not proposed as a replacement for testosterone measurement or for careful clinical assessment of hirsutism, acne, and cycle regularity, and the study’s authors emphasize that their results underscore the heterogeneity of PCOS and the need for comprehensive phenotypic evaluation rather than a single biomarker shortcut. Yet the research adds to a growing recognition that molecules once considered sexually dimorphic in absolute terms may carry meaningful physiological information in both sexes, and that the androgen signaling pathway, so central to PCOS, leaves measurable fingerprints throughout the body. If future longitudinal studies confirm that serum PSA tracks with long-term metabolic risk in women with PCOS, a cheap and widely available immunoassay, already deployed in laboratories worldwide, could find an unexpected second career in women’s health, transforming a prostate cancer biomarker into a lens on the hormonal and metabolic complexity of one of medicine’s most heterogeneous syndromes.

Subject of Research: Serum prostate-specific antigen as a marker of androgenic and metabolic activity in hirsute and non-hirsute phenotypes of polycystic ovary syndrome

Article Title: Serum Prostate-Specific Antigen Concentrations in Polycystic Ovary Syndrome: A Comparative Analysis of Hirsute and Non-Hirsute Phenotypes

Article References: Sahıp, S. D., Eyol, M. M., Ersoy, E., Erden Deveci, E., Bahadır, I. B., & Turgay, B. (2026). Serum Prostate-Specific Antigen Concentrations in Polycystic Ovary Syndrome: A Comparative Analysis of Hirsute and Non-Hirsute Phenotypes. Reproductive Sciences. https://doi.org/10.1007/s43032-026-02187-4

Image Credits: AI Generated

DOI: 10.1007/s43032-026-02187-4

Keywords: polycystic ovary syndrome, prostate-specific antigen, hirsutism, hyperandrogenism, PCOS phenotypes, insulin resistance, free testosterone, biomarkers, reproductive endocrinology, Ferriman-Gallwey score, HOMA-IR, Rotterdam criteria

A new retrospective study from Kocaeli City Hospital in Türkiye now offers one of the clearest quantitative answers to that question. Writing in BMC Endocrine Disorders, endocrinologists Ayşe Merve Ok Kurt and Seda Erem Basmaz analyzed the records of 438 women aged 18 to 35 who had been evaluated for suspected PCOS or related clinical features and who had complete measurements of total testosterone, androstenedione, and DHEAS. Rather than simply observing which patients had abnormal values, the researchers designed their analysis as a formal experiment in classification. They constructed four nested definitions of hyperandrogenism and asked, at each step, how many additional women crossed the threshold for the biochemical criterion and how many saw their overall diagnosis or Rotterdam phenotype change as a result.

The four models formed a deliberate hierarchy. Model 1, the pragmatic baseline, defined hyperandrogenism as documented hirsutism, elevated total testosterone, or both—precisely the elements most clinicians can reliably capture in routine practice. Model 2 added elevated androstenedione to the baseline, Model 3 added elevated DHEAS, and Model 4 combined both additional androgens. Under each definition, the team recalculated whether each woman met the hyperandrogenism criterion, whether she fulfilled the criteria for a PCOS classification, and which of the Rotterdam phenotypes she would be assigned. Statistical comparisons relied on Cochran’s Q test for the overall differences across models and exact McNemar tests with Holm adjustment for pairwise comparisons, a rigorous approach that guards against false positives when multiple related tests are performed on the same patients.

The headline finding is a tale of two magnitudes. Broadening the biochemical definition with androstenedione and DHEAS raised the proportion of women classified as hyperandrogenic from 86.8 percent under the baseline definition to 93.2 percent under the fully expanded definition—a substantial jump in a criterion that sits at the center of the syndrome’s identity. Yet the effect on the overall diagnosis of PCOS was far more modest, climbing from 72.8 percent to 75.6 percent. That asymmetry makes biological sense: hyperandrogenism is only one of several routes into a PCOS diagnosis, and many women who lack the biochemical marker still qualify through oligo-ovulation and polycystic ovarian morphology. The additional androgens, in other words, confirm and sharpen the androgen excess dimension of the syndrome more than they expand its overall footprint.

Where the expanded testing did matter materially was in phenotype assignment. Under the most inclusive definition, 24 women—5.5 percent of the cohort, with a 95 percent confidence interval of 3.7 to 8.0 percent—were assigned to a different Rotterdam phenotype than they would have been under the baseline definition. Because Rotterdam phenotypes are increasingly used to stratify patients in research and to tailor clinical counseling, a shift of this size in roughly one woman in eighteen is not trivial. The two additional hormones, however, were not equal contributors. Adding androstenedione alone changed phenotype assignment in 4.3 percent of women, compared with just 1.8 percent for DHEAS alone, a difference that reached statistical significance at p equals 0.027. Consistent with that pattern, isolated elevation of androstenedione was markedly more common in the cohort than isolated elevation of DHEAS, occurring in 14.4 percent versus 4.1 percent of participants.

Perhaps the most provocative results emerged from an exploratory subgroup analysis. The researchers identified 58 women who had neither documented hirsutism nor elevated total testosterone—women who, under conventional biochemical thinking, would show no laboratory evidence of androgen excess at all. Yet nearly half of them, 48.3 percent, had elevated androstenedione or DHEAS when those hormones were measured. In this subgroup, the expanded definition reclassified 20.7 percent of women from non-PCOS to PCOS, with a confidence interval spanning 12.3 to 32.8 percent, and changed phenotype assignment in 41.4 percent. The authors are careful to frame these figures as exploratory: the subgroup was small, the analyses were not powered for definitive inference, and the findings need confirmation in larger, prospective cohorts. Even so, they point to a population of women whose androgen excess is invisible to the standard testosterone-based screen but detectable with a broader panel.

The technical backbone of the study deserves attention in its own right. Measuring androgens accurately is notoriously difficult: testosterone circulates at low concentrations in women, and immunoassays—the workhorses of many clinical laboratories, including the chemiluminescence and electrochemiluminescence platforms referenced in the study—are known to lose precision at exactly those concentrations. Liquid chromatography–tandem mass spectrometry, or LC–MS/MS, offers superior specificity but is not universally available. Sex hormone-binding globulin further complicates the picture, since it binds testosterone in the circulation and makes total testosterone an imperfect proxy for biologically active hormone, which is precisely why guidelines increasingly favor free testosterone when it can be measured reliably. The authors acknowledge that their pragmatic baseline deliberately used documented hirsutism and total testosterone rather than a full guideline-concordant workup, a choice that maximizes real-world applicability but also limits how directly the results map onto ideal diagnostic practice.

That limitation shapes the study’s most important caveat: quantifying reclassification is not the same as proving diagnostic benefit. The 5.5 percent of women whose phenotypes changed, and the women in the exploratory subgroup who moved from non-PCOS to PCOS, may have been more accurately classified—or they may simply have been labeled differently without any improvement in predicting their actual clinical outcomes, from metabolic risk to fertility. The authors state this explicitly, noting that their findings quantify the classification impact of broader androgen assessment but do not establish improved diagnostic accuracy. They call for prospective studies that incorporate guideline-recommended free testosterone assessment and follow clinical outcomes over time, so that the field can learn whether androstenedione- and DHEAS-driven reclassifications identify women with genuinely different disease trajectories or treatment responses.

For clinicians, the practical message is a measured one. The study suggests that androstenedione, more than DHEAS, carries real informational weight beyond testosterone in women being evaluated for PCOS, and that in a minority of patients—particularly those with suspected hyperandrogenic features but normal testosterone—measuring additional androgens may meaningfully alter both diagnosis and phenotype. For researchers, the work provides a template: nested, prespecified definitions combined with paired statistical testing offer a clean way to measure the incremental value of any proposed addition to a diagnostic workup. And for the millions of women navigating a condition whose boundaries have been debated since the Rotterdam criteria were first articulated, the study is a reminder that diagnostic categories in endocrinology are not fixed walls but thresholds drawn through evidence—thresholds that careful, quantitative studies like this one continue to refine, one hormone and one reclassified patient at a time.

Subject of Research: The incremental diagnostic value of androstenedione and DHEAS testing in the classification of polycystic ovary syndrome in women

Article Title: Incremental classification yield of androstenedione and DHEAS in women evaluated for polycystic ovary syndrome: a retrospective study

Article References: Kurt, A. M. O., & Basmaz, S. E. (2026). Incremental classification yield of androstenedione and DHEAS in women evaluated for polycystic ovary syndrome: a retrospective study. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02551-0

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02551-0

Keywords: polycystic ovary syndrome, hyperandrogenism, androstenedione, DHEAS, testosterone, Rotterdam criteria, PCOS diagnosis, hirsutism, endocrinology, phenotype reclassification, reproductive hormones, retrospective study