The study was designed as a single-center retrospective cohort analysis of treatment-naive patients who had undergone a standardized low-dose bromocriptine test as a marker for dopamine agonist response. Between 2008 and 2017, the test was performed routinely at the Norwegian center as part of the baseline workup for newly diagnosed acromegaly. Of 141 consecutive patients diagnosed during that decade, 71 underwent the test, and 69 were included in the final retrospective analyses after exclusions for logistical reasons, contraindications, acute surgery, hypotension or syncope during testing, prior dopamine agonist treatment, lactose intolerance, pituitary apoplexy, loss to follow-up, or lack of consent.

The bromocriptine test itself is elegantly simple. After an overnight fast, three baseline growth hormone samples are drawn 30 minutes apart and averaged. The patient then swallows a single 2.5 mg oral dose of bromocriptine, and growth hormone is measured again at 2, 4, and 6 hours. A positive response was defined as more than a 50 percent reduction in the nadir growth hormone concentration compared with the baseline mean. In the cohort, responders showed a median growth hormone decline of 74 percent, while non-responders declined only 37 percent. This acute hormonal snapshot served as the surrogate for longer-term dopamine agonist effectiveness, a concept rooted in clinical studies from the 1970s and 1980s that linked early bromocriptine-induced growth hormone suppression with later therapeutic benefit.

To probe the biology behind variable responsiveness, the researchers combined several complementary approaches. Baseline serum hormones, including growth hormone, prolactin, and insulin-like growth factor 1 (IGF1), were measured with standard immunoassays and calibrators. Magnetic resonance images were evaluated retrospectively for tumor size, volume, and invasiveness using the Knosp criteria for cavernous sinus invasion. Immunohistochemical staining of tumor tissue assessed growth hormone, prolactin, thyroid-stimulating hormone, cytokeratin 8, estrogen receptor alpha, and somatostatin receptor subtypes 1, 2, and 5, with staining intensity scored using the immunoreactive score system. Slides were evaluated by an investigator and a senior pathologist, both blinded to clinical data.

A key technical challenge emerged with the dopamine receptor D2 protein itself. Immunohistochemistry using two different commercial antibodies failed repeatedly: on postmortem central nervous system tissue, both showed distinct intracellular granular labeling, but background staining was high and could not be reduced, and on surgical pituitary specimens the staining was diffuse and nonspecific. The team therefore turned to gene expression analysis. Tumor tissue collected during surgery was snap-frozen and stored at minus 80 degrees Celsius, RNA was extracted with a column-based kit after TRIzol homogenization, and dopamine receptor D2 mRNA was quantified by real-time quantitative PCR normalized to two validated reference genes, GAPDH and PSMC4. Gene expression data were available in 54 patients.

The central result was striking. Dopamine agonist test response correlated with higher tumor dopamine receptor D2 gene expression, with a Spearman correlation coefficient of 0.53 and a p-value below 0.001. Patients with a positive test had significantly higher receptor expression than those with a negative test. Crucially, this association remained statistically significant after statistical adjustment for gender, age, tumor volume, growth hormone and prolactin concentrations, and their staining intensities, indicating that the receptor expression carried independent information about drug responsiveness. Higher receptor expression also tracked with higher serum prolactin, stronger tumor prolactin staining, and lower IGF1 levels relative to the age-adjusted upper limit of normal.

Prolactin emerged as a clinically accessible indirect marker. Stronger tumor prolactin expression correlated with better test response, and when prolactin staining was dichotomized as positive or negative, the association with test outcome was significant, with a phi coefficient of 0.39. Notably, 57 of 66 tumors showed prolactin expression by immunohistochemistry, a far higher proportion than the 20 to 30 percent hyperprolactinemia typically reported in acromegaly, reflecting that many tumors secrete prolactin histologically without elevating serum levels beyond normal. When prolactin staining was used as the marker and test response as the outcome, sensitivity was 97 percent, meaning nearly all responders stained positive, while specificity was only 30 percent, since many non-responders also stained positive. The negative predictive value of 89 percent suggests that a prolactin-negative tumor is a strong signal that dopamine agonist therapy will fail.

The statistical architecture of the analysis clarified the causal chain. When the correlation between prolactin and test response was adjusted for dopamine receptor D2 expression, it disappeared, implying that the drug effect is mediated through the receptor itself and that prolactin expression serves as an indirect proxy for receptor abundance and responsiveness. This mechanistic interpretation aligns with known pharmacology: activation of the D2 receptor reduces hormone release and can induce apoptosis in pituitary tumor cells, with the short receptor isoform appearing to exert stronger effects. Somatostatin receptor staining showed no correlation with test response, and the hypothesized link between somatostatin receptor 1 and dopamine receptor D2 expression was not borne out in this cohort.

Estrogen receptor alpha added a second layer of tumor biology. Its expression correlated with prolactin expression, and both were associated with smaller tumor volume and lower invasiveness by Knosp grade. Patients whose tumors stained negative for prolactin were older and had higher IGF1 levels relative to normal. These findings echo the 2022 World Health Organization classification, which distinguishes pure somatotroph tumors from those with combined somatotroph and lactotroph differentiation marked by growth hormone, prolactin, and estrogen receptor alpha positivity. However, the authors caution that the clinical applicability of the estrogen receptor findings remains unclear, as previous studies on estrogen receptor alpha and tumor aggressiveness in acromegaly have yielded conflicting results.

The study has limitations that temper enthusiasm. Gene expression does not necessarily reflect protein abundance, cellular localization, or receptor function, and the analysis did not distinguish between the long and short isoforms of the D2 receptor, which may differ in mechanism. The bromocriptine test is a surrogate for acute response and cannot replace studies of long-term dopamine agonist effectiveness. The 70 patients who did not undergo testing had lower prolactin concentrations and greater growth hormone excess, potentially introducing bias, although age, sex, and tumor size were comparable. Still, the large well-characterized cohort with standardized dynamic testing, supported by molecular and histological analyses, represents a methodological strength over registry-based studies. The authors conclude that readily available prolactin staining of tumor tissue may add valuable information for individualized pharmaceutical management, potentially sparing non-responders from ineffective therapy while guiding responders toward optimized treatment regimens.

Subject of Research: Acromegaly treatment markers

Article Title: Tumor expression of dopamine receptor and prolactin is associated with acute dopamine agonist response in acromegaly

Article References: Atai, S., Abusdal, M., Wessel, M. I., Casar-Borota, O., Øystese, K. A., Winther, J., Bollerslev, J., & Heck, A. (2026). Tumor expression of dopamine receptor and prolactin is associated with acute dopamine agonist response in acromegaly. Frontiers in Endocrinology, 17, Article 1930467. https://doi.org/10.3389/fendo.2026.1930467

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1930467

Keywords: acromegaly, dopamine agonist, prolactin, pituitary tumor, personalized medicine, Tumor, expression, dopamine, receptor, associated, acute, agonist

The study, published in BMC Endocrine Disorders, followed 108 Chinese men with prolactinoma who received dopamine agonist monotherapy and were tracked for more than a year at the single tertiary center. The mean age at diagnosis was 41.8 years, with a wide spread of roughly 15 years on either side. The disease burden at baseline was striking: the median starting prolactin concentration was 1,039 nanograms per milliliter, orders of magnitude above the normal range, and the median tumor volume was about 2,710 cubic millimeters. Nearly 77 percent of the men had macroadenomas, tumors large enough to be clearly visible and potentially compress surrounding structures, while only about 23 percent had smaller microadenomas. This skew toward advanced disease reflects a well-recognized pattern in male prolactinoma, where symptoms such as reduced libido, erectile dysfunction, and headaches are often dismissed or attributed to other causes until the tumor has grown substantially.

Over a mean follow-up of 2.84 years, the treatment worked remarkably well by most conventional standards. Prolactin levels normalized in 69.4 percent of patients, tumor volume shrank by at least half in 79.6 percent, and 54.6 percent achieved both prolactin normalization and recovery of testosterone, the key hormone of the male gonadal axis. In ten patients the tumor disappeared entirely on imaging — an outcome that was far more common in men with microadenomas, where complete disappearance occurred in 28 percent of cases, compared with just 3.6 percent of macroadenomas. That difference, statistically significant at P equals 0.001, underscores how much the starting tumor size shapes what patients can ultimately expect from medication alone.

But the headline numbers conceal the study’s central insight. When the researchers integrated prolactin control and tumor shrinkage into a single combined classification, they found that discordant responses were common. At the last follow-up, 56.5 percent of the men met the criteria for a good response — normal prolactin plus at least 50 percent tumor-volume reduction — while 36.1 percent fell into a partial response category, meaning one measure improved while the other lagged. Some men normalized their prolactin yet retained bulky residual tumors; others saw dramatic shrinkage while the hormone remained stubbornly elevated. Only 7.4 percent had a poor response, with neither prolactin control nor meaningful tumor reduction. In other words, more than a third of patients would have been misclassified by a single-endpoint assessment.

To move beyond static snapshots, the team built what they call a dynamic integrated response framework, evaluating patients at baseline, at three months, and at one year, and asking which measurements at each stage best predicted the final outcome. The statistical machinery behind this included group comparisons, stage-specific logistic regression, receiver-operating-characteristic analysis to identify cutoff values, and bootstrap internal validation to test the robustness of the models. Sensitivity analyses were used to confirm that the findings were not driven by particular subgroups or analytic choices. The result is a time-stamped map of treatment response rather than a single verdict rendered at the end of follow-up.

The predictors that emerged differed sharply by stage. At baseline, the only significant independent predictor of a final good response was body mass index: lower BMI was associated with better outcomes, with an odds ratio of 0.810 per unit increase in BMI. Why body weight should matter remains an open question, but the association hints at metabolic influences on dopamine agonist sensitivity or on tumor biology itself. By three months, the picture shifted to treatment dynamics: each 10 percent greater reduction in prolactin at that early checkpoint nearly tripled the odds of a final good response, with an odds ratio of 3.093. This suggests that the first three months of therapy are a critical window in which the tumor’s behavior reveals its long-term trajectory.

At the one-year mark, two factors independently predicted a good final response. Prolactin normalization by then carried an odds ratio of 17.712 — a very strong signal — while each additional 10 percent of tumor-volume reduction added a more modest but still significant benefit, with an odds ratio of 1.106. The receiver-operating-characteristic analysis translated these associations into practical exploratory thresholds: a prolactin reduction of at least 94.8 percent at three months, and an absolute prolactin level at or below 23.30 nanograms per milliliter at one year, best separated patients destined for good responses from the rest. These cutoffs are exploratory and require external validation, but they offer clinicians concrete numbers to watch at defined moments in follow-up.

The clinical implications are potentially far-reaching. Current guidelines for managing prolactinoma largely assess treatment success through individual endpoints, and a patient whose prolactin has normalized might be considered a treatment success even if a large tumor mass persists and continues to threaten vision or pituitary function. Conversely, a patient with marked tumor shrinkage but persistently elevated prolactin might be labeled a failure despite clear radiological benefit. The integrated framework distinguishes transitional partial responses — patients still moving toward full control — from persistent ones, allowing clinicians to intensify monitoring, adjust drug doses, or consider surgery or radiotherapy at the right time rather than too late. The authors emphasize that the framework is a candidate endpoint structure for future validation studies, not a finished clinical tool.

Several caveats temper the enthusiasm. The study was retrospective and drawn from a single center, which limits generalizability and leaves open the possibility of selection effects; patients who required surgery or radiotherapy during follow-up were excluded, which may have removed the most treatment-resistant cases from the analysis. The cohort was exclusively male and exclusively Chinese, and prolactinoma behavior and drug tolerance can vary across populations. The response classification, while logically constructed, is new and has not yet been tested prospectively or in independent cohorts. Still, the size of the cohort — 108 men followed for nearly three years on average — is unusual for a disease that is rare in men, and the internal validation strengthens confidence in the identified predictors.

For patients, the takeaway is cautiously optimistic. Dopamine agonist monotherapy achieved high rates of both biochemical and structural control across all tumor sizes in this cohort, confirming that pills alone can do the heavy lifting for most men with prolactinoma, even those presenting with large tumors and prolactin levels a thousand times above normal. For clinicians, the study argues for a more nuanced follow-up rhythm: check prolactin and MRI early, watch the trajectory rather than the snapshot, and recognize that a discordant response is not a contradiction but a distinct clinical state deserving its own management strategy. As endocrinology moves toward personalized, time-dependent assessment of chronic endocrine diseases, this integrated response framework offers a template that could extend well beyond prolactinoma — provided that future prospective studies confirm what this Shanghai cohort has revealed.

Subject of Research: Dopamine agonist monotherapy outcomes in men with prolactinoma

Article Title: Dynamic integrated response to dopamine agonist monotherapy in Chinese men with prolactinoma: a retrospective cohort study

Article References: Zheng, H., Hu, B., Xie, Y., Qu, X., Zhang, S., Ye, H., Li, Y., Lu, R., & Ji, L. (2026). Dynamic integrated response to dopamine agonist monotherapy in Chinese men with prolactinoma: a retrospective cohort study. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02636-w

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02636-w

Keywords: prolactinoma, dopamine agonist, prolactin, testosterone, pituitary adenoma, tumor volume, endocrinology, retrospective cohort, treatment response, BMI, macroadenoma, hormonal therapy

The study, published in the Journal of Translational Medicine, applied single-cell RNA sequencing to 55,648 individual cells drawn from 12 somatotroph pituitary neuroendocrine tumors, the benign but hormonally aggressive growths responsible for acromegaly. Rather than treating each tumor as a uniform mass of identical hormone-producing cells, the team dissected them cell by cell, cataloguing the transcriptional states that coexist within a single patient’s tumor. What emerged was a picture of structured heterogeneity: the tumor cells occupied a continuum of states the researchers labeled classic, intermediate, and neuronal-associated, all while retaining the molecular identity of their pituitary lineage. The tumors, in other words, are not blobs of sameness but layered ecosystems of related cell states arranged along a transcriptional gradient.

That finding alone would have been a useful contribution to the growing atlas of pituitary tumor biology. But the Yonsei team, led by neurosurgeons and endocrinologists from the Severance Hospital Pituitary Tumor Center, pushed the analysis one level higher. Using non-negative matrix factorization, a computational technique that decomposes complex expression matrices into additive components, they aggregated the single-cell data into patient-level profiles and asked whether the twelve tumors would sort themselves into meaningful groups. They did — and the dividing line was unexpected. The tumors separated cleanly into two clusters defined not by their cell-state composition, tumor size, or canonical oncogenic mutations, but by how strongly they expressed the gene encoding prolactin, a hormone classically associated with a different pituitary tumor type altogether.

The statistical robustness of this split is notable. Across 100 independent runs of the clustering algorithm, the two groups co-clustered with a mean within-group consensus of 0.925 and a between-group consensus of just 0.058, with an overall consensus silhouette width of 0.915 — figures that indicate the division is not an artifact of algorithmic noise. The team also ruled out obvious confounders: the correlation between prolactin expression and the proportion of classic tumor states was weak, and tumor size did not differ systematically between groups. One tumor showed an intermediate assignment, a reminder that biology rarely respects clean boundaries, but the core separation held firm.

Crucially, the prolactin signal was not confined to sequencing data. The researchers validated it at the protein level using immunohistochemistry on tumor sections, showing that tumors rich in PRL transcript were also rich in prolactin immunoreactivity. Even more striking, tumor prolactin expression correlated with patients’ preoperative serum prolactin levels — a routine blood test already measured in nearly every acromegaly workup. That correlation transforms an esoteric molecular observation into something clinically actionable: a biomarker that could, in principle, be read off a standard preoperative lab panel without any need for fresh tumor tissue or specialized sequencing.

To test whether the prolactin signature actually mattered for patients, the team turned to an independent clinical cohort of 188 individuals with acromegaly. Using logistic regression and stratified analyses, they asked whether prolactin-high tumor status predicted postoperative biochemical remission — the formal endpoint, determined by growth hormone and insulin-like growth factor 1 levels under oral glucose tolerance testing, that defines surgical success. It did. Patients whose tumors fell into the prolactin-high group were significantly more likely to fail to achieve remission after surgery. The association held even as the researchers accounted for other clinical variables, positioning prolactin as a candidate adjunctive risk marker alongside the anatomical and surgical predictors — tumor size, invasiveness, and extent of resection — that surgeons already weigh.

Molecularly, the prolactin-high tumors turned out to be an enigma. Gene set enrichment analysis showed that they lacked enrichment of the canonical oncogenic pathways one might expect to find in a more aggressive tumor. Instead, the differences between prolactin-high and prolactin-low tumors played out at the level of individual genes, with a notable cluster of receptor-associated candidates — including EPHA7, a receptor tyrosine kinase gene — distinguishing the two groups. The authors suggest that these receptor-level differences may shape how tumor cells respond to their hormonal and microenvironmental milieu, though the functional biology remains to be worked out. The finding is intriguing precisely because it does not fit the standard playbook: the high-risk tumors are not more oncogenic in any obvious way, just transcriptionally different in ways that matter for hormone control.

The team took several steps to guard against wishful thinking. In an external cohort of 60 somatotroph tumors from a public dataset, a discovery-derived prolactin-associated signature score — deliberately constructed with prolactin itself and pituitary lineage genes excluded to avoid circularity — tracked strongly with tumor prolactin abundance, with a Spearman correlation of 0.64. As a negative control, the same signature applied to 45 nonfunctioning pituitary tumors from the same dataset showed no such association, confirming that the signal is specific to somatotroph biology rather than a generic pituitary artifact. A sensitivity analysis excluding the one ambiguously assigned tumor left the genome-wide fold-change estimates essentially unchanged, with a concordance of 0.98.

The translational stakes are real. Acromegaly is a rare disease, but its consequences are expensive and disabling, and the current decision tree after surgery is largely reactive: patients are monitored, and second-line treatments — repeat surgery, radiation, or medical therapy with somatostatin analogs, dopamine agonists, or the growth hormone receptor antagonist pegvisomant — are deployed only after remission fails to materialize. A preoperative biomarker that flags high-risk patients could shift that calculus, prompting earlier counseling, closer biochemical surveillance, or more aggressive multimodal treatment planning from the outset. The Yonsei group is already moving in this direction: according to the paper’s competing interests statement, the university is preparing a patent application covering the use of prolactin-associated features and selected receptor-associated markers, including EPHA7, for molecular and clinical characterization of these tumors.

Caveats remain, and the authors are careful to name them. The single-cell discovery cohort comprised only twelve tumors, and while the clinical validation cohort of 188 patients is substantial, the association between prolactin-high status and remission failure was established retrospectively. The researchers themselves state that preoperative prolactin may serve as a potential adjunctive biomarker for risk stratification but that prospective external validation is required before it enters routine practice. Whether the prolactin-high state reflects a distinct developmental origin of the tumor cells, an epigenetic program, or a response to microenvironmental cues is unknown, and the functional role of EPHA7 and the other receptor-associated genes is an open question. Still, the study exemplifies a productive pattern in modern tumor biology: single-cell atlases that do not merely describe heterogeneity but convert it into clinically legible categories. For a disease in which the difference between remission and chronic illness can hinge on molecular features invisible to the surgeon’s eye, a routine blood test that whispers a warning before the first incision is a prospect worth taking seriously.

Subject of Research: Single-cell transcriptomic stratification of somatotroph pituitary tumors by prolactin expression and postoperative remission risk

Article Title: Single-cell transcriptomics reveals prolactin-associated molecular stratification and remission risk in somatotroph PitNETs

Article References: Oh, H.-C., Shim, J.-K., Oh, H., Lee, W. K., Kim, S. H., Kang, S.-G., Lee, E. J., Kim, S. H., Ku, C. R., & Kim, E. H. (2026). Single-cell transcriptomics reveals prolactin-associated molecular stratification and remission risk in somatotroph PitNETs. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-09065-2

Image Credits: AI Generated

DOI: 10.1186/s12967-026-09065-2

Keywords: acromegaly, pituitary neuroendocrine tumor, single-cell RNA sequencing, prolactin, somatotroph tumor, transcriptomics, tumor heterogeneity, EPHA7, biomarker, remission, growth hormone, non-negative matrix factorization

The setting is Ronneby, a municipality of roughly 28,000 inhabitants in southern Sweden. For decades, aqueous film-forming foam, or AFFF, used in firefighting training at a nearby military airbase seeped into the groundwater that fed one of the town’s two water treatment plants. When the contamination was finally discovered in 2013, total PFAS concentrations in the water exceeded 10,000 nanograms per liter, dominated by perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), with perfluorooctanoic acid (PFOA) also present. Retrospective analyses of archived newborn blood spots suggest the exposure began as early as 1985 and climbed steadily until around 2005 to 2007. The contaminated supply was shut off on December 16, 2013, but by then, some residents carried serum PFAS concentrations up to a hundred times higher than those seen in the general Swedish population.

That unusual exposure gradient is precisely what made Ronneby valuable to researchers. Most previous studies of PFAS and reproductive hormones have been conducted in populations with only background exposure, and their findings have been inconsistent. Regulatory bodies, including the European Food Safety Authority and the US National Academies of Sciences, have judged the evidence linking PFAS to reproductive hormone alterations insufficient. By studying children whose bodies span a range of exposures from background levels to extreme contamination, the Swedish team could probe exposure-response relationships that background-level studies simply cannot resolve.

The researchers drew on biobanked serum samples collected between 2014 and 2016 from participants in the Ronneby PFAS Biomarker Cohort, aged 5 to 20 years. The final study group comprised 87 girls and 84 boys aged 5 to 11, and 117 boys aged 12 to 20; girls aged 12 and older were excluded because menstrual cyclicity and contraceptive use would have introduced unmanageable variability. About 23 percent of participants came from nearby Karlshamn, where drinking water PFAS levels were below 5 nanograms per liter, providing a reference group. Serum concentrations of PFOS, PFHxS, and PFOA were measured by liquid chromatography-tandem mass spectrometry, and the sum of these three compounds served as the primary exposure measure. Hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, sex hormone-binding globulin (SHBG), and total testosterone, were quantified with electrochemiluminescence immunoassays at an accredited clinical laboratory.

The exposure levels were striking. Among the younger children from Ronneby, median combined serum concentrations of the three PFAS exceeded 90 nanograms per milliliter, and among adolescent boys the median reached 173 nanograms per milliliter, with some individuals above 600. For context, the European Food Safety Authority considers a serum level of about 6 nanograms per milliliter to be the threshold below which the tolerable weekly intake of PFAS is assumed to be maintained. PFOS and PFHxS were strongly correlated with one another, reflecting their shared source in the contaminated water, and roughly one quarter of participants were classified as prenatally exposed based on residential records from the year of their birth.

The hormone findings split cleanly along developmental lines. Among children aged 5 to 11, higher PFAS concentrations were associated with elevated prolactin in both sexes, an association that held in the continuous models for girls and boys alike. Boys in this younger group also showed lower FSH as exposure increased, while boys in the medium exposure category had higher SHBG. When the researchers formally tested for sex differences, however, the interaction terms were not statistically significant, meaning they could not conclude that boys and girls responded differently. Among adolescent boys aged 12 to 20, the pattern shifted: higher PFAS levels were associated with lower LH, lower total testosterone, and a lower free androgen index, a calculated measure of bioavailable testosterone that combines testosterone and SHBG. In the categorical analysis, the reduction in LH was most evident in the medium-high exposure group, while testosterone and the androgen index declined across the higher exposure categories.

These results align closely with findings from other highly exposed populations. In the C8 Health Project in the Mid-Ohio Valley, where drinking water was contaminated by PFAS production facilities, higher PFOA and PFOS concentrations were linked to delayed puberty and lower testosterone in both boys and girls. More recently, adolescents living near a 3M chemical plant in Belgium showed similar patterns, with higher PFHxS and PFOA associated with lower LH and testosterone and higher SHBG in teenage boys. The convergence of evidence across three independent contamination hotspots on two continents strengthens the case that the associations are not statistical artifacts, though the observational design still cannot prove causation.

The prolactin finding is particularly intriguing because it is comparatively rare in the PFAS literature. Positive relationships between fluorochemical exposure and prolactin were reported in occupational studies in the 1990s, but few modern studies have examined the question. Prolactin is best known for its role in lactation, but it also feeds back on the hypothalamic-pituitary-gonadal axis, and pathological hyperprolactinemia in adults can suppress gonadotropin release and reduce sex steroid production. The Ronneby team is careful to note that their data do not demonstrate a prolactin-mediated suppression of the hormonal axis, since prolactin was elevated in young children but not in adolescent boys, in whom LH and testosterone were instead reduced. The hormone-specific associations may reflect other mechanisms or differing susceptibility across developmental stages, and experimental studies suggest PFAS may impair testosterone production by disrupting steroidogenesis in the Leydig cells of the testes, though exact mechanisms remain uncertain.

The study has limitations worth weighing. Blood samples were drawn at varying times of day, and hormones such as testosterone and LH follow circadian rhythms that peak in the early morning, introducing variability that likely attenuated the observed effect estimates rather than creating spurious ones. Immunoassay-based sex steroid measurements are less sensitive than mass spectrometry, particularly at the low concentrations typical of children, and most estradiol values fell below the laboratory’s reporting limit and could not be analyzed. The researchers also could not disentangle prenatal from postnatal exposure, because the contamination was already pervasive by the mid-1980s and the two exposure routes are highly correlated in this cohort. Sensitivity analyses adjusting for body mass index produced similar estimates for most hormones.

The clinical significance of the hormonal differences remains uncertain. Testosterone concentrations in the exposed adolescents were still within age-appropriate reference ranges, and pediatric reference intervals for prolactin are lacking, making interpretation difficult. What the study does establish is that real-world, AFFF-driven PFAS contamination, the same scenario now unfolding around airports, military bases, and industrial sites worldwide, is associated with detectable alterations in the hormonal regulation of children at multiple levels of the endocrine system. With legacy PFAS persisting in the environment despite regulatory restrictions and being replaced by newer compounds whose health effects are poorly characterized, the researchers call for longitudinal follow-up of highly exposed populations, more sensitive hormone measurement methods, and standardized sampling to determine whether these early hormonal shifts translate into delayed puberty or long-term reproductive consequences.

Subject of Research: Associations between serum PFAS concentrations and reproductive hormone levels in highly exposed children and adolescents

Article Title: Serum PFAS Concentrations and Reproductive Hormones in Highly Exposed Children and Adolescents

Article References: Hammarstrand, S., Andersson, E., Colldén, H., Lindh, C., Nielsen, C., Jakobsson, K., & Andersson, E. M. (2026). Serum PFAS Concentrations and Reproductive Hormones in Highly Exposed Children and Adolescents. Environmental Advances, Article 100764. https://doi.org/10.1016/j.envadv.2026.100764

Image Credits: AI Generated

DOI: 10.1016/j.envadv.2026.100764

Keywords: PFAS, endocrine disruption, puberty, reproductive hormones, testosterone, prolactin, drinking water contamination, firefighting foam, Ronneby, children's health, HPG axis, environmental epidemiology

The study, the first of its kind conducted in Türkiye, used individual semi-structured interviews with four first-time mothers and six women who had given birth before, with a mean age of 29 years. Interviews lasted 30 to 40 minutes and were analyzed using the thematic analysis framework of Braun and Clarke, with recruitment continuing until data saturation was reached. Three dominant themes emerged from the analysis: avoidance of sexuality, maintaining sexuality as a responsibility, and coping with the effects of breastfeeding on sexuality. Within these, the researchers identified six subthemes ranging from physical and psychological changes in sexual dynamics to religious and cultural influences, the fulfillment of the female role, changing perceptions of breasts, and the coping strategies women improvised to manage it all.

The physiological backdrop is well established in the literature. Breastfeeding elevates prolactin, the hormone that drives milk production, while suppressing estrogen. The result is a hormonal profile that commonly produces vaginal dryness, reduced libido, and altered sexual responsiveness. A 2025 meta-analysis cited by the authors found that sexual dysfunction was common among postpartum women regardless of feeding method, but rates were highest among those who exclusively breastfed. The mothers in the new study described these mechanisms in visceral, personal terms. One participant who had a vaginal birth with stitches compared resuming intercourse to her very first sexual experience, describing fear, excitement, desire, and obligation all mixed together, and recounting how she tensed up so severely that her husband had to stop. Another, recovering from a cesarean section, reported stinging sensations at her incision sites nearly six months after delivery.

Vaginal dryness emerged as one of the most distressing physical consequences. One mother described using Vaseline to manage severe dryness and pain so intense that she felt sensitivity for two days afterward, even while urinating. She explained that the anticipation of pain had become self-reinforcing: whenever her husband wanted sex, she would tense her legs in expectation of discomfort, to the point that her husband said he no longer enjoyed it either. Breast fullness, tingling sensations, and milk leakage during intimacy further disrupted sexual encounters, with several women reporting that any attempt to touch their breasts triggered pain or an immediate loss of desire.

But the study’s most revealing findings lie beyond physiology. The psychological weight of breastfeeding shaped sexual experiences in ways that clinical checklists rarely capture. Mothers described chronic fatigue and sleep deprivation, the fear of waking the baby, and anxiety about becoming pregnant again while breastfeeding. One woman recalled a relative who conceived during breastfeeding with only a 13-month gap between children, a pregnancy with twins that left her devastated, and said the same fear haunted her. Others described what one participant called rushed sex: intercourse squeezed into narrow windows before the baby woke, stripped of foreplay and pleasure. She noted that before the child, the couple had sex two or three times a week; now they were grateful for twice a month. Several women reported being unable to reach orgasm at all, and one captured a broader exhaustion, saying that being a woman meant being responsible for the child and the husband while no one asked what she wanted or how she coped.

Feelings of disgust and shame surfaced repeatedly, particularly around the collision of maternal and sexual meanings attached to the breasts. One mother recalled her husband mockingly telling her she smelled of milk while kissing her, a comment she laughed off but which hurt deeply. Another described an incident in which leaked milk soaked her husband’s arm; he initially mistook it for the baby’s urine, and she felt extreme embarrassment, saying she felt like a cow rather than a woman. The same participant described a distinct form of guilt: when milk leaked during sex, she thought of her baby and felt the milk that should be feeding her child was being wasted. These accounts illustrate how lactation can reframe the breast so thoroughly that its sexual role becomes psychologically untenable.

Religious and cultural norms added a further layer, and here the Turkish context proved essential to the study’s contribution. Several participants described avoiding intercourse specifically because of the requirement to perform ghusl, the full ritual ablution required after sexual intercourse before a woman could breastfeed her baby. One mother said she sometimes avoided intercourse for this reason alone, and described rushing to the bathroom to perform ablution while the baby cried in the father’s arms, explaining that she wanted her baby to receive clean milk. Household structure mattered as well: mothers living with in-laws or extended family reported being unable to embrace their husbands, let alone have sex, because an elder might enter the room at any moment. One participant said intimacy with a spouse while elders were in the house felt inappropriate and embarrassing. Even the baby’s presence in the bedroom created a sense of being watched, with one mother insisting the couple had never had sex in front of their child because it felt as though someone was observing them.

Perhaps the most sobering theme was sexuality maintained as duty rather than desire. Multiple women described continuing to have intercourse primarily to satisfy their partners, framing it as a responsibility of their female or spousal role. One mother said her motherhood outweighed everything and her femininity came second, and that if she did not have responsibilities toward her husband she would not force herself to have sex at all. Another asked directly whether it was not a woman’s duty to satisfy her husband, saying she felt she could not fulfill her role as a woman. Alongside this, the study documented how breastfeeding redefined the breasts themselves. Many women came to see them as organs belonging to the infant, instruments of nourishment rather than pleasure, and negotiated explicit agreements with partners that the breasts would not be touched during sex. Yet the picture was not uniformly negative: some participants reported that lactation-related breast enlargement improved their body image and their partners’ attraction, with one hoping the change would persist after weaning.

The women were not passive in the face of these challenges. The researchers catalogued a range of coping practices: keeping bras on during intercourse to contain leakage, expressing milk in advance with a breast pump, setting boundaries about breast contact, and, for some, simply adopting a patient stance that the difficulties would pass with time, as they had after previous births. Notably, participants also called for better education, with one urging that men be taught what their wives experience during breastfeeding so they understand the process. The authors argue that these adaptive strategies, which include redefining intimacy and prioritizing emotional closeness over penetrative sex, may function as a protective factor for relational and sexual well-being, though the exploratory design prevents firm conclusions about their effectiveness.

The study’s limitations are real: a single center, Turkish-speaking participants only, a small sample that cannot be generalized, and a mix of delivery types whose recovery demands may have independently shaped sexual activity. Still, its central message carries broad clinical weight. Breastfeeding and sexuality are intertwined through physical, psychological, social, cultural, and religious threads, and the meanings women attach to milk and motherhood matter as much as prolactin levels. The researchers recommend that healthcare professionals address breastfeeding, breast milk, and sexuality together within breastfeeding education programs, provide individualized and culturally sensitive guidance for couples, and integrate the topic into prenatal education. For the mothers in this study, the tension between being a partner and being a mother was not a passing inconvenience but a defining struggle of the postpartum months, one that most had never been warned about, and one that a more honest conversation between clinicians and couples could help ease.

Subject of Research: Breastfeeding mothers' perceptions and experiences of breast milk and sexuality during the postpartum period

Article Title: Being a Partner or a Mother: Breastfeeding Mothers’ Perceptions and Experiences of Breast Milk and Sexuality in the Postpartum Period

Article References: Akbaş, P., & Özkan Şat, S. (2026). Being a Partner or a Mother: Breastfeeding Mothers’ Perceptions and Experiences of Breast Milk and Sexuality in the Postpartum Period. Archives of Sexual Behavior. https://doi.org/10.1007/s10508-026-03540-z

Image Credits: AI Generated

DOI: 10.1007/s10508-026-03540-z

Keywords: breastfeeding, postpartum sexuality, breast milk, qualitative research, prolactin, vaginal dryness, religious norms, maternal role, body image, Türkiye, sexual dysfunction, coping strategies

The study enrolled 542 adolescents and young adults with mental disorders who underwent in-hospital treatment between October 2022 and December 2023. For each participant, the researchers gathered a broad set of information: clinical characteristics, scores on the Brøset Violence Checklist, a structured instrument for assessing short-term risk of aggression, and serum hormone levels measured in blood samples. The goal was to determine which of these many variables, alone or in combination, were most strongly associated with a baseline history of suicide attempt, meaning an attempt that had occurred before or at the time of admission.

To build a model that would generalize well rather than simply fit the data at hand, the team randomly divided the cohort into a training set of 379 patients and a validation set of 163 patients, in a seven-to-three ratio. All statistical model building was performed on the training set, while the validation set was reserved to test how well the resulting tool performed on patients it had never seen. This internal validation strategy is considered a cornerstone of responsible predictive modeling in clinical research, because a model that only performs well on the data used to build it is of little practical value at the bedside.

Before fitting the final model, the researchers applied least absolute shrinkage and selection operator regression, commonly known as LASSO, a technique that shrinks the coefficients of weak predictors toward zero and effectively filters out redundant or uninformative variables. LASSO regression is particularly useful in medical datasets where many candidate predictors are correlated with one another, as it reduces overfitting and produces a more parsimonious set of features. The variables that survived this screening step were then entered into a multivariate logistic regression model, the standard statistical framework for estimating the independent contribution of each factor to a binary outcome, in this case the presence or absence of a suicide-attempt history.

Five variables ultimately earned a place in the final nomogram: a history of non-suicidal self-injury, serum prolactin levels, plasma total cortisol levels, the number of previous hospitalizations, and educational level. Each of these factors carries its own clinical logic. Non-suicidal self-injury, the deliberate harming of one’s own body without suicidal intent, has long been recognized as a powerful signal of underlying emotional distress and is one of the most consistent correlates of later suicidal behavior in young people. Repeated hospitalizations suggest a chronic or unstable course of illness, while lower educational attainment may reflect the cumulative disruption that mental disorders impose on development and social functioning.

The inclusion of two hormones adds a biological dimension that sets this study apart from many purely psychosocial risk models. Prolactin, best known for its role in lactation, is also influenced by stress and by several psychiatric medications, and altered prolactin levels have been linked in previous research to self-directed violence and emotional dysregulation. Cortisol, the body’s primary stress hormone, reflects the activity of the hypothalamic-pituitary-adrenal axis, the neuroendocrine system that orchestrates the physiological response to stress. Dysregulation of this axis has repeatedly been implicated in mood disorders and suicidal behavior, and measuring plasma total cortisol offers an objective, laboratory-based window into a patient’s stress biology that cannot be captured by interview alone.

A nomogram translates the coefficients of a logistic regression model into a visual chart on which a clinician can plot the value of each predictor, read off assigned points, sum them, and convert the total into an estimated probability. In this case, the estimated probability refers to the likelihood that a given hospitalized adolescent or young adult has a baseline history of suicide attempt. The appeal of the format lies in its simplicity: no calculator or software is required, and the relative weight of each factor is immediately visible, which can help clinicians understand why a particular patient scores as high or low risk.

The performance metrics reported by the team suggest a moderately strong tool. The area under the receiver operating characteristic curve, or AUC, a measure of how well a model distinguishes between those with and without the outcome, reached 0.771 in the training set, with a 95 percent confidence interval of 0.715 to 0.827, and 0.788 in the validation set, with a confidence interval of 0.711 to 0.865. Values in this range indicate discrimination that is useful but not definitive, which the authors explicitly acknowledge. Calibration, meaning the agreement between predicted probabilities and observed outcomes, was strong: the Hosmer-Lemeshow goodness-of-fit test yielded a chi-square of 12.672 with a p-value of 0.123 in the training set and a chi-square of 8.919 with a p-value of 0.349 in the validation set, both indicating satisfactory model fit. Decision curve analysis, a method for quantifying the clinical net benefit of a model across a range of decision thresholds, identified effective thresholds from 19 percent to 73 percent in the training set and from 10 percent to 74 percent in the validation set, supporting the tool’s utility as a risk-stratification reference.

The authors are careful to position the nomogram as an auxiliary quantitative reference rather than a standalone screening instrument. Suicide risk assessment in young people is a complex clinical judgment that must integrate interview findings, collateral information, mental state examination and safety planning, and no statistical model can replace that process. What this tool offers is a structured way to visualize how multiple dimensions of a patient’s profile, from self-injury history to endocrine markers, converge to shape risk, potentially flagging high-risk patients who might otherwise receive insufficient attention during a busy admission. The researchers suggest it may help inform targeted suicide-prevention interventions within inpatient psychiatric settings.

Because the study is cross-sectional, it captures associations at a single point in time and cannot establish that the five predictors cause suicide attempts, nor can it predict future attempts prospectively. The cohort was drawn from a single hospital network in China, so external validation in other countries, cultures and healthcare systems will be needed before broader adoption. Nonetheless, the work represents a meaningful step toward integrating biological and psychosocial data into accessible bedside tools for one of medicine’s most urgent challenges. As the authors note, characterizing the risk profiles of hospitalized adolescents and young adults with mental disorders is essential for targeted suicide prevention, and a validated, visual, multidimensional model gives clinicians one more way to see that risk clearly.

Subject of Research: A nomogram integrating psychosocial and hormonal correlates of baseline suicide-attempt history in hospitalized adolescents and young adults with mental disorders

Article Title: Development and internal validation of a nomogram for visualising multidimensional correlates of baseline suicide‑attempt history among hospitalized adolescents and young adults with mental disorders

Article References: Ren, Y., Liu, Q., Zhu, Y., Wu, J., Chen, H., Pu, L., Dong, Z., Zhu, H., & Zhang, X. (2026). Development and internal validation of a nomogram for visualising multidimensional correlates of baseline suicide‑attempt history among hospitalized adolescents and young adults with mental disorders. BMC Psychiatry. https://doi.org/10.1186/s12888-026-08613-w

Image Credits: AI Generated

DOI: 10.1186/s12888-026-08613-w

Keywords: nomogram, suicide-attempt history, adolescents and young adults, mental disorders, non-suicidal self-injury, prolactin, cortisol, LASSO regression, logistic regression, risk prediction, BMC Psychiatry, inpatient psychiatry