Gynecological Cancers Among American Indian and Alaska Native Women Living in the Upper Midwest, 1995-2019.
Ulmer KK, Greteman B, Gonzalez Bosquet J, Petereit D, Harper D, Nash SH.
Womens Health Rep (New Rochelle). 2025 Feb 25;6(1):199-208. doi: 10.1089/whr.2024.0124. PMID: 40130037; PMCID: PMC11932641
Background: American Indian and Alaska Native (AI/AN) women experience higher rates of mortality from many cancers than their non-Native counterparts.
Objective: To examine recent data on gynecological cancers (cervical, ovarian, and uterine) among AI/AN women living in the Upper Midwest (Iowa, Montana, Nebraska, North Dakota, South Dakota, and Wyoming) for any improvement in equity.
Methods: We used data from the North American Association for Central Cancer Registries Cancer in North America database (1995-2019). We used descriptive statistics, including incidence mortality rates, trends, and time to treatment. Analyses were restricted to non-Hispanic individuals living in a purchased/referred care delivery area (PRCDA) at the time of diagnosis; sensitivity analyses included all AI/AN people, regardless of PRCDA residence or ethnicity.
Results: From 1995 to 2019, there were 647 gynecological cancers diagnosed among AI/AN women living in PRCDA counties in the Upper Midwest (cervical n = 194, ovarian n = 142, uterine n = 311). Incidence and mortality rates for ovarian and uterine cancers were similar between AI/AN and non-Hispanic White (NHW) women; however, the incidence of cervical cancer was 1.87 (95% confidence interval [CI]: 1.60, 2.17) times higher, and mortality was 2.92 (95% CI: 2.29, 3.68) times higher among AI/AN compared to NHW women. The majority of AI/AN women diagnosed with gynecological cancer initiated treatment within 1 month (cervical = 67.2%, ovarian = 80.6%, uterine = 63.1%), which was similar to NHW women.
Conclusions: Differences exist in incidence and mortality for cervical cancer between AI/AN and NHW women in the Upper Midwest, with AI/AN facing continued inequity.
For a full text of the article, click here: https://www.liebertpub.com/doi/pdf/10.1089/whr.2024.0124
Metformin for patients with advanced stage ovarian cancer: A randomized phase II placebo-controlled trial.
Romero IL, Lengyel E, Wahner Hendrickson AE, Rodriguez GC, Leath CA 3rd, Rocconi RP, Goodheart MJ, Dewdney S, Karrison T, Fleming GF, Yamada SD.
Gynecol Oncol. 2025 Feb 8;194:18-24. doi: 10.1016/j.ygyno.2025.02.001. Epub ahead of print. PMID: 39923680.
Objective: The primary aim of this study was to determine if metformin, an oral biguanide administered with first-line chemotherapy and continued as maintenance therapy, improves progression-free survival (PFS) for patients with advanced-stage ovarian cancer.
Methods: Patients with pathologically confirmed advanced-stage ovarian cancer undergoing primary debulking or neoadjuvant platinum-based chemotherapy followed by surgery were eligible to participate. Patients were randomized 1:1 to receive platinum/taxane-based chemotherapy with metformin 850 mg orally twice per day or placebo, followed by maintenance therapy (metformin or placebo) for two years from the date of randomization.
Results: 108 evaluable patients were enrolled; 54 were randomly assigned to metformin, and 54 to placebo. Sixty-six percent (n = 71) received neoadjuvant therapy, 31 % (n = 33) primary debulking surgery, and 88 % (n = 93) had tumors of high-grade serous histology. The primary endpoint, PFS, was not significantly different between the treatment groups (1-sided p-value = 0.31; adjusted hazard ratio [HR] = 0.87, 95 % confidence interval [CI]: 0.56-1.36). Median PFS was 15.4 months (95 % CI: 11.2-23,5) for metformin and 14.3 months (95 % CI: 11.6-18.0) for placebo. Overall survival (OS) was not significantly different (2-sided p-value = 0.21; adjusted HR = 1.49, 95 % CI: 0.86-2.59), with a median of 40.7 months (95 % CI: 28.0-48.2) for metformin versus 43.8 months (95 % CI: 35.3-57.2) for placebo. The addition of metformin was well tolerated, and there were no differences in toxicity between the two groups.
Conclusion: Although it was well-tolerated, adding metformin to first-line platinum/taxane-based therapy does not improve PFS or OS for patients with newly diagnosed advanced stage ovarian cancer.
For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0090825825000289?via%3Dihub
Preterm Births and Maternal-Fetal Medicine Physician Workforce Location in the United States.
Greiner AL, Haeri S, Nidey NL.
Am J Perinatol. 2025 Mar 6. doi: 10.1055/a-2531-2783. Epub ahead of print. PMID: 40049592.
Objective: Examine for association between geographic disparity in the national maternal-fetal medicine (MFM) physician workforce distribution and preterm birth (PTB) rate in counties without MFM presence.
Study Design: Cohort study of PTBs in the United States from 2015 to 2019, utilizing National Center for Health Statistics natality data. The independent risk factor is the presence of an MFM physician in the county or county equivalent where the pregnant woman resides. Bivariate logistic regression analysis estimated the odds of county-level PTB rates higher than the national average (10.2%, March of Dimes 2019 national data) by MFM physician location.
Results: The Northeast, Southeast, and Pacific Coast regions of the United States had the highest density of physician practice locations whereas regions in the Midwest and Western United States had the lowest density. Of the 2,981 counties with PTB rates available, 90.3% (n = 2,691) did not have a practicing MFM physician. U.S. counties without an MFM physician are more likely to have a PTB rate higher than the national average, operating room (OR) = 1.56 (95% confidence interval [CI], 1.22-1.99), compared with a county with at least one MFM physician.
Conclusions: Counties with no practicing MFM physician had a 56% increase in the odds of having PTB rates higher than the national average. The lack of proximate high-risk obstetric care is a geographic health disparity associated with PTB. The location of the MFM workforce has implications for both clinical care and health policy. These data suggest that attention should be directed toward where physicians practice and to increase access to care for at-risk pregnant women. · U.S. regions with the highest concentration of MFM physicians remain unchanged from prior publications.. · Only 9.7% of counties reporting PTB data have practicing MFM physicians.. · Counties without an MFM physician have 56% higher odds of exceeding national PTB rates.. · Regional disparities in MFM physician distribution may impact maternal and neonatal outcomes..
For a full text of the article, click here: https://www.thieme-connect.de/products/ejournals/pdf/10.1055/a-2531-2783.pdf
The Impact of Frequency of Cannabis Use on Hypertensive Disorders During Pregnancy.
Nidey N, Raff E, Ferdous Khan MT, Watkins SL, McAllister JMJ, Kair L, Terplan M, Greiner A.
J Addict Med. 2025 Mar 3. doi: 10.1097/ADM.0000000000001454. Epub ahead of print. PMID: 40028912.
Objectives: Cannabis is 1 of the most commonly used substances during pregnancy, and there is mixed evidence of its impact on maternal outcomes, such as hypertensive disorders. Prior research on cannabis use during pregnancy has not accounted for use frequency, which might explain mixed results across studies. The objective of this study was to examine how frequencies of use during pregnancy are associated with hypertensive disorders.
Methods: This was a retrospective cohort study of the 2017-2018 Pregnancy Risk Assessment Monitoring System survey (n = 10,911/weighted n = 587,486). Frequency of cannabis use was categorized for analysis as follows: no use, minimal use (1 time per month or less), moderate use (2 times per month to 1 day per week), and frequent use (2-6 times per week to daily). Multivariable logistic regression models were used to examine how the frequency of cannabis use influenced the odds of experiencing hypertensive disorders during pregnancy.
Results: Cannabis use, measured as a binary exposure variable (yes/no), was not associated with higher odds of hypertension during pregnancy (odds ratio, 0.86; 95% confidence interval, 0.54, 1.35). However, among those with any cannabis use, frequent use (vs minimal use) was associated with higher odds of hypertensive disorders (odds ratio, 3.44; confidence interval, 1.40, 8.43).
Conclusions: Identifying cannabis use frequency during pregnancy can help identify maternal risk of hypertensive disorders.
For a full text of the article, click here: https://journals.lww.com/journaladdictionmedicine/fulltext/9900/the_impact_of_frequency_of_cannabis_use_on.465.aspx
Pregnancy as an opportunity to explore brain-immune connections in mental health.
Gumusoglu SB, Stelzer IA.
Sci Adv. 2025 Mar 7;11(10):eadu8270. doi: 10.1126/sciadv.adu8270. Epub 2025 Mar 5. PMID: 40043105; PMCID: PMC11881895.
Pregnancy's effects on the brain, behavior, and hormones provide a unique opportunity to study how the immune system integrates these adaptations and influences mental health.
For a full text of the article, click here: https://www.science.org/doi/pdf/10.1126/sciadv.adu8270
Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial.
Eskander RN, Sill MW, Beffa L, Moore RG, Hope JM, Musa FB, Mannel RS, Shahin MS, Cantuaria GH, Girda E, Lokich E, Kavecansky J, Leath CA 3rd, Gien LT, Hinchcliff EM, Lele SB, Landrum LM, Backes F, O'Cearbhaill RE, Baghdadi TA, Hill EK, Thaker PH, John VS, Welch S, Fader AN, Powell MA, Aghajanian C.
Nat Med. 2025 Mar 5. doi: 10.1038/s41591-025-03566-1. Epub ahead of print. PMID: 40044930.
Historically, the treatment of patients with advanced stage or recurrent endometrial cancer included paclitaxel plus carboplatin. Immunotherapy in combination with chemotherapy resulted in improved clinical outcomes in several solid tumors. In the phase 3 NRG GY018 study, pembrolizumab plus chemotherapy significantly improved investigator-assessed progression-free survival (PFS; primary endpoint) versus placebo plus chemotherapy in patients with advanced/metastatic/recurrent endometrial cancer regardless of mismatch repair status. Here we report on key secondary endpoints and exploratory analyses. Patients were women ≥18 years old with newly diagnosed stage III or IVA endometrial cancer with measurable disease, or stage IVB or recurrent endometrial cancer with or without measurable disease. Patients (n = 810) were randomized (1:1) to pembrolizumab or placebo plus paclitaxel-carboplatin followed by maintenance pembrolizumab or placebo for up to 24 months. Overall survival was a secondary endpoint and PFS per RECIST v.1.1 by blinded independent central review was an exploratory endpoint. Overall survival data were immature; hazard ratios favored pembrolizumab (mismatch repair-proficient: 0.79 (0.53-1.17); 1-sided nominal P = 0.1157; mismatch repair-deficient: 0.55 (0.25-1.19); 1-sided nominal P = 0.0617). Hazard ratios (95% confidence intervals) for PFS per blinded independent central review favored pembrolizumab (mismatch repair-proficient: 0.64 (0.49-0.85); P = 0.0008; mismatch repair-deficient: 0.45 (0.27-0.73); P = 0.0005). These findings further support the use of pembrolizumab plus chemotherapy as first-line treatment for patients with advanced stage or recurrent endometrial cancer regardless of mismatch repair status. ClinicalTrials.gov identifier: NCT03914612 .
For a full text of the article, click here: https://www.nature.com/articles/s41591-025-03566-1
Outcomes at 12, 24, and 36 Months in Women Treated for Pelvic Organ Prolapse With Pessary or Surgery: Results From the Multicenter Pelvic Floor Disorders Registry.
Andy UU, Meyn L, Brown HW, Moalli PA, Ferrando CA, Shippey S, Omosigho UR, Kowalski JT, Guaderrama NM, Anger JT, Foster RT Sr, Gutman RE, Yurteri-Kaplan L.
Urogynecology (Phila). 2025 Feb 27. doi: 10.1097/SPV.0000000000001669. Epub ahead of print. PMID: 40043183.
Objective: The aim of this study was to describe real-world outcomes in women treated for pelvic organ prolapse (POP) with pessary or surgery over 36 months.
Study design: We report outcomes of patients in a multicenter, prospective registry who opted for treatment of POP with either pessary (discontinuation or retreatment with surgery rates and subjective improvement) or surgery (retreatment rates or subjective improvement).
Results: Among 1,153 patients, follow-up was available for 248 (84%), 123 (42%), and 98 (33%) in the pessary group and 717 (93%), 407 (53%), and 331 (43%) in the surgery group at 12, 24, and 36 months, respectively. In the pessary group, rates of discontinuation and retreatment decreased over time with 82/248 patients (33%) discontinuing pessary use at 12 months, of whom 32 (39%) had surgery, 17/123 (14%) discontinuing at 24 months, of whom 7 had surgery, and 5/98 (5%) discontinuing at 36 months, of whom 2 had surgery. Subjective recurrence rates were 76/147 (52%), 4/99 (4%), and 11/87 (13%) at 12, 24, and 36 months, respectively. In the surgery group, the rate of retreatment was 15/717 (2%), 6/407 (1%), and 5/331 (2%) and the rate of subjective recurrence was 71/717 (10%), 8/407 (2%), and 13/331 (4%) at 12, 24, and 36 months.
Conclusions: In this real-world registry, we observed that approximately one third of patients discontinued pessary use during the first 12 months, which decreased over time. There were low rates of reintervention following surgical management over the 36-month period. Our data provide valuable information that may be helpful for clinicians in counseling patients about management of their POP.
For a full text of the article, click here: https://journals.lww.com/fpmrs/fulltext/9900/outcomes_at_12,_24,_and_36_months_in_women_treated.360.aspx
A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study.
Bae-Jump VL, Sill MW, Gehrig PA, Merker JD, Corcoran DL, Pfefferle AD, Hayward MC, Walker JL, Hagemann AR, Waggoner SE, O'Cearbhaill RE, McDonald ME, Edelson MI, DiSilvestro PA, McNally AL, Fleury A, Littell RD, Ueland FR, Lankes HA, Aghajanian C.
Gynecol Oncol. 2025 Mar 7;195:66-74. doi: 10.1016/j.ygyno.2025.03.003. Epub ahead of print. PMID: 40056832.
Introduction: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC).
Methods: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary endpoints were objective response, duration of response, and toxicity.
Results: From 3/17/2014 to 12/22/2017, 448 patients were randomized to phase II/III studies, and the data were frozen for interim analysis. The phase II study deemed metformin worthy of further investigation in the phase III study. The interim phase III analysis stopped accrual for futility on 2/1/2018. The addition of metformin to PC had a slightly higher hazard of death compared to the PC regimen (HR = 1.088; 90% CI 0.803 to 1.475), which was sufficient to close the study early. The PFS had (HR = 0.814; 90% CI 0.635 to 1.043). At a median follow-up of 10 months and 121 deaths, median OS was not determined and 28 months, on PC/placebo and PC/metformin, respectively.
Conclusion: The hazard ratios for PFS and OS endpoints was not sufficiently decreased with the addition of metformin to PC to justify continuing the trial.
For a full text of the article, click here: https://www.sciencedirect.com/science/article/pii/S0090825825000721?via%3Dihub
Racial/ethnic disparities in the association of maternal diabetes and obesity with risk of preterm birth among 17 million mother-infant pairs in the United States: a population-based cohort study.
Xie J, Yan Y, Ye Z, Wu Y, Yu Y, Sun Y, Rong S, Santillan DA, Ryckman K, Snetselaar LG, Liu B, Bao W.
BMC Pregnancy Childbirth. 2025 Mar 21;25(1):333. doi: 10.1186/s12884-025-07352-2. PMID: 40119308; PMCID: PMC11929260.
Background: The racial/ethnic disparities in the prevalence of obesity, diabetes, and adverse birth outcomes such as preterm delivery indicate that it is essential to account for the varying risks associated with pregnant women of different races and ethnics during clinical prenatal examinations. However, the racial and ethnic disparities in how pre-pregnancy diabetes in mothers relates to preterm birth as well as the combined association of maternal diabetes and pre-pregnancy obesity with preterm birth remain unclear. In this study, we aimed to 1) examine the racial/ethnic disparities in the association of maternal diabetes including gestational diabetes mellitus (GDM) and pre-pregnancy diabetes with preterm birth 2) and the racial/ethnic disparities in the joint associations of maternal diabetes and pre-pregnancy obesity with preterm birth.
Methods: In this population-based cohort study, we included 17,027,792 mothers documented in the National Vital Statistic System in the U.S. from 2016 to 2020. All these data were analyzed in 2021. Maternal pre-pregnancy diabetes was defined as having diabetes diagnosed prior to this pregnancy, and GDM was defined as having newly diagnosed diabetes in this pregnancy. Pre-pregnancy BMI (kg/m2) was classified as underweight (< 18.5 kg/ m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obesity class I (30.0-34.9 kg/m2), obesity class II (35.0-39.9 kg/m2), and obesity class III (≥ 40 kg/m2). Preterm birth, defined as delivery occurring at less than 37 weeks of gestation, was the main outcome of interest. We further categorized preterm birth into three subtypes: extremely (< 28 weeks), very (28-31 weeks), and moderately (32-36 weeks) preterm birth. Logistic regression models were used for association analyses in this study.
Results: Among 17,027,792 mothers (mean age: 29.4 ± 5.4 years), 1,374,286 (8.07%) mothers delivered a preterm infant. Women with pre-pregnancy diabetes had the highest risk of preterm birth followed by women with GDM overall and across all racial/ ethnic groups. However, from pre-pregnancy underweight to obesity III, the magnitude of the association between pre-pregnancy diabetes and preterm birth decreased for non-Hispanic Black women (underweight, 4.47 [3.34-5.99], normal weight 4.28 [3.98-4.60], overweight 3.29 [3.11-3.49], obesity I 3.09 [2.93-3.26], obesity II 2.98 [2.82-3.16], obesity III 3.19 [3.04-3.35]), while it showed an increasing trend for non-Hispanic Asians ( underweight 1.45 [0.91-2.30], normal weight 2.16 [1.90-2.47], overweight 2.71 [2.47-2.97], obesity I 3.10 [2.82-3.41], obesity II 3.58 [3.13-4.09], obesity III 3.99 [3.34-4.77]). The corresponding OR was (underweight 4.33 [3.21-5.83], normal weight 3.69 [3.47-3.93], overweight 3.26 [3.10-3.42], obesity I 3.33 [3.19-3.49], obesity II 3.47 [3.29-3.65], obesity III 3.89 [3.68-4.11]) among Hispanics and (underweight 5.17 [4.34-6.17], normal weight 5.01 [4.83-5.21], overweight 4.98 [4.80-5.17], obesity I 4.66 [4.48-4.85], obesity II 4.58 [4.38-4.79], obesity III 4.50 [4.31-4.69]) among non-Hispanic White. Comprehensive analysis of the association between diabetes, pre-pregnancy diabetes, obesity, ethnicity, and preterm birth found that compared to white women with normal weight and normal blood glucose levels, any other racial\ethnic group has an elevated risk of preterm birth, particularly when accompanied by unhealthy weight, GDM, or pre-pregnancy diabetes. Specifically, non-Hispanic Black individuals with normal blood sugar levels (1.69 [1.67-1.70]) have a higher risk of preterm birth than non-Hispanic White individuals with GDM (1.37 [1.35-1.40]). Similarly, Asian pregnant women with class 2 and class 3 obesity (1.72 [1.65-1.78], 1.96 [1.83-2.10]), as well as Hispanic pregnant women with class 2 and class 3 obesity (1.46 [1.44-1.48], 1.64 [1.61-1.67]), also have a higher risk of preterm birth than white women with GDM 1.37 [1.35-1.40].
Conclusions: In conclusion, while both pre-pregnancy diabetes and GDM were significantly associated with preterm birth, the associations varied by race/ethnicity. The risk of preterm birth for GDM increased with increasing BMI in all race/ethnicity groups. However, the pattern of the joint association of pre-pregnancy diabetes and BMI levels with preterm birth differed by race/ethnicity. Future studies on the underlying mechanisms of the racial/ethnic disparities in the association of diabetes and obesity with preterm birth are needed.
For a full text of the article, click here: https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-025-07352-2
Enhancing Progestin Therapy with a Glucagon-Like Peptide 1 Agonist for the Conservative Management of Endometrial Cancer.
Hagemann AR, Hagemann IS, Mutch DG, Devor EJ, Malmrose PK, Zhang Y, Morrison AM, Thiel KW, Leslie KK.
Cancers (Basel). 2025 Feb 10;17(4):598. doi: 10.3390/cancers17040598. PMID: 40002193; PMCID: PMC11853405.
Objective: Obesity is a major risk factor for endometrial cancer. In addition to hormone therapy with progestins, glucagon like peptide-1 receptor (GLP-1R) agonists such as semaglutide may be helpful to achieve weight loss during conservative treatment of endometrial hyperplasia or cancer.
Methods: We theorized that the combination of semaglutide and the progestin levonorgestrel would be useful as a novel treatment or prevention regimen and tested this hypothesis using endometrial cancer cell lines and patient-derived organoids (PDOs).
Results: Hec50, KLE, and Ishikawa endometrial cancer cells express GLP-1R, as determined by both qPCR and Western blotting, and GLP-1R agonist treatment induces GLP-1R mRNA transcription through positive feedback mechanisms in cell models. PDOs from six individuals with grade 1 endometrial carcinomas were treated with progesterone, levonorgestrel, semaglutide, or levonorgestrel + semaglutide. Multiple models demonstrated a significant reduction in viability in response to combinatorial treatment, and the effect was noted in models from both PR high- and PR low-expressing tumors. Most interesting was the induction not only of the membrane GLP-1R with treatment, but also the significant upregulation of nuclear and membrane progesterone receptors-PR and PGRMC1/2, respectively-indicating a potential positive feedback loop between semaglutide and progestins such as levonorgestrel.
Conclusion: In summary, we identify synergistic molecular cross-talk between the GLP-1R and steroid hormone receptor pathways, with the potential to enhance the anticancer activity of levonorgestrel when combined with semaglutide.
For a full text of the article, click here: https://www.mdpi.com/2072-6694/17/4/598