Estring (estradiol) / Pfizer - LARVOL DELTA

Palbociclib combined with endocrine treatment in hormone receptor-positive, HER2-negative breast cancer patients with high relapse risk after neoadjuvant chemotherapy: subgroup analyses of premenopausal patients in PENELOPE-B. (PubMed, ESMO Open) - "In premenopausal women, who received tamoxifen plus OFS as ET, the addition of palbociclib to ET results in a favorable iDFS. The safety profile seems favorable and in contrast to chemotherapy palbociclib does not impact OF throughout the treatment period."

Journal • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Ovarian function in young patients (pts) treated with postneoadjuvant palbociclib (PAL) and endocrine therapy (ET) for hormone receptor (HR)-positive, HER2-negative early breast cancer (BC): explorative analysis in Penelope-B (ESMO-BC 2022) - P3 | "Estradiol (E2), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) values might be influenced by post-NACT PAL. EOT analysis will be presented at the meeting. Conclusions PAL does not influence FSH, E2 and the ovarian reserve significantly when added to ET after NACT."

Clinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Association of High-Sensitivity C-Reactive Protein With Metabolic but Not Endocrine Parameters in Women With Polycystic Ovary Syndrome (ASRI 2026) - "After 1 year of treatment, no significant difference in hs-CRP levels was observed between the oral contraceptive group (drospirenone/ethinyl estradiol; Yaz®, Bayer AG, Germany) and the cyclic progestin group (medroxyprogesterone acetate 10 mg; Provera®, Pfizer Italia S.r.l., Italy). In women with PCOS, hs-CRP levels were significantly associated with metabolic parameters but not with endocrine parameters, including hyperandrogenemia. In women with PCOS, hs-CRP levels were significantly associated with metabolic parameters but not with endocrine parameters, including hyperandrogenemia. These findings suggest that hs-CRP may serve as a potential marker of metabolic risk in this population. Further prospective studies are warranted to clarify its clinical implications."

Clinical • Diabetes • Endocrine Disorders • Genetic Disorders • Inflammation • Metabolic Disorders • Obesity • Polyendocrine Metabolic Ovarian Syndrome • Type 2 Diabetes Mellitus • CRP

SONImage: Can molecular imaging predict outcome to first-line endocrine treatment ± CDK 4/6 inhibition in advanced ER+ breast cancer? (ESMO-BC 2026) - P=N/A | "Whether this is also related to outcome on 1st-line aromatase inhibition (AI) ± CDK4/6 inhibition (CDK4/6i), was investigated in imaging biomarker study SONImage (NCT04125277). Prior to 1st-line AI ± CDK4/6i, ER homogenous or heterogeneous MBC was determined with 16α-[18F] fluoro-17β-estradiol positron emission tomography (FES-PET) and FDG-PET (homogenous: FDG+ metastases all FES+; heterogeneous: part of the FDG+ metastases: FES negative)... In SONImage, ER homogenous MBC is related to a better relative 1st-line PFS than ER heterogeneous MBC, irrespective of the treatment group, and with comparable relative CDK4/6i benefit in both groups. The findings of this large imaging biomarker analysis may potentially support treatment choices in MBC patients."

Biomarker • Clinical • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER

Evaluating the Utility and Constraints of the Competitive Counter Flow (CCF) Assay in OATP1B1 Substrate Profiling. (PubMed, AAPS J) - "The assay measures steady-state changes in intracellular [3H]-estradiol-17β-glucuronide retention following exposure to test compounds across multiple concentrations...Notably, the CCF assay enabled identification of four xenobiotics-bumetanide, candesartan, naringin and sulfasalazine-not previously recognized as OATP1B1 substrates using OATP1B1 uptake assay. Overall, this work provides a comprehensive evaluation of the CCF assay as a complementary, early‑stage screening and triage tool for OATP1B1 substrate assessment. The findings underscore the importance of an integrative strategy that combines CCF data with orthogonal in vitro and in vivo evidence to mitigate the risk of both false‑negative and false‑positive conclusions, particularly for ECCS Class 1B compounds where traditional overexpression systems show limited sensitivity."

Journal

Assessment of the Drug-Drug Interaction Potential of Lotiglipron (PF-07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol. (PubMed, J Clin Pharmacol) - P1 | "Based on the results of the two Phase 1 studies reported here along with the results of a Phase 2 study where transaminases elevations were also noted, both Phase 1 studies were prematurely terminated along with the clinical development of lotiglipron. ClinicalTrials.gov identifiers: NCT05671653; NCT05788328."

Journal • Breast Cancer • Genetic Disorders • Obesity • Oncology • Solid Tumor • CYP2C19

Ovarian and reproductive hormone characteristics and risk of cycle cancellation in immediate versus postponed modified natural cycle frozen embryo transfer (mNC-FET) cycles. (PubMed, Hum Reprod) - P=N/A | "The follicular phase of immediate cycles seems to differ from postponed cycles in terms of ovarian morphology, follicular phase length, and early follicular phase levels of progesterone and LH. The rate of cycle cancellation raises concerns about the clinical feasibility of immediate FET treatment in NCs."

Journal • Endocrine Disorders

REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Polly A. Niravath, MD | Trial completion date: Dec 2025 ➔ Jun 2026

Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Adherence to Vaginal Estrogen Therapy in Hypoestrogenic Women With Recurrent Urinary Tract Infections (clinicaltrials.gov) - P4 | N=111 | Active, not recruiting | Sponsor: University of California, Irvine | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jan 2027 ➔ Jun 2027

Enrollment closed • Trial primary completion date • Infectious Disease • Nephrology

REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy (clinicaltrials.gov) - P2 | N=33 | Active, not recruiting | Sponsor: Polly A. Niravath, MD | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy (clinicaltrials.gov) - P2 | N=44 | Active, not recruiting | Sponsor: Polly A. Niravath, MD | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2025 ➔ Dec 2025

Enrollment closed • Trial completion date • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Effects of multiple-dose administration of zavegepant nasal spray on the single-dose pharmacokinetics of ethinyl estradiol-levonorgestrel. (PubMed, Headache) - "Co-administration of zavegepant nasal spray with a single dose of an oral contraceptive resulted in no clinically meaningful changes (<12% increase) in EE-LNG exposure."

Journal • PK/PD data • CNS Disorders • Migraine • Pain

A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses. (PubMed, Nat Immunol) - "Here we constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated KitW-41J mutant immunodeficient pups with human cord blood CD34+ cells, followed by 17β-estradiol conditioning to promote immune cell differentiation...These mice can also develop lupus autoimmunity after pristane injection. By leveraging estrogen activity to support human immune cell differentiation and maturation of antibody responses, THX mice provide a platform to study the human immune system and to develop human vaccines and therapeutics."

Journal • Preclinical • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Respiratory Diseases • CD34 • IFNG • IL4 • TGFB1

METABOLOME AND MICROBIOME ALTERATIONS PROVIDE MECHANISTIC INSIGHT AND PREDICT RESPONSE TO AN INTERMITTENT REDUCED CALORIE DIET IN PATIENTS WITH CROHN'S DISEASE. (DDW 2024) - P=N/A | "Testosterone and estradiol showed increased trend in all patients from baseline to post-IRCD (Fig...This dietary approach may be more effective in individuals with a lower concentration of sex hormones and/or higher Firmicutes abundance in the gut microbiome indicating a potential means to identify patients who may respond to the IRCD (and potentially other diets) a priori . The microbial and metabolomic profiling may discern personalized signatures predicting responsiveness to IRCD."

Clinical • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease

A new humanized mouse mounting mature class-switched, hypermutated and neutralizing antibody responses: estrogen power (IMMUNOLOGY 2024) - "Finally, THX mice develop lupus autoimmunity after one pristane injection. In addition to providing a new and advanced platform to model human immune responses, they reveal and leverage a critical activity of estradiol to promote human immune cell differentiation and maturation of antibody responses."

Preclinical • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Novel Coronavirus Disease • Respiratory Diseases • CD34 • PTPRC

Adherence to Vaginal Estrogen Therapy in Hypoestrogenic Women With Recurrent Urinary Tract Infections (clinicaltrials.gov) - P4 | N=111 | Recruiting | Sponsor: University of California, Irvine

Adherence • New P4 trial • Infectious Disease • Nephrology

Assessment of the Effects of Abrocitinib on the Pharmacokinetics of Probe Substrates of Cytochrome P450 1A2, 2B6 and 2C19 Enzymes and Hormonal Oral Contraceptives in Healthy Individuals. (PubMed, Eur J Drug Metab Pharmacokinet) - P1 | "Based on the study results, abrocitinib is a moderate inhibitor of CYP2C19. Caution should be exercised when using abrocitinib concomitantly with narrow therapeutic index medicines that are primarily metabolized by CYP2C19 enzyme. Abrocitinib is a mild inhibitor of CYP1A2; however, the impact is not clinically relevant, and no general dose adjustment is recommended for CYP1A2 substrates. Abrocitinib does not inhibit CYP3A or induce CYP1A2/2B6/2C19/3A and does not affect the pharmacokinetics of contraceptives."

Journal • PK/PD data • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • CYP2C19

REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Polly A. Niravath, MD | Trial completion date: Jul 2024 ➔ Jul 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Sex differences and estrogen effects in cardiac mitochondria in human aortic stenosis and in the mouse heart. (PubMed, Front Endocrinol (Lausanne)) - "We also examined whether these potential differences may be at least partially due to sex hormones by testing if mitochondrial respiration is affected by estrogen (17ß-estradiol (E2))...E2 and ERβ affect cardiac mitochondrial function in the mouse model, suggesting that they may also contribute to the sex differences in the human heart. Their roles should be further investigated."

Journal • Preclinical • ER

A CASE OF TRANSIENT EXOCRINE PANCREATIC DYSFUNCTION AFTER PFIZER-BIONTECH COVID-19 MRNA VACCINATION. (DDW 2023) - "We present a case of transient exocrine pancreatic insufficiency (EPI) that occurred after administration of the Pfizer-BioNTechCOVID-19 mRNA vaccine (Comirnaty®)...She took loperamide 2 mg four times daily with minimal improvement...Her medications included cholecalciferol 2,000 IU daily, levonorgestrel intrauterine device, estradiol 0.05 mg/24-hour patch, and progesterone 100 mg daily...Due to the severely depressed fecal elastase, she was diagnosed with exocrine pancreatic insufficiency (EPI) and started on pancreatic enzyme supplementation with a pancrelipase (Creon®) 48,000-152,000-240,000 units...Still, causation cannot be confirmed and there is a chance that relationship to the vaccine is incidental. While the benefits of COVID-19 vaccination in prevention of infection are clear, detection and dissemination of rare possible adverse reactions associated with the vaccines is vital to understanding the full clinical implications of these widely used..."

Clinical • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hepatology • Infectious Disease • Long-acting Reversible Contraceptives • Novel Coronavirus Disease • Pancreatitis

Attempting to Unmask the Inhibition of Sulfotransferase 1E1 in 17α-Ethinyl Estradiol Drug Interactions. (PubMed, J Clin Pharmacol) - No abstract available

Journal • SULT1E1

Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells. (PubMed, Int J Mol Sci) - "This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases."

Journal • Cervical Cancer • Endometrial Cancer • Genetic Disorders • Gynecologic Cancers • Immunology • Inflammation • Obesity • Oncology • Solid Tumor • Uterine Cancer • ER • NF-κβ

Ethinylestradiol in combined hormonal contraceptive has a broader effect on serum proteome compared with estradiol valerate: a randomized controlled trial. (PubMed, Hum Reprod) - P4 | "The EE-based COC exerted a broader effect on the serum proteome than the EV-based COC or the DNG-only preparation. These results demonstrate that the effects of EE in COCs go far beyond the established endpoint markers of estrogen action, while the EV combination is closer to the progestin-only preparation. The study indicates that EV could provide a preferable option to EE in COCs in the future and signals a need for further studies comparing the clinical health outcomes of COCs containing EE and natural estrogens."

Journal • Immunology • Inflammation

Boosting Dose of Pfizer-BioNtech mRNA Vaccine Against SARS-CoV-2 Does Not Affect Reproductive Outcomes in In-Vitro Fertilization Patients: A Cohort Study. (PubMed, J Womens Health (Larchmt)) - "Although age differed between study groups, vaccination exposure status did not affect treatment outcome: clinical pregnancy rates, maximal estradiol levels, and number of oocytes retrieved did not differ significantly between study groups (p = 0.78, 0.50, and 0.97, respectively)...Sperm concentration and motility did not differ significantly after boosting (p = 0.49 and 0.49, respectively). Our results provide further reassurance that IVF outcomes are not affected by the anti-SARS-CoV-2 Pfizer-BioNtech mRNA vaccine, in particular the three-dose regimen."

Journal • Preclinical • Gynecology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Polly A. Niravath, MD | Active, not recruiting ➔ Recruiting | Trial completion date: Jul 2022 ➔ Jul 2024 | Trial primary completion date: Dec 2021 ➔ Dec 2023

Enrollment open • Trial completion date • Trial primary completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor