Estring (estradiol) / Pfizer - LARVOL DELTA

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

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

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

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

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

"FWIW, @pfizer is the *only* supplier of Depo-Estradiol, and won’t have orders filled until December." (@rabid_child)

"I love Estrings for pessary users, but the insurance coverage is usually so poor and @pfizer cut me off from samples. Booooooooooo" (@drquinngyn)

Reimbursement

Dydrogesterone and 20α-dihydrodydrogesterone plasma levels on day of embryo transfer and clinical outcome in an anovulatory programmed frozen-thawed embryo transfer cycle: a prospective cohort study. (PubMed, Hum Reprod) - P=N/A | "Daily 10 mg DYD (tid) in an artificial FET cycle is potentially a suboptimal dose for a proportion of the population. Measurement of DYD or DHD levels could be used interchangeably for future studies. The pharmacokinetics of oral DYD and associated reproductive pharmacodynamics need further study."

Clinical data • Journal • Gynecology

Model for Long Acting Injectables (Depot Formulation) Based on Pharmacokinetics and Physical Chemical Properties. (PubMed, AAPS J) - "The PK predictions for several drugs such as estradiol, risperidone, medroxyprogesterone acetate (MPA), and ziprasidone showed how these predictions can guide scientists to target specific depot doses and release rates into the depot formulation...The framework, prediction tools, and depot map will reduce the need for semi-empirical formulation work and preclinical studies to design depot formulations. Graphical Abstract."

Journal • PK/PD data

"Please @costplus please add drugs like @novonordiskus #ozempic @pfizer #Estradiol @SanofiUS #Insulin" (@HIsalvetti)

Estrogen, Probiotics and Vaginal Health to Prevent HIV Infection in ACB Women (clinicaltrials.gov) - P1; N=50; Completed; Sponsor: McMaster University; Recruiting ➔ Completed; N=80 ➔ 50; Trial completion date: Mar 2022 ➔ Dec 2021

Clinical • Enrollment change • Trial completion • Trial completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

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: Dec 2020 ➔ Jul 2022; Trial primary completion date: Dec 2019 ➔ Dec 2021

Enrollment closed • 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

NSABP FB-13: An assessment of the biological and clinical effects of palbociclib with ovarian suppression and letrozole in the neoadjuvant treatment of pts (pts) with premenopausal (preM) estrogen-receptor positive/HER2-negative primary breast cancer (SABCS 2019) - P2; "Pts in both cohorts will receive letrozole 2.5 mg by mouth daily, pal 125 mg by mouth daily for 21 days of a 28-day cycle, and goserelin 3.6 mg SQ injection every 28 days...A 4-wk estradiol level in the postmenopausal range will be required to receive further treatment...Present accrual and target accrual: Currently 12 of a planned 76 pts have been enrolled. NSABP Operations contact information: Diana Gosik, Diana.Gosik@nsabp.org NCT03628066 SUPPORT: Genomic Health Inc, Pfizer, NSABP Foundation"

Clinical • ER • HER2