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estradiol + norethisterone (Estrapak 50 / Sequidot / Estrapack)

✓ Approved

Novartis AG · ESR1 · Small Molecule

What is estradiol + norethisterone?

estradiol + norethisterone is a small molecule developed by Novartis AG. It is approved for therapeutic indications via topical or transdermal.

Drug Profile

Brand NamesEstrapak 50, Sequidot, Estrapack
CompanyNovartis AG
Drug ClassSmall Molecule
Molecular TargetESR1, PGR
RouteTopical, Transdermal
StatusApproved
Sources: ClinicalTrials.gov, Novartis AG

Mechanism of Action

Molecular Targets

estradiol + norethisterone acts on 2 molecular targets:

ESR1estrogen receptor 1 (ER, ESR)
PGRprogesterone receptor (NR3C3, PR)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

estradiol + norethisterone is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Surgical and medical proceduresHormone replacement therapy✓ Approved

Related Research Articles

PubMedBasic & clinical pharmacology & toxicology2026-05-25

Xiao-Jie-An Capsule Attenuates Oestrogen- and Progestogen-Induced Mammary Gland Hyperplasia by Modulating Sex Hormone Levels and Reducing Inflammatory Response.

Tang Kecheng K, Ying Yi Y, Lu Feng F, Liu Jihan J et al.

Xiao-Jie-An capsule (XJA), a traditional Chinese medicine formulation consisting of six herbal components, has been used to treat MGH for a long time. Aim of this study was to determine the therapeutical impact of XJA on an MGH rat model and the underlying mechanism. The MGH model was established by daily intramuscular injections of estradiol benzoate (0.5 mg/kg) for 25 days, then progesterone (5 mg/kg) for 5 days. Network pharmacological analysis and molecular biological assays were conducted to determine the pharmacological targets of XJA. XJA significantly reduced nipple height and diameter and effectively suppressed histopathological hallmarks of MGH. Additionally, XJA markedly decreased the expression of Ki67 and the expression of proliferating cell nuclear antigen, increased the terminal deoxynucleotidyl transferase dUTP nick-end labelling and lowered the Bcl-2/Bax ratio in mammary tissue of MGH rats. Furthermore, XJA modulated endocrine disorder by reducing blood follicle-stimulating hormone and estradiol (E2), while increasing luteinising hormone and androgen concentrations. Concomitant anti-inflammatory effects were found by decreased pro-inflammatory cytokines IL-1β, IL-2, IL-6 and TNF-α; inhibited TLR4 expression and attenuated NF-κB phosphorylation. Our experimental results suggest that XJA effectively mitigated oestrogen- and progesterone-induced MGH by modulating sex hormone levels and reducing inflammatory response.

PMID 42178624
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PubMedInternational journal of chronic obstructive pulmonary disease2026-05-25

Genetic and Molecular Interconnections Between Chronic Obstructive Pulmonary Disease and Osteoporosis: Insights from Single-Cell and Mendelian Randomization Analyses.

Xue Cheng C, Liu Pengcheng P, Zhao Siguo S, Wei Aobo A et al.

Chronic obstructive pulmonary disease (COPD) and osteoporosis are common comorbid conditions, both of which impose a significant health burden. This research employs single-cell data and Mendelian randomization analysis to pinpoint genes associated with both conditions and investigate their possible mechanistic links. Single-cell datasets pertaining to chronic obstructive pulmonary disease and osteoporosis were subjected to analysis to identify DEGs. Mendelian Randomization analysis was employed to prioritize key causal genes. Subsequent functional profiling encompassed the reconstruction of gene regulatory networks, evaluation of Chemical-disease associations, annotation of specific cell types, and development of pseudo-time trajectory models, along with immune cell infiltration analysis, molecular docking, and molecular dynamics simulations. Single-cell analysis found 2,623 genes linked to chronic obstructive pulmonary disease and 2,454 to osteoporosis, with 161 genes upregulated and 106 downregulated in both. Mendelian randomization analysis identified PADI4 and TUBB2A as key regulators. The MAPK signaling pathway was a critical shared pathway. Molecular docking and molecular dynamics simulations revealed strong binding potential between BPA, TCDD, estradiol and the target proteins. NK cells were identified as a key cell type in COPD, and monocytes in osteoporosis. Pseudo-time analysis revealed distinct developmental trajectories for NK and monocyte subpopulations. This study identifies PADI4 and TUBB2A as potential genetic links between COPD and osteoporosis, and highlights BPA, TCDD, and estradiol as potential chemical factors, providing insights into their shared molecular mechanisms.

PMID 42180802
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PubMedFrontiers in endocrinology2026-05-25

Efficacy and safety of dydrogesterone monotherapy versus estradiol-dydrogesterone combination therapy in perimenopausal women: a real-world cohort study.

Liu Shuaiting S, Zeng Yuhui Y, Huang Zhen Z

To compare the 12-week effectiveness and safety of dydrogesterone monotherapy versus estradiol-dydrogesterone (E2/DYD) combination therapy in women with perimenopausal symptoms in a real-world clinical setting. This retrospective cohort study included 150 women treated at a tertiary gynecological outpatient clinic between July 2022 and January 2025 (dydrogesterone: n=60; E2/DYD: n=90). The primary endpoint was change in the Kupperman Menopause Index (KMI) from baseline to week 12. Repeated measures were analyzed using linear mixed-effects models. Secondary outcomes included clinical response (≥50% KMI reduction), endometrial thickness change, and adverse events. Continuous outcomes were evaluated using adjusted linear regression models, and binary outcomes were analyzed using Firth penalized logistic regression. At 12 weeks, KMI decreased by 8.0 ± 6.6 points in the dydrogesterone group and 12.5 ± 7.4 points in the E2/DYD group (adjusted mean difference -4.51, 95% CI -6.90 to -2.12; p<0.001). Clinical response occurred in 31.5% and 51.2% of participants, respectively (adjusted OR 2.08, 95% CI 1.02-4.45; p=0.042). Improvements in vasomotor and mood-related symptoms were more pronounced in the combination group. Endometrial thickness increased modestly in the E2/DYD group (+0.60 mm), with week-12 mean values remaining within physiologic ranges. Any adverse event was reported in 11.1% versus 31.7% of participants (adjusted OR 3.55, 95% CI 1.29-9.77; p=0.014), predominantly mild and self-limited events. In this real-world cohort, E2/DYD combination therapy was associated with greater short-term symptom reduction compared with dydrogesterone monotherapy. Although adverse events were more frequent with combination therapy, they were generally mild and clinically manageable, and no concerning endometrial safety signals were observed over 12 weeks. As a retrospective observational study, causal conclusions cannot be drawn, and these findings should be regarded as hypothesis-generating. They provide real-world contextual evidence to inform clinical discussions around hormone therapy selection in perimenopausal care, pending confirmation in prospective randomized trials.

PMID 42181196
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PubMediScience2026-05-25

Distinct 2-phenylimidazo[1,2-a]pyridine derivatives that inhibit breast cancer cell proliferation identified as AHR ligands.

Koellisch Katrin K, Blattner Christine C, Motta Stefano S, Wesslowski Janine J et al.

X15695 is a 2-phenylimidazo[1,2-a] pyridine derivative previously described as an orally active, selective estrogen receptor (ER) degrader that inhibits the proliferation of ER+ breast cancer cells. Here, we show that X15695 and derivatives are aryl hydrocarbon receptor (AHR) ligands. Knockout of AHR abolishes the anti-proliferative property of the imidazopyridine derivatives. In the presence of estradiol, X15695 and derivatives outperform the standard of care drug fulvestrant in suppressing the growth of ER+ breast cancer cells, expressing either the wild-type or clinically relevant ER mutant forms (Y537S and D538G) and of patient-derived organoids established from ER+ tumors. Using computational techniques, we discovered that a low pKa value resulting from electron-withdrawing substituents in the 2-phenylimidazo[1,2-a] pyridine compounds is a key feature that identifies them as potent AHR ligands, leading to the potential discovery of additional derivatives for future therapeutic development.

PMID 42181287
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PubMedScientific reports2026-05-25

VISFATIN: a novel modulator of placental endocrinology under physiological and pathological conditions-in vitro studies involving INSR, ERK1/2, and PKA signalling pathways.

Dawid Monika M, Gieras Wiktoria W, Milewicz Tomasz T, Rak Agnieszka A

This study aimed to determine the in vitro effects of visfatin on selected endocrine mediators in the human placenta. Using placental BeWo cells and villous explants from normal pregnancies and those complicated by intrauterine growth restriction (IUGR), preeclampsia (PE), and gestational diabetes mellitus (GDM), we determined the effects of visfatin on 3β-hydroxysteroid dehydrogenase (3β-HSD), aromatase (CYP19), human chorionic gonadotropin (hCG), human placental lactogen (hPL), placental growth hormone (GH2) expression, and the secretion of progesterone (P4), estradiol (E2) and mentioned protein hormones. We also investigated the effects of visfatin on the phosphorylation of protein kinase A (PKA), and hormone secretion after the pharmacological inhibition of insulin receptor (INSR), extracellular signal-regulated kinase 1/2 (ERK1/2), and PKA. We noted that visfatin increased or decreased the mRNA and protein expression of HSD3B1/3β-HSD, CYP19A1/CYP19, CGB3/hCG, CSH1/hPL, and GH2/GH2 in the tested groups. Additionally, visfatin lowered the secretion of P4, E2, hCG, hPL, and GH2 in BeWo cells and normal placenta, but modulated it in placenta explants from the pathological groups. The secretion of E2, hPL and GH2 was mediated by INSR, ERK1/2, and PKA, while P4 by INSR and ERK1/2. These data indicated that visfatin acting via selected molecular pathways may be an important regulator of placental endocrine function during normal and complicated pregnancies.

PMID 42178336
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PubMedFrontiers in endocrinology2026-05-25

Transgenerational exposure to plastics-derived endocrine-disrupting bisphenol A and its analogs on male infertility: impact of gut dysbiosis and epigenetic regulation.

Basak Sanjay S, Varma Saikanth S, Nag Subhalakshmi S, Duttaroy Asim K AK

Global declines in male fertility, characterized by reduced sperm count, motility, and quality, raised concerns about environmental exposures to estrogen-mimicking endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA), and reproductive dysfunction. BPA exposure in vivo has been shown to alter gut microbial composition, diversity, and metabolites, leading to dysbiosis. Such gut alterations modulate systemic inflammation, estrogen bioavailability, and the endocrine-immune axis, thereby affecting gonadal function. Even though the gut is the largest endocrine organ in the body, directly regulating multiple metabolites that reach the circulation and influence the functions of peripheral organs and systems, little is known about epigenetic perturbations due to exposure to plastic-derived endocrine-disrupting bisphenols and their role in gut dysbiosis and male infertility risks. Recent evidence on the fetal programming of bisphenol exposure suggests such events can also impact epimutation states beyond diet, potentially carrying across generations. BPA can diffuse across the membrane and enter the nucleus, altering transcription of target genes by modifying nuclear receptor activity and gene promoter methylation, similar to estradiol, a steroid hormone. The genomic imprint is modulated by gene-chemical interactions, which predominantly result in epigenetic alterations. In particular, BPA exposure in utero altered the epigenome, highlighting the urgent need for transgenerational assessment. This narrative review conducted a thorough review of the available data to emphasize the transgenerational impacts of BPA exposure on male infertility risk and the roles of the gut-reproductive axis, underscoring the importance of further research in this area.

PMID 42181199
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