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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

PubMedPhysiological research2026-07-17

Effects and Mechanisms of Action of Acupuncture on Bone and Lipid Metabolism in a Rat Model of Postmenopausal Osteoporosis.

Zhang S-N SN, Zhang C-C CC, Jiang L-H LH, Ouyang G G

This study investigated the effects of acupuncture on bone and lipid metabolism in a rat model of postmenopausal osteoporosis (PMOP). Thirty-two female Sprague-Dawley rats were randomly assigned to four groups: blank control, sham-operated, model (ovariectomy), and acupuncture treatment (ovariectomy plus acupuncture). Following treatment, bone mineral density (BMD), bone tissue morphological changes with quantitative histomorphometry, serum bone metabolism markers, estradiol (E2) levels at multiple time points, body mass index (BMI), blood lipid indicators, inflammatory factors, and gut microbiota composition were measured in each group. Acupuncture increased femoral BMD after adjusting for femoral shaft thickness (P<0.05) and improved trabecular bone structure, with significant rises in trabecular number, thickness, and bone volume fraction (P<0.05). Serum osteoprotegerin levels increased and osteoclast markers decreased. Serial E2 measurements showed progressive restoration from week 4. Acupuncture reduced BMI (P<0.05), with BMI changes negatively correlating with BMD improvements (r=-0.68, P<0.01). Lipid metabolism and inflammatory markers were significantly improved (P<0.05). Gut microbiota analysis indicated increased abundance of Lactobacillus and Bifidobacterium and decreased pathogenic bacteria (P<0.05). Liquid chromatography-mass spectrometry suggested acupuncture may promote osteogenic differentiation via upregulation of the cAMP-PKA-CREB pathway. Overall, acupuncture effectively enhances bone and lipid metabolism in PMOP rats through hormonal regulation, metabolic modulation, and gut microbiota optimization. Key words Acupuncture " Postmenopausal osteoporosis " Bone metabolism " Lipid metabolism " Estradiol " Gut microbiota " cAMP-PKA-CREB pathway.

PMID 42466703
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PubMedJournal of molecular cell biology2026-07-17

Endometrial gland secretome maintains the homeostasis of decidualization.

Lin Leqian L, Li Xintong X, Li Yimeng Y, Li Jianlin J et al.

Decidualization of human endometrial stromal cells (hESCs) during the secretory phase is critical for implantation and pregnancy. In this study, we assessed 25 established in vitro decidualization markers using in vivo single-cell transcriptomic data and found that the expression levels of most of them, including PRL and IGFBP1, were comparable between the proliferative- and secretory-phase hESCs or between the decidualized and non-decidualized hESCs. We hypothesized that the lack of endometrial glands in vitro causes the discrepancy. However, the role of the endometrial glands in decidualization remains unclear. Using a co-culture model, we demonstrated that the secretome of human endometrial organoids attenuates decidualization by reducing canonical marker upregulation and hESC mesenchymal-epithelial transition. Transcriptomic analysis revealed the downregulation of key decidualization regulators CEBPA and EDN1. Consistent with the in vitro findings, an estradiol-stimulated mouse model with increased glandular formation showed reduced decidualization. Collectively, our results identify a novel homeostatic function of endometrial gland secretome in decidualization regulation.

PMID 42466889
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PubMedMolecular oncology2026-07-17

Pharmacological chromatin remodeling enhances response to estrogen therapy in ER+ breast cancer.

Johnson Thomas Anneka L AL, Karakyriakou Barbara B, Muskus Patricia C PC, Roberts Alyssa M AM et al.

Estrogen therapy elicits clinical benefit in ~ 30% of patients with endocrine-resistant estrogen receptor (ER)-positive breast cancer, but its mechanism of action and strategies to increase efficacy remain unclear. Estrogen therapy can induce ER transcriptional hyperactivation and DNA damage; we postulated that such damage could be exacerbated by epigenetic dysregulation via inhibition of histone deacetylases (HDACi). We evaluated the effects of 17b-estradiol and HDACi in three types of ER+ breast cancer models: Cells adapted to growth following long-term estrogen deprivation; cells engineered to overexpress exogenous ER that confers endocrine resistance; mice bearing endocrine-resistant patient-derived xenografts. Assay endpoints included apoptosis, growth, DNA damage, histone post-translational modification, levels of ER-regulated transcripts and encoded proteins, cell cycle and replication status, and genome-wide chromatin accessibility, ER binding, and transcriptional profiles. Entinostat treatment increased histone acetylation and chromatin accessibility. Combination treatment with E2 and entinostat inhibited cell growth and induced apoptosis in ER-overexpressing models. E2 and entinostat induced DNA damage as single agents and in combination. These agents synergized against tumor models, offering HDACi as a strategy to enhance efficacy of estrogen therapy.

PMID 42464636
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PubMedChemico-biological interactions2026-07-17

Sex-Specific Differences in Cadmium Accumulation and Responses in the Freshwater Snail Cipangopaludina cathayensis.

Jinyou Wei W, Shanshan Xiang X, Jing Yu Y, Linli Li L et al.

Cadmium (Cd) is a non-essential element with strong toxicity to aquatic mollusks. Although sex-specific Cd accumulation has been reported, the distinct impacts on males and females and their adaptive strategies remain unclear. We exposed freshwater snails (Cipangopaludina cathayensis) to 0.5 mg/L Cd for 14 days and analyzed Cd accumulation, histology, biochemical indicators, gonadal transcriptomics, and hepatopancreatic metabolomics. Cd levels in ovaries were significantly higher than in testes, while hepatopancreatic levels showed no sex difference. Cd disrupted gonadal antioxidant defenses and induced oxidative stress: testes maintained persistently elevated total superoxide dismutase (T-SOD) and glutathione (GSH), whereas ovarian levels initially rose then declined. Structural damage (seminiferous tubule rupture, follicular wall disruption) and reduced sex steroid hormones (testosterone (T) and estradiol (E2)) further impaired gonadal function. Transcriptomic analysis revealed that testes upregulated protein metabolism pathways (e.g., Protein digestion and absorption, Protein processing in endoplasmic reticulum with HSP70/HSP90) to maintain homeostasis under Cd stress. Hepatopancreatic metabolomics showed disrupted lipid metabolism, with females displaying greater lipid droplet accumulation. Under Cd stress, males retained stronger exogenous nutrient transport and repair capacity, whereas females relied on energy-intensive endogenous synthesis. Overall, Cd effects were more severe in females, highlighting clear sex-specific differences in response and tolerance.

PMID 42462871
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PubMedBiofabrication2026-07-17

Estrogen-loaded scaffolds promote thyrocyte proliferation and endogenous antioxidant expression while preserving functional stability.

Heim Maria M, Handley Ella-Louise EL, Gao Yunxi Y, Mandel Aimee A et al.

Loss of functional thyrocytes following thyroid injury or radiotherapy remains a significant clinical challenge, motivating development of biomaterial-based strategies to support thyroid cell survival and function. 17beta-Estradiol (E2) has been shown to promote thyrocyte proliferation and antioxidant responses, although systemic or bolus delivery may induce cytotoxicity and raises concerns regarding long-term pathological effects. Here, electrospun polycaprolactone (PCL) scaffolds incorporating varying concentrations of E2 were developed as a localized hormone delivery platform for thyroid epithelial cells. E2 incorporation altered scaffold mechanical behaviour, hydrophilicity, and porosity in a concentration-dependent manner while preserving fibre morphology, crystallinity, and thermal stability. Scaffold- mediated E2 delivery supported sustained thyrocyte viability and proliferation compared with bolus E2 exposure, with intermediate E2 concentrations producing the most favourable biological response. Morphological analysis demonstrated extensive cell spreading and organised cytoskeletal structures without features associated with apoptosis. Although E2-loaded scaffolds did not exhibit direct radical scavenging activity, they promoted upregulation of antioxidant-associated genes, indicating indirect modulation of cellular redox homeostasis. Thyroid-specific functional markers associated with hormone synthesis and maintenance of the differentiated thyroid phenotype were largely preserved across scaffold groups during the 14-day culture period. Furthermore, no detectable \textit{BRAF} V600E or V600K mutations were identified under any condition tested. Collectively, these findings demonstrate that electrospun E2@PCL scaffolds provide a tunable microenvironment capable of supporting thyrocyte survival, proliferation, and functional maintenance, highlighting their potential for thyroid tissue engineering applications targeting radiation-induced thyroid injury.

PMID 42462756
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PubMedJournal of applied toxicology : JAT2026-07-17

Melatonin-Zinc MOFs Antimycotic, Molecular, and Antioxidant Protective Effects of Hepatic, Renal, and Testicular Dysfunctions Induced by Aflatoxin B1 in Rats.

Aly Mohamed S MS, Soliman Mona M H MMH, Balabel Esraa A EA, Abdelhameed Reda M RM et al.

Aflatoxin B1 causes renal, hepatic, and reproductive disorders. To investigate the protective effects of melatonin-zinc metal-organic frameworks (Mt-Zn-MOFs) nanoparticles against renal, hepatic, and reproductive toxicity induced by aflatoxins B1, male Sprague-Dawley rats (n = 40) were equally divided into control, Mt-Zn-MOFs, aflatoxins, and Mt-Zn-MOFs + aflatoxins groups. Blood and tissue samples were collected from the livers, kidneys, and testicles. Luteinizing hormone (LH), testosterone, estradiol (E2), interleukin-β (IL-β), transforming growth factor-β (TGF-β), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total antioxidants (TAC), nitric oxide (NO), AST, ALT, and creatinine were measured. Hepatic DNA fragmentation and the expression of CRAT, CYP39A1, and JunB genes were determined. Mt-Zn-MOFs have more antimycotic effects against A. flavus than A. parasiticus, with MIC and MFC of 3.125 and 6.25 mg/mL for A. flavus and 12.5 and 25 mg/mL for A. parasiticus, and 6.25 mg/mL inhibited A. flavus and A. parasiticus sporulation. Mt-Zn-MOFs rats had high (p < 0.001) testosterone, LH, E2, glucose, but low (p < 0.01) SOD, total proteins, albumin, globulin, AST, and ALT, compared to controls. Mt-Zn-MOFs-aflatoxin group had lower (p < 0.01) LH, SOD, GPx, total proteins, globulin, glucose, TGF-β (p < 0.022), DNA fragmentation, and the expressions of JunB, CYP39A1, and CRAT, but high (p < 0.01) NO, CAT, and total cholesterol than aflatoxin-treated rats. Mt-Zn-MOFs protected the liver, kidney, and spermatogenesis to a large extent. Mt-Zn-MOFs maintained normal testicular, hepatic, and renal histopathology in the aflatoxin treatment. Regardless, aflatoxin caused severe renal toxicity, Mt-Zn-MOFs reversed the effects of toxins and restored their normality, and are recommended to treat aflatoxicosis and mycotic infections.

PMID 42464561
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