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estradiol +levonorgestrel (Fem7 Plus / HRT, Merck)

✓ Approved

Merck KGaA · ESR1 · Small Molecule

What is estradiol +levonorgestrel?

estradiol +levonorgestrel is a small molecule developed by Merck KGaA. It is approved for therapeutic indications via topical or transdermal.

Drug Profile

Brand NamesFem7 Plus, HRT, Merck
CompanyMerck KGaA
Drug ClassSmall Molecule
Molecular TargetESR1, PGR
RouteTopical, Transdermal
StatusApproved
Sources: ClinicalTrials.gov, Merck KGaA

Mechanism of Action

Molecular Targets

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

Therapeutic AreaConditionPhase
Surgical and medical proceduresHormone replacement therapy✓ Approved

Related Research Articles

PubMedDrug and alcohol dependence reports2026-08-30

Exploring hormonal influences on nicotine craving and use across the perinatal period: A prospective longitudinal study.

Allen Alicia M AM, Baurley James J, Linde-Krieger Linnea B LB, Chalke Arushi A et al.

Perinatal nicotine use is common despite well-documented adverse consequences. We examined associations between reproductive-related hormones with nicotine craving and use during the perinatal period to identify potential novel intervention points. All participants reported use of nicotine during the perinatal period. Participants were enrolled at gestational week ≥ 36 and followed to postpartum week 12 via daily surveys (i.e., nicotine craving via 100-point scale, dichotomous use) and weekly hormone measurement in saliva (cortisol, oxytocin) or dried blood spots (progesterone, estradiol, testosterone, dehydroepiandrosterone sulfate). Bayesian mixed-effects models accounted for within-person correlation while estimating hormone effects. Participants (n = 46) were 28.9 ± 4.9 years old. During follow-up, exclusive combustible cigarettes (n = 20), electronic nicotine delivery systems (ENDS; n = 13), or dual (n = 2) use was observed, with variability in use and craving across participants and over time. During pregnancy, higher oxytocin was linked to greater craving (β=16.31, 95% CI: 3.71, 28.83). Greater peripartum declines in oxytocin were associated with more craving (β=8.71, 95% CI: 0.75, 16.93) and use (β=1.13, 95% CI: 0.05, 2.43). During postpartum, lower estradiol was linked to more craving (β=-1.17, 95% CI: -2.15, -0.18) and use (β=-0.40, 95% CI: -0.76, -0.03). In models simultaneously evaluating all postpartum hormones, the lone meaningful association was between estradiol and craving (β=-1.66, 95% CI: -2.84, -0.48). The results of this study suggest that oxytocin and estradiol may contribute to the risk of perinatal nicotine use. Additional research is needed to replicate our observations in more diverse study samples and explore implications for clinical intervention.

PMID 42668554
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PubMedJournal of chromatography. A2026-08-29

Preparation of molecularly imprinted polymers based on core-shell magnetic mesoporous silica and application in the determination of estradiol.

Wen Jie J, Han Xiufen X, Zhou Qing Q, Zhai Haiyun H

A selective adsorbent was fabricated and evaluated for its applicability to trace E2 analysis by grafting a molecularly imprinted polymeric shell onto a magnetic nanoparticle encased in a mesoporous SiO2 layer (denoted Fe3O4@mSiO2@MIP) with E2 as the imprinting template. The morphology and microstructure of the resulting Fe3O4@mSiO2@MIP were characterized by scanning electron microscopy and transmission electron microscopy, and its functional groups were determined by Fourier-transform infrared spectroscopy. Its adsorption performance was investigated through kinetic, thermodynamic, and selectivity studies, and relevant models were adopted to interpret the adsorption mechanism. Adsorption followed pseudo-second-order kinetics and was well described by the Freundlich isotherm, yielding a capacity of 4.01 mg g-1 within 30 min together with a notable imprinting factor (2.36). Compared with the control non-imprinted material (Fe3O4@mSiO2@NIP), the imprinted sorbent (Fe3O4@mSiO2@MIP) exhibited markedly enhanced adsorption toward E2. Under the optimized magnetic solid-phase extraction (MSPE) conditions, an MSPE-HPLC-UV method was established for determining E2 residues in egg and milk samples. The method achieved an enrichment factor of 36 with satisfactory recoveries ranging from 86.7% to 101.2%. Furthermore, the prepared Fe3O4@mSiO2@MIP could be regenerated and reused for at least seven cycles, confirming its feasibility for practical use.

PMID 42667767
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PubMedBiosensors & bioelectronics2026-08-29

Responsive reconstruction-driven autocatalysis DNA circuit for efficient and amplifiable electrochemical biosensing.

Song Honglin H, Chen Zhixuan Z, Zhou Yifu Y, Liu Si S et al.

To overcome low strand utilization and slow kinetics in traditional entropy-driven DNA circuits, herein we propose a novel responsive reconstruction-driven Autocatalysis DNA Circuit (rrADC) for constructing highly sensitive electrochemical biosensor. Using 17β-estradiol as a targeted ligand, the specific ligand-aptamer binding triggers the release of an initiator strand (I) via magnetic separation. To operate rrADC process, two single strands (s and s‾) each encoding with one split of I, together with a linker strand are designed to assemble a three-stranded duplex substrate. Upon invading by the as-interpreted I, strand migration reactions are activated to displace s, and further liberate s‾ and I by a fuel strand, till perfect complementary hybridization. The released s and s‾ instantly pair to form a double-stranded duplex via conformational ordering process, in which an analogue of I (I*) in the merged tails is reconstructed as endogenous trigger and cooperates with I to execute repeated interferences for catalyzing rrADC forward for cycling amplification. In the resulting complexes, the labeled electroactive ferrocene generates dose-dependent electrochemical current signal in the modified electrode surface. The distinct structural ordering of the whole system sustains continuous, efficient rrADC operation with minimized steric hindrance, maximized strand utilization and accelerated reaction kinetics. By reusing otherwise discarded intermediate strands, the biosensor achieves an ultralow E2 detection limit of 16.6 fM. This strategy offers a new paradigm for simplified, enzyme-free, efficient electrochemical biosensing to detect trace environmental pollutants and biomolecules.

PMID 42667725
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PubMedThrombosis and haemostasis2026-08-28

Divergent Effects of Estradiol Regimens on Protein S and Global Coagulation in Transgender Women.

Bar-On Shelly S, Barzilai Merav M, Greenman Yona Y, Spectre Galia G et al.

Sublingual estradiol is increasingly used for gender-affirming hormone therapy (GAHT), but its chronic hemostatic effects remain insufficiently characterized. To compare hemostatic changes between oral estradiol plus cyproterone acetate (CPA) with divided-dose sublingual estradiol monotherapy in treatment-naive transgender women. In this prospective, non-randomized study, 30 treatment-naïve transgender women received oral estradiol 2 mg once daily plus CPA 10 mg daily (n=15) or sublingual estradiol 0.5 mg four times daily without an anti-androgen (n=15) for 6 months. Free Protein S antigen, Protein C, thrombin generation assay (TGA), and thromboelastography (TEG) were assessed at baseline and 6 months. Free Protein S antigen decreased in all participants receiving sublingual estradiol (median change, -22%; p<0.001), compared with a smaller, heterogeneous change with oral estradiol plus CPA (median change, -4.2%; p=0.099). At 6 months, median free Protein S antigen was 77% versus 106%, respectively (p=0.003). After adjustment for baseline Protein S and age, sublingual treatment remained associated with lower 6-month levels (B=-15.8; p<0.001). TGA lag time decreased by a median of 19% in the sublingual group, but the between-group difference was not significant after correction (adjusted p=0.063).TEG maximum amplitude increased modestly with oral estradiol plus CPA and differed between groups after correction (adjusted p=0.009), although values remained within physiological ranges. No thrombotic events occurred. The two GAHT protocols were associated with different laboratory hemostatic patterns, including a reduction in free Protein S antigen with sublingual estradiol. These findings warrant further evaluation in larger mechanistic studies.

PMID 42665010
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PubMedClinical biochemistry2026-08-28

Detection of individual false-low total bilirubin results in neonates and young infants using the bilirubin-to-icteric index ratio.

Nwoke Chinelo C, Griffiths Rachel L RL, Harris Steve S, Kalaria Tejas T

Individual analytical errors in neonatal and infant bilirubin testing may pose serious clinical risk, for example, when very small samples are incompletely aspirated without triggering analyser error flags, causing falsely low results which may mask dangerous levels. Because the routinely measured icteric index (ICT) correlates with bilirubin, we evaluated whether a total bilirubin-to-icteric index ratio (TBIL/ICT) could identify discrepantly low TBIL results. The study comprised two phases. In the threshold-derivation phase, routinely reported TBIL results were reviewed for infants aged ≤90 days with ICT >26 from Abbott Alinity platforms across three laboratories between June 2023 and May 2024. Visual outliers in the TBIL-ICT relationship were used to derive a TBIL/ICT threshold. The derived threshold was implemented, and triggered cases were reviewed over 19 months from June 2024 to December 2025 in the post-implementation assessment phase. In the derivation cohort of 12,057 qualifying samples, TBIL correlated strongly with ICT (Pearson r = 0.918, p < 0.001; Passing-Bablok regression TBIL = 0.708 × ICT + 13.361). Forty-nine samples (0.41%) were classified as visual outliers. A TBIL/ICT threshold <0.54 detected all visual outliers, with 99.9% specificity and 84.5% positive predictive value (PPV) against visual outlier classification. During the post-implementation assessment, 69 (0.19%) of 35,820 eligible samples triggered the TBIL/ICT <0.54 threshold. Of these, 55 (79.7%) were classified as individual false-low TBIL errors, seven (10.1%) as genuine results, and seven were unclassifiable. PPV was 79.7% for all flagged samples, and 88.7% when excluding unclassifiable samples. A TBIL/ICT ratio < 0.54 demonstrated a good PPV in detecting false-low TBIL results in infants on the Abbott Alinity system and provided a feasible, low-burden safeguard. Platform-specific validation is required before the adoption of TBIL/ICT on other systems.

PMID 42665243
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PubMedBrain, behavior, & immunity - health2026-08-28

Positive association between sex hormones and inflammatory cytokines in trauma-exposed premenopausal women.

Tahmin Chowdhury Ibtida CI, Kim Jihyun J, Corbin Chasity C, Bracewell Danline D et al.

Young women are disproportionately affected by trauma, developing post-traumatic stress disorder (PTSD) at roughly twice the rate of men. Elevated levels of C-reactive protein, Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) are frequently found in individuals with trauma history. Given that sex hormones have been shown to have a broad range of both pro- and anti-inflammatory effects, the purpose of our study was to investigate associations of subclinical inflammation and sex hormones in trauma-exposed premenopausal women. We hypothesized that circulatory levels of sex hormones, particularly estradiol, would be negatively associated with concentrations of inflammatory cytokines in our cohort of premenopausal women, underscoring the potent cardioprotective nature of estradiol via inhibition of inflammation. We recruited 113 trauma-exposed (56.5% with PTSD) premenopausal women [Age (28 ± 7 years), BMI (27 ± 6 kg/m2)]. We collected blood samples to quantify serum levels of sex hormones, inflammatory cytokines, using the quantitative sandwich enzyme immunoassay technique (ELISA) and a Luminex assay, respectively. A composite inflammatory score was derived from eleven inflammatory biomarkers (IL-1α, IL-1β, IL-1ra, IL-6, IL-8, IL-17E, MCP-1, IFN-γ, TNF- α, IL-6R, TNF-R2) using principal component analysis. Linear regression models on the entire sample revealed that higher circulatory levels of estradiol and progesterone were associated with higher subclinical inflammation. These findings are contrary to our hypothesis and suggest that trauma and psychopathology in premenopausal women might affect how the immune system responds to circulating levels of sex hormones.

PMID 42662811
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