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ethinylestradiol + norethindrone (Lunabell)

✓ Approved

Nobelpharma Co., Ltd. · ESR1 · Small Molecule

What is ethinylestradiol + norethindrone?

ethinylestradiol + norethindrone is a small molecule developed by Nobelpharma Co., Ltd.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesLunabell
CompanyNobelpharma Co., Ltd.
Drug ClassSmall Molecule
Molecular TargetESR1, PGR
RouteOral (PO)
StatusApproved

Mechanism of Action

Molecular Targets

ethinylestradiol + norethindrone 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

ethinylestradiol + norethindrone is developed for 2 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Reproductive system and breast disordersEndometriosis✓ Approved
Reproductive system and breast disordersDysmenorrhoeaBLA/NDA

Related Research Articles

PubMedJournal of hazardous materials2026-10-16

Molecular transformation of dissolved black carbon during photobleaching and its enhanced role in goethite-mediated 17α-ethinylestradiol anaerobic biotransformation.

Liu Feiyuan F, Ma Weiqing W, Liao Zhicheng Z, Lai Chaochao C et al.

Dissolved black carbon (DBC) is an important component of dissolved organic matter, which undergoes continuous photobleaching in the sunlit surface water. The resulting photobleached DBC (P-DBC) can subsequently be transported across the sediment-water interface into sediments rich in minerals and microbes, thereby regulating the transformation of organic contaminants. This study investigated photobleaching-induced molecular transformation of DBC and the mechanism of P-DBC in goethite-mediated 17α-ethinylestradiol (EE2) anaerobic biotransformation. The results showed that photobleaching promoted the oxidation and decarbonization of DBC, driving its molecular composition toward a higher oxidation state and lower energy density. Intensity and H content were the key molecular features governing the photochemical reactivity of DBC. P-DBC was enriched in oxygen-containing functional groups that could enhance electron transfer with goethite. Additionally, the higher bioavailability of P‑DBC enriched aromatic‑degrading bacteria. Species associated with iron reduction and organic matter transformation in the presence of goethite were increased. As a result, P-DBC combined with goethite significantly promoted the anaerobic biotransformation of EE2, achieving a removal efficiency of 73.0%. EE2 transformation involved de-ethynylation and decarboxylation to yield more oxygenated products, contrasting with co‑metabolism alone. These findings provide new mechanistic insights into the natural attenuation of estrogens in iron-rich aquatic environments.

PubMedInternational journal of molecular sciences2026-10-16

Cynaroside Attenuates Ethinylestradiol-Induced Cholestatic Liver Injury by Modulating the FXR/BSEP/CYP7A1/SHP Axis.

Hamed Amany M AM, Al-Nouri Doha M DM, Mahrous Nadia S NS, Bassit Asmaa Sabry AS et al.

Cholestatic liver diseases are characterized by disrupted bile acid homeostasis, oxidative stress, and inflammation, ultimately leading to progressive hepatic injury. Although ursodeoxycholic acid (UDCA) remains the standard pharmacological therapy, its therapeutic efficacy is limited in several cholestatic conditions. This study investigated the hepatoprotective effects of cynaroside (CYN), a naturally occurring flavonoid glycoside, against ethinylestradiol (EE)-induced cholestatic liver injury and explored its underlying molecular mechanisms. Female Wistar rats were randomly allocated into four groups (n = 7): control, EE, EE + CYN, and EE + UDCA. Liver function indices, bile acids, cholesterol, oxidative stress and inflammatory biomarkers, histopathology, immunohistochemistry, Western blotting, qRT-PCR, and molecular docking analyses were performed. EE administration induced pronounced cholestatic liver injury, as evidenced by impaired liver function, hepatic accumulation of bile acids and cholesterol, oxidative imbalance, inflammatory responses, and marked histopathological alterations. CYN significantly ameliorated these biochemical and histological abnormalities, reduced hepatic bile acid and cholesterol accumulation, restored redox homeostasis, and attenuated inflammatory responses. Mechanistically, CYN modulated the hepatic FXR/BSEP/CYP7A1/SHP regulatory network, modulated hepatic FXR and Nrf2 protein expression, suppressed NF-κB activation, and favorably regulated TNF-α, IL-1β, and BCL2 expression. Histopathological and immunohistochemical findings further confirmed substantial preservation of hepatic architecture following CYN treatment. Molecular docking revealed favorable interaction of CYN with the FXR ligand-binding domain, with a predicted binding free energy of -8.18 kcal/mol, comparable to that of UDCA (-7.95 kcal/mol). Cynaroside attenuated EE-induced cholestatic liver injury by improving bile acid homeostasis and mitigating oxidative and inflammatory responses, potentially by modulating FXR-associated signaling and its downstream regulatory network. Collectively, the results provide a rationale for continued investigation of cynaroside in the context of cholestatic liver injury.

PubMedBehavioral ecology : official journal of the International Society for Behavioral Ecology2026-10-14

Widespread endocrine-disrupting pollutant alters male courtship behavior in a livebearing fish.

Ozeki Shiho S, Renner Anna A, Rafeeq Raiko R, Beynon-Fankhauser Jason J et al.

Sexual selection is a potent evolutionary force shaping both precopulatory courtship behavior and postcopulatory sperm traits, with male reproductive effort often adjusted to social and mating context. Endocrine-disrupting contaminants are predicted to alter how males allocate reproductive effort, yet their behavioral effects across different mating contexts remain poorly understood. We examined whether exposure to 17α-ethinylestradiol (EE2; 43 to 1,100 ng/L), a synthetic estrogen used in the contraceptive pill that enters aquatic systems via wastewater effluent, alters male courtship behavior and sperm traits in a freshwater fish (Dermogenys collettei). Using assays in which males encountered females either sequentially or simultaneously, we quantified courtship behavior and latency to interact, alongside sperm viability, morphology, and performance. Exposure to high EE2 consistently reduced male mating effort. Exposed males were slower to initiate interactions with females and expressed less courtship behavior in both sequential and simultaneous assays. In contrast, EE2 had no detectable effects on sperm traits, and male preferences for female gravid spot size were unaffected. These findings suggest estrogenic pollution can disproportionately reduce mating effort, revealing a decoupling between behavioral and postcopulatory responses.

PubMedInternational journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics2026-10-12

RETRACTION: Combined Contraceptive Ring Versus Combined Oral Contraceptive (30-μg Ethinylestradiol and 3-mg Drospirenone.

A.M.M. Mohamed, W.S.M. El-Sherbiny, and W.A.I. Mostafa, "Combined Contraceptive Ring Versus Combined Oral Contraceptive (30-μg Ethinylestradiol and 3-mg Drospirenone," International Journal of Gynecology & Obstetrics 114, no. 2 (2011): 145-148, https://doi.org/10.1016/j.ijgo.2011.03.008. The above article, published online on 12 June 2011 in Wiley Online Library (wileyonlinelibrary.com) has been retracted by agreement between the journal Editor-in-Chief, Michael Geary; and John Wiley & Sons Ltd. Concerns were raised on PubPeer [1] of the viability of the study, which measured several features every three months for a year, including a 12 month follow up, but with only three authors and no listed funding. An unusual pattern involving the last digit of the standard deviations reported in Table 5 was also noted. A review by the editorial team, which included re-calculation of the statistical data, identified further statistical anomalies in Tables 1, 2, and 4 that are incompatible with the reported results. When reached for clarification and access to the full set of study data, the authors were unable to provide the data as the study was conducted more than 10 years ago. They did provide a response to the editorial team's assessment. Lacking the study data for further analysis, along with the inconsistencies present in several places in the article, the Editor-in-Chief considers the data and conclusions to be unreliable. Therefore, a retraction is warranted. [1] B. Mol, "Combined Contraceptive Ring Versus Combined Oral Contraceptive (30-μg Ethinylestradiol and 3-mg Drospirenone," PubPeer 2026, https://pubpeer.com/publications/60212B830C0D42151398B9384FDD6A.

PubMedDrug and chemical toxicology2026-10-12

Enhanced reproductive toxicity following combined exposure to ethinylestradiol and levonorgestrel: evidence of non-additive endocrine disruption in male rats.

Belhamzaoui Khaled K, Dahdouh Faouzi F, Djebbar Mohamed-Réda MR, Berrebbah Houria H et al.

Ethinylestradiol (EE2) and levonorgestrel (LNG) are synthetic hormones widely used in contraceptives and increasingly recognized as endocrine-disrupting contaminants. Although their individual reproductive effects are documented, their combined toxicity remains poorly understood. This study evaluated the sub-chronic reproductive toxicity of EE2 and LNG, administered alone or in combination, in male Wistar rats, with emphasis on potential non-additive endocrine-disrupting interactions. Animals were orally treated with EE2 (1 µg/kg bw), LNG (5 µg/kg bw), or both for four weeks. Individual exposures caused significant alterations in testicular weight, hormone levels, oxidative stress markers, and sperm quality, whereas epididymal weight was not significantly affected. In contrast, combined exposure markedly intensified these effects, causing severe spermatogenic impairment, near-complete sperm depletion, and major histological damage in testicular tissue. This enhanced toxicity was associated with increased lipid peroxidation, reduced antioxidant defenses, and marked suppression of testosterone, FSH, and LH levels, indicating disruption of the hypothalamic-pituitary-gonadal axis. Two-way factorial analysis confirmed statistically significant EE2 x LNG interactions for testicular weight, sperm concentration, sperm motility, LH and testosterone; in each case the observed combined effect was smaller than predicted by effect addition, indicating an infra-additive rather than synergistic interaction, consistent with a floor effect at these already substantial individual effect sizes. These findings highlight the importance of assessing combined endocrine disruptor exposures, as mixture effects modify reproductive toxicity in ways not predictable from single-compound data alone.

PubMedEnvironmental science and pollution research international2026-10-12

Cross-enterprise occurrence patterns and monitoring priorities of shared organic contaminants in pharmaceutical wastewater.

Chen Qian Q, Li Meitong M, Shao Minghui M, Lei Jiayu J et al.

Pharmaceutical manufacturing wastewater contains diverse organic chemicals, yet contaminants recurrently detected across enterprises remain insufficiently characterized. In this study, composite effluents from the final discharge outlets of ten pharmaceutical enterprises in China were analyzed using liquid chromatography-high-resolution mass spectrometry-based non-target screening. Principal component analysis, exploratory Spearman co-variation analysis, BIOWIN biodegradability prediction, predicted no-effect concentration (PNEC) evidence evaluation, and a peak-area-based screening-level prioritization framework were integrated to characterize shared contaminants and identify candidates for follow-up monitoring. A total of 1862 features were detected, and 347 compounds across 20 chemical classes were annotated. Fourteen contaminants detected in all ten enterprises were selected based on MS/MS matching and relative peak-area criteria. Their relative LC-HRMS signal profiles varied mainly along a continuous cross-enterprise gradient, while several contaminant groups showed synchronous variation across samples. BIOWIN classified eight shared contaminants as readily biodegradable and six as not readily biodegradable. By jointly considering predicted biodegradability, PNEC evidence quality, relative peak-area signals, and annotation confidence, norethindrone and norgestrel were identified as high-priority candidates for screening-level monitoring. C12-AE1S remained a tentative tracking candidate requiring structural confirmation and treatment-behavior evaluation. These findings indicate that monitoring priorities should not be determined by detection frequency or relative LC-HRMS signal intensity alone. This screening approach provides a practical basis for selecting recurrent contaminants for targeted quantification, source investigation, and treatment verification in pharmaceutical wastewater.

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