Delving into the Latest Updates on Estradiol/Norethindrone Acetate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Compound Estradiol, Compound Estradiol Patches, Estradiol/Norethisterone acetate

+ [17]

Target

ER x PR

Mechanism

ERs agonists(Estrogen receptors agonists), PR agonists(Progesterone receptor agonists)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseSkin and Musculoskeletal Diseases+ [2]

Active Indication

Vascular DiseasesOestrogen deficiencyOvarian Insufficiency+ [6]

Inactive Indication-

Originator Organization

Noven Pharmaceuticals, Inc.

Active Organization

Noven Pharmaceuticals, Inc.Kunming Sinoway Natural PharmaceuticalsNovo Nordisk, Inc.

+ [4]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (07 Aug 1998),

Hot FlashesHypoestrogenismMenopausal symptoms+ [2]

Regulation-

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Structure

Molecular FormulaC22H28O3

InChIKeyIMONTRJLAWHYGT-ZCPXKWAGSA-N

CAS Registry51-98-9

View All Structures (2)

The objective of this study is to demonstrate the efficacy and safety of BG2109 administered orally once daily at a dose of 100 mg alone or of 200 mg in combination with add-back hormone replacement therapy (ABT: estradiol (E2) 1 mg / norethisterone acetate (NETA) 0.5 mg) versus placebo, while under randomized treatment, in the management of moderate to severe endometriosis-associated pain (EAP) in chinese women with surgically confirmed endometriosis

Start Date14 Jul 2023

Sponsor / Collaborator

Shanghai Baozheng Pharmaceutical Technology Co., Ltd.

NCT06358014 / RecruitingNot ApplicableIIT

Beijing Anding Hospital Affiliated to Capital Medical University

After menopause, there is a certain tendency towards depression, with the risk of developing depression being about 3 to 4 times higher than before menopause. Additionally, postmenopausal women experience varying degrees of cognitive decline, which are closely associated with hormonal changes. Therefore, we should pay more attention to the cognitive levels of postmenopausal depression patients. Increasing evidence suggests that changes in cognitive function during menopause may be related to the effects of estrogen on cognitive function, and estrogen therapy can effectively improve cognitive decline. Estrogen is not only associated with cognitive symptoms after menopause, but estrogen intervention is also an adjunctive treatment for postmenopausal depression symptoms. There is a close relationship between cognitive levels and depression, as depression itself is accompanied by cognitive decline, and early cognitive decline can also manifest depressive symptoms. Therefore, the cognitive levels of postmenopausal depression patients are also worthy of further attention.This study is an 8-week randomized controlled trial. The subjects are patients with postmenopausal depression accompanied by cognitive decline, all of whom have undergone natural menopause for at least one year; with HAMD-17 scores ≥17 points; and MOCA scores ≤26 points. This study aims to recruit patients with postmenopausal depression accompanied by cognitive decline from the outpatient or inpatient departments of Beijing Anding Hospital, Capital Medical University. Patients who meet the inclusion criteria will be randomly assigned to the combination group and the control group using a random number method. The combination group will receive estrogen combined with SSRIs, while the control group will only receive Selective serotonin reuptake inhibitors (SSRIs) intervention. Patients' cognitive function and depressive symptoms will be assessed using scales at baseline, 2 weeks, 4 weeks, and the end of 8 weeks of treatment, and safety evaluations will be conducted. The primary efficacy endpoint is the change in MoCA scores from baseline to the end of the study. Secondary efficacy endpoints include changes in HAMD-17, modified Kupperman Scale, ADL Scale, and hormone levels from baseline to the end of the study. The safety of the study drug will be evaluated through adverse event reporting, clinical laboratory tests, and physical examinations.

Start Date12 May 2023

Sponsor / Collaborator

Capital Medical University

NCT05620355 / RecruitingPhase 3

A Phase 3, Multicentre, Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy and Safety of Daily Oral Administration of BG2109 Alone and in Combination With Add-back Therapy for the Management of Heavy Menstrual Bleeding Associated With Uterine Fibroids in Premenopausal Women.

The primary objective of this study is to demonstrate the superior efficacy versus placebo of BG2109 alone and in combination with add-back therapy for the reduction of heavy menstrual bleeding associated with uterine fibroids in premenopausal women.

Start Date16 Dec 2022

Sponsor / Collaborator-

100 Clinical Results associated with Estradiol/Norethindrone Acetate

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100 Translational Medicine associated with Estradiol/Norethindrone Acetate

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100 Patents (Medical) associated with Estradiol/Norethindrone Acetate

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33

Literatures (Medical) associated with Estradiol/Norethindrone Acetate

01 Dec 2022·World journal of microbiology & biotechnology

Molecular study on recombinant cold-adapted, detergent- and alkali stable esterase (EstRag) from Lysinibacillus sp.: a member of family VI

Article

Author: Khalil, Ahmed I ; Matrawy, Amira A ; Embaby, Amira M

Abstract:

Cold-adapted esterases have potential industrial applications. To fulfil the global continuous demand for these enzymes, a cold-adapted esterase member of family VI from Lysinibacillus sp. YS11 was cloned on pET-28b (+) vector and expressed in E. coli BL21(DE3) Rosetta cells for the first time. The open reading frame (654 bp: GenBank MT120818.1) encodes a polypeptide (designated EstRag: 217 amino acid residues). EstRag amino acid sequence has conserved esterase signature motifs: pentapeptide (GFSQG) and catalytic triad Ser110-Asp163-His194. EstRag 3D predicted model, built with LOMETS3 program, showed closest structural similarity to PDB 1AUO_A (esterase: Pseudomonas fluorescens); TM-align score program inferences. Purified EstRag to 9.28-fold, using Ni2+affinity agarose matrix, showed a single protein band (25 kDa) on SDS-PAGE, Km (0.031 mM) and Kcat/Km (657.7 s−1 mM−1) on p-NP-C2. Temperature and pH optima of EstRag were 35 °C and 8.0, respectively. EstRag was fully stable at 5–30 °C for 120 min and at pH(s) 8.0–10.0 after 24 h. EstRag activity (391.46 ± 0.009%) was impressively enhanced after 30 min preincubation with 5 mM Cu2+. EstRag retained full stability after 30 min pre-incubation with 0.1%(v/v) SDS, Triton X-100, and Tween-80. EstRag promising characteristics motivate performing guided evolution and industrial applications prospective studies.

07 Oct 2022·Emergency medicine international

Effect of Zhuyun I Recipe Capsule Enema on the Immune Microenvironment of the Endometrium during Implantation Window in Rats

Article

Author: Zeng, Qian ; Wang, Yi ; Huang, Jinzhu ; Zhou, Hang ; Wang, Yang ; Guo, Pei ; Yin, Zhixing ; Yan, Li ; Zeng, Pengfei ; Li, Juan ; Xia, Wanting ; Liu, Chang

Background. Preterm birth is the leading cause of neonatal death, and there are no effective clinical means for the prevention and treatment of spontaneous preterm birth, mainly because the mechanism for labor initiation has not been fully elucidated. Objective. The effect of enucleation with Zhuyun I Recipe Capsule enema (ZRC) on the maternal-fetal interface microenvironment in SD rats with kidney deficiency and blood stasis. Methods. In this study, poor endometrial tolerance was induced by hydroxyurea and epinephrine in SD rats with kidney deficiency and blood stasis type of endometrium, and gavage with norethindrone (estradiol) or Bamboo Rhythm No.1 formula. HOXA10 mRNA levels were measured by qPCR. In addition, the expression of IL-6, VEGF, TGF–β, and IGFBP-1 in the uterus was detected by IHC and ELISA. Results. Hydroxyurea- and epinephrine-induced PER was associated with low levels of HOXA10 in the endometrium and reduced levels of IL-6, TGF-β, VEGF, and IGFBP-1 in the endometrium. These were abolished by ZRC and Progynova treatment compared to PER rats, resulting in a dramatic increase in the levels of HOXA10 mRNA, IL-6, TGF-β, VEGF, and IGFBP-1 proteins. Conclusions. ZRC improves metaplasticization of endometrial stromal cells and promotes angiogenesis in rats with kidney deficiency and blood stasis. The moderate dose of kidney tonic to promote blood circulation method is superior in promoting angiogenesis, facilitating the establishment and maintenance of pregnancy, limiting trophoblast invasion of metaplasia, reducing miscarriage, and improving pregnancy rate.

01 Apr 2019·Endocrine connections

Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures

Article

Author: Kriström, Berit ; Ruijgrok, Elisabeth J ; Mazzanti, Laura ; Sas, Theo C J ; Gawlik, Aneta ; Ankarberg-Lindgren, Carina

Objective:

Transdermal estradiol patches are primarily designed for adult women. No low-dose patches are licensed for pubertal induction in hypogonadal girls. Low doses can be achieved by cutting a matrix patch into smaller pieces. However, the manufacturers do not guarantee stability or utility of cut estradiol patches. The aim of the study was to assess 1-month stability of cut estradiol patches from four different manufacturers in the laboratory at room temperature (+21°C) and at an elevated temperature (+35°C).

Design and methods:

Estraderm MX 50 µg, Systen 50 µg and Oesclim 25 µg matrix patches were cut into eight pieces while Estradot 50 µg small patches were cut in half. The cut patches were stored in their respective pouches at +21°C or at +35°C for up to 1 month. The estradiol drug was extracted from the patch by ethyl acetate n-hexane and determined by radioimmunoassay.

Results:

Storage at +21°C or +35°C up to 1 month did not reduce the estradiol concentration in Estraderm MX, Systen and Oesclim patches. However, although the estradiol in Estradot patches was not affected by storage at +21°C, at +35°C, estradiol decreased by 57% (±1%) in cut pieces.

Conclusions:

Unused Estraderm MX, Systen and Oesclim patch pieces may be stored for at least 1 month at ≤+35°C. Where estradiol patches for children are not available, cut pieces of these or similar patches can be used for pubertal induction. The Estradot patch was too small to properly cut into low doses and not stable in elevated temperatures.

100 Deals associated with Estradiol/Norethindrone Acetate

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Estradiol/Norethindrone Acetate	G03	-

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Vascular Diseases	JP	ASKA Pharmaceutical Co., Ltd.	16 Oct 2008
Oestrogen deficiency	CN	Kunming Sinoway Natural Pharmaceuticals	17 Nov 2004
Ovarian Insufficiency	JP	Hisamitsu Pharmaceutical Co., Inc.	02 Jan 2001
Osteoporosis, Postmenopausal	US	Novo Nordisk A/S	11 Apr 2000
Hot Flashes	US	Noven Pharmaceuticals, Inc.	07 Aug 1998
Hypoestrogenism	US	Noven Pharmaceuticals, Inc.	07 Aug 1998
Menopausal symptoms	US	Noven Pharmaceuticals, Inc.	07 Aug 1998
Vasomotor symptom	US	Noven Pharmaceuticals, Inc.	07 Aug 1998
Vulvovaginal atrophy	US	Noven Pharmaceuticals, Inc.	07 Aug 1998

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02693002 (CTgov)	Phase 4	Heart Failure	4	Estradiol/Norethindrone acetate (Hormone Replacement Therapy)	dwmowqysaf(vxqaqcokmc) = iftqcjpazk vwovsylxel (hvjhrtjdoe, fpmjiegpsb - uqjtlkacoy) View more	-	11 Jul 2018
				Placebo (Placebo)	dwmowqysaf(vxqaqcokmc) = yihbswawps vwovsylxel (hvjhrtjdoe, wjfmevffmj - deiwfhfbnj) View more
NCT01181726 (CTgov)	Phase 1	-	40	Norethindrone Acetate+Estradiol (Estradiol/Norethindrone Acetate (Test))	lfpsadzqiv(ikaxaamkyn) = bkyuxpwqty aopnsbxoqi (oxzwkonzwt, ngpyluljsl - zhevkenwwc) View more	-	07 Oct 2010
				Activella (Activella® (Reference))	lfpsadzqiv(ikaxaamkyn) = clgelobmkq aopnsbxoqi (oxzwkonzwt, zkqwukzxjh - nknlmnznsa) View more