Estetrol (E4) is a naturally occurring estrogen produced by the fetal liver during pregnancy. It is a potent estrogen with a unique pharmacological profile compared to other estrogens, exhibiting high selectivity for estrogen receptor beta (ERβ) over estrogen receptor alpha (ERα). E4 has been shown to have a range of potential therapeutic benefits, including:
* **Menopausal symptom relief:** E4 effectively reduces hot flashes and other menopausal symptoms, while potentially exhibiting a lower risk of thromboembolic events compared to traditional hormone replacement therapy.
* **Cardiovascular health:** Studies suggest E4 may have cardioprotective effects, potentially reducing the risk of heart disease.
* **Cognitive function:** E4 may enhance cognitive function and memory, particularly in women experiencing menopause-related cognitive decline.
* **Bone health:** E4 is being investigated for its potential to improve bone density and reduce the risk of osteoporosis.
E4 is synthesized from estrone through a multi-step process involving microbial biotransformation. Its unique properties and potential therapeutic benefits have sparked significant research interest in recent years. Clinical trials are ongoing to evaluate its efficacy and safety in various therapeutic areas.'
Estetrol: A metabolite of ESTRIOL with a 15-alpha-hydroxyl group. Estetrol can be converted from estriol sulfate or DEHYDROEPIANDROSTERONE SULFATE by the fetal-placental unit. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
estetrol : A 3-hydroxy steroid that is 17beta-estradiol which has been substituted at the 15alpha and 16alpha positions by two additional hydroxy groups. It is a natural estrogen produced exclusively during pregnancy by the fetal liver. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 27125 |
| CHEMBL ID | 1230314 |
| CHEBI ID | 142773 |
| SCHEMBL ID | 145580 |
| MeSH ID | M0007767 |
| Synonym |
|---|
| CHEMBL1230314 |
| e-4 |
| 15.alpha.-hydroxyestriol |
| e4 |
| estetrol anhydrous |
| estetrol (anhydrous) |
| estetrol (hydrous) |
| estetrol |
| (14beta,15alpha,16alpha,17alpha)-estra-1,3,5(10)-triene-3,15,16,17-tetrol |
| 4oh , |
| (8r,9s,13s,14s,15r,16r,17r)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,15,16,17-tetrol |
| unii-enb39r14vf |
| 15183-37-6 |
| who 10439 |
| enb39r14vf , |
| estra-1,3,5(10)-triene-3,15,16,17-tetrol, (15alpha,16alpha,17beta)- |
| smr004701329 |
| MLS006010253 |
| SCHEMBL145580 |
| estetrol [inn] |
| estetrol (anhydrous) [usan] |
| estra-1,3,5(10)-triene-3,15.alpha.,16.alpha.,17.beta.-tetrol |
| estetrol [who-dd] |
| estra-1,3,5(10)-triene-3,15,16,17-tetrol, (15.alpha.,16.alpha.,17.beta.)- |
| estetrol (e4) |
| AJIPIJNNOJSSQC-NYLIRDPKSA-N |
| (8r,9s,13s,14s,15r,16r,17r)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6h-cyclopenta[a]phenanthrene-3,15,16,17-tetraol |
| us9034854, e4 |
| bdbm158505 |
| DTXSID50164888 |
| AKOS030254521 |
| estetrol, >=98% (hplc) |
| estell |
| J-008852 |
| DB12235 |
| 1,3,5(10)-estratrien-3,15alpha,16alpha,17beta-tetrol |
| estetrolum |
| donesta |
| oestetrol |
| CHEBI:142773 |
| estra-1,3,5(10)-triene-3,15alpha,16alpha,17beta-tetrol |
| estra-1(10),2,4-triene-3,15alpha,16alpha,17beta-tetrol |
| 3,15alpha,16alpha,17beta-tetrahydroxyestra-1,3,5(10)-triene |
| 15alpha-hydroxyestriol |
| (15alpha,16alpha,17beta)-estra-1(10),2,4-triene-3,15,16,17-tetrol |
| 'estra-1,3,5(10)-triene-3,15 alpha,16alpha,17beta-tetrol' |
| Q5401078 |
| EX-A7107 |
| estetrol (usan) |
| D11513 |
| NCGC00345819-03 |
| CS-0008552 |
| HY-15731 |
| AT27982 |
| nextstellis (us); estetrol monohydrate + drospirenone |
| 15 alpha-hydroxyestriol |
| drovelis (ema); ; estetrol monohydrate + drospirenone |
| gtpl11591 |
| lydisilka (ema); ; estetrol monohydrate + drospirenone |
Estetrol (E4) is a natural estrogen synthesized only during pregnancy. Estetrol/drospirenone is a combined oral contraceptive (COC) with a plant-synthesised foetal oestrogen (estetrol) and a well-established progestin (drospirnone)
As estetrol has weaker oestrogen-related effects, it may potentially reduce the risk for blood clots. Estetrol had estrogenic effects on the vagina and on the uterus of ovariectomized rats.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Estetrol treatment resulted in a decrease of follicle-stimulating hormone and luteinizing hormone and an increase of sex-hormone binding globulin. " | ( Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study. Coelingh Bennink, HJT; Foidart, JM; Gemzell-Danielsson, K; Verhoeven, C; Visser, M; Zimmerman, Y, 2017) | 2.16 |
15mg estetrol combined with 3 mg DRSP is associated with a high-user acceptability and satisfaction, and with a favourable body weight control.
Estetrol exhibits high oral bioavailability in the rat. The rat is considered relevant for pharmacological studies that are predictive for effects on human bone.
| Excerpt | Reference | Relevance |
|---|---|---|
| "To measure the oral bioavailability of estetrol (E(4)) in rats relative to its subcutaneous administration and to test the bone-sparing effect of oral E(4) compared to that of ethinylestradiol (EE)." | ( Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Christiansen, C; Coelingh Bennink, HJ; Heegaard, AM; Holinka, CF; Visser, M, 2008) | 0.87 |
| "Estetrol exhibits high oral bioavailability in the rat, a species considered relevant for pharmacological studies that are predictive for effects on human bone." | ( Oral bioavailability and bone-sparing effects of estetrol in an osteoporosis model. Christiansen, C; Coelingh Bennink, HJ; Heegaard, AM; Holinka, CF; Visser, M, 2008) | 2.04 |
| " However, recent research has demonstrated that due to its favorable pharmacokinetic properties, especially the slow elimination and long half-life, E(4) is an effective orally bioavailable estrogen agonist with estrogen antagonistic effects on the breast in the presence of estradiol." | ( Clinical applications for estetrol. Coelingh Bennink, HJ; Visser, M, 2009) | 0.65 |
| " The pharmacolokinetic and pharmacodynamic properties of these estrogens are compared to those of EE (absorption, metabolization, bioavailability etc." | ( Pharmacological profile of estrogens in oral contraception. Bitzer, J, 2011) | 0.37 |
| Role | Description |
|---|---|
| estrogen | A hormone that stimulates or controls the development and maintenance of female sex characteristics in mammals by binding to oestrogen receptors. The oestrogens are named for their importance in the oestrous cycle. The oestrogens that occur naturally in the body, notably estrone, estradiol, estriol, and estetrol are steroids. Other compounds with oestrogenic activity are produced by plants (phytoestrogens) and fungi (mycoestrogens); synthetic compounds with oestrogenic activity are known as xenoestrogens. |
| estrogen receptor agonist | An agonist at the estrogen receptor. |
| human metabolite | Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens). |
| human xenobiotic metabolite | Any human metabolite produced by metabolism of a xenobiotic compound in humans. |
| oral contraceptive | A compound, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| 3-hydroxy steroid | Any hydroxy steroid carrying a hydroxy group at position 3. |
| 17beta-hydroxy steroid | A 17-hydroxy steroid in which the hydroxy group at position 17 has a beta-configuration. |
| 16alpha-hydroxy steroid | A 16-hydroxy steroid in which the hydroxy group at position 16 has alpha-configuration. |
| 15alpha-hydroxy steroid | A 15-hydroxy steroid in which the hydroxy group at position 15 has an alpha-configuration. |
| steroid hormone | Any steroid that acts as hormone. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 63 (45.00) | 18.7374 |
| 1990's | 3 (2.14) | 18.2507 |
| 2000's | 13 (9.29) | 29.6817 |
| 2010's | 28 (20.00) | 24.3611 |
| 2020's | 33 (23.57) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.
| This Compound (55.07) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 22 (15.38%) | 5.53% |
| Reviews | 22 (15.38%) | 6.00% |
| Case Studies | 1 (0.70%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 98 (68.53%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||