estradiol stearate estradiol stearate estradiol stearate (e2-17-st), also known as estradiol octadecanoate and sold under the brand name depofollan, is a naturally occurring estrogen and an estrogen ester – specifically, the c17β stearate ester of estradiol. it occurs in the body as a very long-lasting metabolite and prohormone of estradiol. the compound is one of the components that collectively constitute lipoidal estradiol, another of which is estradiol palmitate. it is extremely lipophilic and hydrophobic. estradiol stearate has no affinity for the estrogen receptor, requiring transformation into estradiol via esterases for its estrogenic activity. the compound does not bind to sex hormone-binding globulin or α-fetoprotein, instead being transported by lipoproteins such as high-density lipoprotein and low-density lipoprotein. estradiol stearateclinical datatrade namesdepofollanother namese2-17-st; estradiol octadecanoate; estradiol 17β-stearate; estradiol 17β-octadecanoateroutes ofadministrationintramuscular injectiondrug classestrogen; estrogen esteridentifiers iupac name phenanthren-17-yl] octadecanoate cas number82205-00-3 ypubchem cid67100chemspider60448unii59g2kr8qbgcomptox dashboard (epa)dtxsid401002548 chemical and physical dataformulac36h58o3molar mass538.857 g·mol−13d model (jsmol)interactive image smiles cccccccccccccccccc(=o)o1cc23ccc4cc(o)ccc43cc12c inchi inchi=1s/c36h58o3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-35(38)39-34-24-23-33-32-21-19-28-27-29(37)20-22-30(28)31(32)25-26-36(33,34)2/h20,22,27,31-34,37h,3-19,21,23-26h2,1-2h3/t31-,32-,33+,34+,36+/m1/s1key:kiadyvoycqrxre-imtrjtthsa-n estradiol stearate has a prolonged duration of action relative to estradiol regardless of whether it is given by intravenous injection or subcutaneous injection. this is in contrast to short-chain fatty acid esters of estradiol, such as estradiol benzoate, which do not show a prolonged duration with intravenous injection. when administered by intravenous injection in rodents, estradiol stearate has a greatly increased terminal half-life relative to estradiol (6 hours vs. 2 minutes). estradiol stearate also had a half-life that was 60% longer than that of estradiol arachidonate, despite similar ester chain lengths. in contrast to the long-chain esters, the half-lives of short-chain estradiol esters such as estradiol acetate and estradiol hexanoate were the same as that of estradiol. as such, whereas short-chain estradiol esters are rapidly hydrolyzed, long-chain estradiol esters like estradiol stearate are resistant to metabolism. thus, the prolongation of effect of short-chain estradiol esters is purely due to their increased lipophilicity and slow release from the injected depot, whereas the prolonged duration of long-chain estradiol esters is due both to this property and to their resistance to metabolism. estradiol stearate is susceptible to first-pass metabolism in the liver, and hence has much greater potency by subcutaneous injection than by oral administration. in addition to its endogenous role, estradiol stearate was previously available as a pharmaceutical drug for use via depot intramuscular injection. the medication was introduced between 1938 and 1941 under the brand name depofollan. it has been used to treat prostate cancer. estradiol stearate is a long-acting estrogen and is said to have been the first long-acting estrogen used in medicine, although it was never widely employed. it was reported to have a duration of more than one month. the medication was provided as an oil solution in ampoules containing 15 mg estradiol stearate. it was manufactured by chinoin, a hungarian pharmaceutical company. the compound was studied by karl miescher in 1938 and was patented by miescher and chinoin in 1939 and 1941, respectively. a similar clinically used long-acting estradiol ester is estradiol undecylate, which has 11 carbon atoms instead of the 18 carbon atoms in estradiol stearate. affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors estrogen other names rba (%)a rep (%)b er erα erβ estradiol e2 100 100 100 estradiol 3-sulfate e2s; e2-3s ? 0.02 0.04 estradiol 3-glucuronide e2-3g ? 0.02 0.09 estradiol 17β-glucuronide e2-17g ? 0.002 0.0002 estradiol benzoate eb; estradiol 3-benzoate 10 1.1 0.52 estradiol 17β-acetate e2-17a 31–45 24 ? estradiol diacetate eda; estradiol 3,17β-diacetate ? 0.79 ? estradiol propionate ep; estradiol 17β-propionate 19–26 2.6 ? estradiol valerate ev; estradiol 17β-valerate 2–11 0.04–21 ? estradiol cypionate ec; estradiol 17β-cypionate ?c 4.0 ? estradiol palmitate estradiol 17β-palmitate 0 ? ? estradiol stearate estradiol 17β-stearate 0 ? ? estrone e1; 17-ketoestradiol 11 5.3–38 14 estrone sulfate e1s; estrone 3-sulfate 2 0.004 0.002 estrone glucuronide e1g; estrone 3-glucuronide ? <0.001 0.0006 ethinylestradiol ee; 17α-ethynylestradiol 100 17–150 129 mestranol ee 3-methyl ether 1 1.3–8.2 0.16 quinestrol ee 3-cyclopentyl ether ? 0.37 ? footnotes: a = relative binding affinities (rbas) were determined via in-vitro displacement of labeled estradiol from estrogen receptors (ers) generally of rodent uterine cytosol. estrogen esters are variably hydrolyzed into estrogens in these systems (shorter ester chain length -> greater rate of hydrolysis) and the er rbas of the esters decrease strongly when hydrolysis is prevented. b = relative estrogenic potencies (reps) were calculated from half-maximal effective concentrations (ec50) that were determined via in-vitro β‐galactosidase (β-gal) and green fluorescent protein (gfp) production assays in yeast expressing human erα and human erβ. both mammalian cells and yeast have the capacity to hydrolyze estrogen esters. c = the affinities of estradiol cypionate for the ers are similar to those of estradiol valerate and estradiol benzoate (figure). sources: see template page. structural properties of selected estradiol esters estrogenstructureester(s)relativemol. weightrelativee2 contentblog pc position(s)moiet(ies)typelengtha estradiol––––1.001.004.0 estradiol acetatec3ethanoic acidstraight-chain fatty acid21.150.874.2 estradiol benzoatec3benzenecarboxylic acidaromatic fatty acid– (~4–5)1.380.724.7 estradiol dipropionatec3, c17βpropanoic acid (×2)straight-chain fatty acid3 (×2)1.410.714.9 estradiol valeratec17βpentanoic acidstraight-chain fatty acid51.310.765.6–6.3 estradiol benzoate butyratec3, c17βbenzoic acid, butyric acidmixed fatty acid– (~6, 2)1.640.616.3 estradiol cypionatec17βcyclopentylpropanoic acidaromatic fatty acid– (~6)1.460.696.9 estradiol enanthatec17βheptanoic acidstraight-chain fatty acid71.410.716.7–7.3 estradiol dienanthatec3, c17βheptanoic acid (×2)straight-chain fatty acid7 (×2)1.820.558.1–10.4 estradiol undecylatec17βundecanoic acidstraight-chain fatty acid111.620.629.2–9.8 estradiol stearatec17βoctadecanoic acidstraight-chain fatty acid181.980.5112.2–12.4 estradiol distearatec3, c17βoctadecanoic acid (×2)straight-chain fatty acid18 (×2)2.960.3420.2 estradiol sulfatec3sulfuric acidwater-soluble conjugate–1.290.770.3–3.8 estradiol glucuronidec17βglucuronic acidwater-soluble conjugate–1.650.612.1–2.7 estramustine phosphatedc3, c17βnormustine, phosphoric acidwater-soluble conjugate–1.910.522.9–5.0 polyestradiol phosphateec3–c17βphosphoric acidwater-soluble conjugate–1.23f0.81f2.9g footnotes: a = length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = relative estradiol content by weight (i.e., relative estrogenic exposure). c = experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). retrieved from pubchem, chemspider, and drugbank. d = also known as estradiol normustine phosphate. e = polymer of estradiol phosphate (~13 repeat units). f = relative molecular weight or estradiol content per repeat unit. g = log p of repeat unit (i.e., estradiol phosphate). sources: see individual articles.