EES was first synthesized in 1967, was first introduced as a birth control pill in 1978, and was introduced for the treatment of prostate cancer in 1980.[1][3] It has been marketed inGermany, but may no longer be available.[8][9][10]
EES has been used in combination withnorethisterone acetate as a once-a-weekbirth control pill and by itself as a form ofhigh-dose estrogen therapy in the treatment ofprostate cancer.[1][5][3][6][11] It has also been assessed in the treatment ofbreast cancer.[4][7] The medication is used at a dosage of 1 mg once per week in birth control pills and 1 to 2 mg once per week in the treatment of prostate cancer.[12][5][2] The 1 week and 2 mg/week dosages of EES are equivalent to daily doses of 0.143 mg and 0.285 mg EES, respectively.[13]
EES was available alone for the treatment of prostate cancer in men in the form of 1 mg oral tablets[14][15] and in combination withnorethisterone acetate in the form of oral tablets containing 1 mg EES and 5 mg norethisterone acetate for use as a birth control pill for women.[15][16][1]
EES has been described as having goodtolerability compared to EE in the treatment of prostate cancer, a property that has been described as "remarkable".[2] The unique C3sulfonateester of EES seems to reduce itshepaticestrogenicity, which in turn reduces itsadverse effects onliver protein synthesis.[2] In particular, EES is said to have considerably reducedcardiovascular side effects relative to EE when used as a form of high-dose estrogen therapy in the treatment of prostate cancer.[2] This may in part be related to the greatly reduced oral dosing frequency of EES relative to EE, asparenteral EE, which bypasses thefirst pass through the liver that occurs with oral EE, has been found to have a 5-fold lower impact onliver protein synthesis by weight than oral EE.[2] Conversely however, studies with EE-containingcontraceptive vaginal rings andcontraceptive patches have shown similarmetabolic effects and VTE risk as combined birth control pills containing EE.[17][18][19]
EES is anestrogen ester and long-actingprodrug ofethinylestradiol (EE) which is takenorally.[2][3] Themolecular weight of EES is about 136% of that of EE due to the presence of its C3isopropylsulfonate ester, and hence EES contains about 74% of the amount of EE of an equal dose of EE.[20][8] EES is morelipophilic than EE, and this results in adepot effect in which EES is taken up intofat and then slowly released from it.[2] Following its release from fat, EES ishydrolyzed into EE.[2] As a result of this depot effect, EES has a very longelimination half-life of about 6 days.[4] This allows it to be taken once per week.[3][2] Both EES and the related medicationquinestrol have been described as depot oral estrogens.[1][12][2]
EES is a powerfulantigonadotropin, and is capable of suppressing circulating totaltestosterone levels in men to concentrations comparable to those seen withcastration (less than 1 to 3% of initial values).[6][21][11] In addition, EES can strongly increasesex hormone-binding globulin (SHBG) levels, thereby additionally decreasing free testosterone levels.[5][22][23][21] As such, EES is a powerful functionalantiandrogen, which makes it useful for treating prostate cancer.[24][21]
The biological half-life of EES in blood has been reported to be 3 hours.[14]
EES was firstsynthesized in 1967 atJenapharm.[1][3] It was first introduced for use in combination withnorethisterone acetate under the brand name Deposiston as a once-a-week birth control pill for women in 1978.[1] The medication was subsequently introduced by itself under the brand name Turisteron for the treatment of prostate cancer in men in 1980.[1]
Ethinylestradiol sulfonate is thegeneric name of the drug, but it is also commonly known by its brand namesDeposiston andTuristeron.[1][20][8] It does not appear to have anINNTooltip International Nonproprietary Name or other such designations.[20][8] EES has also been known by its former developmental code nameJ96.[3]
EES has been marketed in combination withnorethisterone acetate under the brand name Deposiston for use as a birth control pill in women and under the brand name Turisteron for use in prostate cancer in men.[1][20][8]
^abcdefghijklmnSchwarz S, Onken D, Schubert A (July 1999). "The steroid story of Jenapharm: from the late 1940s to the early 1970s".Steroids.64 (7):439–445.doi:10.1016/S0039-128X(99)00003-3.PMID10443899.S2CID40156824.6.2. New estrogens. In 1967, Jenapharm, in conjunction with the Academy of Sciences (Kurt Ponsold, Gu¨nter Bruns, and Kurt Schubert in Jena and Hans Schick and Bernard Lu¨cke in Berlin), started a program of searching for new estrogens. [...] orally administered, strongly active estrogens with a depot effect. [...] the second objective was successfully attained. The rationale that an a-branched alkanesulfonic acid ester of ethinyl estradiol with a medium chain length should lead to a depot effect without the danger of active ingredient accumulation on longer usage [15] led in 1978 to the first once-a-week oral contraceptive (DEPOSISTONt), a combination of ethinylestradiol 3-isopropylsulfonate (17) and norethisterone acetate [16]. TURISTERONt, an estrogenic monotherapy with compound 17 that can still justify its position today [17], followed in 1980, as a therapy of prostate cancer. [...]
^abcdefghijklmnopElger W, Palme HJ, Schwarz S (April 1998). "Novel oestrogen sulfamates: a new approach to oral hormone therapy".Expert Opinion on Investigational Drugs.7 (4):575–589.doi:10.1517/13543784.7.4.575.PMID15991994.
^abcdeGürtler R, Tanneberger S, Bodek B, Morack G (1982). "[Clinical experience with the depot estrogen Turisteron in the treatment of metastatic breast cancer (author's transl)]".Archiv für Geschwulstforschung (in German).52 (2):129–139.PMID7103689.
^abcdefghHöfling G, Heynemann H (1998). "Die orale Östrogentherapie des fortgeschrittenen Prostatakarzinoms — Anlaß für eine Neubewertung?" [Oral Estrogen Therapy for Advanced Prostate Cancer — Reason for Revaluation?].Der Urologe B.38 (2):165–170.doi:10.1007/s001310050185.ISSN0042-1111.
^abcDörner G, Schnorr D, Stahl F, Rohde W (December 1985). "Successful treatment of prostatic cancer with the orally active depot estrogen ethinylestradiol sulfonate (Turisteron)".Experimental and Clinical Endocrinology.86 (2):190–196.doi:10.1055/s-0029-1210486.PMID3912197.
^abStahl F, Schnorr D, Bär CM, Fröhlich G, Dörner G (1989). "Suppression of plasma androgen levels with a combination therapy of depot-estrogen (Turisteron) and Dexamethasone in patients with prostatic cancer".Experimental and Clinical Endocrinology.94 (3):239–243.doi:10.1055/s-0029-1210905.PMID2630306.S2CID40497389.
^abRabe T, Runnebaum B, Kellermeier-Wittlinger S (17 April 2013)."Hormontherapie". In Runnebaum B, Rabe T (eds.).Gynäkologische Endokrinologie und Fortpflanzungsmedizin: Band 1: Gynäkologische Endokrinologie. Springer-Verlag. pp. 88–.ISBN978-3-662-07635-4.
^abcGuddat HM, Schnorr D, Dörner G, Stahl F, Rohde W (December 1987). "[Behavior of LH, FSH, total testosterone, free testosterone and SHBG serum levels in the therapy of prostatic cancer with Turisteron (ethinyl estradiol sulfonate)]".Zeitschrift für Urologie und Nephrologie (in German).80 (12):665–668.PMID3126615.
^Schnorr D, Dörner G, Stahl F, Rohde W, Guddat HM (March 1987). "[Conservative therapy of prostate cancer using Turisteron]".Zeitschrift für Urologie und Nephrologie (in German).80 (3):149–157.PMID3111122.
^Elger W, Barth A, Hedden A, Reddersen G, Ritter P, Schneider B, et al. (2001). "Estrogen sulfamates: a new approach to oral estrogen therapy".Reproduction, Fertility, and Development.13 (4):297–305.doi:10.1071/RD01029.PMID11800168.
^Elger W, Wyrwa R, Ahmed G, Meece F, Nair HB, Santhamma B, et al. (January 2017). "Estradiol prodrugs (EP) for efficient oral estrogen treatment and abolished effects on estrogen modulated liver functions".The Journal of Steroid Biochemistry and Molecular Biology.165 (Pt B):305–311.doi:10.1016/j.jsbmb.2016.07.008.PMID27449818.S2CID26650319.
Höfling G, Heynemann H (2014). "Die orale Östrogentherapie des fortgeschrittenen Prostatakarzinoms — Anlaß für eine Neubewertung?" [Oral Estrogen Therapy for Advanced Prostate Cancer — Reason for Revaluation?].Der Urologe B.38 (2):165–170.doi:10.1007/s001310050185.ISSN0042-1111.
