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 in
Germany, but may no longer be available.[8][9][10]
Medical uses
EES has been used in combination with
norethisterone acetate as a once-a-week
birth control pill and by itself as a form of
high-dose estrogen therapy in the treatment of
prostate cancer.[1][5][3][6][11] It has also been assessed in the treatment of
breast 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 with
norethisterone 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 good
tolerability compared to EE in the treatment of prostate cancer, a property that has been described as "remarkable".[2] The unique C3
sulfonateester of EES seems to reduce its
hepaticestrogenicity, which in turn reduces its
adverse effects on
liver protein synthesis.[2] In particular, EES is said to have considerably reduced
cardiovascular 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, as
parenteral EE, which bypasses the
first pass through the liver that occurs with oral EE, has been found to have a 5-fold lower impact on
liver protein synthesis by weight than oral EE.[2] Conversely however, studies with EE-containing
contraceptive vaginal rings and
contraceptive patches have shown similar
metabolic effects and VTE risk as combined birth control pills containing EE.[17][18][19]
Pharmacology
EES is an
estrogen ester and long-acting
prodrug of
ethinylestradiol (EE) which is taken
orally.[2][3] The
molecular weight of EES is about 136% of that of EE due to the presence of its C3
isopropylsulfonate ester, and hence EES contains about 74% of the amount of EE of an equal dose of EE.[20][8] EES is more
lipophilic than EE, and this results in a
depot effect in which EES is taken up into
fat and then slowly released from it.[2] Following its release from fat, EES is
hydrolyzed into EE.[2] As a result of this depot effect, EES has a very long
elimination half-life of about 6 days.[4] This allows it to be taken once per week.[3][2] Both EES and the related medication
quinestrol have been described as depot oral estrogens.[1][12][2]
EES is a powerful
antigonadotropin, and is capable of suppressing circulating total
testosterone levels in men to concentrations comparable to those seen with
castration (less than 1 to 3% of initial values).[6][21][11] In addition, EES can strongly increase
sex hormone-binding globulin (SHBG) levels, thereby additionally decreasing free testosterone levels.[5][22][23][21] As such, EES is a powerful functional
antiandrogen, 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 first
synthesized in 1967 at
Jenapharm.[1][3] It was first introduced for use in combination with
norethisterone 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]
Society and culture
Generic names
Ethinylestradiol sulfonate is the
generic name of the drug, but it is also commonly known by its brand names Deposiston and Turisteron.[1][20][8] It does not appear to have an
INNTooltip International Nonproprietary Name or other such designations.[20][8] EES has also been known by its former developmental code name J96.[3]
Brand names
EES has been marketed in combination with
norethisterone 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]
Availability
EES has been marketed in
Germany, though it appears that it may no longer be available.[8][9][10]
^
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.
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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.
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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.
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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.
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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.
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"Hormontherapie". In Runnebaum B, Rabe T (eds.). Gynäkologische Endokrinologie und Fortpflanzungsmedizin: Band 1: Gynäkologische Endokrinologie. Springer-Verlag. pp. 88–.
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^
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.
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^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.
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^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.
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Further reading
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.