Эстрадиол валераты: қолданылуы, түрлері және жағымсыз әсерлері

Chemical compound
Estradiol valerate was first described in 1940 and was introduced for medical use in 1954. It is available as a generic medication.

The medical uses of estradiol valerate are the same as those of estradiol and other estrogens. Examples of indications for the medication include hormone therapy and hormonal contraception. In regard to the latter, estradiol valerate is available in combination with a progestin as a combined estradiol containing oral contraceptive (with dienogest) and as a combined injectable contraceptive. Along with estradiol cypionate, estradiol undecylate, and estradiol benzoate, estradiol valerate is used as a form of high dose estrogen therapy in feminizing hormone therapy for transgender women. It is also used as a form of high dose estrogen therapy in the treatment of prostate cancer in men. Injectable estradiol valerate has been used to suppress sex drive in sex offenders. In the United States, the approved indications of estradiol valerate injections include the treatment of moderate to severe hot flashes and vaginal atrophy associated with menopause in women, the treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure in women, and the palliative treatment of advanced prostate cancer in men. Elsewhere in the world, oral estradiol valerate is similarly approved for the treatment of symptoms associated with menopause or hypoestrogenism due to castration in women. Such symptoms may include hot flashes, outbreaks of sweat, sleep disturbances, depressive moods, irritability, headaches, and dizziness. Estradiol valerate is usually used in the treatment of advanced prostate cancer in men at a dosage of 30 mg or more every 1 to 2 weeks by intramuscular injection.

Estradiol valerate is and has been available in the form of vials and ampoules of oil solution for intramuscular injection in concentrations of 4, 5, 10, 20, and 40 mg/mL and in the form of oral tablets at doses of 0.5, 1, 2, and 4 mg per tablet. In the United States, it is specifically available in formulations of 10, 20, and 40 mg/mL in oil solution (as Delestrogen, as well as generics). In addition to single drug formulations, oral estradiol valerate is available in combination with the progestin dienogest as a combined oral contraceptive and intramuscular estradiol valerate is marketed at a concentration of 5 mg/mL in combination with the progestin hydroxyprogesterone caproate and with the progestin norethisterone enantate as combined injectable contraceptives.

The side effects of estradiol valerate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma. High dose estrogen therapy with estradiol valerate injections may also cause an increased risk of thromboembolism, changes in blood lipid profile, increased insulin resistance, and increased levels of prolactin. Symptoms of estrogen overdosage may include nausea, vomiting, bloating, increased weight, water retention, breast tenderness, vaginal discharge, heavy legs, and leg cramps. These side effects can be diminished by reducing the estrogen dosage.

Estradiol valerate is an estradiol ester, or a prodrug of estradiol. Oral ethinylestradiol at 10 μg/day has been found to have about 1.5 to 2.5 fold the impact of 2 mg/day oral estradiol valerate on HDL cholesterol and triglycerides. The influence of 20 or 50 μg/day oral ethinylestradiol on coagulation factors and HDL cholesterol is markedly greater than that of 2 mg/day oral estradiol valerate. Estradiol containing birth control pills, which contain 1 to 3 mg/day estradiol or estradiol valerate, have been found to increase sex hormone binding globulin (SHBG) levels by 1.5 fold. Oral estradiol valerate at 6 mg/day has been found to increase SHBG levels by 2.5 to 3 fold in transgender women. For comparison, combined birth control pills containing ethinylestradiol and a progestin with minimal androgenic or antiandrogenic activity have been found to increase SHBG levels by about 3 to 4 fold.

Regardless of the route of administration, estradiol valerate behaves as a prodrug of estradiol via cleavage by esterases into estradiol and the natural fatty acid valeric acid. This cleavage occurs not only in the liver, but also in the blood and in tissues, and the hydrolysis of estradiol valerate into estradiol and valeric acid is complete regardless of whether the medication is administered orally or parenterally. These concentrations of estradiol and estrone are comparable to those observed with 1 and 2 mg/day oral estradiol. Likewise, other studies found that levels of estradiol and estrone are very similar after oral administration of roughly equimolar doses of estradiol (1.5 mg) and estradiol valerate (2 mg). A study of high dose oral estradiol valerate found levels of estradiol of about 250 pg/mL after a single 10 mg dose in three women. It has been investigated for this indication, along with vaginal and transdermal estradiol, because oral estradiol valerate is sometimes unable to achieve adequate estradiol levels and hence proper cycle control in this situation. The administration of 2 mg oral micronized estradiol valerate tablets (Progynova, Schering) sublingually 3 or 4 times per day has been found to result in circulating estradiol levels of about 290 pg/mL to 460 pg/mL in premenopausal women (time of measurements not given).

The administration of estradiol valerate by intravenous injection has been studied.]] Estradiol valerate is a synthetic estrane steroid and the C17β valerate (pentanoate) fatty acid ester of estradiol.

Estradiol valerate was patented by Ciba in 1940 and 1941, with a priority date of 1936. It was synthesized and studied, along with a variety of other estradiol esters, by Karl Junkmann of Schering AG in 1953. The medication was first introduced for medical use via intramuscular injection in 1954 by Schering in Europe under the brand name Progynon Depot and by Squibb in the United States under the brand name Delestrogen. In 1966, oral estradiol valerate was introduced by Schering for medical use in Europe under the brand name Progynova. A report of its metabolism was published in 1967. Esterification of estradiol, as in estradiol valerate, has been claimed to improve its metabolic stability with oral administration. In 1968, micronized preparations of oral estradiol valerate were first introduced under the brand names Progynova 21 and Progynova 21 mite. and estradiol cypionate (1952), estradiol valerate is one of the most widely used esters of estradiol.

Estradiol valerate is the generic name of the drug and its , , , and , while oestradiol valerate was formerly its .

Estradiol valerate has been marketed under the brand names Altadiol, Androtardyl Oestradiol, Ardefem, Climaval, Cyclabil, Cyclocur, Deladiol, Delahormone Unimatic, Delestrogen, Delestrogen 4X, Depogen, Diol 20, Dioval, Ditate, Dura Estate, Dura Estradiol, Duratrad, Duragen, Estate, Estra L, Estradiol Depot, Estraval, Estraval Depot, Estraval PA, Estravel, Femogen, Femogex, Gynogen L. A., Gynokadin, Lastrogen, Menaval, Merimono, Neofollin, Nuvelle, Oestrogynal, Ostrin Depo, Pelanin, Pharlon, Postoval, Primogyna, Primogyn, Primogyn Depot, Progynon, Progynon Depot, Progynova, Repestrogen, Repo Estra, Reposo E, Retestrin, Ronfase, Span Est, Testaval, and Valergen, among others.

Oral estradiol valerate is used primarily in Europe, under the brand name Progynova. Although oral estradiol valerate was previously available in the United States, It was investigated clinically as a treatment for breast cancer and was found to be effective, but was never marketed.