Estradiol dipropionate
Estradiol dipropionate, sold under the brand names Agofollin, Di-Ovocylin, and Progynon DP among others, is an estrogen medication which has been used in hormone therapy for menopausal symptoms and low estrogen levels in women and in the treatment of gynecological disorders. It has also been used in feminizing hormone therapy for transgender women and in the treatment of prostate cancer in men. Although widely used in the past, estradiol dipropionate has largely been discontinued and is mostly no longer available today. It appears to remain in use only in Japan, Macedonia, and Australia. Estradiol dipropionate is given by injection into muscle at intervals ranging from once or twice a week to once every week and a half to two weeks.
Side effects of estradiol dipropionate include breast tenderness, breast enlargement, nausea, headache, and fluid retention. Estradiol dipropionate is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol. It is an estrogen ester and a prodrug of estradiol in the body. Because of this, it is considered to be a natural and bioidentical form of estrogen.
Estradiol dipropionate was patented in 1937 and was introduced for medical use by 1940. It was one of the earliest estradiol esters to be used. Along with estradiol benzoate, estradiol dipropionate was among the most widely used esters of estradiol for many years following its introduction.
Medical uses
The medical uses of estradiol dipropionate are the same as those of estradiol and other estrogens. Estradiol dipropionate is used in hormone therapy for the treatment of menopausal symptoms such as hot flashes and vaginal atrophy and in the treatment of hypoestrogenism and delayed puberty due to hypogonadism or other causes in women. It is also used in feminizing hormone therapy for transgender women. Aside from hormone therapy, estradiol dipropionate is used in the treatment of gynecological disorders such as menstrual disorders, dysfunctional uterine bleeding, and breast engorgement. In addition, it is used as a form of high-dose estrogen therapy in the palliative treatment of prostate cancer in men.Estradiol dipropionate has typically been used at a dosage of 1 to 5 mg once or twice per week by intramuscular injection for relevant indications. It has been used in the treatment of menopausal symptoms at a dosage of 1 to 5 mg initially for two to three injections and 1 to 2.5 mg for maintenance once every 10 to 14 days, and in the treatment of hypoestrogenism and delayed puberty at a dosage of 2.5 to 5 mg once per week. As a component of feminizing hormone therapy for transgender women, estradiol dipropionate has been used at dosages of 2 to 10 mg once per week or 5 to 20 mg once every 2 weeks. In the treatment of prostate cancer, estradiol dipropionate has been used at a dosage of 5 mg once per week.
Available forms
Estradiol dipropionate was previously available by itself as an oil solution for intramuscular injection provided as vials and ampoules at concentrations of 0.1, 0.2, 0.5, 1, 2.5, and 5 mg/mL. The medication has largely been discontinued, with most of these formulations no longer being available. Estradiol dipropionate remains available at a concentration of 1 mg/mL in combination with 50 mg/mL hydroxyprogesterone caproate under the brand name EP Hormone Depot in Japan.Contraindications
Contraindications of estrogens include coagulation problems, cardiovascular diseases, liver disease, and certain hormone-sensitive cancers such as breast cancer and endometrial cancer, among others.Side effects
The side effects of estradiol dipropionate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma.Overdose
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.Interactions
Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels.Pharmacology
Pharmacodynamics
Estradiol dipropionate is an estradiol ester, or a prodrug of estradiol. As such, it is an estrogen, or an agonist of the estrogen receptors. Estradiol dipropionate is of about 41% higher molecular weight than estradiol due to the presence of its C3 and C17β propionate esters. Because estradiol dipropionate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.Pharmacokinetics
Compared to estradiol benzoate, a related estradiol ester, estradiol dipropionate has enhanced and prolonged effects. Whereas the duration of action of estradiol benzoate is said to be 2 to 3 days, the duration of estradiol dipropionate has been said to be 1 to 2 weeks. However, newer estradiol esters have longer durations than either estradiol benzoate or estradiol dipropionate; the duration of estradiol valerate has been said to be 1 to 3 weeks, and the duration of estradiol cypionate has been said to be 3 to 4 weeks. A single intramuscular injection of 5 mg estradiol dipropionate has a duration of about 5 to 8 days.A single intramuscular injection of 50 μg/kg estradiol dipropionate in oil in 15 pubertal girls was found to produce peak estradiol levels of about 215 pg/mL after 1.5 days. Estradiol levels declined to about 90 pg/mL after 4 days.
Chemistry
Estradiol dipropionate, also known as estradiol 3,17β-dipropionate, is a synthetic estrane steroid and a derivative of estradiol. It is an estrogen ester; specifically, it is the C3,17β dipropionate ester of estradiol.The experimental octanol/water partition coefficient of estradiol dipropionate is 4.9.