Index
It is a synthetic medicine very similar to the female sex hormone estrogen, produced by the ovaries.
It is used mainly in combination with other medications as an oral contraceptive. It is also used to treat conditions deficient in hormones and other associated complications.
Ethinylestradiol was the first orally active synthetic estrogen described in 1938 by Hans Harloff Inhoffen and Walter Hohlweg of Schering AG in Berlin. It was approved by the Food and Drug Administration (FDA) in the USA. UU
On June 25, 1943, it was marketed by Schering under the Estinyl brand. The food and medicine administration withdrew Estinyl’s approval as of June 4, 2004, at the request of Schering, which had suspended its commercialization.
It was used for the first time in combined oral contraceptives, as an alternative to mestranol, in 1964, and shortly after that, it replaced mestranol in combined oral contraceptives.
Ethinylestradiol (EE) is an estrogen medication widely used in contraceptive pills in combination with progestins. It is also occasionally used as a component of menopausal hormone therapy to treat menopausal symptoms in combination with progestins.
In the past, Ethinylestradiol was widely used only for various indications, such as the treatment of gynecological disorders and prostate cancer, but this is no longer the case. It is usually taken orally.
The general side effects of Ethinylestradiol include sensitivity and enlargement of the sinuses, headache, fluid retention, and nausea, among others.
It can also cause breast development, feminization in general, hypogonadism, and sexual dysfunction in men. Rare but severe side effects include blood clots, liver damage, and uterine cancer.
Ethinylestradiol is estrogen or an estrogen receptor agonist. It is a synthetic derivative of natural estrogen estradiol and differs from estradiol.
Compared to estradiol, ethinylestradiol has greatly improved bioavailability when taken orally, is more resistant to metabolism, and shows a relative increase in effects in certain body parts such as the liver and uterus.
These differences make the ethinylestradiol more favorable for birth control pills than estradiol. Still, it also increases the risk of blood clots and other rare side effects.
Ethinylestradiol was developed in the 1930s and was introduced for medical use in 1943. The drug began to be used in contraceptive pills in the 1960s.
Ethinylestradiol is found in almost all combined forms of birth control pills and is virtually the exclusive estrogen used for this purpose, making it one of the most used estrogens.
Medical Uses of Ethinylestradiol
There are many uses for Ethinylestradiol. It is most often used in combined oral contraceptives (COCs) to prevent pregnancy after sex.
Ethinylestradiol in its contraceptive formulation is used to prevent pregnancy, but it can also treat the absence of menstruation, symptoms during menstruation, and acne. The amount of ethinylestradiol in combined oral contraceptives has been reduced.
Ethinylestradiol is also used as hormone therapy for menopause. The main reason for hormone replacement therapy in menopausal women is to relieve common vasomotor symptoms, such as hot flashes, night sweats, and redness.
Studies have found that estrogen replacement helps improve these symptoms compared to a placebo.
Other common symptoms of menopause, such as vaginal dryness (which can cause pain during intercourse), vaginal itching, and depressed mood, can benefit from hormone replacement therapy.
In addition to treating the symptoms of menopause, Ethinylestradiol has been used as a component of feminizing hormone therapy for transgender women. However, it is no longer commonly used or recommended since estradiol has largely replaced it.
Ethinyl estradiol or any estrogen alone is contraindicated for women who have a uterus because of the increased risk of endometrial cancer; administering a progestogen with an estrogen mitigates the risk.
In addition, Ethinylestradiol can also be used to treat female hypogonadism, prevent osteoporosis, and be used as palliative care for prostate cancer (in men).
Contraindications of Ethinylestradiol
Ethinylestradiol should be avoided in women with a history or known susceptibility to arterial or venous thrombosis (blood clots) due to an increased risk of venous thromboembolism (VTE), myocardial infarction, and ischemic stroke. This includes women with:
- A history of deep vein thrombosis or pulmonary embolism that does not receive anticoagulants.
- Acute deep venous thrombosis or pulmonary embolism.
- Prolonged immobilization due to major surgery.
- It has advanced diabetes mellitus with vascular disease.
- Migraine with aura.
- Hypertension ≥160 / 100.
- Vascular disease
- Current and history of ischemic heart disease.
- There are multiple risk factors for atherosclerotic cardiovascular disease (e.g., old age, smoking, diabetes, hypertension, low-density lipoprotein cholesterol, low-density lipoprotein, or high triglyceride levels).
- Age ≥35 and smoking ≥15 cigarettes/day.
- History of stroke.
- Systemic lupus erythematosus with positive (or unknown) antiphospholipid antibodies.
- It is a complicated cardiac valvular disease.
Ethinylestradiol should be avoided in women with current breast cancer due to a possible worsening of the prognosis.
Ethinylestradiol should also be avoided in breastfeeding women less than 21 days after delivery due to an increased risk of venous thromboembolism.
Ethinylestradiol in breastfeeding women at least 21 days after delivery should be discussed with a provider and include information on the advantages, disadvantages, and alternatives for using Ethinylestradiol.
Due to the risk of cholestatic hepatotoxicity, it is widely considered that combined oral contraceptives containing ethinylestradiol should be avoided in women with a history of cholestasis during pregnancy, liver tumors, active hepatitis, and familial defects in biliary excretion.
Significant and minor side effects
All drugs interact differently from person to person. You should check all possible interactions with your doctor before starting any medication.
- Pain and sensitivity in the breasts.
- He retched.
- Weight gain.
- Dizziness.
- Depression.
- Back pain.
- Headache.
- Vaginal discharge without odor.
- Symptoms are similar to the flu.
- Inflammation of the face, lips, eyelids, tongue, hands, and feet.
- Problems breathing and swallowing
- Change in the texture of the skin and nipples of the breasts.
- Inverted nipples
Contact your doctor immediately if you experience any of these symptoms regularly.
The severity of side effects may vary depending on the dose and route of administration of ethinylestradiol.
The general side effects of Ethinylestradiol are the same as for other estrogens and include breast tenderness, headache, fluid retention (swelling), nausea, dizziness, and weight gain.
The estrogenic component of oral contraceptives, almost always ethinylestradiol, can cause breast tenderness and fullness.
Ethinylestradiol has additional side effects in men, including gynecomastia (breast development), feminization, hypogonadism, infertility, and sexual dysfunction (e.g., decreased libido and erectile dysfunction ).
Venous thromboembolism:
Ethinylestradiol carries a greater risk of blood clot formation and venous thromboembolism than natural estradiol, which is due to different degrees of hepatic metabolism between the two drugs.
The original formulations of combined oral contraceptives contained up to 150 μg of Ethinylestradiol. However, it was soon discovered that ethinylestradiol is associated with the incidence of venous thromboembolism and that the risk depends on the dose.
Subsequently, the dosage of Ethinylestradiol was significantly reduced, and now it is generally between 25 and 35 μg, in some cases, less than 20 μg and not more than 50 μg.
These lower doses have a significantly reduced risk of venous thromboembolism without loss of contraceptive efficacy.
However, the interruption of oral contraceptives is familiar with doses of estrogen of 10 to 20 μg due to its association “with higher rates of bleeding pattern disorders.”
According to a newsletter published by the US Food and Drug Administration. US,
The rate of deep vein thrombosis in women taking COCs with 20 to 40 μg of Ethinylestradiol is 4 per 10,000, approximately 3 per 10,000 in women who do not take a combined oral contraceptive.
No study has shown an additional reduction in the risk of venous thromboembolism below a dose of Ethinylestradiol of 30 or 35 μg.
Cholestatic hepatotoxicity:
Although rarely (in the low doses now used in combined oral contraceptives), Ethinylestradiol has been associated with cholestatic hepatotoxicity like the anabolic steroids 17α-alkylated and 17α-ethylated progestins of 19-nortestosterone.
The glucuronide metabolites of Ethinylestradiol affect ABCB11 (BSEP) and MRP2 (ABCC2) proteins, and the consequent changes in bile flow and bile salt excretion seem to be responsible for cholestasis.
High concentrations of estradiol, through its metabolite estradiol D-glucuronide, are also involved in cholestasis, for example, in cholestasis of pregnancy.
However, the incidence and severity of cholestatic hepatotoxicity seem to be much greater with ethinylestradiol than with estradiol, which is due to its 17α-ethynyl substitution and, consequently, reduced metabolism.
Endometrial cancer:
The high doses of ethinylestradiol used in the first combined oral contraceptives were associated with a significantly increased risk of endometrial cancer in specific preparations, such as those containing the progestin dimetisterone.
Unopposed estrogens such as Ethinylestradiol have carcinogenic effects on the endometrium, and progestogens protect against these effects. Still, dimetisterone is a relatively weak progestogen and could not adequately antagonize the endometrial carcinogenic effects of Ethinylestradiol, which increases the risk of endometrial cancer.
Since then, combined oral contraceptives containing dimetisterone (using more potent progestogens instead) have been discontinued, and doses of ethinylestradiol in combined oral contraceptives have generally been drastically reduced, nullifying the risk.
Most studies of modern combined oral contraceptives have found a decreased risk of endometrial cancer.
Mechanism of action
This medication works by replacing or replenishing the hormone estrogen generally produced in the body. The effect of this medicine can be observed within 4-6 hours after oral administration. The result of this medication lasts 3 to 4 days.
Highlights and frequently asked questions about Ethinylestradiol
Is ethinylestradiol safe with alcohol?
Moderate, avoid alcohol intake while taking this medication. The use of alcohol can cause an increase in the frequency and severity of specific adverse effects.
Use of ethinylestradiol in pregnancy:
This medication is not recommended if you are pregnant or planning a pregnancy in the immediate future. Contact your doctor if you suspect pregnancy while receiving treatment with this medication.
Use of Ethinylestradiol during lactation:
This medicine should be used with caution in women who are breastfeeding. Consult your doctor before using this medicine.
Indications
Postmenopausal hormone replacement therapy:
This medication is used to replenish hormone estrogen levels in women after menopause.
Hipogonadismo femenino:
This medication is used to treat sexual hormone deficiency due to the delay in developing certain glands in women.
Palliative treatment of cancer:
This medication is used to treat specific symptoms in a patient with end-stage breast or prostate cancer.
Oral contraceptives:
This medication is used as the estrogenic component of an oral contraceptive pill.
Contraindications
Allergies:
This medication is not recommended in patients who have a known allergy to estrogen products or any other ingredient present along with it.
Undiagnosed vaginal bleeding:
This medication is not recommended if you have an abnormal episode of vaginal bleeding that was not diagnosed. Appropriate tests should be performed to rule out cancer in all cases of abnormal and persistent bleeding before treatment with ethinylestradiol is initiated.
Breast cancer:
Ethinylestradiol increases the risks of breast cancer and, therefore, should be used with the lowest doses, and the duration of treatment should be kept as low as possible.
Jaundice :
This medication can cause yellowing of the eyes and skin due to its effect on the liver and gallbladder. Report the presence of any symptoms indicative of jaundice to the doctor with priority. The use of this medication should be discontinued in such cases.
Edema:
This medication, especially topical forms, can cause fluid retention or other associated problems in women. Any swelling of the eye, throat, tongue, arms, and feet should be reported to the doctor.
Abnormalities in vision:
This medication has been associated with partial or total loss of vision in some exceptional cases. Any abnormality in the eye should be reported immediately to the doctor. Special precautions should be taken if the patient wears contact lenses.
Formation of blood clots:
This medication has been associated with blood clots, especially in older adults and people who smoked.
Pediatric use:
The use of ethinylestradiol in children is not recommended since safety and efficacy have not yet been established.
Heart disorder, cardiovascular risks, and blood vessels:
The use of ethinylestradiol is not recommended in patients who have heart, cardiovascular, or blood vessel disease, deep vein thrombosis, heart attack or recent infarction, other disorders of blood coagulation, etc.
This medication has been associated with an increased risk of stroke, heart attack, and other complications related to the heart. It should be used with caution in patients who have heart disease or are exposed to risk factors.
Estrogen-dependent tumor:
This drug is not recommended in patients with cancer that is attributed to abnormal levels of the hormone estrogen in the body for a prolonged period.
Liver disease:
This medication is not recommended in patients who have impaired liver function due to disease or other contributing factors.
Interactions of ethinylestradiol with diagnosed diseases
Abnormal vaginal bleeding:
This medication should be used with caution if the patient has had an episode of abnormal vaginal bleeding, especially if the intended use is of a long duration.
It is recommended to undergo a diagnostic test to determine the reason for the abnormal bleeding. Conditions such as endometrial hyperplasia should be ruled out before starting therapy with ethinylestradiol.
Estrogen-dependent tumor:
The use of this medication is not recommended in patients who have a tumor due to abnormal estrogen levels in the body. Cancer may be from the endometrium or sinuses. Appropriate diagnostic tests must be performed before starting estradiol treatment.
Hypertension :
Ethinylestradiol should be used with extreme caution in patients with high blood pressure. The risk of adverse effects on the heart and blood vessels is extremely high in such cases. Adequate dose adjustment and safety monitoring are essential in such cases.
Disorder of the heart and blood vessels:
The use of ethinylestradiol is not recommended in patients who have had or are currently having cardiovascular disease or heart and blood vessel disease. Your doctor can determine the best course of treatment after assessing the severity of the condition.
Liver neoplasms:
This medication is not recommended if the patient is suspected of having liver cancer. Your doctor can decide the best course of treatment after evaluating the condition.
Pharmacology
pharmacodynamics:
Ethinylestradiol is an estrogen similar to natural estrogens such as estradiol and conjugated estrogens (Premarin) and synthetic estrogens such as diethylstilbestrol. It binds and activates both isoforms of the estrogen receptor, ERα, and ERβ.
In one study, it was discovered that Ethinylestradiol has 233% and 38% of the affinity of estradiol for ERα and ERβ, respectively. Ethinylestradiol also seems to indicate through the GPER, a membrane estrogen receptor, similar to estradiol.
Estrogens have antigonadotropic effects through ERα activation.
As a contraceptive, Ethinylestradiol acts in conjunction with a progestin to inhibit the increase in the average cycle of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) through its antigonadotropic effects, inhibiting folliculogenesis and preventing ovulation, and therefore, the possibility of pregnancy.
Orally, Ethinylestradiol is approximately 100 times more potent in weight than natural estrogens such as micronized estradiol and conjugated estrogens, which is mainly due to substantially more excellent resistance to first-pass metabolism.
In contrast, the potencies of ethinylestradiol and natural estrogens are similar when administered intravenously due to the cancellation of the first-pass metabolism. Ethinylestradiol is approximately 1.7 times more potent by weight orally than its prodrug mestranol.
Antiandrogenic effects:
Ethinylestradiol is a powerful functional antiandrogen in both women and men.
Antiandrogenic effects through:
1) Stimulate the production of sex hormone-binding globulin (SHBG) in the liver, which decreases the free and, therefore, bioactive concentrations of testosterone in the blood.
2) Suppress the secretion of luteinizing hormone (LH) from the pituitary gland, which decreases testosterone production by the gonads.
Contraceptive pills containing ethinylestradiol are helpful in the treatment of androgen-dependent conditions such as acne and hirsutism by their antiandrogenic effects.
It has been found that contraceptive pills containing Ethinylestradiol increase circulating levels of sex hormone globulin by 2 to 4 times in women and reduce free testosterone levels by 40 to 80%.
Therefore, free testosterone levels are deficient during treatment with birth control pills that contain ethinylestradiol.
In men, one study found that treatment with a relatively low dose of 20 μg / day of Ethinylestradiol for five weeks increased circulating levels of sexual hormone globulin by 150% and decreased free testosterone levels, increasing the total circulating levels of testosterone.
The stimulation of the production of hepatic sex hormone-binding globulin by Ethinylestradiol is much stronger than with other estrogens such as estradiol due to the high resistance of Ethinylestradiol to inactivation in the liver and, therefore, its disproportionate effects in this body part.
Estrogens are antigonadotropins and can suppress the secretion of luteinizing hormone from the pituitary gland and, by extension, gonadal testosterone production.
High-dose estrogen therapy, even with ethinylestradiol, can suppress testosterone levels in men by about 95% or in the castrate / female range.
Differences with estradiol:
As seen in the tables, Ethinylestradiol shows substantial and disproportionate effects on hepatic protein production about estradiol.
Both the liver and the uterus express 17β-hydroxysteroid dehydrogenase (17β-HSD), and this enzyme serves to inactivate estradiol and effectively suppress its potency in these tissues.
Converting it reversibly into the much less potent estrogen estrone (which has approximately 4% of the oestrogenic activity of estradiol, most of which is due to conversion to estradiol).
Unlike estradiol, the 17α-ethynyl group of Ethinylestradiol prevents oxidation of the C17β position of Ethinylestradiol by 17β-HSD. For this reason, Ethinylestradiol is not inactivated in these tissues and has a much stronger relative estrogenic activity in them.
This is the mechanism of the disproportionately strong effects of ethinylestradiol on the production of hepatic protein, which results in a much greater effect magnitude in the risk of venous thromboembolism about estradiol.
On the other hand, due to the loss of inactivation of ethinylestradiol by 17β-HSD in the endometrium (uterus) is relatively more active than estradiol in the endometrium and, for this reason, is associated with a significantly lower incidence of bleeding Vaginal and spots in comparison.
This is particularly true in the case of combination estrogen-progestin therapy (as in combination oral contraceptives or menopausal hormone replacement therapy) since progestogens induce the expression of 17β-HSD in the endometrium.
The reduction of vaginal bleeding and spotting with ethinylestradiol is one of the main reasons it is used in combined oral contraceptives in place of estradiol, despite its potentially lower safety profile (related to its adverse effects on protein synthesis). Hepatic and the incidence of venous thromboembolism).
Ethinylestradiol has been found to have similar effects on hepatic protein production and risk of venous thromboembolism regardless of whether the route of administration is oral, transdermal, or vaginal, indicating that oral versus non-oral courses do not reduce hepatic actions of Ethinylestradiol in comparison with – hepatic activities.
In contrast, at typical doses of menopause, oral estradiol shows significant effects on hepatic protein production, while transdermal estradiol shows little or no impact on this type.
Pharmacokinetics
Absorption:
The oral bioavailability of ethinylestradiol is 45% on average, with a wide range of 20% to 65% (although more frequently between 38% and 48%), due to the high interindividual variability.
Although it is relatively low, the oral bioavailability of ethinylestradiol is considerably higher than that of micronized estradiol (5%).
After a single dose of 20 μg of ethinylestradiol in combination with 1 mg of norethisterone in postmenopausal women, it has been found that ethinylestradiol concentrations reach a maximum of 50 pg/ml in an average of 1.5 hours.
After the first dose, the average levels of Ethinylestradiol in general increase even more by approximately 50% until the steady-state concentrations are reached; the steady-state is reached after one week of daily administration.
For comparison, the maximum average levels of estradiol achieved with 2 mg of micronized estradiol or estradiol valerate are 40 pg/ml after the first dose and 80 pg/ml after three weeks of administration.
These estradiol concentrations are in the same range as the ethinylestradiol concentrations produced by an oral dose of ethinylestradiol, which is 100 times less in weight, which is in agreement with the oral potency of ethinylestradiol approximately 100 times higher than the estradiol.
In agreement with the high interindividual variability in the oral bioavailability of Ethinylestradiol, there is a high degree of interindividual variation in Ethinylestradiol levels.
Distribution
Unlike estradiol, which binds with high affinity to sex hormone-binding globulin, ethinylestradiol has no affinity for this protein and, on the other hand, binds almost exclusively to albumin (97-98%).
Since estradiol attached to sex hormone-binding globulin is considered hormonally inactive, the lack of binding of ethinylestradiol to sex hormone-binding globulin may be implicated in its increased comparative power.
Metabolism
Due to the high first-pass metabolism in the intestines and the liver, only 1% of an oral dose of an ethinylestradiol appears in the circulation as the ethinylestradiol itself.
During the first-pass metabolism, Ethinylestradiol is extensively conjugated via sulfation in hormonally inert Ethinylestradiol sulfate, and circulating Ethinylestradiol sulfate levels are between 6 and 22 times higher than those of Ethinylestradiol.
For comparison, with oral administration of 2 mg of micronized estradiol, the estrone and estrone sulfate levels are 4 to 6 times and 200 times higher than those of estradiol, respectively.
In contrast to estradiol, ethinylestradiol, due to steric hindrance by its ethinyl group C17α, is not metabolized or inactivated by 17β-hydroxysteroid dehydrogenases, and this is the main factor responsible for the drastically increased potency of oral ethinylestradiol compared with the Oral estradiol.
Due to the formation of ethinylestradiol sulfate, the enterohepatic circulation is involved in the pharmacokinetics of ethinylestradiol in a similar way to estradiol, although to a lesser extent.
In addition to sulfate conjugation, ethinylestradiol is metabolized primarily by hydroxylation in catechol estrogens. This is mainly by 2-hydroxylation in 2-hydroxy-ethinylestradiol, which is primarily catalyzed by CYP3A4.
Hydroxylation of ethinylestradiol at positions C4, C6α, and C16β in 4-, 6α- and 16β-hydroxy-ethinylestradiol has also been reported, but it seems to contribute to its metabolism only to a small extent.
2- and 4-methoxy-ethinylestradiol are also formed by transformation by catechol-O-methyltransferase of 2- and 4-hydroxy-ethinylestradiol.
Unlike the case of estradiol, 16α-hydroxylation does not occur with ethinylestradiol due to steric hindrance due to its ethinyl group in C17α. The ethinylestradiol methylation is mainly irreversible so that the EE is not metabolized into estradiol, unlike the estradiol esters.
One review found that the range of the terminal half-life of ethinylestradiol in the literature was 13.1 to 27.0 hours.
Another review reported a terminal half-life of Ethinylestradiol of 10-20 hours. However, the terminal half-life of Ethinylestradiol has also been reported by other sources in just 7 hours and up to 36 hours.
Unlike the case of estradiol, in which there is a rapid increase in its levels, and it remains elevated in a curve similar to a plateau for many hours, the levels of ethinylestradiol fall rapidly after the peak.
This is because estrone and estrone sulfate can be reversibly converted to estradiol and serve as a hormonally inert reservoir for estradiol. In contrast, the deposit of ethinylestradiol sulfate for ethinylestradiol is much smaller.
After the oxidative formation of a highly reactive metabolite, Ethinylestradiol irreversibly inhibits the cytochrome P450 enzymes involved in its metabolism. This may also play a role in the increased potency of ethinylestradiol relative to estradiol.
It is said that ethinylestradiol has a marked effect on hepatic metabolism, and this is one of the reasons, among others, that natural estrogens such as estradiol may be preferable.
Elimination
Ethinylestradiol is eliminated by 62% in the feces and 38% in the urine.
Chemistry
Ethinylestradiol is a synthetic steroid of estrano and an estradiol derivative with Ethinyl substitution at the C17α position. It is also known as 17α-ethinylestradiol or as 17α-ethinylestra-1,3,5 (10) -tries-3,17β-diol.
The 17α-ethylation of Etinilestradiol is analogous to the 17α-substitution of testosterone derivatives such as 17α-ethynylated progestins such as ethisterone (17α-methyltestosterone) and norethisterone (17α-ethynyl-19-nortestosterone), as well as 17α-alkylated anabolic steroids such as methyltestosterone (17α-methyltestosterone).
Analogs
Existen varios derivados del Etinilestradiol. Estos incluyen mestranol (Etinilestradiol 3-metil éter), quinestrol (Etinilestradiol 3-ciclopentil éter), Etinilestradiol sulfonato (Etinilestradiol 3-isopropilsulfonato) y moxestrol (11β-metoxi-Etinilestradiol).
The first three are prodrugs of Ethinylestradiol, while the latter is not.
There are some 17α-substituted analogs of ethinylestradiol. Examples include methyl estradiol (17α-methyl estradiol), ethinylestradiol (17α-ethynyltriol) and nilestriol (17α-ethynyltriol-3-cyclopentyl ether).
Generic names
Ethinylestradiol is the generic name in English, and its International Common Names, Accepted Names of the United States, British Approved Names, and Adopted Japanese Names.
It has also been spelled as ethynylestradiol, ethinyloestradiol, and ethinyloestradiol (all have the same pronunciation), and the latter was previously their British approved name but was eventually changed.
In addition, a space is often included in the name of Ethinylestradiol, so it is written as Ethinylestradiol (as well as its variations), and this is, in fact, its name in the United States Pharmacopoeia.
The generic name of Ethinylestradiol in French and its common French words are ethinylestradiol; in Spanish, it is Ethinylestradiol. In Italian and its Denominazione Comune Italiana is ethinylestradiol, and in Latin, it is Etinilestradiolum.
The name of the drug is often abbreviated as Ethinylestradiol or as EE2 in the medical literature.
Brand names
Ethinylestradiol has been marketed as an independent oral drug under Esteed, Estinyl, Feminine, Lynoral, Menolyn, Novestrol, Palonyl, Spanestrin, and Ylestrol, among others. However, most or all of these formulations are now discontinued.
It is marketed under many commercial brands throughout the world in combination with progestins for use as an oral contraceptive.
