Estetrolum

Estetrolum Uses, Dosage, Side Effects, Food Interaction and all others data.

Naturally or synthetically produced steroid estrogens have a wide range of pharmaceutical uses ranging from hormonal contraception to the treatment of menopausal symptoms. Estetrolum (E4) is a native estrogen occurring naturally during pregnancy, but can be synthesized from a plant source and used for contraception. It is more potent and is safer than the synthetic estrogen ethinylestradiol (EE2) found in 97% of oral contraceptive pills, reducing the environmental accumulation of unwanted endocrine disrupting chemicals (EDCs) that often lead to harmful epigenetic effects.

On April 15 2021, Mayne Pharma Group Limited and Mithra Pharmaceuticals were granted FDA approval for the oral contraceptive Estelle/Nextstellis, a combination of drospirenone and estetrol. Estetrolum is the first new estrogen introduced to the USA in over 50 years and is the first approved estetrol product in the world. The combination of drospirenone and estetrol offers a new choice with a favourable safety profile for women seeking contraceptive therapy. In Canada, Nextstellis was approved for use in March 2021; it was developed by Mithra and is marketed by Searchlight Pharma.

Estetrolum prevents pregnancy by suppressing ovulation.

Estetrolum
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Estetrolum
Generic	Estetrol
Estetrol Other Names	Estetrol, Estétrol, Estetrolum, Oestetrol
Type
Formula	C₁₈H₂₄O₄
Weight	Average: 304.3808 Monoisotopic: 304.167459256
Protein binding	Estetrol is 46-50% bound to plasma proteins. Estetrol does not bind to Sex Hormone Binding Globulin (SHBG). In one study, estetrol showed moderate binding to human plasma proteins (45.5%-50.4%) and human serum albumin (58.6%) with low binding to human alpha-glycoprotein (11.2%).
Groups	Approved, Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Estetrolum is an estrogen used in combination with drospirenone for oral contraception.

Estetrolum is indicated in combination with drospirenone for the prevention of pregnancy.

Estetrolum is also used to associated treatment for these conditions: Oral Contraceptives

How Estetrolum works

Estetrolum is a synthetic analogue of a naturally occurring estrogen present during pregnancy, demonstrating selectivity for both estrogen receptor-α (ER-α) and ER-β and suppressing ovulation. Estetrolum binds with a low to moderate affinity human estrogen receptor alpha (ER alpha) and ER beta with a preference for ER alpha. Estetrolum demonstrates a unique mechanism of action via tissue selective activity, showing estrogen receptor agonist activity on the vagina, the uterus and the endometrium, and negative estrogenic activity on breast tissue.

Toxicity

LD50 information for estetrol is not readily available in the literature. Subjects receiving a dose of 20 mg, 40 mg or 60 mg of estetrol per day over 12 weeks were tolerated without dose-limiting toxicity. Symptoms that may occur in association with overdose, based on existing information on overdosage with oral contraceptives include nausea, vomiting, and vaginal bleeding. In one clinical study, 1 of 32 healthy research subjects receiving a dose of 75 mg of estretol with 15 mg of drospirenone for 10 days experienced deep vein thrombosis of the lower right limb. There is no known antidote to an estretol overdose; conduct laboratory testing for electrolytes and evidence of metabolic acidosis and provide symptomatic treatment.

Food Interaction

Take with or without food. Take at the same time each day.

Volume of Distribution

Limited distribution of estetrol into red blood cells has been demonstrated.

Elimination Route

Estetrolum is rapidly absorbed from the gastrointestinal tract. The Cmax of estetrol is 18 ng/mL according to the results of a pharmacokinetic study, with an AUC of 36.4 ng•h/mL. When estetrol and drospirenone are taken in a single product, maximum serum concentrations of approximately 48.7 ng/mL are achieved within 1-3 h. Bioavailability of the combination ranges between 76 and 85%. The Tmax can range from 0.5 to 2 hours and time to steady state is approximately 4 days, according to the results of one clinical study.

Half Life

The elimination half-life of estetrol is approximately 27 hours. Half-life may range between 19-40 hours.

Elimination Route

Estrogens are generally excreted as sulfated and glucuronidated derivatives. Approximately 69% of a dose of estetrol is excreted in the urine, and about 22% is excreted in the feces as unchanged drug.