Estradiol benzoate butyrate (EBB), sold under the brand names Neolutin N, Redimen, Soluna, and Unijab and formerly known under the developmental code name Unimens, is an estrogen medication which is used in hormonal birth control for women. It is formulated in combination with dihydroxyprogesterone acetophenide (DHPA; algestone acetophenide), a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

, and is used specifically as a combined injectable contraceptive. EBB is not available for medical use alone. The medication, in combination with DHPA, is given by

injection into muscle Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have l ...

once a month. Side effects of EBB include breast tenderness, breast enlargement, nausea,

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, and fluid retention. EBB is an estrogen and hence is an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the estrogen receptor, the biological target of estrogens like estradiol. It is an estrogen ester and a

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

of estradiol in the body. Because of this, it is considered to be a natural and bioidentical form of estrogen. EBB was first described in 1938. It was developed for use as a form of birth control in the 1970s and was introduced for medical use for this indication by the 1980s. The medication is used in combination with DHPA as a combined injectable contraceptive in Peru and Singapore.

Medical uses

EBB is used in combination with DHPA as a once-a-month combined injectable contraceptive to prevent pregnancy in women.

Available forms

The combination of EBB and DHPA contains 10 mg estradiol benzoate butyrate (EBB), an estrogen, and 150 mg

algestone acetophenide Algestone acetophenide, also known more commonly as dihydroxyprogesterone acetophenide (DHPA) and sold under the brand names Perlutal and Topasel among others, is a progestin medication which is used in combination with an estrogen as a form of ...

(dihydroxyprogesterone acetophenide; DHPA), a

Side effects

The combination of EBB and DHPA is said to be associated with poor control of

menstrual bleeding The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...

when used as a once-a-month combined injectable contraceptive.

Pharmacology

Pharmacodynamics

EBB is an estradiol ester, or a

of estradiol. As such, it is an estrogen, or an

of the estrogen receptors. EBB is of about 64% higher molecular weight than estradiol due to the presence of its C3 benzoate and C17β

butyrate The conjugate acids are in :Carboxylic acids. {{Commons category, Carboxylate ions, Carboxylate anions Carbon compounds Oxyanions ...

esters. Because EBB is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen. The estrogenic potency of oral ethinylestradiol is approximately 30-fold higher than that of parenteral EBB. In accordance, 50 μg/day oral ethinylestradiol has been reported to be about 3 times stronger in estrogenic effect than once-a-month injections of 10 mg EBB.

Pharmacokinetics

A single 10 mg

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

of EBB has a duration of approximately 3 weeks. Its duration is shorter than that of

estradiol enantate Estradiol enantate (EEn or E2-EN), also spelled estradiol enanthate and sold under the brand names Perlutal and Topasel among others, is an estrogen medication which is used in hormonal birth control for women. It is formulated in combination wi ...

. A preliminary study of the duration of EBB relative to other estradiol esters was conducted in 1952.

Chemistry

EBB is a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

estrane

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

and the C3 benzoate (benzenecarboxylate) and C17β

butyrate The conjugate acids are in :Carboxylic acids. {{Commons category, Carboxylate ions, Carboxylate anions Carbon compounds Oxyanions ...

(butanoate) diester of estradiol. It is also known as estradiol 3-benzoate 17β-n-butyrate or as estra-1,3,5(10)-triene-3,17β-diol 3-benzoate 17β-n-butyrate. The experimental octanol/water partition coefficient (logP) of EBB is 6.3.

History

EBB, along with a variety of other estradiol esters, was first described in 1938 by Karl Miescher and colleagues of Ciba in Basel, Switzerland. It was developed in combination with DHPA as a combined injectable contraceptive in the 1970s. The combination was marketed for use as a combined injectable contraceptive in Peru by 1987.

Society and culture

Brand names

EBB is marketed in combination with DHPA under the brand names Neolutin N, Redimen, Soluna, and Unijab.
/ref> It was originally developed under the tentative brand name Unimens, but ultimately was not marketed under this particular brand name.

Availability

The combination of EBB and DHPA is available only in Peru and Singapore.

References

{{Estrogen receptor modulators Benzoate esters Butyrate esters Estradiol esters Prodrugs Synthetic estrogens