Segesterone acetate (SGA), sold under the brand name Nestorone among others, is 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 female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...

medication which is used in

birth control Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth control only be ...

and in the treatment of

endometriosis Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...

. It is available both alone and in combination with an

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

as segesterone acetate/ethinylestradiol. It is not effective

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

and must be given by other

route Route or routes may refer to: * Air route, route structure or airway * GPS route, a series of one or more GPS waypoints * Route (gridiron football), a path run by a wide receiver * Route (command), a program used to configure the routing table * ...

s, most typically as a

vaginal ring Vaginal rings (also known as intravaginal rings, or V-Rings) are polymeric drug delivery devices designed to provide controlled release of drugs for intravaginal administration over extended periods of time. The ring is inserted into the vagina ...

or implant that is placed into fat.

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of segesterone acetate are similar to those of other progestins. Segesterone acetate is a progestin, or a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...

, and hence is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resi ...

, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

of progestogens like

progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

. It has some

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

for the

glucocorticoid receptor The glucocorticoid receptor (GR or GCR) also known by its gene name ''NR3C1'' ( nuclear receptor subfamily 3, group C, member 1) is the steroid receptor for glucocorticoids such as cortisol. The GR is expressed in almost every cell in the bod ...

and has no other important

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

activity. Segesterone acetate was developed by the

Population Council The Population Council is an international, nonprofit, non-governmental organization. The Council conducts research in biomedicine, social science, and public health and helps build research capacities in developing countries. One-third of its re ...

and was introduced for medical use by 2000. It is under development in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

and

Europe Europe is a continent located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south, and Asia to the east ...

as a gel in combination with

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

for use as a method of birth control in women and in men, respectively. In August 2018, a first-of-its-kind one-year

contraceptive vaginal ring A contraceptive vaginal ring is a type of hormonal insert that is placed in the vagina for the purpose of birth control. The rings themselves utilize a plastic polymer matrix that is inlaid or embedded with contraceptive drug. This drug, often one ...

containing segesterone acetate in combination with

ethinyl estradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological dis ...

was approved in the United States.

Medical uses

Segesterone acetate is used as a

hormonal contraceptive Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original ...

and in the treatment of

Side effects

s of segesterone acetate are similar to those of other progestins.

Pharmacology

Pharmacodynamics

Segesterone acetate acts primarily as a high-

of the

(272% of the affinity of

and 136% of that of promegestone). It does not bind significantly to the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

, or

mineralocorticoid receptor The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...

. As such, segesterone acetate does not have

ic,

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

ic,

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking t ...

ic, or

antimineralocorticoid A mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which receptor antagonist, antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive t ...

activity. However, segesterone acetate does have significant affinity for the

(38% of that of

dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...

), but in spite of its relatively high affinity for the glucocorticoid receptor, it either does not have any

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

effects or shows glucocorticoid effects only at exceptionally high doses in animals. Segesterone acetate has no

antiglucocorticoid Antiglucocorticoid drugs are a class of medications that act to reduce the effects of glucocorticoids, primarily cortisol, in the body. They include direct glucocorticoid receptor antagonists such as mifepristone and synthesis inhibitors such as ...

activity in animals either. The

ovulation Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...

-inhibiting dosage of

parenteral In pharmacology and toxicology, a route of administration is the way by which a drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance is applied. ...

segesterone acetate has been reported to be 150 μg per day, while the endometrial transformation dosage has been reported to be 600 μg per cycle. Segesterone acetate has antigonadotropic effects and functional

antiestrogen Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inh ...

ic effects via its progestogenic activity similarly to other progestogens. In healthy young men, segesterone acetate alone at a dose of 2 to 3 mg/day as a transdermal gel (delivering 200–300 μg/day SGA) for 2 weeks suppressed testosterone levels from ~581 ng/dL to ~276 ng/dL (–52%).

Pharmacokinetics

Segesterone acetate is only weakly active orally, and is instead given as a subcutaneous

implant Implant can refer to: Medicine *Implant (medicine), or specifically: **Brain implant **Breast implant **Buttock augmentation, Buttock implant **Cochlear implant **Contraceptive implant **Dental implant **Fetal tissue implant **Implantable cardiov ...

. The oral

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of segesterone acetate has been reported to be only 10%. However, it has also been reported that the medication is more than 100-fold as potent when delivered via subcutaneous implant relative to oral administration in rats. It has been estimated that segesterone acetate administered at a dose of 2 to 3mg/day in the form of a transdermal gel delivers approximately 200 to 300μg/day segesterone acetate based on a transdermal

of about 10 to 12%. Segesterone acetate is bound to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

. It does not bind to

sex hormone-binding globulin Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it is called androgen-binding prot ...

. Segesterone, the deacetylated form of segesterone acetate, is a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of the medication. The

biological half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...

segesterone acetate has been reported to be 24 to 72 hours. One study specifically reported a biological half-life of 26.8 hours. It has been reported that the biological half-life of segesterone acetate with oral administration is only 1 to 2 hours. In contrast to all of the preceding however, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA)

label A label (as distinct from signage) is a piece of paper, plastic film, cloth, metal, or other material affixed to a container or product. Labels are most often affixed to packaging and containers using an adhesive, or sewing when affix ...

for Annovera, a one-year vaginal ring containing ethinylestradiol and segesterone acetate, lists a circulating half-life of segesterone acetate of 4.5 hours.

Chemistry

Segesterone acetate, also known as 16-methylene-17α-acetoxy-19-norprogesterone or as 16-methylene-17α-acetoxy-19-norpregn-4-ene-3,20-dione, is a

norpregnane

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

and a

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

. It is a combined derivative of 17α-hydroxyprogesterone and 19-norprogesterone, or a derivative of gestronol (17α-hydroxy-19-norprogesterone). The medication is the C17α

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic, or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

of segesterone, which, in contrast, was never marketed. Other 19-norprogesterone derivatives include demegestone,

gestonorone caproate Gestonorone caproate, also known as gestronol hexanoate or norhydroxyprogesterone caproate and sold under the brand names Depostat and Primostat, is a progestin medication which is used in the treatment of benign prostatic hyperplasia, enlarged p ...

(norhydroxyprogesterone caproate),

nomegestrol acetate Nomegestrol acetate (NOMAC), sold under the brand names Lutenyl and Zoely among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. It is available ...

, promegestone, and

trimegestone Trimegestone, sold under the brand names Ondeva and Totelle among others, is a progestin medication which is used in menopausal hormone therapy and in the prevention of postmenopausal osteoporosis. It was also under development for use in birth c ...

. Segesterone acetate is a derivative of 16-methylene-17α-hydroxyprogesterone acetate, and is the analogue of methenmadinone acetate without the C19

methyl group In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated a ...

or the C6

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

. A derivative of segesterone acetate with even greater progestogenic potency in comparison to segesterone acetate is 18-methylsegesterone acetate.

History

Segesterone acetate was developed by the

.Prasad, P. V., & Shrivastav, T. G. (2015). Nestorone: A new hope for Gynecologists, Andrologists and Neurologists. of, 3, 2. It has been marketed since at least 2000.

Society and culture

Generic names

Segesterone acetate is the generic name of the drug and its . It is also known by its brand names Nestorone and Elcometrine, as well as by its former developmental code names ''ST-1435'', ''AC-6844'', and ''CS-0411''.

Brand names

Segesterone acetate is marketed alone under the brand names Nestorone and Elcometrine and in combination with

ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological ...

as segesterone acetate/ethinylestradiol under the brand name Annovera among others.

Availability

Segesterone acetate is available alone in several South American countries, including Brazil. It is available in the United States and Canada as a

in combination with

ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological ...

Research

combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are ...

of segesterone acetate and the

is under development in a

transdermal Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointm ...

gel

formulation Formulation is a term used in various senses in various applications, both the material and the abstract or formal. Its fundamental meaning is the putting together of components in appropriate relationships or structures, according to a formula ...

for use as a

contraceptive Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth control only be ...

in women by the Population Council in conjunction with Antares Pharma in the United States and Europe. As of December 2017, it is in phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s for this indication. The medication has the tentative brand name NestraGel. A combination of segesterone acetate and the estrogen

ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological ...

in a

formulation for use as a one-year contraceptive was developed by the Population Council in multiple regions including

Latin America Latin America is the cultural region of the Americas where Romance languages are predominantly spoken, primarily Spanish language, Spanish and Portuguese language, Portuguese. Latin America is defined according to cultural identity, not geogr ...

, Europe, and

Australia Australia, officially the Commonwealth of Australia, is a country comprising mainland Australia, the mainland of the Australia (continent), Australian continent, the island of Tasmania and list of islands of Australia, numerous smaller isl ...

. It completed phase III clinical trials and was approved in the United States in August 2018. A combination of segesterone acetate and the

is under development as a transdermal gel formulation for use as a hormonal contraceptive in men by the Population Council. As of December 2017, it is in phase II clinical studies for this purpose. In a trial, 100 couples used segesterone/testosterone dermal gel as the sole contraception method, which resulted in no pregnancy. Side effects were described as mild, comprising

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

, weight gain and nocturnal sweating.

References

{{Authority control Acetate esters Alkene derivatives Contraception for males Diketones Hormonal contraception Norpregnanes Progestogen esters Progestogens Vinylidene compounds