Segesterone acetate (SGA), sold under the brand names Nestorone, Elcometrine, and Annovera, is a progestin medication which is used in birth control and in the treatment of endometriosis in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

, and other

South America South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the sout ...

n countries.https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209627s000lbl.pdf It is available both alone and in combination with an

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

. It is not effective

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

and must be given by other routes, 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 a ...

or implant that is placed into fat.

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of SGA are similar to those of other progestins. SGA is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, 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. 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 Par ...

for the

glucocorticoid receptor The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates ...

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 by complex biological processes to regulate physiology and behavior. Hormones are required f ...

activity. SGA 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 res ...

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

and

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...

as a

gel A gel is a semi-solid that can have properties ranging from soft and weak to hard and tough. Gels are defined as a substantially dilute cross-linked system, which exhibits no flow when in the steady-state, although the liquid phase may still dif ...

in combination with

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development o ...

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

for use as a method of birth control in women and in men, respectively. On August 10, 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. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological dis ...

was approved in the

. It is marketed under the brand name Annovera and is reusable for up to one year as a method of birth control in women. Annovera does not require refrigeration which is very useful for low resource areas.

Medical uses

SGA is used as a hormonal contraceptive and in the treatment of endometriosis.

Available forms

Side effects

s of SGA are similar to those of other progestins.

Pharmacology

Pharmacodynamics

SGA acts primarily as a high-

agonist of the progesterone receptor (272% of the affinity of progesterone and 136% of that of

promegestone Promegestone, sold under the brand name Surgestone, is a progestin medication which is used in menopausal hormone therapy and in the treatment of gynecological disorders. It is taken by mouth. Side effects of promegestone include menstrual ...

). It does not bind significantly to the androgen receptor,

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...

, 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, SGA does not have

ic,

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

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 the ...

ic, or

antimineralocorticoid An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is ofte ...

activity. However, SGA does have significant affinity for the

(38% of that of

dexamethasone Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...

), 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 verteb ...

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

antiglucocorticoid An antiglucocorticoid is a drug which reduces glucocorticoid activity in the body. They include direct glucocorticoid receptor antagonists such as mifepristone and synthesis inhibitors such as metyrapone, ketoconazole, and aminoglutethimide. ...

activity in animals either. The

ovulation Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilize ...

-inhibiting dosage of

parenteral A route of administration in pharmacology and toxicology 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. ...

SGA has been reported to be 150 μg per day, while the endometrial transformation dosage has been reported to be 600 μg per cycle. SGA 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 ...

ic effects via its progestogenic activity similarly to other progestogens. In healthy young men, SGA 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

SGA is only weakly active orally, and is instead given as a subcutaneous implant. 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%. Ho ...

of SGA 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 SGA administered at a dose of 2 to 3mg/day in the form of a transdermal gel delivers approximately 200 to 300μg/day SGA based on a transdermal

of about 10 to 12%. SGA is

bound Bound or bounds may refer to: Mathematics * Bound variable * Upper and lower bounds, observed limits of mathematical functions Physics * Bound state, a particle that has a tendency to remain localized in one or more regions of space Geography *B ...

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

. 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 has also been called androgen ...

. Segesterone, the deacetylated form of SGA, is a metabolite of the medication. The

biological half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

SGA 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 SGA with oral administration is only 1 to 2 hours. In contrast to all of the preceding however, the

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 respon ...

(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, on which is written or printed information or symbols about the product or item. Information printed ...

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

Chemistry

SGA, also known as 16-methylene-17α-acetoxy-19-norprogesterone or as 16-methylene-17α-acetoxy-19-norpregn-4-ene-3,20-dione, is a synthetic norpregnane steroid and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

of progesterone. It is a combined derivative of

17α-hydroxyprogesterone 17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many o ...

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

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

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 enlarged prostate and cancer of the en ...

(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.http://www.ema. ...

, 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 ...

. SGA 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 . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...

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 betwee ...

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

History

SGA 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 .https://searchusan.ama-assn.org/undefined/documentDownload?uri=%2Funstructured%2Fbinary%2Fusan%2Fsegesterone-acetate.pdf 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

SGA 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. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disord ...

under the brand name Annovera.

Availability

SGA is available alone in several

South American South America is a continent entirely in the Western Hemisphere and mostly in the Southern Hemisphere, with a relatively small portion in the Northern Hemisphere at the northern tip of the continent. It can also be described as the southe ...

countries, including

. It is available in the United States as a

in combination with

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

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 th ...

of SGA 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 ointme ...

formulation for use as a contraceptive in women by the Population Council in conjunction with Antares Pharma in the

and

. As of December 2017, it is in phase III

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

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

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

in a

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

Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...

, Europe, and Australia. It completed phase III clinical trials and was approved in the United States in August 2018. A combination of SGA 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 skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...

, weight gain and nocturnal sweating.

References

{{Glucocorticoid receptor modulators Acetate esters Alkene derivatives Contraception for males Diketones Hormonal contraception Norpregnanes Progestogen esters Progestogens Vinylidene compounds

Medical uses

Available forms

Side effects

Pharmacology

Pharmacodynamics

Pharmacokinetics

Chemistry

History

Society and culture

Generic names

Brand names

Availability

Research

See also

References