Dienogest, sold under the brand name Visanne 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. Pro ...
medication which is used in
birth control pill
The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progest ...
s and in the treatment of
endometriosis.
It is also used in
menopausal hormone therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...
and to treat
heavy periods.
Dienogest is available both alone and in combination with
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 ...
s.
[Bartsch, V., & Römer, T. (2015). Gynaecological uses of dienogest alone and in combination with oestrogens. http://www.jmdrev.com/fileadmin/user_upload/Medien-Dateien/JMDR_Dienogest_E_2015.pdf] It is taken
by mouth.
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 dienogest include
menstrual irregularities,
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 of ...
s,
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
,
breast tenderness
Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a ...
,
depression, and
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 po ...
, among others.
Dienogest is a progestin, or a
synthetic progestogen, 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
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 re ...
, 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 major ...
.
It is a unique progestogen, with strong effects in the
uterus
The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. Th ...
.
The medication has some
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 activity, which may help to improve
androgen-dependent symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...
s like
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 po ...
, 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.
Dienogest was discovered in 1979 and was introduced for medical use in 1995.
Additional formulations of dienogest were approved between 2007 and 2010.
It is sometimes referred to as a "fourth-generation" progestin.
Dienogest is marketed widely throughout the world.
It is available as a
generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
.
Medical uses
Birth control
Dienogest is used primarily in
birth control pill
The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progest ...
s in combination with
ethinylestradiol under the brand name Valette.
It is also available in a quadriphasic birth control pill combined with estradiol valerate, marketed as Natazia 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 territo ...
and Qlaira in some
European countries and
Russia.
Endometriosis
Dienogest is approved as a standalone medication under the brand names Visanne and Dinagest in various places such as
Europe,
Australia,
Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
,
Singapore
Singapore (), officially the Republic of Singapore, is a sovereign island country and city-state in maritime Southeast Asia. It lies about one degree of latitude () north of the equator, off the southern tip of the Malay Peninsula, bo ...
, and
Malaysia
Malaysia ( ; ) is a country in Southeast Asia. The federal constitutional monarchy consists of thirteen states and three federal territories, separated by the South China Sea into two regions: Peninsular Malaysia and Borneo's East Malay ...
for the treatment of
endometriosis.
It has been found to be equally effective as
gonadotropin-releasing hormone agonist
A gonadotropin-releasing hormone agonist (GnRH agonist) is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatm ...
s (GnRH agonists), such as
leuprorelin
Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, as part of transgender hormone therapy, for early puberty, or to perform chemical cast ...
, in the treatment of endometriosis.
Heavy periods
Birth control pills containing dienogest and estradiol valerate are approved 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 territo ...
for the treatment of
menorrhagia (heavy menstrual bleeding).
Menopausal symptoms
Dienogest is used in combination with estradiol valerate in the treatment of
menopausal
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
symptom
Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...
s in certain countries such as
Germany and the
Netherlands
)
, anthem = ( en, "William of Nassau")
, image_map =
, map_caption =
, subdivision_type = Sovereign state
, subdivision_name = Kingdom of the Netherlands
, established_title = Before independence
, established_date = Spanish Neth ...
.
Available forms
Dienogest is available both alone and in combination with estrogens.
The following formulations are available:
* Dienogest 1 mg oral tablets (Dinagest) and 2 mg oral tablets (Valette) (not available in U.S.) – indicated for endometriosis
* Dienogest 2 mg and
estradiol valerate
Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy ...
3 mg oral tablets (Natazia) (U.S.) – indicated for contraception and menorrhagia
** 2 dark yellow tablets each containing 3 mg estradiol valerate
** 5 medium red tablets each containing 2 mg estradiol valerate and 2 mg dienogest
** 17 light yellow tablets each containing 2 mg estradiol valerate and 3 mg dienogest
** 2 dark red tablets each containing 1 mg estradiol valerate
** 2 white tablets (inert)
* Dienogest 2 to 3 mg and estradiol valerate 1 to 3 mg oral tablets (Qlaira) (not available in U.S.) – indicated for contraception
** Each dark yellow active tablet contains 3 mg estradiol valerate
** Each medium red active tablet contains 2 mg estradiol valerate and 2 mg dienogest
** Each light yellow active tablet contains 2 mg estradiol valerate and 3 mg dienogest
** Each dark red active tablet contains 1 mg estradiol valerate
* Dienogest 2 mg and
ethinylestradiol 30 µg oral tablets (Valette) – indicated for contraception
* Dienogest 2 mg and estradiol valerate 1 or 2 mg oral tablets (various) – indicated for menopausal hormone therapy
The availability of these formulations differs by country (see
Availability
In reliability engineering, the term availability has the following meanings:
* The degree to which a system, subsystem or equipment is in a specified operable and committable state at the start of a mission, when the mission is called for at ...
).
Contraindications
Contraindication
In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...
s of dienogest include active
venous thromboembolism
Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off ( embolizes) and flows to the lungs t ...
, previous or current
cardiovascular disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...
,
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
with cardiovascular complications, previous or current severe
liver disease or
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s,
hormone-dependent cancers such as
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a ...
, and undiagnosed
vaginal bleeding
Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproducti ...
.
[http://db.cbg-meb.nl/IB-teksten/h104058.pdf ]
Side effects
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 associated with dienogest are the same as those expected of a progestogen.
They include
menstrual irregularities,
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 of ...
s,
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of th ...
,
breast tenderness
Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a ...
,
depression,
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 po ...
,
weight gain,
flatulence
Flatulence, in humans, is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed environm ...
, and others.
Dienogest produces no
androgenic
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 ...
side effects and has little effect on
metabolic
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
and
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...
hemostatic parameters.
Birth control pills containing
estradiol valerate/dienogest are associated with a significantly increased risk of
venous thromboembolism
Venous thrombosis is blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off ( embolizes) and flows to the lungs t ...
.
However, they are associated with a significantly lower risk of venous thromboembolism than birth control pills containing
ethinylestradiol and a progestin.
Overdose
In safety studies, dienogest has been assessed in women with endometriosis at high doses of as much as 20 mg/day for up to 24 weeks and produced no clinically relevant effects on
lipid metabolism
Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In anim ...
,
liver enzymes, the
coagulatory system, or
thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
.
Interactions
Dienogest is
metabolized
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
mainly by the
cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various com ...
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
,
and for this reason,
inhibitors and
inducer
In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely:
*By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to t ...
s of CYP3A4 can alter the amount of exposure to dienogest when administered concomitantly with it.
(For a list of CYP3A4 inhibitors and inducers, see
here
Here is an adverb that means "in, on, or at this place". It may also refer to:
Software
* Here Technologies, a mapping company
* Here WeGo (formerly Here Maps), a mobile app and map website by Here
Television
* Here TV (formerly "here!"), a ...
.) The strong CYP3A4 inhibitors
ketoconazole
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...
and
erythromycin
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...
have been found to increase exposure to dienogest by up to 3-fold, whereas the strong CYP3A4 inducer
rifampicin
Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used t ...
(rifampin) was found to decrease
steady-state
In systems theory, a system or a process is in a steady state if the variables (called state variables) which define the behavior of the system or the process are unchanging in time. In continuous time, this means that for those properties ''p'' ...
and
area-under-curve concentrations of dienogest by 50% and 80%, respectively.
Pharmacology
Pharmacodynamics
Dienogest has
progestogenic activity, possibly some
antiprogestogenic activity, and has
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 activity.
The medication does not interact with the
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 t ...
, 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 ...
, or the
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 ...
, and hence has no
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 ...
ic,
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 vertebr ...
, or
antimineralocorticoid activity.
Because of its relatively high
selectivity
Selectivity may refer to:
Psychology and behaviour
* Choice, making a selection among options
* Discrimination, the ability to recognize differences
* Socioemotional selectivity theory, in social psychology
Engineering
* Selectivity (radio), a ...
as a progestogen, dienogest may have favorable
safety
Safety is the state of being "safe", the condition of being protected from harm or other danger. Safety can also refer to the control of recognized hazards in order to achieve an acceptable level of risk.
Meanings
There are two slightly dif ...
and
tolerability
Tolerability refers to the degree to which overt adverse effects of a drug can be tolerated by a patient. Tolerability of a particular drug can be discussed in a general sense, or it can be a quantifiable measurement as part of a clinical study. U ...
compared to various other progestins.
Progestogenic activity
Dienogest 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
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 re ...
(PR), and hence is a
progestogen.
It has relatively weak
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 PR ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' in human
uterine tissue, about 10% that of
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 major ...
.
Despite its low affinity for the PR however, dienogest has high progestogenic ''activity'' ''
in vivo''.
In addition, although its
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 ...
s, such as 9α,10β-dihydrodienogest and 3α,5α-tetrahydrodienogest, have greater affinity for the PR than does dienogest itself, the medication is not considered to be 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 dru ...
.
Dienogest has been described as "special" progestogen, possessing low or moderate
antigonadotropic efficacy but strong or very strong
endometrial
The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...
efficacy.
In relation to its endometrial activity, dienogest is said to be one of the strongest progestogens available.
The high endometrial activity of dienogest underlies its ability to stabilize the
menstrual cycle
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 egg ...
when combined with either ethinylestradiol or estradiol valerate (which has lower relative effects on the uterus compared to ethinylestradiol) in birth control pills, and also its use in the treatment of endometriosis.
The combination of most other progestins 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 of ...
or an
estradiol ester like estradiol valerate as birth control pills was unsatisfactory due to a high incidence of
irregular menstrual bleeding.
This is a property that ethinylestradiol does not share with estradiol, because of its resistance to
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
in the endometrium and hence its greater relative effects in this part of the body.
In contrast to other progestins, due to its high endometrial efficacy, the combination of dienogest with estradiol valerate in birth control pills is able to prevent
breakthrough bleeding, and is uniquely able to treat
heavy menstrual bleeding
Heavy menstrual bleeding (HMB), previously known as menorrhagia or hypermenorrhea, is a menstrual period with excessively heavy flow. It is a type of abnormal uterine bleeding (AUB).
Abnormal uterine bleeding can be caused by structural abnorm ...
.
The absence of
withdrawal bleeding, otherwise known as "silent menstruation", also may occur.
Dienogest has antiovulatory potency that is similar to that of
17α-hydroxyprogesterone derivatives like
cyproterone acetate but endometrial potency that is much stronger and similar to that of
gonane
Gonane is a chemical compound with formula , whose molecule can be described as three molecules or entities of cyclohexane and one of cyclopentane, fused in a particular way. More specifically, the molecule can be described as that of cyclohe ...
19-nortestosterone progestins like
levonorgestrel.
Unlike other progestogens, except in the case of its strong effects in the uterus, dienogest has been described as lacking
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, and does not antagonize beneficial effects of estradiol, for instance in the
metabolic
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
and
vascular system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
s.
Dienogest showed some possible
antiprogestogenic activity in one animal
bioassay when administered before but not at the same time as
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 major ...
.
The minimum effective dose of oral dienogest required to inhibit
ovulation is 1 mg/day.
The inhibition of ovulation by dienogest occurs mainly via a direct peripheral action in the
ovary
The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. ...
of inhibiting
folliculogenesis
:''Although the process is similar in many animals, this article will deal exclusively with human folliculogenesis.''
In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an ...
as opposed to a central action of inhibiting
gonadotropin secretion.
Oral therapy with 2 mg/day dienogest in cyclical premenopausal women reduced serum progesterone levels to
anovulatory levels, but circulating levels of
luteinizing hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnR ...
and
follicle-stimulating hormone were not considerably affected.
At this dosage, estradiol levels are reduced to early
follicular phase
The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the estrous cycle (or, in primates for example, the menstrual cycle) during which follicles in the ovary mature from primary follicle to a fully ...
levels of about 30 to 50 pg/mL.
Such levels are insufficient for reactivation of endometrioses, but are sufficient to avoid
menopausal-like symptoms such as
hot flash
Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...
es and
bone loss.
This is in contrast to
gonadotropin-releasing hormone analogue
A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing hormon ...
s (GnRH analogues), which suppress estradiol levels to lower concentrations and readily induce menopausal-like symptoms.
Dienogest appears to have similar effects in the
breast
The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues.
In females, it serves as the mammary gland, which produces and sec ...
s as
norethisterone acetate, and may likewise increase the risk of
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a ...
when combined with an estrogen in postmenopausal women, although this has yet to be confirmed in clinical studies.
Antigonadotropic effects
Dienogest has been found to suppress testosterone levels in men by 43% at 2 mg/day, 70% at 5 mg/day, and 81% at 10 mg/day.
The suppression of testosterone levels with 10 mg/day dienogest was comparable to that with 10 mg/day
cyproterone acetate.
In general, progestogens are able to suppress testosterone levels in men by a maximum of about 70 to 80% at sufficiently high doses.
Antiandrogenic activity
Dienogest is one of the only 19-nortestosterone derivative progestins that does not have
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 incl ...
ic properties.
In fact, it is actually an
antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, ri ...
of 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 the ...
(AR), and hence has
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 activity.
The antiandrogenic activity of dienogest in the
Hershberger test is about 30 to 40% of that of
cyproterone acetate.
It may be able to improve
androgen-dependent symptoms such as
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 po ...
and
hirsutism
Hirsutism is excessive body hair on parts of the body where hair is normally absent or minimal. The word is from early 17th century: from Latin ''hirsutus'' meaning "hairy". It usually refers to a "male" pattern of hair growth in a female that ...
.
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 ...
s of dienogest, such as 9α,10β-dihydrodienogest and 3α,5α-tetrahydrodienogest, show greater affinity for the AR than does dienogest itself.
Dienogest has no affinity for
sex hormone-binding globulin (SHBG), and hence does not displace
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 characteristic ...
or
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 of ...
from this
plasma protein
Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood pr ...
or increase the free fractions of these hormones.
Other activities
Dienogest does not
inhibit
Inhibitor or inhibition may refer to:
In biology
* Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity
* Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotr ...
or
induce CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
, unlike many other related progestins.
Because of this, it may have a lower propensity for
drug interaction
Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug ...
s.
Dienogest weakly stimulates the
proliferation of
MCF-7
MCF-7 is a breast cancer cell line isolated in 1970 from a 69-year-old White woman. MCF-7 is the acronym of Michigan Cancer Foundation-7, referring to the institute in Detroit where the cell line was established in 1973 by Herbert Soule and co-wo ...
breast cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a ...
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
s ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'', an action that is independent of the classical PRs and is instead mediated via the
progesterone receptor membrane component-1 (PGRMC1).
Certain other progestins are also active in this assay, whereas
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 major ...
acts neutrally.
It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in
clinical studies
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, dietar ...
.
Pharmacokinetics
Dienogest is rapidly
absorbed with
oral administration
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 in ...
and has high
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 approximately 90%.
Peak levels of dienogest occur within approximately 2 hours after an oral dose.
The pharmacokinetics of dienogest are linear; single oral doses of dienogest were found to result in maximal levels of 28 ng/mL with 1 mg, 54 ng/mL with 2 mg, 101 ng/mL with 4 mg, and 212 ng/mL with 8 mg.
The corresponding
area-under-the-curve levels were 306, 577, 1153, and 2293 ng/mL, respectively.
Dienogest reaches
steady-state concentrations within 6 days of continuous administration, and does not accumulate in the body.
The
plasma protein binding
Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...
of dienogest is 90%, with a relatively high free fraction of 10%.
It is exclusively bound to
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. Albumin ...
, with no binding to SHBG or
corticosteroid-binding globulin.
The lack of affinity of dienogest for SHBG is in contrast to most other 19-nortestosterone progestins.
The
volume of distribution
In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the sam ...
of dienogest is relatively low at 40 L.
Dienogest is
metabolized
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
in the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
.
Metabolic pathway
In biochemistry, a metabolic pathway is a linked series of chemical reactions occurring within a cell. The reactants, products, and intermediates of an enzymatic reaction are known as metabolites, which are modified by a sequence of chemical rea ...
s of dienogest include
reduction of its Δ
4-3-
keto group,
hydroxylation
In chemistry, hydroxylation can refer to:
*(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound.
*(ii) the ''degree of hydroxylation'' refers to the number of OH groups in ...
mainly via
CYP3A4
Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
, removal of its C17α
cyanomethyl group, and
conjugation
Conjugation or conjugate may refer to:
Linguistics
*Grammatical conjugation, the modification of a verb from its basic form
* Emotive conjugation or Russell's conjugation, the use of loaded language
Mathematics
*Complex conjugation, the change ...
.
The
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 ...
s of dienogest are quickly
excreted and are said to be mostly inactive.
The
elimination 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 ...
of dienogest is relatively short at approximately 7.5 to 10.7 hours.
The short half-life of dienogest relative to other 19-nortestosterone progestins is in part due to its lack of binding to SHBG and hence prolongation in the circulation.
The
clearance of dienogest is 3 L/h.
It is
eliminated mainly in the
urine
Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.
Cellular m ...
, both as
sulfate
The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...
and
glucuronide
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides.
Glucuronidation, the conversion of chemical compounds to glucur ...
conjugates and as free steroid.
Chemistry
Dienogest, also known as δ
9-17α-cyanomethyl-19-nortestosterone or as 17α-cyanomethylestra-4,9-dien-17β-ol-3-one, is a
synthetic estrane
Estrane is a C18 steroid derivative, with a gonane core.
''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. '' Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, fo ...
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 ...
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
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 characteristic ...
.
It is a member of the estrane subgroup of the
19-nortestosterone family of progestins, but unlike most other 19-nortestosterone progestins, is not a derivative of
norethisterone
Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in b ...
(17α-ethynyl-19-nortestosterone).
This is because it uniquely possesses a
cyanomethyl group (i.e., a
nitrile group) at the C17α position rather than the usual
ethynyl group.
It is also unique among most 19-nortestosterone progestins in that it has a
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 bet ...
between the C9 and C10 positions.
Dienogest is the C17α cyanomethyl derivative of the
anabolic–androgenic steroid
Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects t ...
(AAS)
dienolone, as well as the C17α cyanomethyl
analogue of the AAS
methyldienolone (17α-methyldienolone) and
ethyldienolone (17α-ethyldienolone).
In terms of
structure–activity relationships, the C17α cyanomethyl group of dienogest is responsible for its unique antiandrogenic instead of androgenic activity relative to other 19-nortestosterone progestins.
A loss of ability to activate the AR is also seen with other testosterone derivatives with extended-length C17α substitutions such as
topterone (propyltestosterone) (compare to the AAS
ethyltestosterone and
methyltestosterone
Methyltestosterone, sold under the brand names Android, Metandren, and Testred among others, is an androgen and anabolic steroid (AAS) medication which is used in the treatment of low testosterone levels in men, delayed puberty in boys, at low ...
) and
allylestrenol (compare to the AAS
ethylestrenol).
Studies with steroids similar to dienogest (e.g., dienolone) have found that the introduction of a double bond between the C9 and C10 positions is associated with similar/almost unchanged affinity for the PR and AR.
On the other hand, the C9(10) double bond of dienogest appears to inhibit
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...
via
5α-reductase
5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of ...
and/or
5β-reductase, which is the major metabolic route for other 19-nortestosterone progestins like
norethisterone
Norethisterone, also known as norethindrone and sold under many brand names, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medication is available in b ...
,
norgestrel, and
etonogestrel, and this may serve to improve the
metabolic stability and
potency of dienogest.
History
Dienogest was synthesized in 1979 in
Jena
Jena () is a German city and the second largest city in Thuringia. Together with the nearby cities of Erfurt and Weimar, it forms the central metropolitan area of Thuringia with approximately 500,000 inhabitants, while the city itself has a popu ...
,
Germany under the leadership of Kurt Ponsold, was initially referred to as ''STS-557''.
It was found that its potency was 10 times that of
levonorgestrel.
The first product on the market to contain dienogest was a combined birth control pill (with ethinylestradiol), Valette, introduced in 1995 and made by
Jenapharm.
In 2007, dienogest was introduced as Dinagest in Japan for the treatment of endometriosis, and it was subsequently marketed for this indication as Visanne in Europe and Australia in December 2009 and April 2010, respectively.
Qlaira was introduced in Europe in 2009 and Natazia was introduced in the United States in 2010.
Society and culture
Generic names
''Dienogest'' is the
generic name of the drug and its , , , and , while ''diénogest'' is its .
It is also known by its synonyms ''dienogestril'' and ''cyanomethyldienolone'' as well as by its numerous former developmental code names including ''BAY 86-5258'', ''M-18575'', ''MJR-35'', ''SH-660'', ''SH-T00660AA'', ''STS-557'', and ''ZK-37659''.
Brand names
Dienogest is marketed in combination with
estradiol valerate
Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy ...
as a
birth control pill
The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progest ...
primarily under the brand names Natazia and Qlaira and in combination with
ethinylestradiol as a birth control pill primarily under the brand name Valette, although these combinations are marketed under numerous other brand names as well.
In the case of the dienogest and estradiol valerate birth control pill, these other brand names include Gianda and Klaira.
Dienogest is also marketed in combination with estradiol valerate for use in
menopausal hormone therapy
Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...
under a variety of brand names including Climodien, Climodiène, Estradiol Valeraat / Dienogest, Klimodien, lafamme, Lafleur, Mevaren, Valerix, and Velbienne.
Dienogest is marketed as a standalone medication for the treatment of
endometriosis primarily under the brand name Visanne, but is also available under the brand names Alondra, Dinagest, Disven, Visabelle, and Visannette in various countries.
Availability
Dienogest is available both alone and in combination with ethinylestradiol and estradiol valerate widely throughout the world, including but not limited to
Canada
Canada is a country in North America. Its Provinces and territories of Canada, ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world ...
,
Europe,
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 ...
, and
Southeast Asia
Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical south-eastern region of Asia, consisting of the regions that are situated south of mainland ...
.
[http://www.micromedexsolutions.com/micromedex2/] It is available specifically as a standalone medication in Canada, Europe, Latin America,
Russia,
Australia,
South Africa
South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring coun ...
,
Georgia,
Israel
Israel (; he, יִשְׂרָאֵל, ; ar, إِسْرَائِيل, ), officially the State of Israel ( he, מְדִינַת יִשְׂרָאֵל, label=none, translit=Medīnat Yīsrāʾēl; ), is a country in Western Asia. It is situated ...
,
Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
,
South Korea
South Korea, officially the Republic of Korea (ROK), is a country in East Asia, constituting the southern part of the Korean Peninsula and sharing a land border with North Korea. Its western border is formed by the Yellow Sea, while its eas ...
,
Hong Kong
Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China (abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delt ...
, and
Thailand
Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...
.
It is notably not available as a standalone medication 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 territo ...
or the
United Kingdom
The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and No ...
.
Research
Dienogest has been studied as a form of
male hormonal contraception.
As of July 2018, dienogest 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 in
Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
for the treatment of
adenomyosis
Adenomyosis is a medical condition characterized by the growth of cells that proliferate on the inside of the uterus (endometrium) atypically located among the cells of the uterine wall ( myometrium), as a result, thickening of the uterus occurs. ...
and
dysmenorrhea.
The combination of estradiol valerate and dienogest is in
pre-registration in
Europe for the treatment of
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 po ...
.
Dienogest is also being evaluated for the potential treatment of
anorexia nervosa
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
.
References
Further reading
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External links
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