Medrogestone is a progestin

Progestin

A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...

, a synthetic drug with similar effects as progesterone

Progesterone

Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

, a hormone involved in the menstrual cycle

Menstrual cycle

The menstrual cycle is the scientific term for the physiological changes that can occur in fertile women for the purpose of sexual reproduction. This article focuses on the human menstrual cycle....

 and pregnancy

Pregnancy

Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

. As of 2010, it is no longer available in Germany or Austria.

Indications

In the past, medrogestone was used in the treatment of endometrial cancer

Endometrial cancer

Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...

 and in some regimens for breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, and, in men, for benign prostatic hyperplasia

Benign prostatic hyperplasia

Benign prostatic hyperplasia also known as benign prostatic hypertrophy , benign enlargement of the prostate , and adenofibromyomatous hyperplasia, refers to the increase in size of the prostate....

. It still finds use in the treatment of amenorrhea and as the progestin component in certain forms of menopausal hormone replacement therapy

Hormone replacement therapy (menopause)

Hormone replacement therapy is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women...

.

Contraindications

Intrahepatic cholestasis of pregnancy

Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy in the United Kingdom, is a medical condition in which cholestasis occurs during pregnancy...

 (acute or in history), vaginal bleeding

Vaginal bleeding

Vaginal bleeding refers to bleeding in females that is either a physiologic response during the non-conceptional menstrual cycle or caused by hormonal or organic problems of the reproductive system. Vaginal bleeding may occur at any age, but always needs investigation when encountered in female...

 of unknown origin, and severe diseases of the liver such as tumours are absolute contraindications for medrogestone. Relative contraindications include a history of jaundice

Jaundice

Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...

 or itch

Itch

Itch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...

ing in pregnancy or gestational pemphigoid

Gestational pemphigoid

Gestational Pemphigoid or Pemphigoid Gestationis is a dermatosis of pregnancy, being an autoimmune blistering skin disease that occurs during pregnancy, typically in the second or third trimester, and/or immediately following pregnancy...

.

Pregnancy and lactation

Medrogestone is contraindicated during pregnancy because progestagens are associated with risks for the foetus in animals and humans. Studies in pregnant rabbits have shown skeletal deformations under 3 mg medrogestone per kilogram body weight but not under 1 mg/kg. Typical therapeutic doses are between 0.1 and 0.25 mg/kg.

It is not known whether medrogestone passes into breast milk

Breast milk

Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...

, but it is to be expected given its lipophilicity and studies with chemically related progestins.

Adverse effects

Medrogestone seldom produces adverse effects, all of which are typical of progestogens. They include lack of appetite, nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, headache, dizziness, and depression

Depression (mood)

Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

.

Overdose

The acute toxicity

Acute toxicity

Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short space of time...

 of the drug is low. Overdose causes only harmless side-effects such as nausea and vaginal bleeding. The has been found to range between 500 mg/kg in dogs and over 3000 mg/kg in rats. Chronic toxicity

Chronic toxicity

Chronic toxicity is a property of a substance that has toxic effects on a living organism, when that organism is exposed to the substance continuously or repeatedly. Compared with acute toxicity.Two distinct situations need to be considered:...

 has been examined in animals, but nothing but the typical adverse effects of progestogens, and reduction of prostatic weight in Rhesus Monkeys, have been found. Accidental intake of the drug, including in children, is not dangerous.

Chemical properties

Medrogestone is a steroid

Steroid

A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...

. More specifically, it is a derivative of pregna-4,6-diene

Pregnadiene

A pregnadiene is a diene derivative of a pregnane.Dienes have two double bonds. The first is usually between carbon 4 and carbon 5 on ring A....

 structurally related to the progestagen chlormadinone

Chlormadinone

Chlormadinone is a progestagen.-Synthesis:Bruckner, K.; Hampel, B.; Johnson, V.; Chem. Ber. 1961, 94, 1225.http://dx.doi.org/10.1002/cber.19610940510...

 and the androgen antagonist cyproterone

Cyproterone

Cyproterone acetate is an antiandrogen...

. As is frequently found in other synthetic steroid hormones, medrogestone possesses a lipophilic group at position 6. However in contrast to chlormadinone and cyproterone or to fluocinolone that contain a chlorine

Chlorine

Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...

 or fluorine

Fluorine

Fluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...

 respectively at position 6, medrogestone contains a methyl substituent at this position. The methyl in position 17 is unusual for a steroid, as many such drugs carry an oxygen

Oxygen

Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

 atom in that position.

Pharmacokinetics

The drug is absorbed quickly and completely from the gut and reaches peak plasma concentrations after about one to four hours. Unlike many other steroids it binds neither to transcortin

Transcortin

Transcortin, also corticosteroid-binding globulin or CBG, is officially called serpin peptidase inhibitor, clade A , member 6.It is an alpha-globulin.-Binding:...

 (corticosteroid-binding globulin, CBG, which binds progesterone) nor to sex hormone-binding globulin (SHBG), but to albumin

Albumin

Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...

. Medrogestone itself cannot be excreted. The substance is hydroxylised

Hydroxylation

Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...

 and glucuronidised

Glucuronidation

Glucuronidation is the addition of glucuronic acid to a substrate. Glucuronidation is often involved in xenobiotic metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids...

 in the liver, and the resulting metabolites are eliminated via urine and faeces.

Pharmacodynamics

The profile of medrogestone is similar to the natural hormone progesterone. It has pronounced progestogenic effects and opposes the proliferative effects of estrogen

Estrogen

Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

 in the utereus, but lacks anabolic, androgen

Androgen

Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...

ic, estrogenic and corticoid activity. In extremely high doses it is an androgen antagonist (in 2500-fold therapeutic doses) as well as an antigonadotropin

Gonadotropin

Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...

.

Interactions

Enzyme inducer

Enzyme inducer

An enzyme inducer is a type of drug which binds to an enzyme and increases its metabolic activity.Classic examples: barbiturates , antiepileptics and rifampin....

s such as barbiturate

Barbiturate

Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...

s, phenylbutazone

Phenylbutazone

Phenylbutazone, often referred to as bute, is a non-steroidal anti-inflammatory drug for the short-term treatment of pain and fever in animals. In the United States, it is no longer approved for human use.-In humans:...

, phenytoin

Phenytoin

Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

, ampicillin

Ampicillin

Ampicillin is a beta-lactam antibiotic that has been used extensively to treat bacterial infections since 1961. Until the introduction of ampicillin by the British company Beecham, penicillin therapies had only been effective against Gram-positive organisms such as staphylococci and streptococci...

 or tetracyclines are expected to reduce plasma concentrations of medrogestone, but no systematic research has been done.