Dimethisterone, formerly sold under the brand names Lutagan and Secrosteron among others, is a progestin medication which was used in birth control pills and in the treatment of

gynecological disorder Gynaecology or gynecology (see spelling differences) is the area of medicine that involves the treatment of women's diseases, especially those of the reproductive organs. It is often paired with the field of obstetrics, forming the combined area ...

s but is now no longer available. It was used 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 taken

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 ...

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 dimethisterone are similar to those of other progestins. When used in combination with high doses of an estrogen, an increased risk of endometrial cancer can occur. Dimethisterone 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

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 and 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. Dimethisterone was first described and was introduced for medical use in 1959. It started being used in birth control pills in 1965. However, due to its low

potency Potency may refer to: * Potency (pharmacology), a measure of the activity of a drug in a biological system * Virility * Cell potency, a measure of the differentiation potential of stem cells * In homeopathic dilutions, potency is a measure of how ...

and consequent inability to prevent the increased risk of endometrial cancer with estrogens, dimethisterone was soon discontinued for such purposes.

Medical uses

Dimethisterone was used alone in the treatment of

s 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 ...

in birth control pills.

Side effects

s of dimethisterone are similar to those of other progestins.

Pharmacology

Pharmacodynamics

Dimethisterone was derived from modification of ethisterone via introduction of

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 ...

s at the C6α and C21 positions. Relative to ethisterone, it is 12 times as potent orally as a progestogen in animals ( Clauberg test), and, unlike ethisterone, is a pure progestogen with no

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 (or

ic) activity in animals even at very high doses (although some weak

activity was observed at high doses in animals). However, in spite of its improved potency over ethisterone, it is a weak progestogen relative to most other progestins, in fact one of the weakest known.

Chemistry

Dimethisterone, also known as 6α,21-dimethylethisterone or as 6α,21-dimethyl-17α-ethynyltestosterone, as well as 17α-ethynyl-6α,21-dimethylandrost-4-en-17β-ol-3-one or as 6α,21-dimethyl-17β-hydroxy-17α-pregn-4-en-20-yn-3-one, is a synthetic

androstane Androstane is a C19 steroidal hydrocarbon with a gonane core. Androstane can exist as either of two isomers, known as 5α-androstane and 5β-androstane. File:androstane.png, 5α-Androstane File:androstane 5beta.png, 5β-Androstane Pharmacology ...

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. ...

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 ...

Synthesis

Chemical syntheses of dimethisterone have been published.

History

Dimethisterone was developed by the

British British may refer to: Peoples, culture, and language * British people, nationals or natives of the United Kingdom, British Overseas Territories, and Crown Dependencies. ** Britishness, the British identity and common culture * British English, ...

pharmaceutical company The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate sympto ...

British Drug Houses The Merck Group, branded and commonly known as Merck, is a German multinational science and technology company headquartered in Darmstadt, with about 60,000 employees and present in 66 countries. The group includes around 250 companies; the m ...

(which subsequently merged with

Merck KGaA The Merck Group, branded and commonly known as Merck, is a German multinational science and technology company headquartered in Darmstadt, with about 60,000 employees and present in 66 countries. The group includes around 250 companies; the ma ...

) and was first reported in the medical literature in 1959, with introduction for medical use under the brand name Secrosteron following in the same year. It was introduced 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 ...

as an

oral contraceptive Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. Female Two types of female oral contraceptive pill, taken once per day, are widely available: * The combi ...

in combination with high doses of

under the brand name Oracon (25 mg dimethisterone, 100 μg ethinylestradiol) in 1965. Due to the fact that it contains a weak progestogen in combination with a large dose of a potent

, this preparation was eventually found to be associated with a substantially increased risk of endometrial cancer in women, and is now no longer marketed. The improved potency of dimethisterone due to 6α-methylation reportedly served as the basis for the synthesis of medroxyprogesterone acetate. Whereas hydroxyprogesterone acetate (the 6α-demethylated analogue of medroxyprogesterone acetate) is around twice as potent as ethisterone orally, medroxyprogesterone acetate shows 10 to 25 times the potency of ethisterone.

Society and culture

Generic names

''Dimethisterone'' is the generic name of the drug and its , , and .

Brand names

Dimethisterone was marketed alone under the brand names Lutagan and Secrosteron and in combination with

under the brand names Oracon, Ovin, Secrodyl, Secrovin, and Tova.

References

{{Mineralocorticoid receptor modulators Abandoned drugs Androstanes Antimineralocorticoids Merck brands Enones Progestogens Alkyne derivatives