Dimethisterone, formerly sold under the brand names Lutagan and Secrosteron 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 product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

medication which was used in

birth control pills 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 combin ...

and in the treatment of gynecological disorders but is now no longer available. It was used both alone and in combination with an estrogen. It is taken by mouth. Side effects 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 Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...

can occur. Dimethisterone is a progestin, or a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

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

, 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 resid ...

, the biological target 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 m ...

. It has some antimineralocorticoid activity and no other important hormonal 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 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 gynecological disorders and in combination with ethinylestradiol in

Side effects

Side effects of dimethisterone are similar to those of other progestins.

Pharmacology

Pharmacodynamics

Dimethisterone was derived from modification of ethisterone via introduction of methyl groups at the C6α and C21 positions. Relative to ethisterone, it is 12 times as potent

orally The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

as a

in animals (

Clauberg test Carl Clauberg (28 September 1898 – 9 August 1957) was a German gynecologist who conducted medical experiments on human subjects (mainly Jewish) at Auschwitz concentration camp. He worked with Horst Schumann in X-ray sterilization experimen ...

), and, unlike ethisterone, is a pure progestogen with no androgenic (or estrogenic) activity in animals even at very high doses (although some weak antimineralocorticoid 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

androstane

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 a ...

and a derivative of testosterone.

Synthesis

Chemical syntheses As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In moder ...

of dimethisterone have been published.

History

Dimethisterone was developed by the British pharmaceutical company British Drug Houses (which subsequently merged with Merck KGaA) 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 as an oral contraceptive in combination with high doses of ethinylestradiol 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 estrogen, this preparation was eventually found to be associated with a substantially increased risk of

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 Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors ** Organic synthesis, the chemical synthesis of organ ...

medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...

. Whereas

hydroxyprogesterone acetate Hydroxyprogesterone acetate (OHPA), sold under the brand name Prodox, is an orally active progestin related to hydroxyprogesterone caproate (OHPC) which has been used in clinical and veterinary medicine. It has reportedly also been used in bi ...

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

References

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