PROGESTINS (synonym: progestogens, gestagena) — the progesterones and their synthetic analogs used as pharmaceuticals. The greatest the wedge, use received analogs of 17alfa-hydroxyprogesterone (a medroksiprogesteron acetate or kapronat) and 19-norsteroid (Norethisteronum, an etinodiol diacetate, Norgestrelum and a noretynodrel). These connections on the chemical structure are close to to progesterone (see), and on the biol, action is much more active than it since are exposed to oxidation less. This property gives the chance to use these drugs orally and in small doses. The item for contraception (see. Contraceptives ) and the medical purposes appoint in the form of individual connections (so-called pure P.) or in a combination with estrogen (see) which strengthen biol, P.'s effect (the so-called combined progestinoestrogenny drugs). There are more than 30 types of the combined progestinoestrogenny drugs, a ratio of estrogen and progestins in which it is equal 1:25 or 1:50. Depending on a type of estrogen and progestins and their ratio in a dosage form the combined drugs can have preferential androgenic, gestagenny, oestrogenic or anabolic action. It is established, e.g., that removal of 19-methyl group of a molecule is native, about a steroid strengthens gestagenny action of P. (see. Norsteroida ).
In total P. have ability to inhibit formation of gonadotrophins, addition to P. of estrogen strengthens this effect and leads to braking of development of follicles in ovaries, to suppression of an ovulation and decrease in concentration of estrogen in blood. Items cause transition of an endometria to a secretory phase and have the expressed effect on a giperplazirovanny endometria which under their influence is exposed to a decidual necrosis and an atrophy. Items promote a delay in an organism of water and NaCl, possess anabolic action, increase the content in plasma of the proteinaceous and connected cortisol and thyroxine, and also a renin that leads to strengthening of angiotensin and Aldosteronum in blood by 2 — 3 times. Items level effect of estrogen on a mucous membrane of a vagina, a neck of uterus and an endometria, and also cause relaxation of smooth muscles of a uterus.
Long purpose of the combined progestinoestrogenny (gestagenestrogenny) drugs (more than 12 months) for the purpose of contraception causes atipichesky development of a secretory phase of an endometria therefore systematically it is recommended to accept them no more than 12 months P. have thermogene effect, rectal temperature during their reception at many women rises higher than 37 °. The oral contraceptives containing P. can cause increase in content of triglycerides and phospholipids in blood, to reduce tolerance to glucose, to break exchange of tryptophane and to be the cause of a hypovitaminosis of B6. Observations showed that efficiency of the oral contraceptives containing P. can decrease at a concomitant use of Rifadinum, ampicillin and barbiturates.
From the combined progestinoestrogenny drugs which are oral hormonal contraceptives most were widely adopted Bisecurinum and nonovlon. With the contraceptive purpose these drugs accept from the 5th day of a 28-day menstrual cycle within 21 days on 1 tablet daily. Then do a break for 7 days; through 1—4 in the afternoon after the end of reception of tablets poyav menstrualnopodobny reaction lyatsya.
Pure P. — Norethisteronum or an etinodiol diacetate (sometimes they are called by mini-pills) — for the purpose of contraception apply daily. Pure P. (Norethisteronum) use also for treatment of dysfunctional uterine bleedings and a defective lyuteinovy phase; drug intake is begun in 10 days prior to the expected periods and continued within 8 days on 5 — 10 mg daily; treatment is carried out by discontinuous courses (3 months — treatment, 2 months — a break). Pure progestin (drug «Turinal») at the usual not incubation of pregnancy menacing or the begun abortion is appointed on 5 mg by 2 — 3 times a day, duration of use of drug is established individually, at algodismenory drug is appointed in 8 days prior to the expected periods within 6 days on 5 mg daily. At an atipichesky hyperplasia of an endometria, adenomatosis and a polypose of an endometria, right after a scraping of a cavity of the uterus appoint Norethisteronum on 10 mg daily within 90 days. After the termination of a course of treatment the control diagnostic scraping is necessary.
The combined progestinoestrogenny drugs (Infecundinum, Anovlarum) with to lay down. the purpose apply at endometriosis, a hyperplasia and a polypose of an endometria, since 5th day of a menstrual cycle within 21 days, then do a break for 7 days, and also in the II phase of a menstrual cycle within 8 days at dysfunctional climacteric uterine bleedings against the background of oestrogenic insufficiency and at some forms of juvenile bleedings. The combined progestinoestrogenny drugs or pure P. are appointed at dysfunctional uterine bleedings for the purpose of recovery of a normal hemostasis on 2 — 6 tablets a day; after the termination of bleeding the number of tablets is gradually reduced to 1 tablet a day, in such dose drug is accepted within 15 — 20 days. The combined drugs with the smaller maintenance of generally oestrogenic component (Bisecurinum, nonovlon) accept discontinuous courses for treatment of ovulatory pains, an algodismenorea, a hypomenstrual molimina, some forms of a premenstrual syndrome and so-called endocrine infertility against the background of a defective lyuteinovy phase. For treatment of climacteric and postkastratsionny syndromes the combined progestinoestrogenny drugs appoint on tablets 2 times a day within 5 — 7 days with the subsequent reception on 1/4 tablt ki daily during 2 weeks. Repeated courses are conducted during the resuming a wedge, symptoms. The combined progestinoestrogenny drugs find application for treatment of endocrine cardiopathies, osteoporosis, inflammatory processes in genitalias. Items in the form of 17a-hydroxyprogesterone of a kapronat apply to treatment of dishormonal giperplaziya of mammary glands.
Side reactions at reception of P., especially combined progestinoestrogenny drugs, vomitings, a nagrubaniye of mammary glands, additions in the weight, a headache, dizzinesses, an itch, allergic rashes, depressions, a moniliasis of a vagina, bloody allocations in the menstrual period can be shown in the form of nausea.
At treatment of complications by pure P. practically does not happen. The combined progestinoestrogenny drugs in this respect are not so neutral. Positive correlation between the maintenance of an oestrogenic component in drug and a risk degree of a thromboembolism, myocardial infarction, arterial hypertension, cholelithiasis and adenoma of a liver is established. The risk degree increases during the smoking, obesity, a diabetes mellitus, a hypercholesterolemia, existence of heavy late toxicoses of pregnancy in the anamnesis, and also at women 35 years are more senior. After reception of oral contraceptives within more than 1 year the amenorrhea or anovulatory cycles can appear. Jaundice is among rare complications.
Contraindications to P.'s reception and progestinoestrogenny drugs pregnancy, diseases of a liver and bilious ways, a varicosity, acute and hron, thrombophlebitises, epilepsy, a hypertension, the allergized state, heavy toxicoses of pregnancy in the anamnesis, migraine, hron, pyelonephritis, a diabetes mellitus, malignant tumors or suspicion on their existence, myoma of a body of the womb (serve at increase in a uterus more than 12 weeks of pregnancy). For prevention of complications at treatment by progestins synthetic P. should be accepted only together with vitamin B 6 and only according to instructions of the doctor, under control of the ABP, hepatic tests and definitions of a condition of coagulant system of blood. Teratogenic action of synthetic P. on a fruit is not proved, but reception of derivative 19-norsteroid during pregnancy, except turinal, can cause virilescence in a fruit. Adverse action of P. on the newborn is not revealed. To any dependence between synthetic P.' reception and a carcinogenesis it is not established.
Bibliography: Kulavsky V. A. Synthetic progestins and their use in gynecology, Wenger, a pharmakoter., No. 4, page 138, 1974; Manuylova I. A. About the mechanism of action of hormonal contraceptives, Akush. and ginek., No. 2, page 3, 1971; it, About use of synthetic progestins with the medical and contraceptive purpose, in book: Some aktualn. vopr. akush., ginek., endokrinol., under the editorship of L. S. Persianinov and I. A. Manuylova, page 125, M., 1971; Kistner R. The use of progestins in obstetrics and gynecology, Chicago, 1969; Macdonald R. R. Clinical pharmacology of progestagens, in book: Scientific basis of obstetrics and gynaecol., ed. by R. R. Macdonald, p. 393, Edinburgh a. o., 1978.
I. A. Manuylova.