Progesterone - instructions for use, dose, side effects, contraindications

It is a hormone of the yellow body. Linking to the cytosolic receptors of target organ cells, penetrates into the nucleus, activates DNA and stimulates the synthesis of RNA.

Promotes the transition of the mucous membrane of the uterus from the proliferative (caused by follicle stimulating hormone - FSH) into the secretory phase, creates the necessary conditions for implantation of the fertilized egg, reduces the sensitivity of the uterus to oxytocin and relaxes its muscles (tocolytic effect). In small doses increases, and in large doses it suppresses the production of hypothalamic factors releasing LH and FSH and, accordingly, biosynthesis of gonadotropic hormones of the pituitary gland, inhibits ovulation.It stimulates lipoprotein lipases, increases fat stores, raises basal and induced insulin levels, glucose utilization, glycogen accumulation in the liver, aldosterone production, causes hypoazotemia and hyperaosuria.

In the tissues of the breast, it activates the growth of the secretory section of the mammary glands and induces lactation. Promotes the development of normal endometrium. Reduces the permeability of capillaries, reduces edema of connective tissue stroma, dependent on the phase of the menstrual cycle, inhibits proliferation and mitotic activity of the duct epithelium (when applied in the form of a gel).

Pharmacokinetics:

When ingestion, intravaginal (capsule), sc, and / m injection quickly absorbed. BIodidity is low (can be increased by micronisation or use of lipid carriers). Eating significantly increases the absorption rate, without affecting the time to reach maximum concentration. Cmax for oral administration is achieved in 1-3 hours, with intravaginal application in 2-6 hours. Binding with proteins - 96-99%, mainly with albumin (50-54%) and transcortin (43-48%).In the liver it is converted mainly into pregnanediol and pregnanolone, which are then conjugated to form glucuronides and sulfates. It is excreted by the kidneys (50-60%) and with bile (more than 10%); Progesterone metabolites excreted with bile are excreted with feces and can undergo enterohepatic recirculation. The half-life is a few minutes after absorption and is limited by the rate of absorption.

When applied to the skin in the form of a gel for external use is practically not absorbed and does not enter the systemic bloodstream.

Efficacy of vaginal gel application is indicated in the treatment of secondary amenorrhea due to a lack of progesterone, as well as in reproductive technologies to compensate for the lack of progesterone in egg donation.

Indications:

Dysfunctional uterine bleeding, metrorrhagia, amenorrhea, habitual miscarriage.

Capsules: for oral administration - premenstrual syndrome, fibrocystic mastopathy; Premenopause, menopause, incl. premature, postmenopause - as a progestational component of hormone replacement therapy (HRT) in combination with estrogens; intravaginal - hormone replacement therapywith non-functioning ovaries in the absence of progesterone (egg donation), support for the luteal phase during preparation for in vitro fertilization, support for the luteal phase in the spontaneous or induced menstrual cycle, prevention of habitual and threatening miscarriage due to gestagenic failure, endocrine infertility, prevention of uterine fibroids, endometriosis.

Solution in oil: amenorrhoea, oligomenorrhoea, algodismenorea (on the basis of hypogenitalism), anovulatory metrorrhagia, endocrine infertility (including insufficiency of the corpus luteum), threat of abortion, diagnosis of estrogen secretion.

Gel for external use: mastodynia, mastopathy.

ICD-10

II.D10-D36.D25 Leiomyoma of the uterus

IV.E20-E35.E28 Dysfunction of the ovaries

XIV.N60-N64.N60.1 Diffuse cystic mastopathy

XIV.N60-N64.N64.4 Mammalgia

XIV.N60-N64.N64.8 Other specified diseases of mammary gland

XIV.N80-N98.N80 Endometriosis

XIV.N80-N98.N91.2 Amenorrhea, unspecified

XIV.N80-N98.N91.5 Oligomenorrhea, unspecified

XIV.N80-N98.N92.1 Abundant and frequent menstruation with an irregular cycle

XIV.N80-N98.N94.3 Premenstrual tension syndrome

XIV.N80-N98.N94.6 Dysmenorrhea, unspecified

XIV.N80-N98.N94.8 Other specified conditions associated with female genital organs and the menstrual cycle

XIV.N80-N98.N95 Menopause disorders and other disorders in the perimenopausal period

XIV.N80-N98.N95.1 Menopause and menopause in women

XIV.N80-N98.N96 Habitual miscarriage

XIV.N80-N98.N97 Female infertility

XV.O20-O29.O20.0 Threatening abortion

XXI.Z30-Z39.Z31.1 Artificial insemination

Contraindications:

Hypersensitivity.

Capsules: expressed violations of liver function, a tendency to thrombosis, acute forms of phlebitis or thromboembolic diseases, acute disturbance of cerebral circulation, vaginal bleeding of unknown genesis, incomplete abortion, porphyria.

Solution in oil: breast and genital cancers (for monotherapy), expressed violations of liver function, pregnancy (II and III trimester), propensity to thrombosis, acute forms of phlebitis or thromboembolic diseases, vaginal bleeding of unknown genesis, abortive miscarriage, porphyria.

Breastfeeding period.

Carefully:

Capsules: diseases of the cardiovascular system, incl. arterial hypertension, cardiovascular failure, bronchial asthma, severe renal dysfunction; diseases of the central nervous system, incl. depression, epilepsy, migraine; diabetes; giprelypoproteinemia.

Solution in oil: diseases of the cardiovascular system, incl. Arterial hypertension, bronchial asthma, severe renal dysfunction, CNS diseases, incl. depression, epilepsy, migraine; diabetes, ectopic pregnancy.

During treatment, the concentration of attention is weakened (care must be taken when driving vehicles and engaging in other potentially dangerous activities requiring rapidity of psychomotor reactions).

Pregnancy and lactation:

Recommendations FDA category D.

In cases of extreme necessity, it is possible to use progesterone in pregnancy with established deficiency of the hormones of the yellow body. The use of the drug in the late period of pregnancy is not recommended.

Progesterone is not used in women planning pregnancy in the near future.

Penetrates into breast milk and, depending on the type and dose, increases, reduces or does not change the quality and quantity of milk. The drug is contraindicated in the period of breastfeeding.

Dosing and Administration:Dosing regimen is individual. Dose, frequency and duration of treatment are determined according to the scheme depending on the indications and the clinical situation.
The progestogenic effect of 20-25 mg of progesterone when administered intramuscularly is equivalent to intravaginal injection (as a suppository) of 100 mg of progesterone.
Secondary amenorrhea (caused by hormonal imbalance, in the absence of organic pathology).
Inside in a dose of 400 mg once a day (in the evening) for 10 days.
Intramuscularly at 5-10 mg / day for 6-10 consecutive days.
Intramuscularly once in a dose of 100-150 mg.
Intramuscularly adult, the highest single dose of 0.025 g (2.5 ml of 1% or 1 ml of 2.5% of r-ra).
Intravaginally (in the form of a vaginal gel) at a dose of 45 mg (one applicator 4% gel) every other day in 6 doses. You can increase the dose to 90 mg (one applicator 8% of the gel) every other day to 6 injections (8% vaginal gel is used only if the inefficiency of 4% gel).
With full ovarian activity or previous treatment with estrogens for 2 weeks before the administration of progesterone, bleeding cancellation develops within 48-72 hours after the last injection. When menstrual bleeding occurs against the background of treatment, the use of progesterone is stopped. After this, spontaneous normal menstruation can develop.
Increasing the dose to 90 mg by using a 4% vaginal gel does not provide the necessary absorption of the substance: 8% of the gel is needed.
In secondary amenorrhea 4 and 8%, the vaginal gel of progesterone more often causes progestogen changes in 92 and 100% of patients, respectively, and the occurrence of withdrawal bleeding in 81 and 82% of patients, respectively, in the absence of serious side effects and the associated need for withdrawal (2%).
Dysfunctional uterine bleeding (for parenteral administration).
Intramuscularly at 5-10 mg / day (15 mg / day) for 6-8 consecutive days.
Inside for 400 mg / day for 10 days.
Bleeding should stop within 6 days. When combined with estrogen treatment progesterone begin 2 weeks after they are taken. With the development of menstruation against the background of treatment, the use of progesterone is stopped.
Induction of menstruation (with parenteral administration): before the appointment of a progestin, adequate stimulation of the secretory phase of the endometrium with estrogens is necessary. Bleeding cancellation in women with an intact uterus usually develops within 3-7 days after the discontinuation of the progestin.
Intramuscularly at 5-10 mg / day for 5-10 consecutive days, stopping 2 days before the expected menstruation.
Inside at a dose of 400 mg / day for 10 days.
Intravaginally (in the form of a gel) at a dose of 45 mg every other day, on the 15-25th day of the menstrual cycle.
Reproductive technologies: maintaining the luteal phase in women.
Intravaginally (in the form of a gel) at a dose of 90 mg (one applicator 8% gel) 1 time per day. With in vitro fertilization, treatment is started within 24 hours after embryo transfer and is continued for 30 days. At the onset of pregnancy, therapy is continued until placental autonomy is achieved (10-12th week of pregnancy).
Partial or complete ovarian failure: intravaginally (in the form of a gel) at a dose of 90 mg (one applicator 8% gel) 2 times a day before the transfer of donor oocyte; at the onset of pregnancy continue treatment until the placenta is autonomous (10-12th week of pregnancy).
With the donation of eggs (against the background of estrogen therapy): intravaginally (in the form of capsules) at a dose of 100 mg / day on the 13th and 14th days of the cycle, then 100 mg twice a day from the 15th to the 25th day of the cycle. From the 26th day and in the case of pregnancy determination, the dose is increased by 100 mg / day every week, reaching a maximum (600 mg in 3 divided doses for 60 days).
To maintain the luteal phase during the in vitro fertilization cycle: intravaginally (in the form of capsules) at 400-600 mg / day, from the day of injection of the chorionic gonadotropin and up to the 12th week of pregnancy.
Intravaginally (in the form of suppositories) 25-100 mg 1-2 times a day, starting a few days before ovulation. At the onset of pregnancy, treatment is continued until the 11th week.
Insufficiency of the yellow body (maintenance of the luteal phase in women).
Intramuscularly at least 12.5 mg / day, starting a few days before ovulation. Duration of treatment - about 2 weeks, but if necessary continue therapy until the 11th week of gestation.
Intravaginally (in the form of a gel) at a dose of 90 mg (one applicator 8% gel) 1 time per day. At the onset of pregnancy, treatment is continued until placental autonomy is achieved (10th to 12th week of gestation).
Intravaginally (in the form of capsules) to 200-300 mg / day, starting from the 17th day of the menstrual cycle for 10 days. When delaying menstruation and the onset of pregnancy treatment should continue.
Intravaginally (in the form of suppositories) in a dose of 25-100 mg 1-2 times a day, starting a few days before ovulation. At the onset of pregnancy, treatment is continued until the 11th week of gestation.
In case of a deficiency of the yellow body, intravaginal application of micronized progesterone in the first trimester of pregnancy exceeds its IM in the probability of continuing pregnancy (30.5 vs. 19.1%, p <0.05).
Estimation of endogenous production of estrogens: for parenteral use - diagnosis of menopause by measuring the concentration of estrogens in the absence of menstruation after the cancellation of the progestin. The standard method of verification of menopause is the measurement of gonadotropins in the blood.
Intramuscularly once in a dose of 100 mg.
Prophylaxis of endometrial hyperplasia in patients in postmenopause who receive estrogens in the form of hormone replacement therapy.
Inside in a dose of 200 mg once a day before going to bed for 14 days (from the 8th to the 21st day of the 28-day cycle or from the 12th to the 25th day of the 30-day cycle).
Intravaginally (in the form of a gel) at a dose of 45 mg every other day for 12 days in a 28-day cycle.
The dose is adjusted based on the achievement of the desired uterine response (regular withdrawal bleeding or amenorrhea). In many regimens of therapy in the last 5-7 days of each month, hormones are not taken at all.
Premature menopause.
Preventing a habitual and threatening miscarriage, due to gestational deficiency of the yellow body.
Intravaginally (in the form of capsules) to 100-200 mg 2 times a day daily (before the 12th week of pregnancy).
Intramuscularly at a dose of 10-25 mg daily or every other day until the symptoms of a possible miscarriage disappear completely. With habitual abortion, treatment is continued until the 4th month of pregnancy.
Intramuscularly in a dose of 25-100 mg daily, starting from the 15th day and continuing until the 8-16th week of pregnancy.
Intravaginally (in the form of a gel) for 90 mg / day, continuing for 30 days after laboratory confirmation of pregnancy.
Threat of abortion: There is no evidence of the efficacy of using progestins in threatening abortion, except for the administration of progesterone to patients with deficiency.
Intravaginally (in the form of capsules) to 100-200 mg 2 times daily, up to the 12th week of pregnancy.
Intramuscularly at a dose of 10-25 mg daily or every other day until the symptoms of a possible miscarriage disappear completely. With habitual abortion, treatment is continued until the 4th month of pregnancy.
When threatened with abortion(p <0.005) and the likelihood of miscarriage within 60 days (p <0.05 ).
Prevention of uterine fibroids.
Endometriosis.
Oligomenorrhoea and algodismenorea, caused by hypogenitalism.
Inside at a dose of 200-300 mg for 10 days (from the 17th to the 26th day of the cycle).
Hypogenitalism and amenorrhea: after application of estrogens - in / m in a dose of 5 mg daily or 10 mg every other day for 6-8 days.
Algodismenorea: treatment is started 6-8 days before menstruation. The drug is given in / m in a dose of 5-10 mg daily for 6-8 days. With algodismenosis caused by uterine underdevelopment, combined with estrogens at a rate of 10 thousand units every other day for 2-3 weeks, then within 6 days introduce progesterone.
Fibro-cystic disease of the breast, mastodynia.
Inside at a dose of 200-300 mg for 10 days (from the 17th to the 26th day of the cycle).
Outer (in the form of a gel). One dose of gel (2.5 g) 2 times a day is applied to the skin of the breast until it is completely absorbed (including during menstruation).
Use in children
Efficiency and safety have not been studied. There are descriptions of severe side effects in children who accidentally used high doses of oral contraceptives.

Side effects:

Capsules: drowsiness, transient dizziness (1-3 hours after admission), menstrual cycle disorders (shortening, intermediate bleeding).

Solution in oil

From the cardiovascular system: increased blood pressure, thromboembolism (including pulmonary arteries and cerebral vessels), thrombophlebitis, retinal vein thrombosis.

From the side of metabolism: edema.

From the digestive system: violations of the liver, jaundice; rarely (with prolonged use) - nausea, vomiting, decreased appetite, abdominal pain, calculous cholecystitis, cholestatic hepatitis.

From the endocrine system: rarely (with prolonged use) - decreased libido, weight gain; increase, pain and tension in the mammary glands, irregular uterine bleeding, galactorrhea, hirsutism, menstrual cycle disorders (contraction, intermediate bleeding).

From the side of the central nervous system: rarely (with prolonged use) - headache, drowsiness, depression, apathy, dysphoria.

Other: impaired vision, change in body weight, alopecia, tenderness at the injection site, allergic reactions.

Overdose:Not described. Treatment symptomatic.

Interaction:

Griseofulvin, carbamazepine, rifabutin, rifampicin, phenytoin, phenobarbital - increase the concentration of globulin, binding sex hormones, in blood plasma, significantly reducing the concentration of free progestins and weakening their effect. Care should be taken when combining with contraceptives.

Inducers of liver enzymes (carbamazepine, rifabutin, rifampicin, phenytoin, phenobarbital) - stimulate the metabolism of progestins and reduce their effect.

Hypoglycemic drugs - progesterone changes the concentration of glucose in the blood plasma; a dosage adjustment of a hypoglycemic drug may be required.

Cyclosporine - can inhibit metabolism, increase the concentration of progesterone in the plasma and the risk of toxicity.

Progesterone reduces the lactogenic effect of oxytocin.

Progesterone weakens the action of drugs that stimulate smooth uterine muscles, anabolic steroids, gonadotropic hormones in the anterior pituitary gland.

It is not recommended to be used together with other intravaginal drugs.

Special instructions:

A natural hormone with progestagenic, androgenic and antiestrogenic activity.

Do not use for contraceptive purposes.

The vaginal gel contains sorbic acid, which can cause a local skin reaction (contact dermatitis).

With prolonged therapy, regular gynecological examinations are necessary in order to exclude the possibility of developing endometrial hyperplasia.

When using a vaginal gel, the concentration of chorionic gonadotropin should be determined or an ultrasound should be performed (to prevent the occurrence of a "threatening" abortion).

Impact on the ability to drive vehicles and manage mechanisms

Instructions

Progesterone (Progesteronum)