Progesterone tablets and injections: instructions for use, price, reviews for delayed menstruation

Compound

1 ml of Progesterone 1% injection solution contains 0.01 grams of the active substance, as well as benzyl benzoate (Benzylii benzoas) and refined olive/peach oil (Oleum Olivarum/Oleum Persicorum).
One milliliter of injection solution Progesterone 2.5% includes 0.025 grams of the active substance, benzyl benzoate (Benzylii benzoas) and refined olive/peach oil (Oleum Olivarum/Oleum Persicorum).

Progesterone 1% and 2.5% is available in 1 ml ampoules, packaged in packages of 5 or 10 pieces.

The composition of the gel and capsules varies depending on which pharmaceutical company produces these dosage forms.

Pharmacodynamics and pharmacokinetics

Progestogen is a steroid hormone that is produced in the body by the corpus luteum of the ovaries .

The mechanism of action of progesterone drugs is associated with their ability to interact with specific progestin receptors, which are located on the surface of target cells.

By binding to them, the substance penetrates the cell nucleus, activates deoxyribonucleic acid and stimulates the synthesis of ribonucleic acid.

The effect on a woman’s body is that the drug:

stimulates the transition of the endometrium (the mucous layer of the inner mucous membrane that lines the body of the uterus) from the proliferative phase, which coincides with the ovulatory and follicular phases of the ovarian cycle, to the secretory phase;
creates optimal conditions for embryo , reduces the sensitivity of the uterus and fallopian tubes to the action of oxytocin and has a tocolytic effect;
stimulates lipoprotein lipases ;
increases body fat reserves;
helps increase the level of induced and basal (background) insulin glucose utilization ;
enhances the accumulation of glycogen in the liver;
stimulates the synthesis by the adrenal cortex of the mineralocorticosteroid hormone aldosterone ;
provokes hypoazotemia ;
increases the excretion of nitrogen-containing metabolic products in the urine;
suppresses the production of a number of hypothalamic factors for the release of luteotropin (LH) and follicle-stimulating hormone (FSH) and, accordingly, the biosynthesis of pituitary gonadotropic hormones ;
reduces the permeability of the capillary wall in the tissues of the mammary glands;
reduces swelling of the connective tissue framework, depending on the phase of the menstrual cycle ;
suppresses the proliferative and mitotic activity of ductal epithelial tissue (in the case when progesterone is used in the form of a gel).

When taken orally, intravaginally using the drug in capsules, or injecting an injection solution under the skin and into the muscle, the substance is quickly absorbed. When applied to the skin in gel form, it is almost not absorbed and does not enter the systemic circulation.

The maximum plasma concentration when taking the tablet orally is observed after 1-3 hours; with intravaginal application, this figure is achieved after 2-6 hours.

protein binding (mainly albumin (approximately 50–54%) and 43–48% corticosteroid binding globulin ).

In the liver, the substance is biotransformed into inactive metabolites (mainly pregnanediol and pregnanolone ).

From 50 to 60% of the substance is eliminated by the kidneys , more than 10% - with bile ; Progesterone metabolization products excreted in bile intestinal and can undergo enterohepatic recirculation .

Pharmacological properties of the drug Progesterone

Hormone of the corpus luteum has a progestogenic effect. By binding to receptors on the surface of cells of target organs, it penetrates into the nucleus, where, activating DNA, it stimulates RNA synthesis. Promotes the transition of the uterine mucosa from the proliferation phase caused by follicular hormone to the secretory phase, and after fertilization, it creates the necessary conditions for implantation and development of a fertilized egg. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes, stimulates the growth of the secretory section of the acini of the mammary glands and induces lactation. By stimulating protein lipase, it increases fat reserves, increases glucose utilization, increasing the levels of basal and stimulated insulin, promotes the accumulation of glycogen in the liver, increases the production of aldosterone; in low doses it accelerates, and in high doses it suppresses the production of gonadotropic hormones of the pituitary gland; reduces azotemia, increases nitrogen excretion in urine. It is quickly and almost completely absorbed after subcutaneous and intramuscular administration. Metabolized in the liver to form conjugates with glucuronic and sulfuric acid. The half-life is several minutes. Approximately 50–60% is excreted in the urine, more than 10% in bile. The amount of metabolites excreted in the urine varies depending on the phase of the corpus luteum.

Indications for use

Progesterone: What is it for in oral capsule form?

Taking capsules is indicated for premenstrual syndrome and if a woman is diagnosed with fibroadenomatosis (fibrocystic disease).

As a progestational component, the drug is prescribed for HRT ( hormone replacement therapy ) in the period preceding menopause , immediately during menopause (including if menopause is premature ), as well as in the postmenopausal period .

Capsules for intravaginal administration: indications for use

Capsules for intravaginal use are indicated:

if it is necessary to prescribe HRT to a woman in case of ovarian dysfunction accompanied by a lack of progesterone ( oocyte donation );
to maintain the luteal phase during preparation for IVF ;
to maintain the luteal phase in the induced or spontaneous menstrual cycle .

For prophylactic purposes, the drug is prescribed to prevent habitual and threatening spontaneous abortion caused by gestagen insufficiency ; for endocrine infertility ; to prevent the development of fibroids and endometriosis .

Indications for use of the oil solution

Since progesterone causes menstruation (if their delay is associated with a deficiency of this hormone), it is prescribed to correct various types of menstrual irregularities .

Thus, the use of an oil solution is advisable for amenorrhea (absence of menstrual bleeding for several cycles) and oligomenorrhea (that is, a delay in menstrual bleeding for more than 40 days).

In addition, injections are prescribed for:

algomenorrhea (painful periods) associated with insufficiency of the gonads
anovulatory metrorrhagia (uterine bleeding not associated with ovulation);
endocrine infertility (including those caused by insufficiency of the corpus luteum);
threat of spontaneous abortion ;
diagnostic procedures, the purpose of which is to determine the level of estrogen+ .

When menstruation is delayed, progesterone can be used both in tablet form and in injections. However, more often an injection solution is prescribed, since the effect after it is noticeable much faster than after taking tablets.

Indications for use of the gel

Applications using Progesterone in gel form are prescribed for mastalgia and mastopathy .

secondary amenorrhea associated with progesterone deficiency , as well as in reproductive programs if a woman needs to compensate for the lack of progesterone during oocyte donation .

Gestagens (gestagena; Latin gesto - wear, be pregnant + Greek genes - generating, producing; synonyms: progestins, progestogens) - a group of natural hormones and their synthetic analogues that have the biological activity of progesterone. They belong to the C21 steroids, which are based on the pregnane skeleton. The most important natural gestagen is 4-pregnene-3,20-dione, or progesterone [1].

The physiological function of progesterone in women is mainly to enable the onset and then maintain pregnancy (gestation) - hence the name of both the hormone itself - progesterone, and the entire class of drugs - progestins, or gestagens.

Progesterone and its synthetic analogues, progestins, promote the formation of normal secretory endometrium in women, cause the transition of the uterine mucosa from the proliferation phase to the secretory phase, and after fertilization contribute to its transition to the state necessary for implantation and development of the fertilized egg.

A. Csapo et al. [2] showed the important role of progesterone during the first weeks of pregnancy. In the first study, removal of the corpus luteum before 7 weeks of gestation resulted in termination of pregnancy. It was further discovered that even after removal of the corpus luteum, pregnancy can be maintained by introducing external progesterone.

Insufficient secretion of progesterone in the luteal phase of the cycle can lead to a decrease in endometrial receptivity and is considered one of the main causes of implantation failure in spontaneous and stimulated cycles. Progesterone also reduces the excitability and contractility of the smooth muscles of the uterus and fallopian tubes, inadequate contractile activity of which can lead to ectopic pregnancy and spontaneous miscarriage.

Recent findings [3, 4] suggest that the protective effect of progesterone in early pregnancy may be due to changes in the maternal immune response. During a normal pregnancy, progesterone receptors are present in peripheral blood lymphocytes, and the proportion of cells containing such receptors increases. In the presence of progesterone, these lymphocytes produce a protective protein, progesterone-inducible blocking factor (PIBF). The physiological course of pregnancy is characterized by a high level of expression of the PIBP gene in decidual tissue. With recurrent miscarriage or threat of miscarriage, the synthesis of PIBP is impaired, which necessitates the need for additional administration of progesterone [3, 4].

Thus, the main properties of progesterone - protecting the endometrium, ensuring full implantation and maintaining pregnancy - allow the widespread use of progesterone-like drugs in obstetric and gynecological practice. The range of use of these drugs is quite large - they include progesterone testing, hormonal hemostasis, treatment of insufficiency of the luteal phase of the menstrual cycle, treatment and prevention of endometrial hyperplastic processes, endometriosis, endocrine forms of infertility, as well as eliminating the threat of miscarriage and, in addition, use as a replacement hormonal therapy (HRT) in women with physiological or pathological amenorrhea.

Currently on the pharmaceutical market there are many drugs with progesterone-like effects, introduced into clinical practice at different times and having certain disadvantages and advantages.

Previously used synthetic derivatives of progesterone (acetoxyprogesterone, pregnin) had a number of side effects, and therefore their use in clinical practice was discontinued or limited. The first drugs were derivatives of norsteroids - norethisterone (Norcolut, Primolut-nor), allylestrenol (Turinal), which, in addition to progesterone-like, also had minor estrogenic, mineralocorticoid and androgenic activity.

Due to advances in pharmacology, natural progesterone and its analogues are now preferred in clinical practice. They do not have androgenic, anabolic and estrogenic effects. The first derivatives of pregnane (natural progesterone) were 17-hydroxyprogesterone capronate and an oil solution of progesterone, intended for intramuscular administration. Then drugs for oral administration (Duphaston, Utrozhestan) and vaginal administration (Utrozhestan, Endometrin, Utrogest, Kraynon) appeared.

In 1961, the drug dydrogesterone for oral administration appeared on the pharmaceutical market for the first time. Duphaston is an analogue of natural progesterone and is widely used today in gynecological practice. Recognizing the undoubted positive effects of the drug, it should be noted that there are only a few studies indicating the comparative effectiveness of dydrogesterone in the treatment of gynecological diseases, in particular hyperplastic processes and endometriosis, as well as the tolerability of the drug with long-term use. In addition, administered dydrogesterone is not tested in peripheral blood plasma.

For oral administration, until the end of the 80s of the 20th century, natural micronized progesterone (utrozhestan) was also used. An important property of utrozhestan for maintaining pregnancy is its ability to inhibit the effect of oxytocin on the myometrium due to the activity of the main metabolites. At the same time, some sedative effect on the central nervous system after oral administration of utrozhestan is also associated with the activity of metabolites. In this case, patients often complain of weakness, drowsiness, and dizziness.

In connection with the above, most specialists prefer the vaginal route of administration of micronized progesterone, since there are no side effects on the central nervous system.

The transvaginal route of administration has the following advantages: the absence of local pain as with the intramuscular route of administration, the absence of systemic side effects [6] and the absence of the effect of primary metabolism in the liver, as with oral administration, as well as rapid absorption, high bioavailability and local effect on the endometrium [ 7].

The first vaginal preparations were not commercial, but were formulated by pharmacists. The first commercial vaginal progesterone product in the United States was a vaginal gel with proven high efficacy. In some European countries, natural micronized progesterone for vaginal administration (utrogestan) was approved even earlier than the gel. Another newer natural progesterone product in the US is FDA-approved endometrin in the form of vaginal tablets [5].

Research shows that vaginally administered progesterone (suppositories) can achieve serum progesterone levels similar to those during the ovulatory and luteal phases of the cycle [7].

As established by T. Levy et al. [6], due to the “uterine first pass effect,” vaginally administered progesterone results in high concentrations of progesterone in the uterus.

A study of the pharmacokinetics of vaginally administered progesterone (in the form of 100 mg tablets) with constant use did not reveal any effect on the hormonal, lipid profile and liver function, as well as cases of endometrial hyperplasia; good tolerability and safety were noted [6].

Despite all the obvious advantages of the vaginal route of administration of micronized progesterone, in clinical practice there are cases of itching, burning in the vagina, and swelling of the external genitalia. Patients often complain of discomfort associated with the feeling of “leakage” of the drug.

Currently, new approaches have been developed to overcome the limitations of conventional vaginal dosage forms, such as the use of mucoadhesive or bioadhesive polymers sensitive to pH and temperature, liposomes, nanoemulsions, nanoparticles, multiple emulsions and hydrogels to control and prolong the release of drugs [8]. ].

An experimental study [9] revealed that the physicochemical properties of water-insoluble polymers are important for adhesion to the epithelium of the mucous membrane (the experiment compared the ability of bioadhesion of various polymers to the gastric mucosa of a rabbit). Bioadhesiveness increases as the charge density increases and the higher the simpler the polymer structure. In this process, the acidity and amount of water on the surface control the adhesion process. The acidity of the environment - pH is a controlling factor. The role of physical interaction between polymer chains is most pronounced in polycarbophil. Due to these properties, polycarbophil was chosen as a carrier for the gel.

The bioadhesive polymer polycarbophil, a lightweight polyacrylic acid, can remain on vaginal tissue for 3 to 4 days and thus serve as a platform for drug release. The properties of the polymer, such as the acidic pH and the polyelectrolyte nature of the ionized form of the polymer, can change the local pH and level of tissue hydration, which is effective for the treatment of local pathology and long-term biological protection of the vaginal mucosa from the penetration of infectious agents. Hydration of vaginal tissue occurs by increasing vaginal blood flow. Finally, filling the polymer gel with natural progesterone makes it possible to achieve complete secretory transformation of the endometrium with a low level of the drug in the blood serum, which is manifested by a lower incidence of side effects [10].

The form of progesterone for vaginal administration, containing the bioadhesive polymer polycarbophil, is a long-acting gel - Krynon 8%, (manufactured in Switzerland).

Crinone (progesterone gel) is a bioadhesive vaginal gel containing micronized progesterone in the form of an emulsion. The carrier is an oil-in-water emulsion containing a water-swelling but water-insoluble polycarbophil polymer. The drug is supplied in the form of a one-component polyethylene applicator for single use. Each applicator contains 1.125 g of Crinona gel, which contains 90 mg (8% gel) of progesterone and excipients.

Crinone provides the controlled, continuous release of progesterone, which is necessary to realize all the benefits of direct delivery to the target organ, since diffusion of progesterone from the cervix to its fundus takes about 5 hours, after which steady tissue concentrations are achieved. The continuous functioning of the bioadhesive delivery system ensures the availability of progesterone for at least 48 hours after a single vaginal application, so the drug is effective when administered once a day. Without the special controlled continuous release system developed for Crinon, maintaining a steady-state concentration in the endometrium during this dosing interval (24-48 hours) is impossible.

The main side effect of progesterone gel is the accumulation of masses in the vagina, which can sometimes cause local irritation [5].

When comparing the effectiveness of oral and vaginal administration of micronized progesterone, several studies have established the advantages of the vaginal route of administration.

Although micronized progesterone is absorbed when taken orally, its bioavailability is low due to extensive metabolism in the liver [11]. Complete predecidual transformation of the endometrium cannot be achieved with oral administration. With intramuscular and vaginal routes of administration, changes in the endometrium are similar to those during the normal menstrual cycle, although the level of progesterone in tissues is higher with intramuscular administration [11].

D. De Ziegler and R. Fanchin [11] found that vaginal application of progesterone gel (Crinon 8% once a day) is as effective as intramuscular injections in women with inactive ovaries. It is suggested that due to its low incidence of systemic side effects, vaginal progesterone gel may improve the acceptability of long-term HRT in amenorrheic women.

A study in postmenopausal women showed that the bioavailability of vaginal progesterone gel (Crinon 8% 90 mg) was higher than that of oral progesterone capsules (Prometrium 100 mg) [12].

When comparing the effectiveness of the intramuscular and vaginal routes of administration of progesterone, studies have noted comparable effectiveness of both methods, but acceptability and ease of use are undoubtedly higher with the vaginal route of administration.

A study [13] found that the vaginal route of administration provides progesterone concentrations in the endometrium that are much higher than those expected to be obtained with the achieved serum progesterone concentrations. The authors showed that endometrial progesterone concentrations were markedly higher in women receiving vaginal progesterone (1.38 ± 0.6 and 0.38 ± 0.19 ng/mg protein in the vaginal and intramuscular groups, respectively; p < 0.02 ), despite its lower values in the blood serum (4.17±0.56 and 32.32±11.06 ng/ml, respectively; p<0.001).

Another study [14] also found that endometrial progesterone concentrations were higher following vaginal administration of micronized progesterone in female embryo recipients with nonfunctioning ovaries than in women with normal ovulation or in female recipients with the highest plasma progesterone concentrations after intramuscular injection of progesterone 2 times a day (36.56±8.27, 4.45±1.27, 0.95±0.32 nmol/l, respectively). Vaginally administered micronized progesterone provides synchronous secretory transformation of the endometrium in women with non-functioning ovaries who are preparing for the transfer of donor embryos.

In a large prospective study, K. Silverberg et al. [15] found that in young patients (25-35 years old) in the IVF program, support of the luteal phase using vaginal gel (Crinon 8%) provides a significantly higher pregnancy rate than intramuscular administration of an oil solution of progesterone. In older patients (35-44 years), Crinone and an oil solution of progesterone are apparently equally effective.

Another study [16] found that vaginal gel (Crinon 8%) and intramuscular progesterone solution were equally effective in supporting the luteal phase of an IVF cycle.

A meta-analysis [17] found that with daily use of intramuscular progesterone 50 mg, vaginal capsules of progesterone oil solution 200 mg 3 times a day and 90 mg vaginal progesterone in a bioadhesive gel, the effect on the incidence of clinical and progressive pregnancy during ART was comparable. A significantly lower rate of miscarriages was noted when using vaginal gel compared to intramuscular progesterone.

A retrospective study [18] showed that the vaginal route of administration of progesterone (Crinon 8% 90 mg/day) to support the luteal phase is better than the intramuscular route (Prontogest 50 mg/day), since there was a higher implantation rate, as well as pregnancy and clinical pregnancy in ICSI cycles, but not IVF.

When comparing different dosage forms of progesterone for vaginal administration, a number of studies have obtained conflicting results.

A study in young healthy women showed that one vaginal capsule containing 200 mg of progesterone (Utrogest 200 mg). has higher bioavailability than a gel dose containing 90 mg of progesterone. Almost 50% more progesterone was bioavailable after capsule administration than after gel application, but progesterone levels were tested only in peripheral blood plasma [19].

A prospective, multicenter, randomized, controlled, open-label, parallel-group phase III study [20] demonstrated that luteal phase support in ART cycles using Utrogest (TM) 200 mg capsules (3 times daily) or Crinone (TM) 8% gel (2 times per day) when administered vaginally leads to similar results in terms of implantation rate, progressive pregnancy and miscarriage rate, both types of therapy are equivalent and safe.

The clinical pregnancy rate (58.7% vs. 44.3%) and implantation rate (32.04% vs. 23.89%) were significantly higher in the Crinona group (vaginal 8% gel 90 mg, 1 time per day) compared with those in the Utrozhestan group (vaginal capsules 200 mg 4 times a day), used to support the luteal phase in IVF/ICSI cycles with embryo transfer at the blastocyst stage [21].

When comparing combined luteal phase support in an IVF cycle using oral micronized progesterone in capsules (Utrozhestan 100 mg 3 times a day) and vaginal gel (Crinon 8%) and monotherapy with vaginal gel (Crinon 8%), it was found that the effectiveness and tolerability Combination therapy and monotherapy are comparable, but the bleeding and miscarriage rates are higher with monotherapy [22].

When comparing a weekly vaginal ring with progesterone and vaginal gel with progesterone (Crinon 8% 90 mg) as luteal phase support, it was found that the use of a vaginal ring with progesterone ensures adequate transformation of the endometrium and is comparable in effectiveness and safety with vaginal gel, but has the advantage of form of use once a week instead of daily administered doses [23].

Conducted by N. Polyzos et al. [24] a meta-analysis provides evidence that there is no significant difference between vaginal gel and other vaginal forms of progesterone in terms of clinical pregnancy rates.

Finally, the benefits of luteal phase support with vaginal progesterone gel in ovarian stimulation and intrauterine insemination cycles have been confirmed.

A randomized prospective study [25] revealed that the incidence of clinical pregnancy per cycle and per patient was significantly higher in the group of patients who received luteal phase support in the form of vaginal progesterone gel (Crinon 8%) in cycles of ovarian stimulation and intrauterine insemination for unexplained infertility genesis (21.1 and 39.4%, respectively), compared with that in the control group without luteal phase support (12.7 and 23.8%, respectively).

Thus, there are reports in the literature of the use of various vaginal suppositories with progesterone and their comparison with vaginal gel. Despite the differences in the results obtained regarding the effectiveness of progesterone forms, some advantages of progesterone gel should be emphasized. In a study by V. Mahaguna et al. [26] noted that the pH of most vaginal suppositories ranged from 4.22 to 7.68, averaging 6.30 (normal vaginal pH <5.0), while the gel had a pH of 2.8. This is due to the acidic environment of the bioadhesive polymer polycarbophil, which has a pKa of 4.3 and has a high buffering capacity. Application of the gel leads to a decrease in vaginal acidity. Changes in vaginal pH provide an objective indicator of the duration of action of the gel. One study in postmenopausal women examined the duration of action of the gel based on measurements of vaginal acidity - pH. It was noted that after the first application, the vaginal pH did not change significantly, but 24 and 72 hours after the first application, a significant decrease in pH was noted. Acidity remained significantly reduced for 168 hours after 3 or 5 applications, with mean vaginal pH maintained below 5.0 during this period. It was shown that the duration of action of the gel was 4 days, confirmed by subjective assessments of the feeling of the moisturizing effect of the gel. Maintaining an acidic environment in the vagina over a long period of time is known to have additional benefits in terms of providing protection against infections [27].

Thus, doctors currently have at their disposal a large selection of progesterone-like drugs that have sufficient clinical effectiveness in terms of ensuring full secretory transformation of the endometrium and supporting early pregnancy, which allows individual selection of drugs and routes of administration, taking into account tolerability, side effects and patient preferences. At the same time, from the point of view of implementing the principle of “maximum benefit, minimum harm,” the use of natural progesterone derivatives is preferable, especially during pregnancy and in infertility treatment cycles. The most effective and well-tolerated vaginal gel containing natural progesterone, the use of which contributes to the formation of a number of positive biological effects: adequate transformation of the endometrium and long-term biological protection of the vaginal mucosa from the penetration of infectious agents, which is ensured by the properties of the bioadhesive polymer polycarbophil. All of these effects are especially significant when it is necessary to prescribe progesterone for a long time: HRT, pregnancy, infertility treatment in IVF programs.

Contraindications

All dosage forms of Progesterone are contraindicated:

in case of hypersensitivity to the components of the drug;
in the presence of serious impairment of renal function and/or hepatic function ;
if the patient is diagnosed with hepatitis ;
in the acute form of inflammation of the venous walls , as well as in acute thromboembolic diseases ;
patients who have an increased risk of blood clots ;
vaginal (vaginal) bleeding of unknown origin;
missed miscarriage;
incomplete abortion;
porphyrin disease.

Additional contraindications to the use of an oil solution are:

the presence of a malignant tumor of the mammary gland or genital organs (for breast carcinoma, exceptions are cases when progesterone is prescribed as part of complex therapy);
pregnancy (starting from 14 weeks).

Side effects

Treatment with progesterone drugs can cause the development of allergic reactions.

The effect on a woman’s body of the drug in capsule form is in some cases accompanied by:

increased drowsiness;
dizziness that occurs 1-3 hours after taking the tablet;
various types of menstrual cycle disorders (for example, a reduction in its duration or the appearance of intermediate bleeding).

The most common side effects of injections:

acute blockage of the lumen of blood vessels by a thrombus;
thrombophlebitis (thrombosis accompanied by inflammation of the venous wall);
thrombosis of retinal blood vessels;
increased blood pressure ;
the appearance of edema ;
chronic cholecystitis , characterized by the formation of stones in the gallbladder (calculous cholecystitis);
increased drowsiness ;
headache;
apathy;
visual impairment;
hair loss ( alopecia );
decreased libido ;
hirsutism (male pattern hair growth in women);
attacks of nausea and vomiting;
deterioration of appetite and, as a result, loss of body weight;
menstrual irregularities;
cholestatic hepatitis;
depression;
dysphoria (gender identity disorder);
release of milk from the mammary glands not associated with breastfeeding ( galactorrhea );
enlargement, tenderness and tension of the mammary glands;
local reactions (redness of the skin and pain at the injection site).

Progesterone solution IM oil 2.5% cor 1 ml x10

Trade name: Progesterone International name: Progesterone

Release form: oil injection solution 1%, 2.5% (ampoules) 1 ml

Composition: benzyl benzoate 200/200 ml, progesterone 10/25 g - 1 l

Pharmacological group: gestagen

Pharmacological group according to ATK: G03DA04 (Progesterone)

Pharmacological action: gestagenic,

Indications: Amenorrhea, anovulatory metrorrhagia, endocrine infertility (including corpus luteum insufficiency), threat of miscarriage, oligomenorrhea, algomenorrhea (due to hypogenitalism), diagnosis of the formation of endogenous estrogens.

Dosage regimen: IM or SC, for bleeding associated with ovarian dysfunction - 5-15 mg daily, for 6-8 days, if the mucous membrane of the uterine cavity has been previously curetted, injections begin after 18-20 days (if curettage is impossible, inject during bleeding). During the treatment period, bleeding may temporarily increase (for 3-5 days); severely asthenized patients must first undergo a blood transfusion (200-250 ml). After bleeding stops, therapy is continued for 6 days. If bleeding has not stopped after 6-8 days of treatment, further administration is not advisable. For hypogenitalism and amenorrhea, it is administered after the use of estrogenic drugs in the form of injections of 5 mg daily or 10 mg every other day, for 6-8 days. For algodismenorrhea, treatment begins 6-8 days before menstruation, 5 or 10 mg daily, for 6-8 days. For algodismenorrhea caused by underdevelopment of the uterus, it is combined with estrogens at the rate of 10 thousand units every other day for 2-3 weeks, then progesterone is administered for 6 days. For the prevention and treatment of threatening and incipient miscarriage associated with insufficient function of the corpus luteum, 10-25 mg daily or every other day, until the symptoms of a possible miscarriage completely disappear. With a routine abortion, it is administered up to 4 months of pregnancy. In case of corpus luteum deficiency - 12.5 mg/day IM, for 2 weeks from the moment of ovulation (if necessary - up to 11 weeks of pregnancy). Diagnosis of the formation of endogenous estrogens: intramuscularly, 100 mg once.

Contraindications: Hypersensitivity, breast and genital cancer (as monotherapy), liver failure, pregnancy (II-III trimesters), tendency to thrombosis, acute forms of phlebitis or thromboembolic diseases, vaginal bleeding of unknown origin, failed miscarriage, porphyria.

Side effects: From the nervous system: drowsiness, headache, depression, apathy, dysphoria. From the digestive system: cholestatic hepatitis, nausea, vomiting, loss of appetite, calculous cholecystitis. From the genitourinary system: decreased libido, shortened menstrual cycle, intermediate bleeding. From the senses: visual impairment. From the cardiovascular system: increased blood pressure, edema, thromboembolism (including pulmonary artery and cerebral vessels), thrombophlebitis, retinal vein thrombosis. From the endocrine system: galactorrhea, alopecia, weight gain, enlargement, pain and tension of the mammary glands, hirsutism. Allergic reactions. Local reactions: pain at the injection site.

Pharmacodynamics: Hormone of the corpus luteum, has a gestagenic effect. By binding to receptors on the surface of cells of target organs, it penetrates into the nucleus, where, activating DNA, it stimulates RNA synthesis. Promotes the transition of the uterine mucosa from the proliferation phase caused by follicular hormone to the secretory phase, and after fertilization creates the necessary conditions for implantation and development of a fertilized egg. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes, stimulates the development of the end elements of the mammary gland. By stimulating protein lipase, it increases fat reserves, increases glucose utilization, increasing the concentrations of basal and stimulated insulin, promotes the accumulation of glycogen in the liver, increases the production of aldosterone, in small doses accelerates, and in large doses suppresses the production of gonadotropic hormones of the pituitary gland, reduces azotemia, increases nitrogen excretion from urine. Activates the growth of the secretory section of the acini of the mammary glands and induces lactation. Promotes the development of normal endometrium.

Pharmacokinetics: Rapidly and almost completely absorbed after subcutaneous and intramuscular administration. Metabolized in the liver to form conjugates with glucuronic and sulfuric acid. The CYP2C19 isoenzyme is also involved in metabolism. T1/2 - several minutes. Excreted by the kidneys - 50-60%, with bile - more than 10%. The amount of metabolites excreted by the kidneys varies depending on the phase of the corpus luteum.

Special instructions: During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions. Carefully. Cardiovascular diseases, arterial hypertension, chronic renal failure, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, ectopic pregnancy, lactation.

Interaction: Reduces the lactogenic effect of oxytocin. Reduces the intensity of the action of drugs that stimulate the smooth muscles of the uterus, anabolic steroids, gonadotropic hormones of the anterior pituitary gland. When used simultaneously with barbiturates, a decrease in the effect of progesterone is observed.

Drug registration number: P No. 002804/01-2003

Date of registration (re-registration) of the drug: 08/25/2003

Instructions for Progesterone (Method and dosage)

Progesterone injections: instructions for use

Progesterone injections are given into the muscle or under the skin.

For dysfunctional uterine bleeding, daily administration of 0.5-1.5 ml of a one percent solution is indicated for 6-8 days. If the patient has undergone a uterine cavity curettage procedure, the course of injections begins after 18-20 days.

If curettage is not possible, the drug can be administered even during bleeding. When using Progesterone during bleeding, bleeding may temporarily increase (usually for 3-5 days).

For this reason, patients with moderate or severe forms of anemia are recommended to first transfuse 0.2-0.25 liters of donor blood. If bleeding has stopped, do not interrupt the course of treatment before 6 days. If the bleeding has not stopped after 6-8 days of treatment, it is considered inappropriate to continue administering the solution.

For algodismenorrhea (painful periods), treatment begins 6-8 days before the start of menstruation. Patients are advised to administer 0.5 to 1 ml of a one percent solution daily for 6-8 days. The course of treatment can be repeated several times.

For preventive purposes, to prevent spontaneous abortion, 0.5 to 2.5 ml of a one percent solution is administered daily or every other day. Injections continue to be given until the threatening symptoms disappear completely. In case of habitual miscarriage, the drug should be administered until the fourth month of pregnancy.

The maximum single and daily dose for adult patients when Progesterone is administered into the muscle is 0.025 g.

Progesterone to induce menstruation: how to inject when menstruation is delayed

For hypogonadism, amenorrhea , as well as to induce menstruation in case of delay, treatment begins with the prescription of estrogenic drugs. The goal of therapy is to achieve sufficient proliferation of endometrial cells . Upon completion of the course using estrogenic drugs, the patient is prescribed Progesterone injections.

Treatment involves administering 0.5 ml daily or every other day 1 ml of a one percent oil solution (in some cases, Progesterone 2.5% may be prescribed to induce menstruation). Typically, 5 to 10 injections are required.

Instructions for Progesterone in tablets and gel form

The tablets are taken orally (without being tied to the time of meals) or used intravaginally, the gel is used as a local remedy. The dosage regimen, optimal dosage form and duration of treatment are determined depending on the indications and characteristics of the course of the disease.

As a rule, the daily dose is from 200 to 400 mg of progesterone. To maintain the luteal phase during IVF, the patient is prescribed a dose of 600 mg of progesterone, with a frequency of applications 3 times a day (200 mg every 8 hours).

One application requires 2.5 g of gel (equivalent to 25 mg of progesterone). The gel is applied using a special dispenser applicator to the skin of the mammary glands once or twice a day daily (until completely absorbed) or in the second phase of the menstrual cycle (from the 16th to the 25th day). Treatment is usually carried out over 3 cycles.

A repeated course is possible according to indications.

Use of the drug Progesterone

Oral administration (capsules) In most cases, the average daily dose is 200–300 mg in 2 divided doses (100 mg in the morning no earlier than 1 hour after meals and 100–200 mg in the evening before bedtime). For luteal phase deficiency (premenstrual syndrome, fibrocystic mastopathy, menstrual irregularities, premenopause), the daily dose is 200–300 mg (100 mg in the morning and 100–200 mg in the evening before bed) for 10 days (from 17 to 26 th day of the cycle). For hormone replacement therapy in menopause while taking estrogen, the drug is prescribed 200 mg in the evening before bed for 12–14 days. If there is a threat of premature birth, 400 mg of progesterone is prescribed once, then 200-400 mg can be taken every 6-8 hours until symptoms disappear. The dose and frequency of use are determined individually depending on the clinical manifestations of the threat of premature birth. After the symptoms disappear, the dose of progesterone is gradually reduced to a maintenance dose of 200–300 mg per day (100 mg in the morning 1 hour after meals and 100–200 mg in the evening before bedtime). At this dose, the drug can be used up to 37 weeks of pregnancy. If clinical manifestations of the threat of premature birth occur again, treatment is resumed at an effective dose. Intravaginal administration (capsules) In the complete absence of progesterone in women with non-functioning (absent) ovaries (egg donation) against the background of estrogen therapy, the drug is prescribed 100 mg/day on the 13th and 14th days of the cycle, then 100 mg 2 times a day day (morning and evening) from the 15th to the 25th day of the cycle, from the 26th day and in case of pregnancy, the dose is increased by 100 mg per day weekly, reaching a maximum daily dose of 600 mg in 3 doses (200 mg each every 8 hours). The drug is used at this dose for 60 days. In the future, it is possible to take progesterone at a dose of 400–600 mg/day (200 mg every 8–12 hours), up to 27 weeks of pregnancy inclusive. To support the luteal phase during an in vitro fertilization cycle, the drug is prescribed at 400–600 mg/day (200 mg every 8–12 hours) starting from the day of human chorionic gonadotropin injection until 27 weeks of pregnancy inclusive. To support the luteal phase in a spontaneous or induced menstrual cycle for infertility associated with dysfunction of the corpus luteum, 200–300 mg/day is prescribed in 2 doses, starting from the 17th day of the cycle for 10 days. If menstruation is delayed and pregnancy is detected, the drug should be resumed. Treatment at the recommended dose (100 mg in the morning and 100–200 mg in the evening before bed) can be continued up to 27 weeks of pregnancy inclusive. In case of threatened miscarriage or for the prevention of habitual miscarriage due to progesterone deficiency, 200–400 mg/day (100–200 mg every 12 hours) is prescribed until 27 weeks of pregnancy. The effective dose is selected individually depending on the clinical manifestations of the threat of miscarriage. IM or s/c For bleeding caused by ovarian dysfunction - 5-15 mg daily for 6-8 days; if curettage of the mucous membrane of the uterine cavity has been previously performed, it is started after 18–20 days (if curettage is impossible, it is administered during bleeding). During the treatment period, bleeding may temporarily increase (for 3–5 days); asthenized patients must first undergo a blood transfusion (200–250 ml). After bleeding stops, therapy is continued for 6 days. If bleeding has not stopped after 6–8 days of treatment, further administration is not advisable. For hypogenitalism and amenorrhea, after using estrogen drugs, 5 mg of progesterone is administered daily or 10 mg every other day for 6–8 days. For algodismenorrhea, treatment begins 6–8 days before menstruation, 5 or 10 mg daily for 6–8 days. For algodismenorrhea caused by uterine hypoplasia, it is combined with estrogens at the rate of 10,000 units every other day for 2–3 weeks; then progesterone is administered for 6 days. For the prevention and treatment of threatening and incipient miscarriage caused by insufficient function of the corpus luteum - 10–25 mg daily or every other day, until the risk of miscarriage is completely eliminated. With a routine abortion, it is administered up to 4 months of pregnancy. In case of corpus luteum deficiency: 12.5 mg/day IM for 2 weeks from the moment of ovulation (if necessary, up to 11 weeks of pregnancy). Diagnosis of the formation of endogenous estrogens: intramuscularly, 100 mg once. Local Gel: 1 dose (2.5 g of 1% gel) is applied to the skin of each breast until completely absorbed 1 time per day, regardless of the days of the menstrual cycle.

Interaction

Reduces the intensity of the action of anabolic steroid drugs , oxytoxic drugs (that is, agents that stimulate the contractile activity of the uterus gonadotropic hormones synthesized in the anterior lobe of the pituitary gland . Reduces the lactogenic effect of oxytocin .

When used simultaneously with diuretics , bromocriptine ; drugs that reduce high blood pressure ; systemic coagulants , immunosuppressants Progesterone enhances the effect of these drugs.

When taking the drug in combination with barbiturates , a decrease in its pharmacological activity is observed.

Progesterone reduces the effectiveness of anticoagulants.

Progesterone injection solution in oil 2.5% 1 ml ampoule 10 pcs. in Moscow

Latin name

Progesterone

International nonproprietary name

progesterone

Release form

Oily solution for intramuscular injection

Package

1 ml - ampoules (5) - contour cell packaging (2) - cardboard packs. 1 ml - ampoules (10) - cardboard boxes.

pharmachologic effect

Gestagen. Corpus luteum hormone. Causes a transition of the uterine mucosa from the proliferation phase caused by follicular hormone to the secretory phase, and after fertilization contributes to its transition to the state necessary for the development of a fertilized egg. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes, stimulates the development of the end elements of the mammary gland. Does not have androgenic activity. Progesterone has a weak effect on protein metabolism, promotes the deposition of fats and the accumulation of glucose in the liver, and also reduces the reabsorption of sodium in the renal tubules. Progesterone has a blocking effect on the secretion of hypothalamic release factors of LH and FSH, inhibits the formation of gonadotropic hormones in the pituitary gland and inhibits ovulation.

Indications

Dysfunctional uterine bleeding, metrorrhagia, amenorrhea, recurrent miscarriage. Contraception.

Directions for use and doses

The dosage regimen is individual. The dose, frequency and duration of treatment are determined according to the regimen depending on the indications and clinical situation.

Compound

2 ml of solution in olive oil contains active substance: progesterone 25 mg

Contraindications

Severe liver or kidney dysfunction, hepatitis, thromboembolic diseases, vaginal bleeding of unknown origin, breast carcinoma (except for cases in which progesterone is used as part of combination therapy for this disease).

Use during pregnancy and breastfeeding

In cases of extreme necessity, it is possible to use Progesterone during pregnancy if there is an established deficiency of corpus luteum hormones. Progesterone is not used in women planning pregnancy in the near future.

special instructions

Progesterone is used with caution in patients with cardiovascular diseases, impaired liver or kidney function, diabetes mellitus, bronchial asthma, epilepsy, migraine, and depression.

Side effects

From the cardiovascular system: increased blood pressure. Metabolism: edema. From the digestive system: liver dysfunction, jaundice; rarely (with long-term use) - nausea, vomiting. From the endocrine system: rarely (with long-term use) - decreased libido, weight gain, pain and tension in the mammary glands, irregular uterine bleeding. From the side of the central nervous system: rarely (with long-term use) - headache, depression.

Drug interactions

Reduces the intensity of the action of drugs that stimulate the smooth muscles of the uterus, anabolic steroids, gonadotropic hormones of the anterior pituitary gland. Reduces the lactogenic effect of oxytocin. Enhances the effect of diuretics, antihypertensive drugs, immunosuppressants. When used simultaneously with barbiturates, a decrease in the effect of progesterone is observed.

Storage conditions

At a temperature not exceeding 25 C.

special instructions

Use with caution and under constant monitoring for diseases of the heart and blood vessels , epilepsy , mild or moderate renal dysfunction , for the treatment of diabetics, patients suffering from bronchial asthma and migraines .

Progesterone is also prescribed with caution to patients with a history of mental disorders . When the first signs of depression occur, treatment is stopped. You should also pay attention to early signs of thromboembolism . Their appearance is a reason to discontinue the drug.

Patients with diabetes mellitus during treatment with Progesterone should constantly monitor blood glucose levels .

Since steroid hormones are metabolized in the liver, progesterone is not prescribed to patients with impaired liver function .

Treatment with progesterone drugs may be accompanied by a weakening of concentration, so care should be taken when driving vehicles and engaging in other activities that require a high speed of psychomotor reactions or pose a potential threat to health and life.

Long-term use of increased doses of Progesterone can cause cessation of menstruation.

The drug in gel form is applied without rubbing it into the skin of the mammary glands or massaging them. After applying the cream, you should not be in direct sunlight.

Analogs

Matches by level 4 ATX code:
Iprozhin

Utrozhestan

Crinon

Prajeesan

Progestogel

Progesterone-containing drugs are Utrozhestan , Iprozhin , Crinon , Prajisan , Progestogel , Endometrin . A multicomponent analogue of the drug - vaginal capsules Triozhinal .

Use of Progesterone during pregnancy

Tablets and injections during pregnancy are indicated only in cases where it is necessary to prevent spontaneous miscarriage. There are no reliable data on the safety of using the drug in gel form during pregnancy.

During breastfeeding, you should refrain from using Progesterone tablets and injections. The gel is prescribed when there are no alternative treatments and the benefit to the mother potentially outweighs the risk to the baby.

There is an opinion that the drug helps get rid of an unwanted pregnancy, which is why the questions often arise: “How to disrupt an early pregnancy with the help of Progesterone?”

However, this is impossible, since progesterone, on the contrary, helps strengthen pregnancy (for this reason, the drug is prescribed to women who have been diagnosed with infertility, as well as to women who are about to undergo IVF). But a deficiency of this hormone can lead to miscarriage.

How does progesterone affect infusion during IVF?

The chance that an embryo will be able to implant depends on three main factors:

embryo quality;
endometrial conditions;
tone of the muscular layer of the uterus.

The quality of the embryos at this stage cannot be changed, but the other two factors are influenced by progesterone. He:

reduces the excitability of the uterus and fallopian tubes;
causes changes in the endometrium that will facilitate implantation of the embryo: it stops the division of endometrial cells and causes the formation of a secretion in it: it will increase the lumen of the uterine cavity;
reduces the tone of the muscles of the uterus and eliminates as much as possible the possibility of individual contractions of its sections - so that the embryo can gain a foothold in the endometrium.

In addition, progesterone suppresses the immune system so that it does not reject the embryo as a foreign body, it suppresses the next ovulation. When its concentration decreases, the female body receives a signal that it is time to give birth.

Therefore, in order for the embryo to implant normally, the body must have a sufficient level of this important hormone. Therefore, before replanting, it is very important to determine exactly the concentration of progesterone and, if it is less than 8.7 nmol/l, not to go through the protocol, but to freeze the embryos until the next cycle.

Reviews about Progesterone

The largest number of reviews about the drug can be found on special forums dedicated to the problem of female infertility.

Most women who have had difficulty conceiving and bearing a child note the effectiveness of Progesterone, even in cases where the patient suffered several miscarriages before starting a course of using this drug when another pregnancy occurred. That is, in some cases, Progesterone is the only chance to save a pregnancy.

However, there are also negative reviews about the drug. They are associated with a fairly large number of side effects of the drug and the presence of contraindications to its use. In addition, some of the women treated with Progesterone did not notice any effect from the prescribed therapy.

Be that as it may, as is the case with other medications, self-medication with progesterone preparations is unacceptable. You can begin a course of use only after a comprehensive examination and based on test data.

The hormone progesterone in women

Progesterone is a hormone produced by a special endocrine gland, which lives for only about 14 days in a non-pregnant woman, and another 12-16 weeks in a pregnant woman, and then dies. This gland is the corpus luteum. Its main function is the synthesis of progesterone, and when it dies, it passes the “relay race” for the synthesis of this hormone to the placenta. What does progesterone affect? Why is it so important?

This hormone prepares the body for pregnancy and tries to support it by acting on the uterine tissue and the immune system (more details in the next section). It promotes the development of glands inside the mammary glands, but if a woman is breastfeeding, then her lactation is inhibited. The hormone stores subcutaneous fat, accumulates glycogen in the liver, a precursor to glucose, that is, it prepares reserves in case conception “takes place.”

Progesterone price, where to buy

The price of injections in Russia is from 105 rubles for a package of ampoules with a one percent solution and from 360 rubles for a package of ampoules with a 2.5% oil solution. You can buy tablets for an average of 180 rubles (the price depends on the place of purchase, the manufacturer of the drug, the concentration of the active substance in one tablet and the number of tablets in the package).

In Ukrainian pharmacies the price of Progesterone in tablets is on average 45 UAH. The cost of ampoules with a 1% solution is from 12 UAH, ampoules of 2.5% cost an average of 32 UAH.

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine
Online pharmacies in KazakhstanKazakhstan

ZdravCity

Progesterone solution for in.
oil 1% 1ml 10 pcs. JSC Dalkhimfarm 392 rub. order

Pharmacy Dialogue

Oxyprogesterone capronate (amp. 12.5% 1ml No. 10) DHF OJSC
RUB 1,035 order
Progesterone (amp. 2.5% 1ml No. 10) DHF JSC
934 rub. order
Progesterone (amp. 1% 1ml No. 10) DHF JSC
RUB 312 order

Pharmacy24

Progesterone 1% 1 ml No. 10 solution TOV FZ Biopharma, Ukraine
68 UAH order
Progesterone 2.5% 1 ml No. 10 solution TOV FZ BIOPHARMA, Ukraine / PrAT Biopharma, Ukraine
75 UAH order
Oxyprogesterone capronate 12.5% 1 ml No. 10 solution for injection TOV"FZ "Biopharma", Ukraine
114 UAH order

PaniPharmacy

Oxyprogesterone capronate ampoule Oxyprogesterone capronate solution d/in. 12.5% amp. 1ml No. 10 Ukraine, Biopharma CJSC
114 UAH order
PROGESTERONE ampoule Progesterone solution oil. d/in. 2.5% amp. 1ml No. 10 Ukraine, Biopharma CJSC
57 UAH order
PROGESTERONE ampoule Progesterone solution oil. d/in. 1% amp. 1ml No. 10 Ukraine, Biopharma CJSC
59 UAH order