Syndrome of early menopause or ovarian exhaustion. What is premature ovarian failure syndrome

Sometimes, for various reasons, in women who have not reached menopausal age, there is a premature extinction of reproductive function. Usually, young women around the age of 40, and sometimes even earlier, face such a problem. Gynecologists call this ovarian failure syndrome (OSS) or early menopause. The problem lies not only in the untimely loss of childbearing function, but also in the fact that in the female body there are processes characteristic of - hormonal changes and, in most cases, a decrease in fertility. This process is irreversible, restoration of natural reproductive function, unfortunately, is impossible in most cases. However, a woman needs therapy aimed at restoring hormonal levels normal for her young age.

Causes of premature ovarian failure

Several factors that may contribute to the occurrence of this pathology have been studied. In most cases, ovarian failure syndrome occurs in women who have a hereditary predisposition. Almost 25% of women who turn to a gynecologist with such a problem have older female relatives who have experienced amenorrhea, late menarche or early menopause.

A possible cause of SIA could be congenital genetic anomaly, resulting from gene mutations (when examined, a third X chromosome is often found in women). If, during the pregnancy of a girl, the mother used alcoholic and narcotic substances, experienced stress and suffered serious illnesses or injuries, then the likelihood of SIA in her daughter increases significantly.

Sometimes this pathology develops as a result of any autoimmune processes, when antibodies appear in the body that attack the tissues of the ovaries. Often this occurs against the background of autoimmune diseases of other organs that produce hormones.

Other causes not related to congenital anomalies are also possible:

• chemical poisoning, including drugs, chronic intoxication;
• exposure to radiation;
• infectious diseases transferred in severe form with complications (, etc.);
• permanent;
• metabolic disorders (in particular, galactosemia);
• constant malnutrition, exhaustion, anorexia;
• ovarian surgery (resection to remove a cyst or tumor).

Symptoms of ovarian failure syndrome

Symptoms usually occur suddenly in the context of normal reproductive function. A woman pays attention to what becomes irregular, menstruation becomes scarce, and after a while it stops altogether.

A couple of months after the cessation of menstruation, symptoms inherent in menopause appear:

The appearance of the tides(hot flashes, excessive sweating, palpitations, dizziness and blackouts, sometimes with excitement, but most often for no reason).

Deterioration of psycho-emotional status(increased irritability, tearfulness, anxiety, depression, insomnia, etc.).

Decreased libido, often associated with the fact that a decrease in estrogen production leads to atrophy of the mucous membrane of the vagina and vulva. As a result, unpleasant symptoms appear, such as dryness and itching in the vagina and urethra, which leads to discomfort during intercourse.

Frequent, and other inflammatory diseases of the genitourinary system. It is also associated with atrophy of the mucous membranes and a decrease in the production of substances with protective properties.

Aging of the skin and the whole organism. Hormones produced by the ovaries are involved in maintaining the tone and elasticity of the skin and other body tissues. Therefore, after the onset of menopause, the aging process accelerates.

These symptoms often disrupt the usual rhythm of life and cause many different problems. That is why women who have experienced SIA need hormone replacement therapy, which helps to almost completely get rid of these unpleasant symptoms.

Diagnostics

Usually, the diagnosis of this pathology does not cause serious difficulties for the doctor. The gynecologist can suspect SIA after collecting an anamnesis from the patient. On examination, the doctor may pay attention to the dryness of the vaginal mucosa and a decrease in the size of the uterus. An ultrasound also determines a decrease in the size of the uterus, thinning of the endometrium, a decrease in the ovaries, as well as the absence of follicles in them.

To clarify the diagnosis, a study of the concentration of hormones in the blood is carried out. Usually, a decrease in the level of estrogen and progesterone is determined, while the level of follicle-stimulating (FSH) and luteinizing (LH) hormones produced by the pituitary gland is increased. Also, the doctor may prescribe hormonal tests with various hormones for differential diagnosis with other pathologies that have a similar clinical picture (for example, resistant ovarian syndrome).

The most objective and reliable method is diagnostic laparoscopy with subsequent examination of the histological material taken during the manipulation.

SIA treatment

Therapy is aimed at correcting hormonal changes that are the cause of autonomic disorders. For this purpose, women are prescribed oral contraceptives containing estrogen and progesterone. Patients should be constantly monitored by a gynecologist, periodically conducted control studies of the level of sex hormones in the blood. Such maintenance therapy continues until the average age of menopause (45-50 years).

Also, patients are recommended multivitamin complexes, dietary supplements containing phytoestrogens (remens, climadinone, climactoplan, etc.) and sedatives (mainly of plant origin). It is useful to introduce foods rich in vitamins A, E, unsaturated fatty acids (omega-3,6,9), and natural phytoestrogens into the diet.

Ovarian failure syndrome and pregnancy

Since this pathology often occurs in young women planning to have children, they are concerned about the question of whether it is possible to become pregnant with ovarian failure syndrome.

In 5-10% of cases, hormone therapy still leads to spontaneous restoration of the normal menstrual cycle and reproductive function. Most often this happens if SIA is a consequence of any disease, intoxication or exhaustion.

In most cases, the only way to get pregnant is IVF (in vitro fertilization). Before the procedure, hormonal therapy is performed, aimed at restoring the endometrium and preparing it for implantation of the embryo. Then a donor egg is implanted in the woman, fertilized by the partner's seed. During pregnancy, hormone therapy is also needed to replace the normal functioning of the ovaries.

Cryopreservation of eggs

In some cases, SIA occurs in women at a very young age (20-25 years). In this case, the alarm is often sounded by the parents of young girls, whose menstrual cycle begins late and takes a long time to establish, sometimes it never becomes regular. As a result of the examination, the doctor may suspect this pathology or suggest its occurrence in the future.

If SIA is detected at an early age, cryopreservation of a woman's eggs is, in fact, the only way to give birth to a genetically native child in the future. To date, methods have been developed for freezing and thawing eggs, which allow them to be stored for several decades. The preservation process does not damage the structure of oocytes and does not affect their function in any way. Children born with the help of cryotechnology do not differ from those conceived naturally, the risk of congenital pathologies also does not increase in them.

Which doctor to contact

With a late onset of menstruation or early symptoms of menopause, you should consult a gynecologist. In some cases, consultation with an IVF specialist is indicated. In addition, an examination by a cardiologist, neurologist, psychologist is prescribed. Timely hormone replacement therapy helps to restore a woman's hormonal background and improve her well-being.

Ovarian exhaustion syndrome, which is also called "premature menopause" in the medical literature, is a whole complex of various symptoms that indicate the premature extinction of female reproductive function and a sharp decrease in the follicular supply in the body. As a rule, the onset of menopause in women over the age of 45 is considered normal.

Menopause is considered a completely natural extinction of the female reproductive function, which does not require any treatment. But if the fading of the reproductive function is observed in the fair sex, who have not reached the age of 37-40 and have absolutely no problems with childbearing before, we can talk about ovarian exhaustion syndrome.

According to medical statistics, the prevalence of ovarian failure syndrome is at least 1.65-1.85%. Most often, ovarian failure is diagnosed in women in the age group from 35 to 40 years. It should be noted that ovarian failure syndrome is not only a violation of the reproductive function and depletion of the follicular reserve in the female body, but also many other pathological processes accompanied by malfunctions in the functioning of the endocrine, vegetative-vascular and central nervous systems. It can be summed up that the depletion of the ovaries is a premature depletion of the follicular apparatus in the female body.

Causes of ovarian failure

To date, the definitive causes of the development of ovarian failure syndrome have not been established. But there are a number of factors that can have a direct impact on the process of disease formation.

1. A very important role in the development of ovarian failure syndrome is assigned to the genetic factor - in this case, the pathology occurs due to the mutation of certain genes. Also, this disease is hereditary and can be transmitted from mother to daughter. The family factor is also extremely important - if a girl has a late first menstruation, there is amenorrhea, or there is an early menopause in her mother or sister, then the risk of developing ovarian failure syndrome is very high.
2. Inflammatory and infectious diseases suffered by a woman can provoke ovarian exhaustion. Such inflammatory and infectious diseases include measles, rubella, toxoplasmosis, streptococcal infection, preeclampsia.
3. The causes of the syndrome may be associated with various pathologies of an autoimmune nature in the female body.
4. Various damage to ovarian tissue during fetal development - such reasons include the mother taking certain medications, smoking, taking alcohol or drugs, or the aggressive effects of radiation. These reasons lead to serious damage to the follicular apparatus in the future girl.
5. Other factors also have a very important impact on the state of the female reproductive system - regular stress and strong nervous shocks, malnutrition and the lack of vitamins and useful trace elements in the diet, a sharp decrease in the level of immunity.
6. The occurrence of the disease may be associated with surgical interventions on the ovaries, suffered by a woman.

Symptoms of ovarian failure

The first signs of pathology appear already at the age of 35-37. But in some cases, the symptoms of ovarian failure are noticeable even at an earlier age. A woman should be alerted by the following changes in the body:

• A woman's normal menstrual cycle is disrupted - at the same time, such failures can lead to both an increase and a decrease in the duration of the cycle. Persistent oligomenorrhea or amenorrhea develops, accompanied by the cessation of menstruation. Subsequently, this extinction of the functioning of the ovaries leads to complete infertility.
• Ovarian wasting syndrome is often accompanied by pain in the lower abdomen, discomfort, reminiscent of PMS. Pain can be both spasmodic and pulling, prolonged.
• The general well-being of a woman noticeably worsens - she feels causeless fatigue, weakness, body aches, constant drowsiness or insomnia, irritability and sudden mood swings, a rapid decrease in activity and ability to work.
• A characteristic sign of the extinction of the reproductive function in women is a sharp "tides" of heat to the face and upper body, characterized by increased sweating. The hot flashes are especially aggravated at night, after eating, and also after a nervous shock. Usually, such hot flashes occur absolutely suddenly - a woman blushes sharply, her heartbeat increases, she sweats a lot, it can darken before her eyes, which can cause dizziness or loss of consciousness.
• One of the signs of the fading of the female reproductive function is frequent dizziness, accompanied by constant, severe headaches.

Treatment of ovarian failure syndrome

It is worth noting that with all the progression of modern medicine, even timely treatment cannot lead to a complete restoration of the functioning of the reproductive organs. Treatment of this disease is aimed primarily at correcting the hormonal background in the female body, as well as improving the patient's well-being. To normalize the hormonal balance, hormonal drugs are used, which include estrogen and progesterone.

In the overwhelming majority of cases, women are recommended substitution treatment, which continues until the age of onset of a natural, natural menopause. One of the most common options for hormone replacement therapy is the regular use of specially selected oral contraceptives.

Ovarian wasting syndrome is treated by other methods. An excellent addition to traditional drug therapy will be various physiotherapy, which include regular exercise therapy, electrophoresis, acupuncture, electroanalgesia, Charcot's shower, swimming in the pool and other water procedures.

Treatment of ovarian failure syndrome necessarily includes proper, nutritious nutrition, containing all the vitamins, trace elements and other useful substances necessary for the female body. You can supplement the treatment with an additional intake of multivitamin complexes.

Additional treatment aimed at improving the general well-being of a woman may consist of massage and hydromassage sessions, radon or iodine-bromine baths, taking homeopathic sedative medicines, as well as maintaining a proper diet.

The diet of a woman who has been diagnosed with ovarian failure syndrome should include the maximum amount of food products that contain natural phytoestrogens. Such useful products include rice, peanuts and various nuts, wheat germ, rye and rye bread, ginger root, products containing soy. Be sure to include in your daily menu foods that include vitamin E and lecithin - in this case we are talking about cauliflower, legumes, peanuts, hazelnuts and walnuts. Nutrition should be of the highest quality and balanced, as well as regular. Strict diets, the direction of rapid, rapid weight loss, is strongly discouraged.

The most important step after the diagnosis of spontaneous primary ovarian failure is to inform the patient of the diagnosis in a sensitive and caring manner, to provide accurate data on the diagnosis of ovarian failure, to recommend what to do to avoid complications, and to suggest accessing appropriate resources for emotional support. The most common words that women use to describe their emotional state in the first hours after the announcement of the diagnosis are “devastated”, “shocked” and “confused”.

Young women with POF are usually not ready for a diagnosis and most are unhappy with how they were informed about their condition. In one survey conducted among women with early ovarian failure, respondents expressed a desire for doctors to spend more time with the patient and provide more information about the condition of ovarian failure and how to treat it.

Unfortunately, women diagnosed with ovarian failure syndrome cannot boast of "I have fully recovered", however, doctors should inform patients that 50-75 percent of women with early ovarian failure have episodes of spontaneous ovarian function recovery and that 5 to 10 percent of women can become pregnant after being diagnosed with it.

When first diagnosed with SIA, patients often feel an urgent need to act immediately to achieve pregnancy. At this point, it is useful to emphasize the importance of considering other aspects of SIA that may have adverse effects on their health in the future, such as emotional health, autoimmune endocrinopathies, and osteoporosis. Constant, obsessive thoughts about being diagnosed with ovarian failure and how to restore fertility often trigger the development of related depression and anxiety disorders.

There are many important issues to consider when treating women diagnosed with ovarian failure syndrome: how to recover emotionally; how to cope with symptoms of estrogen deficiency, sexual dysfunction; how to support fertility, bone health, cardiovascular health and avoid the risk of adrenal insufficiency (in women with autoimmune oophoritis).

After a lengthy discussion with the patient about the diagnosis of POI, its clinical implications, and her plans for pregnancy, the importance of estrogen therapy before the middle age of menopause is explained. Often, patients ask the question "can the diagnosis of ovarian failure be cured?". Unfortunately, the answer is no, but hormone replacement therapy can help reduce its symptoms to a minimum.

It is important to inform the woman that hormone replacement therapy is not a contraceptive and therefore additional contraception is needed if she does not want to become pregnant.

Unless there are absolute contraindications to estrogen therapy, women with POF should receive hormone replacement therapy to reduce the risk of osteoporosis, cardiovascular disease, and genitourinary atrophy, and to maintain sexual health and quality of life.

Hormone replacement therapy for young women with wasted ovary syndrome should mimic normal ovarian function as much as possible. Girls or young women with primary amenorrhea who have not developed their secondary sexual characteristics should initially be given very low doses of estrogen without progesterone to mimic the gradual maturation of the sex organs. For women with secondary amenorrhea, we give full estrogen replacement.

Some patients report fatigue, lack of energy, decreased libido or sexual function despite an adequate dose of estrogen. This is common in women who have had their ovaries removed. In this case, additional testosterone therapy should be considered.

Approximately 75 percent of women with spontaneous ovarian failure have potentially functional follicles remaining in the ovary.
And although some women were able to get pregnant without treatment, the percentage of such “lucky women” is very small. Naturally, women have a question: is their motherhood sentenced to depleted ovaries and what to do? Options include in vitro fertilization with a donor egg, embryo donation and adoption. Some women undergo ovulation induction with clomiphene and/or exogenous gonadotropins, but this method of dealing with infertility has not been proven effective.

Women often ask about the possibility of egg cryopreservation during impending or diagnosed ovarian failure syndrome. Oocyte banking for ovarian wasting may be indicated in women with a known genetic risk for POI prior to ovarian failure, but is unlikely to be effective once the diagnosis is made.

If you are already diagnosed with ovarian failure syndrome, what should you do then? In vitro fertilization of donor oocytes is the most acceptable choice for women with primary and secondary premature ovarian failure. Choosing this option, women can be calm in the absence of the urgency of infertility treatment and the implementation of reproductive plans "in this very second." It is the age of the oocyte donor, not the age of the recipient, that determines the likelihood of success.

Menopausal symptoms and the risk of cardiovascular disease can be managed with lifestyle modifications. These include stopping smoking, maintaining a healthy weight, drinking moderately, and exercising regularly. A calcium-rich diet for ovarian depletion will reduce the risk of osteoporosis.

Examination for wasted ovary syndrome

Suspicion of exhausted ovary syndrome arises on the basis of the patient's complaints about menstrual irregularities, general weakness, and excessive sweating.

Diagnosis of this disease includes a number of studies:

• pneumopelviography or ultrasound;
• laparoscopy;
• hormonal studies;
• biopsy.

When assessing the objective status in women with the syndrome, no significant external changes are observed, the mammary glands are of normal size and developed.

In a patient during a vaginal examination, a significant decrease in the size of the uterus and ovaries can be detected, while the vaginal mucosa is dry. A functional test determines the low content of cervical mucus, as well as the presence of basal and parabasal epithelial cells in it.

Ultrasound picture

In the process of transvaginal ultrasound scanning, the doctor gets a clear picture of the size of the female internal genital organs and their structure. In the presence of the disease, a decrease in the uterus in thickness, width and length is observed. The structure of the uterus remains homogeneous. The ovaries are significantly reduced in size, have a homogeneous structure, the follicles in them are not visualized.

Laparoscopy with biopsy

Based on the data of laparoscopy, it is revealed that the ovaries in patients are reduced in size, have a dense structure, yellow color, sometimes they are wrinkled. The cortical layer in some cases is replaced by connective tissue, while there is a complete absence of follicles. Biopsy analysis shows complete atrophy of ovarian tissue.

skull x-ray

An X-ray of the skull is necessary to exclude changes in the Turkish saddle. After studying the encephalogram of the brain, carried out to determine its electrical activity, in most patients, a reduction in the alpha rhythm is detected.

Hormonal studies

Hormonal research involves a number of tests:

• progesterone;
• estrogenic;
• clomiphene;
• dexamethasone.

As a result of the study, it is found that the patient has a significantly reduced level of estrogens, even in comparison with the early follicular phase. At the same time, the background level of follicle-stimulating hormone is much higher, in contrast to healthy patients, and the ovular level is 3 times higher than normal. The level of luteinizing hormone is the same as during the period of ovulation and is 4 times higher than the level of tonal secretion of LH. It is noticed that in patients with the syndrome, the amount of prolactin decreases by 2 times, if we focus on its normal level.

progesterone test

When conducting a progesterone test, menstrual-like bleeding does not occur.

The result of the test in most cases is negative, which allows us to conclude that such stimulation is insufficient for the mucosal layer of the uterine mucosa.

Estrogen-gestagenic test

When taking an estrogen-gestagen sample, patients show a significant improvement in their physical condition, and the occurrence of menstrual bleeding on the 3rd day.

Based on the conducted hormonal studies, it can be concluded that the normal functioning of the uterine mucosa is preserved in patients with a diagnosis of wasted ovary syndrome, while the work and sensitivity of the ovaries are impaired.

Estrogen test

An estrogen test allows you to find out the cause of a violation of the secretion of gonadotropic hormones. Communication of sex steroids and hypothalamic-pituitary structures is not broken. This conclusion can be drawn from the fact that with the regular introduction of estrogen into the body, the electrical activity of the brain is restored.

The exception is patients with a lack of receptor sensitivity to estrogen and gonadotropic hormones. In such cases, depletion of the ovaries is detected, a violation of their functionality, which has developed as a result of an increase in neurohormonal activity.

Clomiphene test

Clomiphene test is done within 5 days, at a dosage of 100 ml. After its introduction, there are no significant changes in the woman's body, the functioning of the ovaries is not observed. With the introduction of chorionic gonadotropin, activation of ovarian function was also not noticed.

Drawing a conclusion from the studies of G. P. Korneva, in patients with primary ovarian dysfunction, the level of dopamine is reduced, and serotonin is increased.

The diagnosis of wasted ovary syndrome is confirmed if the patient has the following indicators:



• infertility during reproductive age;
• regular sharp sensation of heat;
• increased sweating;
• high levels of gonadotropins;
• ovarian dysfunction;
• reduced uterus and ovaries;
• follicles are not observed in the ovaries;
• lowering the hormonal background;
• lack of ovarian response to samples with clomiphene;
• negative hCG and MCHG.

Most women experience an improvement in their general condition after hormone replacement therapy.

Differential Diagnosis

Wasted ovary syndrome must be differentiated from the following diseases:

• pituitary tumor;
• resistant ovary syndrome;
• organic lesions;
• genital tuberculosis.

In the presence of all these symptoms of wasted ovary syndrome, a differential examination is necessary to exclude a pituitary tumor. For this purpose, the patient is prescribed the following types of diagnostics:

• CT scan of the brain;
• examination of the fundus by an ophthalmologist;
• craniography.

A distinctive feature of hypogonadotropic hypogonadism from lean bowel syndrome is the presence of follicles in the ovaries. During laparoscopy, a decrease in ovarian function and a decrease in their size are detected in women.

WOS also needs to be differentiated from refractory or resistant ovarian syndromes, as many of the symptoms overlap in these diseases. For this, morphological examinations of the tissue are carried out.

Often a woman is also assigned an additional consultation of an endocrinologist, mammologist, psychotherapist and urologist.

Hirudotherapy

Leech therapy is an effective and popular alternative treatment for many gynecological conditions that has been used by healers for centuries.

Hirudotherapy - treatment with medicinal leeches and products derived from them. Hirudotherapy as a method of treatment has been known for a very long time, from about 200 BC. This method of therapy was most widely used in medieval and early modern medicine. Currently, leeches are used in gynecology, urology, dermatology, rheumatology and surgery.

Medical leeches are bred on special hirudo farms under sterile conditions, and then sold in pharmacies.
They are used only once, after which they are disposed of, so the risk of infection is completely eliminated. Medicinal leeches have three rows of jaws with tiny teeth. During the session, live leeches attach themselves to the target area and suck blood. They secrete proteins and peptides that improve the rheological properties of the blood. Leeches leave small, Y-shaped wounds that heal without leaving scars.

Hirudotherapy for ovarian depletion is indicated primarily because of its complex therapeutic effect on the human body. Leeches in ovarian depletion have a general immunostimulating and thrombolytic effect, improve blood circulation and tissue oxygenation, promote resorption of inflammatory infiltrates, adhesions, scarring, eliminate stagnation in the pelvic organs and improve lymph flow, normalize hormone levels.

The procedure for applying leeches to a woman's body does not cause discomfort and passes quickly. In one session, from two to seven leeches are usually used. Leeches are placed not only vaginally when the ovaries are depleted, but also in different parts of the woman's body: in the sacrum, lower back, liver, near the anus. As a rule, the therapeutic effect occurs after one or two courses of hirudotherapy with ovarian exhaustion.

Treatment should only be carried out by an experienced hirudotherapist. Even considering all the positive aspects, the use of leeches for the treatment of ovarian failure syndrome has a number of contraindications. Thus, you cannot use them for women who are marked by the presence of the following pathological conditions:

• severe hypotension;
• low hemoglobin level;
• blood clotting disorder;
• cancer diseases.

Acupuncture

Clinical studies on the effectiveness of acupuncture in early ovarian failure have found that this method of therapy is an effective tool for correcting the symptoms of this disease.

In girls diagnosed with ovarian failure, acupuncture used directly over the adnexal area stimulates the normal functioning of the ovaries and increases blood flow to them. Many studies show that acupuncture and Chinese herbs lower FSH levels while increasing estrogen levels. For patients with early ovarian failure, acupuncture has been shown to improve the chances of conception.

Wasted ovary syndrome is premature ovarian failure caused by a violation of the central regulation of reproductive function in women. Patients under 40 years of age have complaints of:

• cessation of menstruation;
• inability to get pregnant;
• hot flashes;
• sharp mood swings;
• sweating.

In fact, they experience the symptoms of menopause, but at a young age.

The traditional treatment for wasted ovary syndrome depends on the causes of the condition, but is usually associated with the appointment of hormone replacement therapy (combined estrogen-progestin drugs). Despite the high efficiency and elimination of unwanted symptoms, long-term treatment with high doses of hormones can lead to neoplasms of target organs (mammary glands, adrenal glands). Therefore, some doctors resort to homeopathic remedies for this problem.

Folliculinum and emaciated ovary syndrome

Folliculinum is a homeopathic remedy representing the natural ovarian follicular hormone. The medicinal effect of the drug is similar to the action of estrogens: together with gestagens, the drug regulates menstrual function, eliminates the symptoms of hormonal imbalance.

Folliculinum and emaciated ovary syndrome are the subject of intense study.
It has been proven that long-term therapy with the drug has a positive effect on the endometrium: when taken together with progesterone preparations, the main monthly hormonal fluctuations are imitated in a woman's body. Thus, the patient will be able to endure and give birth to a healthy child after IVF with a donor egg.

Folliculinum is an oily solution for intramuscular injection in ampoules of 5000 or 10000 IU (1 ml). The dosage of the drug and the course of treatment should be selected by the doctor, depending on the initial level of hormones and the age of the patient.

Homeopathic medicine is contraindicated in:

• oncological diseases;
• mastopathy and other benign formations of the mammary glands; endometritis;
• tendency to uterine bleeding;
• phase of menopause, accompanied by an increased release of female sex hormones.

Treatment of wan ovary syndrome with Folliculinum should be carried out under the supervision of an experienced physician. The criteria for the success of therapy are an increase in the level of estrogen in the blood, an improvement in mood, and the normalization of menstrual function.

Hormones

One of the main goals of treating primary ovarian failure is to replace the estrogen that the ovaries have stopped producing. This is important because the vanished hormones in ovarian depletion are vital to certain bodily processes. Bones, for example, need estrogen stimulation to stay strong and resistant to fracture.

The main form of estrogen normally produced by the ovaries is called estradiol. As a hormone replacement therapy, women can get it in the form of tablets, a skin patch, or a vaginal ring. The estradiol patch and vaginal ring may have a number of advantages over the pill:



• They contain the same hormone that the ovaries produce;
• Estrogen does not have to pass through the liver to enter the bloodstream
• Estrogen enters the body gradually, and not immediately in a peak dose.

Despite the benefits that the patches and ring have, other forms of estrogens are also effective.

Ovariamin

In addition to banal hormone replacement therapy, medicine can now offer a number of alternative drugs to restore and maintain ovarian function in the initial stages of ovarian failure syndrome.

One such drug that has shown good results in clinical trials in women diagnosed with ovarian failure is ovariamin. The effectiveness of the drug was evaluated by doctors based on a decrease in complaints about menopausal symptoms (hot flashes, mood lability, dyspareunia, etc.) on the part of women, changes in laboratory data on FSH and estradiol levels, and data from instrumental research methods.

Ovariamin is a complex drug obtained by processing the tissues of the ovary of cattle and extracting active components from it. The main active ingredient of the drug are cytamines. The drug is available in the form of tablets for oral administration in dosages of 155 mg and 355 mg.




The nuances of the mechanism of action of Ovariamin on the woman's body in general and the function of the ovaries in particular are still not fully understood. However, it is known for certain that the components of the dietary supplement help to reduce the concentration of follicle-stimulating hormone, due to the estrogen-like effect on the female body. A decrease in the content of adrenocorticotropic and thyroid-stimulating hormones in the blood was also noted, which further proves the suppressive effect of ovariamin on the adenohypophysis. Laboratory indicators and ultrasound data confirm an increase in the volume of the appendages and an improvement in their hormone-producing function.

58% of women who took ovariamin for emaciated ovary syndrome left reviews indicating that this drug contributed to the establishment of their monthly cycle and a decrease in the psychosomatic and psychoemotional manifestations of the disease.

Patients who took ovariamin for ovarian depletion write on the forum about the positive effects of this dietary supplement. They note a decrease and even complete disappearance of such symptoms of early ovarian failure as tearfulness, irritability, sleep disturbances, dryness and itching in the vagina and stress urinary incontinence. More than half of women confirm an improvement in the quality of sexual function, restoration of libido.

Currently, Ovariamin is widely used in patients with various forms of ovarian dysfunction in preparation for the in vitro fertilization protocol, due to the fact that the active substances of the drug help restore the gamete-forming function of the woman's sex glands.




Based on all of the above, we can draw logical conclusions that taking Ovariamin in courses during the year in women with premature ovarian failure syndrome helps to establish metabolism in the woman's gonadal tissue, normalize the mechanisms of growth and development of follicles and balance the processes of nervous regulation of the reproductive system. Thus, to such a question as, to drink ovariamin with ovarian exhaustion or not? Our answer is definitely to drink!

Let's take a look at how to take ovariamin for ovarian failure based on the feedback of those who have helped ovariamin get pregnant with ovarian failure.

Since the drug is a dietary supplement, it is recommended to individually approach the prescription of the drug ovariamin for ovarian depletion, the regimen may vary depending on the severity of the symptoms of the disease and the patient's reproductive plans. Instructions for use of the drug suggests the following scheme: take 1-2 tablets 3-4 times a day 15-20 minutes before meals with plenty of water. The maximum daily dose of the drug is 1400 mg. In order to achieve the maximum effect of the drug, it should be taken in courses of 14-30 days 3-4 times a year.

Ovarium

Another popular drug for the treatment of ovarian dysfunction on the market is Ovarium compositum. This drug is a homeopathic medicine and has established itself as an effective medicine in the complex therapy of early ovarian failure syndrome.

Ovarium compositum is a multicomponent drug that includes extracts from the genital organs of farm animals, substances of plant and mineral origin, as well as biocatalysts.

Due to its complex structure and multicomponent composition, Ovarium compositum immediately has a number of effects on a woman's body, namely:

• normalizes the menstrual cycle;
• accelerates reparative processes in the tissues of the female reproductive system;
• improves blood circulation and lymph flow in the pelvic organs, increasing tissue oxygenation and activating their hidden reserves;
• suppresses tissue alteration during the inflammatory process;
• stabilizes the nervous system.

Considering the complexity and wide range of action, the use of Ovarium in ovarian failure is quite common. This is justified by the fact that most doctors, prescribing Ovarium compositum, write reviews that with ovarian depletion, this drug as part of complex therapy showed very good results. The state of health of almost all women improved significantly, there was a regression of menopausal symptoms, and in patients in the initial stages of the disease, in some cases, it was possible to restore a regular menstrual cycle.

The question is natural, how to take ovarium compositum with ovarian exhaustion? The treatment regimen and duration of use in this case will depend on whether the woman has menstruation or not.

In the event that a woman is still menstruating, the Ovarium injection schedule for ovarian exhaustion adjusts to her menstrual cycle: the first injection is administered the day after the end of menstruation at the time of day when it began. The next four injections are administered at the same time of day at intervals equal to the duration of the last menstruation.

If a woman does not menstruate, then the drug is administered at the same time with a break of 2 days, a total of 5 injections. The course is repeated in a month, only 3-6 courses or when menopausal symptoms return.

Femoston

The most common drug for hormone replacement therapy in our market is Femoston.

Femoston is a two-component drug, which includes estrogen - estradiol hemihydrate and progestin - dydrogesterone. Due to the presence of the progestin component, Femoston is ideal for young women with a preserved uterus, since the progestogen has a protective effect on the endometrium of the uterus and reduces the risk of developing hyperplastic processes.

On the shelves of pharmacies there are several varieties of the drug Femoston, each of which differs from each other in the dose of the estrogen component. When choosing femoston for ovarian exhaustion as HRT, a number of points should be considered. While in physiological menopause, doctors strive to find the minimum effective dose of estrogens,
in order to minimize the manifestations of side effects, the same dose in women with depleted ovaries will be insufficient, and we will not get the desired results, namely, a decrease in the manifestations of menopausal syndrome, a decrease in the risk of osteoporosis and cardiovascular diseases. In women at the age of physiological menopause, the body's need for estrogen decreases due to the natural aging of the body and the shutdown of a number of its functions. For young women under the age of 45-50 years, the need for estrogen is at a high level, and the hypoestrogenic state due to the failure of the glandular tissue of the ovary is "emergency" and must be fully replenished.

Based on the foregoing, the logical conclusion would be the use of the drug Femoston 2/10 in ovarian failure syndrome, since it contains a sufficient content of estradiol in its composition, which fully compensates for the dose of the hormone normally produced in young women before the onset of physiological menopause.

Ovarian wasting and taking femoston with it have shown good results in a number of clinical trials. It has been reliably established that taking the drug contributes to the regression of symptoms such as hot flashes, dryness and discomfort in the vagina, dyspareunia, insomnia, mood lability. Moreover, in women diagnosed with ovarian failure syndrome and taking femoston, normalization of the lipid composition of the blood was noted, which in turn contributed to the prevention of the development of cardiovascular diseases.

claira

In the process of choosing the most successful method of therapy for the syndrome of early ovarian failure, it would be a big mistake to forget about the possibility of spontaneous remissions and unpredictable episodes of the restoration of a woman's reproductive function. Recall that HRT, which is most often prescribed to patients with SIA, does not have a contraceptive effect.

For women who have not yet realized their reproductive plans, such episodic remissions can be a real blessing. At the same time, for women who have experienced the joys of motherhood, an unplanned pregnancy can become a serious problem. To avoid such difficult situations, it is worth recommending that patients take oral contraceptives instead of standard HRT. The most optimal drug from this vast category of drugs, which is most suitable for women diagnosed with ovarian failure syndrome, is Qlaira. The choice of Qlaira for ovarian failure syndrome is due to the fact that only natural estrogen, estradiol valerate, is included in its composition. Taking this COC provides a reliable contraceptive effect, and also eliminates the hypoestrogenic state.

Other drugs

Commitment to sound wholesome nutrition is an important strategy we have in our arsenal to combat the symptoms and long-term health risks associated with early ovarian failure. In an ideal world, we would get all the nutrients we need from natural sources, but in cases where this is not possible, for women diagnosed with ovarian failure syndrome, vitamin and mineral supplements are a vital alternative. Taking nutritional supplements does not mean that you should not eat healthy. But it can help you more effectively relieve the symptoms of premature menopause and fight your increased risk of osteoporosis and heart disease—whether you're taking HRT or not.

Below is a brief list of vitamins that can help you with ovarian failure.

1. Vitamin A helps fight vaginal dryness and an increased risk of urinary tract infections caused by low estrogen levels.
2. B vitamins support liver function in women on HRT; prevent dryness of the vaginal mucosa; increase the body's resistance to infection; help maintain the estrogen-producing function of the adrenal glands.
3. Vitamin D is essential for maintaining bone strength, as it helps the body absorb calcium and phosphorus, the building blocks of your bones.
4. Vitamin C helps fight infections, has anti-stress properties, acts as an antioxidant, helps maintain adequate levels of collagen, thereby slowing down the aging process.
5. Sufficient intake of vitamin E prevents atrophy of the vaginal mucosa, especially when applied topically. In addition, vitamin E is an antioxidant and is effective in preventing cancer and heart disease.
6. Calcium is needed to fight osteoporosis and also helps lower blood pressure and triglyceride levels.
7. Iodine is very important for maintaining thyroid health, as well as in the prevention of breast disease.
8. Lecithin in ovarian failure syndrome may improve cardiovascular health and cognitive performance.
9. Choline and inositol in ovarian depletion help to reduce the manifestations of emotional spectrum disorders.

Folk remedies

Wasted ovary syndrome is a condition in which a woman's fertility is significantly reduced. In this case, there is a significant decrease, or complete cessation, of ovarian function. A similar pathology, which is diagnosed in women whose age does not exceed 45 years, is often called early menopause. This syndrome is accompanied by symptoms such as lack of ovulation, amenorrhea, vegetative-vascular disorders. However, the main problem that early menopause leads to is the inability to become pregnant and give birth to healthy offspring. Therefore, for women who have been diagnosed with lean ovary syndrome, treatment is the only correct solution.

To date, there are several methods that help to cope with early menopause. First of all, this is treatment with the help of medications: hormonal, sedative and others.
Also, if the patient has depleted ovaries, treatment involves various physiotherapy procedures: massage, mud therapy, electrophoresis. Phytotherapy has a positive effect on women's health in general and on the problem of early menopause in particular. With a diagnosis such as emaciated ovary syndrome, herbal treatment can help not only get rid of unpleasant symptoms, but also solve the problem at the root.

Wasted Ovarian Syndrome: Treatment with Traditional Medicine

Since one of the main features of early menopause is the deficiency of the so-called female hormones, the main emphasis in treatment is on hormone replacement therapy. In the presence of depleted ovaries, treatment of such a plan helps to get rid of urogenital disorders and prevent metabolic disorders.

The optimal treatment regimen necessarily contains the following types of hormonal drugs:

• natural estrogens (estradiol valerate, 17-estradiol, micronized estradiol);
• conjugated estrogens (estrone piperazine, estrone sulfate);
• gestagens (natural progesterone and synthetic gestagens).

The choice of this or that drug depends solely on the characteristics of the body and the age of the woman and is determined by the doctors.

As a rule, this method of treatment helps to get rid of hot flashes in a few weeks, improve the psycho-emotional state, and regulate the menstrual cycle. In most cases, pregnancy is possible.

Depleted ovaries: treatment with physiotherapy

With emaciated ovary syndrome, treatment with hormonal drugs is not always possible. In this case, the use of physiotherapy procedures is recommended. A good effect gives a massage of the collar zone, as well as regular acupuncture sessions. Doctors recommend paying attention to therapeutic exercises: with its help, blood circulation in the small pelvis improves and the work of "female" organs improves. Even better results are shown by the use of electrophoresis and electroanalgesia procedures.

With such a diagnosis as depleted ovaries, it is recommended to supplement the treatment with a visit to sanatoriums with a special gynecological bias. Here, a woman will be given the opportunity to regularly undergo balneological procedures, mud therapy, treatment with leeches. All this, combined with the methods of traditional medicine, improves the prognosis for gonadal wasting syndrome.

Wasted Ovarian Syndrome: Herbal Treatments

Phytotherapy is a popular method of correcting the condition of a sick woman diagnosed with depleted ovaries. Treatment in this case is carried out with the help of medicinal herbs under the mandatory supervision of a competent physician.
A decoction of blackberries or viburnum fruits has a good effect. It normalizes the general condition of a woman, returns her lost vitality. With excessive nervousness, which often accompanies this pathology, it is recommended to regularly drink lemon balm tea. And fresh red beet juice, pre-mixed with natural honey, not only helps replenish the body with vitamins, but is also an excellent remedy for hot flashes.

With emaciated ovary syndrome, herbal treatment is usually combined with conventional medicine. In addition, in such conditions, the intake of certain vitamins is recommended. In particular, we are talking about vitamin E, which is very important for women's health and, with regular use, can eliminate many pathologies. Doctors also advise additional intake of lecithin - a substance that is directly involved in the renewal of damaged body cells and helps restore ovarian function.

Women with emaciated ovary syndrome are advised to supplement herbal treatment with proper nutrition. It is very important that the patient's diet is rich in natural oils, fatty fish, vegetables and fruits.

Video: How to restore ovarian depletion

Ovarian wasting syndrome (OIS) is a pathological symptom complex, including secondary amenorrhea, infertility, vegetative-vascular disorders in women younger than 38 years old with normal menstrual and reproductive function in the past. The frequency of SIA in the population is 1.5%, and in the structure of secondary amenorrhea - up to 10%.

What triggers / Causes of Ovarian Waste Syndrome:

The leading cause is considered to be chromosomal abnormalities and autoimmune disorders, expressed in small congenital ovaries with a deficiency of the follicular apparatus, pre- and post-pubertal destruction of germ cells, primary damage to the central nervous system and the hypothalamic region. SIA - generalized autoimmune diathesis.

In the occurrence of SIA, many factors play a role, in the ante and postnatal period leading to damage and replacement of the gonads by connective tissue. Probably, against the background of an inferior genome, any exogenous effects (radiation, various drugs, starvation, hypo- and beriberi, influenza and rubella virus) can contribute to the development of SIA. In most patients, unfavorable factors acted during fetal development (toxicosis of pregnant women, extragenital pathology in the mother). The onset of the disease is often associated with severe stressful situations, infectious diseases.

SIA is hereditary: in 46% of patients, relatives noted menstrual dysfunction - oligomenorrhea, early menopause.

Symptoms of Ovarian Waste Syndrome:

Patients with SIA have a correct physique, satisfactory nutrition, usually without obesity. The onset of the disease is considered to be amenorrhea or oligomenorrhea, followed by persistent amenorrhea. Subsequently, vegetovascular manifestations typical of postmenopause appear - “hot flashes”, sweating, weakness, headaches with disability. Against the background of amenorrhea, progressive atrophic processes develop in the mammary glands and genitals.

Diagnosis of Ovarian Waste Syndrome:

Diagnosis is based on the history and clinical picture. Menarche is timely, menstrual and reproductive functions are not disturbed for 10-20 years.

The function of the ovaries is characterized by a pronounced persistent hypoestrogenism: a negative symptom of the "pupil", monophasic basal temperature, low CPI - 0-10%. Hormonal studies also indicate a sharp decrease in ovarian function: the level of prostaglandin E2 practically corresponds to the content of this hormone in young women after oophorectomy. The level of gonadotropic hormones - FSH and LH is sharply increased: FSH is 3 times the ovulatory peak and 15 times the basal level in healthy women of the same age; the level of LH approaches the ovulatory peak and is 4 times higher than the basal level of LH in healthy women. The level of prolactin is 2 times lower than in healthy women.

Gynecological and additional research methods reveal a decrease in the uterus and ovaries. With ultrasound, in addition to reducing the uterus, there is a sharp thinning of the uterine mucosa when measuring the M-echo. With laparoscopy, small, “wrinkled” yellowish ovaries are also noted, the corpus luteum is absent, the follicles do not shine through. A valuable diagnostic sign is the absence of the follicular apparatus, confirmed by histological examination of ovarian biopsy specimens.

For the purpose of in-depth study of the functional state of the ovaries, hormonal tests are used. The introduction of progesterone does not lead to a menstrual-like reaction, possibly due to irreversible organic changes in the endometrium.

A test with estrogens and progestogens (respectively, a conditional menstrual cycle) causes a menstrual-like reaction 3-5 days after the completion of the test and a significant improvement in the general condition.

In the first years of the disease, the functional state of the hypothalamic-pituitary system is not disturbed and there is a natural response to stimulation of RGHL and the introduction of estrogen. The introduction of estrogens reduces the secretion of gonadotropic hormones, which indicates the safety of the feedback mechanism. The test with RHLH emphasizes the preservation of the reserve capacity of the hypothalamic-pituitary system in patients with SIA. The initially high level of FSH and LH rises in response to the introduction of RHLH, but, despite a significant increase in the level of gonadotropins, "hot flashes" do not become more frequent.

There are usually no signs of organic damage to the central nervous system.

Treatment for Ovarian Waste Syndrome:

Treatment of patients with SIA is aimed at the prevention and treatment of estrogen deficiency conditions.

Patients can have a child only through assisted reproduction - IVF with a donor egg. Stimulation of the depleted ovarian follicular apparatus is inappropriate and not indifferent to the woman's health.

Patients with SIA are shown hormone replacement therapy until the age of natural menopause to prevent urogenital disorders and late metabolic disorders against the background of a chronic estrogen deficiency state. For this purpose, natural estrogens are used: 17-estradiol, estradiol valerate, micronized estradiol; conjugated estrogens: estrone sulfate, piperazine estrone; estriol and its derivative - estriol succinate. Gestagens must be added to them.

To achieve full proliferation, a total dose of estradiol valerate 80 mg, conjugated estrogens 60 mg, estriol 120-150 mg is required. These doses should be taken within 14 days.

Be sure to cyclically add progestogens for 10-12 days. For this purpose, progesterone (natural micronized - utrozhestan) and synthetic progestogens are used. Against the background of cyclic hormone therapy, a menstrual-like reaction appears and the general condition improves: “hot flashes” disappear, and working capacity increases. Treatment is also the prevention of osteoporosis and premature aging.

With parenteral administration of estrogens, they are administered intramuscularly, transdermally (patch), subcutaneous implants, ointments are used. For the treatment of urogenital disorders, vaginal administration of estrogens in the form of ointments and suppositories is possible. Gestagens can also be administered orally or parenterally (intramuscularly, transdermally, vaginally).

For hormone replacement therapy, you can also use femoston, klimen, divina, kliogest, etc.

Which doctors should be consulted if you have Ovarian Waste Syndrome:

Gynecologist

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Other diseases from the group Diseases of the genitourinary system:

Ovarian exhaustion syndrome refers to gynecological diseases that interfere with normal. The disease develops in women of reproductive age. Let us consider in more detail such a pathology as ovarian exhaustion, the treatment of its manifestations, we will highlight the main symptoms and causes.

What is "ovarian exhaustion"?

The term "ovarian exhaustion" in gynecology is used to denote a complex of symptoms, which is characterized by an increase in the level of gonadotropin, the absence of menstruation, and a decrease in concentration. Pathology occurs in women of reproductive age who previously had normal menstruation. The disease has other names - premature menopause, premature menopause, ovarian failure. The incidence of the disease among women of reproductive age is 1.6%. Early ovarian failure can develop at 20-25 years of age.

Ovarian exhaustion - causes

Premature ovarian failure, the causes of which are often difficult to establish, is characterized by impaired reproductive function. When analyzing the possible causes of pathology, doctors in the first place put forward a hormonal imbalance, which becomes a trigger for the development of pathologies of the reproductive system. Among other causes of the disease, it is worth noting:

• heredity, chromosomal abnormalities transmitted from mother to daughter (ovarian underdevelopment);
• autoimmune reactions, accompanied by the formation in the body of antibodies to ovarian tissue;
• disruption of the centers of the brain that control the activity of the sex glands;
• infectious diseases accompanied by damage to the ovarian tissue - rubella;
• malnutrition, vitamin deficiency;
• constant stressful situations;
• teratogenic effects on the body at the stage of intrauterine development (use of pregnant women, bad habits, exposure to ionizing radiation).

Ovarian exhaustion - symptoms

Signs of ovarian exhaustion have bright features, so a woman can identify the pathology on her own. The first thing the patient notes is sudden amenorrhea, which occurs at 36-38 years and earlier. Often she is preceded by scanty, not abundant menstrual flow, which eventually stops. It should be noted that amenorrhea can take on a cyclical nature - ovulation occurs in separate cycles, so the possibility of pregnancy remains.

In addition to cycle disorders, ovarian wasting syndrome is also accompanied by vegetative-vascular manifestations. They are typical for women of menopausal age, when there is a decline in reproductive function. The development of the following symptoms in women of reproductive age indicates SIA:

• hot flashes;
• increased sweating;
• constant weakness;
• irritability;
• sleep disturbance;
• headache;
• dizziness.

Ovarian exhaustion syndrome is accompanied by a decrease in the concentration of estrogens. This causes gynecological disorders. Ovarian exhaustion syndrome, the symptoms of which are named above, provokes:

• atrophic changes in the mammary glands;
• atrophic;
• decrease in bone density;
• disorders of the urogenital system - frequent urination, urinary incontinence;
• decrease in the size of the glands, depletion of the uterine mucosa (determined by ultrasound).

Ovarian Waste Syndrome - Treatment

Before treating SIA, doctors conduct a comprehensive examination. It involves a pelvic ultrasound, a blood test for hormones. After the diagnosis is made, therapy is prescribed. It is aimed at correcting vegetative-vascular disorders, improving overall well-being, and excluding cardiovascular disorders. The best results of treatment are observed with the use of hormonal drugs, hormone replacement therapy. The drugs are selected by the doctor individually, the dosage, frequency and duration of administration are indicated.

Can ovarian failure be cured?

Treatment of SIA is aimed at improving general well-being, excluding additional pathologies. It is impossible to completely cure the disease. The use of drugs allows you to support the work of the sex glands. Hormone replacement therapy is carried out until the onset of natural menopause. This reduces the risk of developing urogenital diseases, which often develop against the background of a lack of estrogen in the female body.

Ovarian exhaustion - drugs

With the development of ovarian failure syndrome in young women, doctors prescribe combinations of ethinyl estradiol with desogestrel, gestodene, or norgestimate to treat the disorder. Such hormonal compounds completely mimic the normal functioning of the gonads. For older women, doctors recommend combinations of estradiol with dydrogesterone. Preparations with these hormones are taken orally, administered intramuscularly. With SIA, hormone treatment is carried out according to the prescribed scheme. Estrogens are used more often than 14 days:

• 17-estradiol;
• micronized estradiol;
• estriol succinate;
• estrone sulfate.

Often a combination is used. So, Ovarium Compositum with ovarian depletion helps to reduce the manifestations of the disorder, and improves the patient's well-being. With the help of the drug, it is often possible to completely restore the functioning of the sex glands. Because of this, the drug is used if a woman wants to become pregnant, to restore ovulation, the cycle. Other combination treatments include:

• Divina;
• Klymen;
• Femoston.

Ovarian exhaustion - treatment with folk remedies

Premature ovarian failure syndrome can be corrected by taking folk remedies. Their use helps to reduce symptoms. Eating a large amount of vitamin E, facilitates the course of the disease. It contains:

• peanut;
• hazelnut;
• Walnut;
• germinated wheat.

An effective recipe for SIA is a collection of medicinal herbs.

Ovarian exhaustion and pregnancy

Premature exhaustion of the ovaries becomes an obstacle in the process of planning a pregnancy. When spontaneous remission occurs during the disease - the menstrual cycle resumes on its own, pregnancy becomes possible. In most cases, a woman needs medical treatment. Rare ovulation, which makes it possible to conceive a child, occurs in 5-10% of patients.

Can you get pregnant with ovarian failure?

Even when diagnosed with ovarian failure syndrome, pregnancy is possible, but often only after undergoing a course of special therapy. Independent attempts to get pregnant do not bring results. The absence of the ovulatory process prevents the onset of pregnancy. Often the only way for a woman to become a mother is in vitro fertilization.

IVF for ovarian failure

Early ovarian failure syndrome often becomes an indication for IVF. At the same time, taking an egg from a woman for further fertilization is not always possible. Because of this, it becomes necessary to use a donor germ cell. Fertilization is carried out with the sperm of the partner, the patient's spouse. After fertilization, the egg is implanted into the uterine cavity. With successful implantation, the process of pregnancy begins.