Ovarian failure

from Wikipedia, the free encyclopedia
Classification according to ICD-10
E28.3 Primary ovarian failure
E23.0 Hypopituitarism
E89.4 Ovarian failure after medical measures
ICD-10 online (WHO version 2019)

When ovarian failure (Engl. Ovarian insufficiency or ovarian failure ), the ovaries of the woman who called in the jargon ovaries, for different reasons inadequately or no longer fulfill their missions. The tasks of the ovaries consist of the maturation of egg cells for reproduction and the production of female sex hormones such as progesterone and estrogen , for reproduction, for regulating the menstrual cycle and for influencing numerous other processes in the female body. The function and production of the ovaries are normally monitored and fine-tuned by the hypothalamus and the pituitary gland using gonadoliberin (GnRH) and the two gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). An error at one of these three levels, that is, the hypothalamus level, the pituitary gland level or the ovarian level, leads to a malfunction of the ovaries, an ovarian failure. Depending on the level of the disorder, a distinction is made between different forms of ovarian failure, which are based on different causes. The main symptom of ovarian failure is an irregularity in the menstrual cycle to the point of non- menstruation with a decrease in fertility of the affected woman to the point of infertility . Depending on the form and cause of the ovarian insufficiency, further complaints can arise. To diagnose ovarian failure, conversation, physical examination, blood tests, imaging tests and / or an analysis of the genetic information are used. Treatment for ovarian failure is determined by its form and cause. In particular, the missing female sex hormones must be replaced.

to form

In ovarian insufficiency, an error has occurred in the control cycle between the hypothalamus, the pituitary gland and the ovaries, so that the ovaries can only insufficiently perform their tasks, which in the women concerned usually manifests itself in the form of an irregular menstrual cycle. Depending on where the error occurred, a distinction is made between primary and secondary ovarian failure. Secondary ovarian failure can be further divided into hypothalamic ovarian failure, pituitary ovarian failure, and hyperandrogenemic ovarian failure.

The primary ovarian failure is due to a change in the ovaries themselves. It may be a malformation act or a malfunction of the ovaries, which are innate or acquired in the course of life. Primary ovarian insufficiency is also referred to as hypergonadotropic hypogonadism . Because in primary ovarian insufficiency the ovaries, which are the female gonads , are sufficiently driven by the hypothalamus and the pituitary gland with the help of an increased amount of the releasing hormone GnRH and the gonadotropins LH and FSH for hormone production and egg maturation, therefore hypergonadotropic, but they can not performing their duties because of a change, hence hypogonadism. Normally, there is a supply of egg cells in the ovaries of newborn women, which is sufficient for one month of ovulation from puberty to around the age of 50. Subsequently, there are no more eggs in the ovaries to mature, and the production of hormones in the ovaries is significantly reduced. With this, the woman changes from the fertile to the sterile phase. This transition is known as climacteric or menopause. If this transition occurs before the age of 40, i.e. if the ovaries have been removed or if the eggs in the ovaries are used up prematurely, or if the ovaries are not able to allow egg cells to mature regularly, primary ovarian insufficiency occurs, whereby there is talk of a climacteric praecox or premature menopause . Other possible terms for this early transition are premature ovarian failure or premature ovarian failure (POI) and in English primary ovarian insufficiency or premature ovarian failure (POF).

In secondary ovarian failure , the ovaries are fully functional. Secondary ovarian failure occurs as a result of a change in another organ or tissue in the body, such as a change in the pituitary gland or the hypothalamus. This also includes psychological changes. Secondary ovarian insufficiency is also referred to as hypogonadotropic hypogonadism . Because in secondary ovarian insufficiency, the ovaries, the female gonads, are no longer sufficiently driven by the hypothalamus and the pituitary gland for hormone production and egg cell maturation, therefore hypogonadotropic, so that the ovaries no longer perform their tasks, therefore hypogonadism. Secondary ovarian failure can be divided into hypothalamic ovarian failure, pituitary ovarian failure, and hyperandrogenemic ovarian failure. In hypothalamic ovarian insufficiency, the function of the hypothalamus as the control organ of the ovaries is disturbed. In pituitary ovarian failure, a change in the pituitary gland can no longer mediate between the hypothalamus and the ovaries. In hyperandrogenemic ovarian insufficiency, various diseases in which the amount of male sex hormones, the so-called androgens, is increased in the blood, impair the function of the ovaries.

In a hypothalamic ovarian failure a certain area of the brain, an error in the hypothalamus occurred. The hypothalamus constantly measures the amount of sex hormones in the blood. Depending on whether the amount of sex hormones in the blood is too low, sufficient or too high, the hypothalamus produces more, the same amount or less of the hormone GnRH. It releases the GnRH produced into the blood at an interval of 90 minutes, with which it is transported to the pituitary gland and translated there for the ovaries. If the hypothalamus can no longer measure the amount of sex hormones in the blood or if it can no longer produce enough or no GnRH at all or if the rhythm with which the hypothalamus releases GnRH into the blood is disrupted, the hypothalamus can no longer tell the ovaries that they are sex hormones and let the eggs mature. Thus, the ovaries cease to function and ovarian insufficiency develops, although the ovaries are completely normal, functional and have sufficient egg cells.

In pituitary ovarian failure , the pituitary gland is restricted in its functions. Normally, she receives instructions from the hypothalamus in the form of GnRH to tell the ovaries what to do in the form of the gonadotropins LH and FSH. When the pituitary gland changes, the pituitary gland can no longer drive the ovaries to function. As a result, the ovaries cease to function and ovarian failure develops, although the ovaries are completely normal, functional and have enough egg cells. If it is not possible to clearly differentiate whether secondary ovarian insufficiency is due to a disorder of the hypothalamus or to a disorder of the pituitary gland, it is referred to as hypothalamic-pituitary ovarian insufficiency . To hyperandrogenemic ovarian failure three diseases are counted, which occur frequently in certain families. These are polycystic ovarian syndrome (PCOS), hyperthecosis ovarii and adrenogenital syndrome (AGS). In all three, the function of the ovaries is disturbed up to the occurrence of ovarian insufficiency and increased production of male sex hormones. The male sex hormones, the androgens, include testosterone , androstenedione , dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS). The increased amount of male sex hormones in the blood causes differently pronounced masculinization symptoms in the affected girls, adolescents and women, known in technical terms as virilization symptoms .

causes

Primary ovarian failure

Multiple processes can lead to primary ovarian failure. First, during pregnancy, the ovaries may not have fully formed and may not have any eggs. Secondly, the supply of egg cells in the ovaries can be used up prematurely, i.e. before the age of 40, or the ovaries can be surgically removed before the age of 40. Third, the ovaries cannot function properly and fail to produce hormones and the regular maturation of existing eggs. In all three cases, the ovaries can no longer fulfill their tasks, namely the maturation of the egg cells for reproduction and the production of the female sex hormones estrogen and progesterone.

Primary ovarian insufficiency can occur in the context of various congenital disorders of the genetic information in which there are no functioning egg cells in the ovaries and instead of the normal ovaries there are only connective tissue ridges, so-called streak gonads. These diseases are called gonadal dysgenesis . Examples of such congenital diseases are Turner syndrome , pure XX gonadal dysgenesis and Swyer syndrome .

Primary ovarian insufficiency can also occur in women with normal ovaries and egg cells if their supply of egg cells is already used up before the age of 40. It is spoken of climacteric praecox, premature ovarian failure (POI) or premature menopause. Possible reasons for such a premature drying up of the egg cells in the ovaries are harmful external influences or changes in the body. External harmful influences include radiation treatment , chemotherapy , operations on the ovaries, surgical removal of the ovaries, severe infections and smoking. The changes in the body that cause primary ovarian insufficiency include tumors of the ovaries, enzyme defects with changes in metabolism or so-called autoimmune diseases . Possible enzyme defects with changes in metabolism are galactosemia , thalassemia major and hemochromatosis . To an ovarian failure causing autoimmune diseases include certain malfunctions of the thyroid , a polyglandular deficiency type I or II, a parathyroid gland hypofunction (hypoparathyroidism) , a rheumatoid arthritis , a idiopathic thrombocytopenic purpura (ITP), the blood-sugar disease diabetes mellitus type 1, a pernicious anemia , an adrenal insufficiency , a vitiligo or a systemic lupus erythematosus (SLE). In autoimmune diseases, the body's defense system, the so-called immune system , makes a mistake and therefore attacks tissue in its own body.

In various studies to investigate the genetic background of primary ovarian insufficiency, various changes in the genetic information were discovered that could be related to the development of primary ovarian insufficiency. A prolongation of a triplet repeat in the FMR1 gene (fragile X mental retardation gene) was discovered in around ten percent of women who suffer from premature ovarian insufficiency with a transition from the fertile to the infertile phase before the age of 40 . The FMR1 gene is located on the long arm of the X chromosome and is involved in the processing of the mRNA . In the normal population there are up to 40 repetitions of the triplet. By extending the FMR1 gene, a functional FMR protein can no longer be produced. The extension of the triplet repeat ( trinucleotide repeat disease ) in the FMR1 gene also causes the fragile X syndrome (FXS) and the fragile X-associated tremor / ataxia syndrome (FXTAS). Those affected by these diseases can also suffer from premature ovarian insufficiency or those affected by primary ovarian insufficiency give birth to children with fragile X syndrome or a fragile X-associated tremor / ataxia syndrome if they pass on the change in the gene to the children. In addition to the FMR1 gene, a mutation in the BMP15 gene ( Human Bone Morphogenetic Protein 15 gene), which is located on the short arm of the X chromosome , was found in around 4.7 percent of women suffering from premature ovarian insufficiency . The gene is needed in the ovaries for egg cells to mature. In addition, other genes are known that cause the wearer to develop premature ovarian insufficiency. These include POF2 (DIAPH2) and POF5 (AFF2) on the long arm of the X chromosome, POF4 (LHCGR) and POF6 (FSHR) on the short arm of chromosome 2 and POF3 (FOXL2) on the long arm of chromosome 3 . A rare special form of premature ovarian insufficiency is the so-called Resistant Ovary Syndrome . The ovaries have enough egg cells and are fully functional, but the FSH receptor is defective in this syndrome. Therefore, the ovaries do not understand the commands transmitted by the gonadotropin FSH from the hypothalamus and the pituitary gland for hormone production and egg cell maturation and stop functioning. In very many cases the exact cause of primary ovarian failure cannot be determined. It is then referred to as idiopathic hypergonadotropic ovarian insufficiency .

Hypothalamic ovarian failure

Hypothalamic ovarian failure is tertiary ovarian failure. Because the cause of ovarian insufficiency is not in the ovaries, but in the area of ​​the hypothalamus, which drives the ovaries to produce sex hormones and to ripen the eggs. If the hypothalamus no longer drives the ovaries because of a change, the ovaries stop producing female sex hormones and the egg cells mature. Possible causes of hypothalamic ovarian failure are mental stress, eating disorders with significant weight loss as an anorexia (anorexia nervosa) or bulimia addiction (bulimia), a malnutrition , excessively driven competitive sports or taking certain medications. They all disrupt the production and rhythmic release of GnRH in the hypothalamus, with which the hypothalamus drives the ovaries. But also tumors such as a craniopharyngioma , injuries, strokes , inflammation, infiltrative processes such as sarcoid , radiation or operations in the area of ​​the hypothalamus or an underactive thyroid can cause hypothalamic ovarian insufficiency. A rare cause of hypothalamic ovarian insufficiency is the so-called Kallmann syndrome , also called olfactogenital syndrome because of the symptoms. This is a change in genetic information that can be passed on from one generation to the next. The change in genetic information manifests itself with a reduced or absent sense of smell and an underfunction of the ovaries due to a failure of the rhythmic release of GnRH from the hypothalamus, that is, hypothalamic ovarian insufficiency.

Pituitary ovarian failure

Pituitary ovarian failure is also secondary ovarian failure. The cause of the ovarian insufficiency lies in the area of ​​the pituitary gland, which no longer translates the production commands of the hypothalamus for the ovaries, so that the ovaries are no longer driven to produce the female sex hormones and the maturation of the egg cells and consequently stop working . Possible causes of pituitary ovarian insufficiency are inflammation, tumors including the craniopharyngioma, injuries or strokes in the pituitary gland, which damage the pituitary gland tissue to such an extent that it is no longer able to produce sufficient gonadotropins and thus the function of the Control ovaries. But also an excess of prolactin , a benign tumor of the pituitary gland that produces an abundance of adrenocorticotropin (ACTH) or growth hormone (GH), the rare Sheehan syndrome or the rare Laurence-Moon-Biedl-Bardet syndrome can cause hypophyseal ovarian insufficiency. Prolactin is a hormone that, like gonadotropins, is produced in the pituitary gland and is responsible for the growth of the female breast during pregnancy and, after pregnancy, for the production of breast milk during breastfeeding. An excess of prolactin in the blood, known as hyperprolactinemia in technical terms, inhibits the production of the gonadotropins LH and FSH in the pituitary gland and thus leads to secondary ovarian failure, which in this case is also known as hyperprolactinemic ovarian failure. Such excess prolactin is perfectly natural during pregnancy and breastfeeding. Causes of excess prolactin outside of pregnancy and breastfeeding include the use of certain medications, such as certain psychotropic drugs , a prolactinoma , an underactive thyroid and stress. A prolactinoma is a benign tumor of the pituitary gland whose tissues make as much prolactin as it wants and not as much as the body needs. A benign tumor of the pituitary gland that produces an excess of ACTH or growth hormone (GH) results in what is known as Cushing's syndrome , also called Cushing 's disease, or acromegaly , which also inhibit the production of gonadotropins and thus result in secondary ovarian insufficiency. In the rare Sheehan syndrome, the pituitary gland is no longer adequately supplied with blood and oxygen and nutrients in a woman giving birth due to major blood loss during childbirth, so that the pituitary gland tissue dies and the pituitary gland can no longer produce sufficient gonadotropins LH and FSH. This, in turn, leads to the ovaries no longer performing their tasks and secondary ovarian failure. In those affected by Laurence-Moon-Biedl-Bardet syndrome, there is a change in the genes that leads to an insufficiency of the anterior lobe of the pituitary gland and thus also to an inadequate production of the gonadotropins LH and FSH, so that the ovaries no longer adequately perform their duties follow, which in turn manifests itself as secondary ovarian failure.

Hyperandrogenemic ovarian failure

Hyperandrogenemic ovarian insufficiency is, in turn, a secondary ovarian insufficiency. Hyperandrogenemic ovarian failure can occur in the context of polycystic ovarian syndrome, hyperthecosis ovarian or adrenogenital syndrome. In the case of polycystic ovarian syndrome (PCOS) and hyperthecosis ovarii, the cause of the disorder in the ovaries with increased formation of androgens, the male sex hormones, has not yet been fully clarified. In the case of the adrenogenital syndrome, various errors in the genetic information have occurred, which can be inherited in an autosomal recessive manner from one generation to the next and which, through disruption of the enzymes in the adrenal cortex, lead, among other things, to an increased production of male sex hormones with hyperandrogenemic ovarian insufficiency.

frequency

About one to two percent of the female population shows primary ovarian insufficiency with premature drying up of the eggs in the ovaries and a premature transition from the fertile to the sterile phase of life before the age of 40. It affects about 1 in 10,000 women by the age of 20, about 1 in 1,000 women by the age of 30, and about 1 in 100 women by the age of 40. The incidence of secondary ovarian failure in the female population is determined by the incidence of the causative disease.

Symptoms

Most often, ovarian failure manifests itself with an irregular menstrual cycle. Ovarian insufficiency can vary in severity. In the mildest form, this manifests itself in what is known as a corpus luteum weakness , known as corpus luteum insufficiency in technical terms. If the luteal body is weak, the eggs in the ovaries mature and ovulation occurs in the middle of the menstrual cycle . After ovulation, however, the corpus luteum does not develop sufficiently and cannot produce enough of the hormone progesterone during the second half of the menstrual cycle, which is necessary for a good quality structure of the endometrium and the occurrence of pregnancy. Such corpus luteal weakness often manifests itself to those affected in the form of spotting that occurs before the actual menstrual bleeding. In addition to the spotting, some people also suffer from breast tenderness, depressive moods or fluid retention in the tissue during the second half of the menstrual cycle. The fertility of the affected women is reduced, making conception more difficult.

If ovarian insufficiency is more pronounced, the egg cells mature incompletely, which is why ovulation does not occur, which is called anovulation in technical terms . Menstruation can occur in women despite the lack of ovulation. However, conception is not possible without complete egg maturation and without ovulation. Affected women therefore suffer from infertility, so that their desire to have children cannot be fulfilled, which can lead to psychological changes in those affected, such as the occurrence of depression or fear of failure, and a heavy burden on the partnership. The most severe form of ovarian insufficiency manifests itself with the absence of menstruation, in technical language it is referred to as amenorrhea . With primary amenorrhea, girls do not menstruate up to the age of 15. In secondary amenorrhea, a woman or girl with monthly menstrual periods has suddenly stopped menstruating for at least three months without becoming pregnant. In these affected people, egg cells no longer mature and the production of estrogen, the most important female sex hormone, is stopped in the ovaries, so that the lining of the uterus, the endometrium , no longer matures and menstruation does not occur. In addition to infertility, those affected suffer from the consequences of estrogen deficiency, including a decrease in bone stability, a so-called osteoporosis , an increased degree of calcification of the blood vessels ( atherosclerosis ) with an increase in the likelihood of developing cardiovascular disease, and that Occurrence of symptoms typical of menopause . Symptoms typical for menopause are hot flashes, mood disorders, sleep disturbances, tiredness up to exhaustion, reduced ability to concentrate, regression of the vaginal mucous membrane and bladder with vaginal dryness, discomfort during intercourse as well as decreasing control of bladder emptying and decrease in sexual desire. The exact symptoms of an affected girl or woman depend on the form and cause of the ovarian failure.

Primary ovarian failure

In primary ovarian insufficiency, menstruation either never occurs (primary amenorrhea) or suddenly stops (secondary amenorrhea) and the fertility of affected women is significantly reduced or the women are sterile after removal of the ovaries or if gonadal dysgenesis is present . There may also be symptoms such as those described for menopause. These include hot flashes, night sweats, sleep disorders, fatigue, exhaustion, mood disorders, vaginal dryness, decreased bladder control, and decreased sexual desire. Depending on the cause of the primary ovarian failure, further symptoms and changes are possible. In the case of primary ovarian insufficiency, which occurs as part of gonadal dysgenesis due to an error in the genetic information, in addition to primary amenorrhea and infertility, the absence of puberty development and other complaints and abnormalities can be observed. People with Turner syndrome are typically short stature , insufficient development of the female breast and pubic hair, skin folds on the neck, called pterygium colli, and a shield thorax. Heart defects and other malformations can also occur. In pure XX gonadal dysgenesis, the female breast is underdeveloped, while the pubic hair is normal. Malformations are possible. In Swyer syndrome , secondary sexual characteristics do not develop during puberty. The secondary female sexual characteristics are the female breasts, the female distribution pattern of body hair, for example the pubic hair, and the female body fat distribution.

Hypothalamic ovarian failure

Hypothalamic ovarian insufficiency also manifests itself in those affected with irregularities in the menstrual cycle up to the absence or not at all of menstruation with a reduction in fertility up to infertility. Depending on the cause of the hypothalamic ovarian insufficiency, further complaints may arise. These include, for example, an eating disorder such as anorexia, underweight and psychological abnormalities, a tumor in the hypothalamus, headaches, dizziness, visual disturbances and / or complaints due to a failure of other hormones that are produced by the hypothalamus in addition to the GnRH and in cooperation with The pituitary gland is necessary for the control of numerous tasks in the body, such as the production of thyroid hormones .

Pituitary ovarian failure

A pituitary ovarian insufficiency also manifests itself in those affected with irregularities in the menstrual cycle up to the absence or not at all of menstruation with a reduction in fertility up to infertility. As with hypothalamic ovarian failure, other complaints may arise depending on the cause of the pituitary ovarian failure. In the case of hyperprolactinemia, the cause of the hypophyseal ovarian insufficiency is galactorrhea with secretion of a milky fluid from the nipples. In addition, sexual desire and bone stability decrease. Tumors, injuries, infections or strokes in the area of ​​the pituitary gland can lead to headaches, visual disturbances and / or complaints due to a failure of other hormones that are produced by the pituitary gland in addition to the gonadotropins LF and FSH and in cooperation with the hypothalamus for the control of numerous tasks in the body, such as the production of thyroid hormones, are necessary. With Laurence-Moon-Biedl-Bardet syndrome, those affected can also suffer from a delay in intellectual development, obesity , retinopathia pigmentosa , polydactyly or other anomalies .

Hyperandrogenemic ovarian failure

The symptoms of hyperandrogenemic ovarian insufficiency are determined by the disease that causes the ovarian insufficiency, that is to say by the polycystic ovarian syndrome, the hyperthecosis ovarian or the adrenogenital syndrome. With all three diseases, in addition to the irregularities in the menstrual cycle until menstruation does not occur or does not occur at all due to the excessive production of male sex hormones, further complaints, such as differently pronounced virilization symptoms or increased acne , are possible. Virilization symptoms include masculinization of body hair, known as hirsutism , a lower pitch of the voice, clitoral hypertrophy , hair loss , male body proportions due to an increase in muscle mass and / or a regression of the female breast. In adrenogenital syndrome, the external genitals can be masculinized when girls are born. In addition, due to the failure of the production of glucocorticoids in the adrenal cortex in the adrenogenital syndrome, loss of appetite, weight loss, hypoglycaemia, low blood pressure (hypotension) with dizziness and fainting spells (syncope), weakness, rapid fatigue, states of confusion and psychoses are possible. A life-threatening salt loss syndrome can occur in those affected by adrenogenital syndrome if the change in genetic information also disrupts the production of the mineralocorticoid aldosterone in the adrenal cortex.

Diagnosis

Should a woman stay early, i.e. before the age of 40, menstruation will stop or become irregular or menstruation will not start in girls until the age of 16 or in a girl the signs of puberty will not develop until the age of 14, should a gynecologist should be consulted. In a detailed discussion, the doctor will inquire about symptoms, changes, development, menstrual cycle, previous illnesses and treatments. The doctor will then carefully examine the person affected, including determining the external appearance including the female breast and pubic hair and examining the vagina with palpation of the uterus and ovaries. An ultrasound can also be performed to assess the ovaries. The doctor will do a pregnancy test for everyone, as one of the most common reasons for not menstruating is pregnancy. If pregnancy is ruled out, the doctor will then take a blood sample to determine the amount of the female sex hormone estradiol and the hormones FSH and LH in the blood. The determination of the FSH should take place on the third day of the menstrual cycle, with the first day of the menstrual cycle corresponding to the first day of menstruation. It can therefore only be carried out on the third day of the menstrual cycle if menstruation is present. The amount of estradiol in the blood is reduced in the presence of ovarian insufficiency. If the amount of FSH and LH in the blood is significantly increased in two blood samples that are taken at least one month apart, the person concerned suffers from primary ovarian failure. If the amount of FSH and LH in the blood is normal or significantly reduced, it is a question of secondary ovarian failure. A GnRH test, in which the affected person is given GnRH and then the amount of FSH and LH is measured again, can be used to differentiate between hypothalamic and pituitary ovarian insufficiency. This is because in hypothalamic ovarian insufficiency, the amount of FSH and LH in the blood increases in a second blood sample after administration of GnRH, while it remains unaffected in hypophysial ovarian insufficiency. In hypothalamic and pituitary ovarian insufficiency, in addition to LH and FSH, the levels of other hormones in the blood can be changed. For example, an increase in the hormone prolactin in the blood indicates hyperprolactinemia , which is a possible cause of pituitary ovarian failure. An excess of male sex hormones, such as testosterone, androstenedione, dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEAS), in the blood indicates hyperandrogenemic ovarian insufficiency. In the case of polycystic ovarian syndrome in particular, not only androgens but also prolactin in the blood can be increased. The function of the thyroid gland and the adrenal cortex should also be checked in the presence of primary ovarian insufficiency, since in the presence of primary ovarian insufficiency, an underactive thyroid and / or adrenal insufficiency occur more frequently. With the help of an analysis of the genetic information, the presence of Turner syndrome, for example, can be excluded or confirmed in patients with primary ovarian insufficiency. With the help of imaging tests, such as computed tomography (CT) or magnetic resonance imaging (MRI), changes in the area of ​​the hypothalamus or the pituitary gland can be shown. With the help of a bone density measurement , such as a dual energy x-ray absorptiometry (DEXA), it can be determined how much the deficiency in female sex hormones has affected the structure of the bone. If the cause of primary ovarian insufficiency is gonadal dysgenesis, the cardiovascular system, the urogenital tract , the skeletal system and the visual and hearing function should also be examined, since gonadal dysgenesis can be accompanied by other malformations. To diagnose ovarian insufficiency, it can also help to keep a diary in which the body temperature measured in the morning when getting up is entered. If ovarian insufficiency is present, there is a lack of egg cells that could mature, which is why ovulation does not take place, so that the increase in body temperature that is normally observed in the middle of the menstrual cycle parallel to ovulation does not take place.

therapy

Treatment for ovarian failure depends on the form and cause of the ovarian failure.

Primary ovarian failure

Primary ovarian insufficiency cannot be reversed, so that the possibility of a naturally occurring pregnancy is significantly reduced or infertility exists after removal of the ovaries or in the case of gonadal dysgenesis. About ten percent of affected women will become pregnant within ten years despite primary ovarian failure. The only way to increase the likelihood of pregnancy is through egg donation from another woman. The legal regulations for egg donation vary around the world. In some countries it is forbidden by law, in others it is allowed. If primary ovarian insufficiency occurs before the age of 40, replacement of the missing female sex hormones should be considered in all affected persons up to the age of 50, when natural menopause would occur. Because the female sex hormones are not only necessary for pregnancy, but also take on other functions in the female body, for example stabilizing the bones. The missing female sex hormones, preferably in the form of the artificially produced ethinylestradiol , can be replaced with plasters or tablets. The administration in the form of patches is generally preferred, as this means that the body always receives an even amount of estradiol and smaller amounts can be prescribed, since the estradiol is not first processed in the liver after absorption from the intestine, as is the case with tablets is made partially inoperable. The administration of female sex hormones prevents a premature decrease in bone stability with the occurrence of osteoporosis and enables normal female development in affected girls. The administration of estrogens should always be supplemented by the administration of progestins in order to prevent excessive growth of the mucous membrane in the uterus, a so-called endometrial hyperproliferation , with possible tissue degeneration and mastopathy with lump formation in the breast. Before starting HRT, those affected must be informed that ovarian failure and menopause are not identical and that their HRT is not identical to HRT and its side effects in menopausal women. In addition to replacing female sex hormones, those affected should consume sufficient calcium and vitamin D with their food or in the form of food supplements to stabilize their bones . Regular physical activity is also recommended to those affected, also to strengthen the bones and promote the cardiovascular system. Primary ovarian insufficiency is a major psychological burden. Various measures can help to cope with this burden. In any case, it is important to provide the girls, adolescents and women affected with sufficient information about their diagnosis, its significance and its therapeutic options. In addition to the person affected, the relatives, in particular the life partner, should be included in the education about the disease and the treatment. In addition, the treating physicians should allow sufficient time and understanding for the information and discussion about the disease and its consequences. There are also numerous self-help groups whose members have experienced the same fears and worries as the patient. Psychotherapeutic support may also be necessary in certain cases. If the cause of primary ovarian insufficiency, as in Swyer syndrome, is gonadal dysgenesis with a male karyotype , i.e. with an X and a Y chromosome, the connective tissue gonads should also be surgically removed, as there is a significantly increased risk of this Tissue degenerates and a malignant tumor develops.

Hypothalamic ovarian failure

Therapy for hypothalamic ovarian failure depends on its cause. If a tumor is responsible for hypothalamic ovarian failure, the tumor must be treated with surgery, radiation and / or chemotherapy. If stress, eating disorders or other psychological stress are responsible for hypothalamic ovarian insufficiency, psychotherapeutic treatment should be included in the treatment of hypothalamic ovarian insufficiency in addition to the treatment of the physical complaints. If an underactive thyroid is the cause of hypothalamic ovarian failure, this must be treated, among other things, by replacing thyroid hormones.

Until the cause of the ovarian insufficiency has been completely eliminated or in the long term, if the cause of the ovarian insufficiency can only be treated incompletely or not at all, the complaints of the girls, adolescents and women concerned should be replaced with the missing female sex hormones if they do not want to have children at the moment or the Gonadotropins LH and FSH can be alleviated if there is a desire to have children. The missing female sex hormones are replaced with estrogens in tablet form or in the form of patches, which are supplemented with gestagens if the uterus is present. If you wish to have children, the sole replacement of the female sex hormones is not sufficient, as this does not start the normal menstrual cycle, which is essential for pregnancy. In order to fulfill their desire to have children, these women have to replace the gonadotropins LH and FSH in the form of injections or a pump in the rhythm in which they are normally released into the blood by the pituitary gland.

If a change in the area of ​​the hypothalamus leads not only to a GnRH deficiency with ovarian insufficiency, but also to a deficiency of one, several or all of the hormones that are produced by the hypothalamus in addition to the GnRH, these must also be replaced.

Pituitary ovarian failure

Therapy for pituitary ovarian failure also depends on its cause. If an excess of prolactin is responsible for the pituitary ovarian failure, it must be remedied. In the case of a prolactinoma, certain drugs, so-called dopamine agonists , also known as prolactin inhibitors, can be taken or an operation can be performed if the tumor is growing rapidly, the drugs are intolerant or neurological deficits. The dopamine agonists include bromocriptine , lisuride maleate , cabergoline and quinagolide . If drugs are responsible for the prolactin excess, they should, if possible, be reduced, discontinued or replaced by others. If tumors or infections are responsible for the pituitary ovarian failure, a tumor must be treated with surgery, radiation and / or chemotherapy; an infection with medication.

Until the cause of the ovarian insufficiency has been completely eliminated or in the long term, if the cause of the ovarian insufficiency can only be treated incompletely or not at all, the complaints of the girls, adolescents and women concerned should be replaced with the missing female sex hormones if they do not want to have children at the moment or the Gonadotropins LH and FSH can be alleviated if there is a desire to have children. The missing female sex hormones are replaced with estrogens in tablet form or in the form of patches, which are supplemented with gestagens if the uterus is present. If you wish to have children, the sole replacement of the female sex hormones is not sufficient, as this does not start the normal menstrual cycle, which is essential for pregnancy. In order to fulfill their desire to have children, these women have to replace the gonadotropins LH and FSH in the form of injections or a pump in the rhythm in which they are normally released into the blood by the pituitary gland.

If a change in the area of ​​the pituitary gland not only leads to a gonadotropin deficiency with ovarian insufficiency, but also to a deficiency in one, several or all of the hormones that are produced by the pituitary gland in addition to the gonadotropins LH and FSH, these must also be replaced.

Hyperandrogenemic ovarian failure

Treatment is to treat the disease that causes hyperandrogenemic ovarian failure. So far, however, these diseases cannot be cured. Those affected can take various medications to alleviate the symptoms. For example, if the cause of hyperandrogenemic ovarian insufficiency is an adrenogenital syndrome, those affected have to take glucocorticoids and, if aldosterone production in the adrenal cortex is disturbed, also mineralocorticoids, which reduces the overproduction of male sex hormones and relieves the affected person of the symptoms. Affected women who do not wish to have children can also take contraceptives that contain antiandrogenic substances such as chlormadinone acetate or cyproterone acetate . Women with adrenogenital syndrome can become pregnant and give birth to children, but they pass the change in genetic information on to their children, so that these are carriers of the adrenogenital syndrome.

In polycystic ovarian syndrome with obesity, a reduction in body weight through a change in diet and increased physical activity often leads to regular menstrual cycles with the desire to have children. If this is not enough, drugs can be used to counteract the androgens. These include the anti-androgenic substances chlormadinone acetate or cyproterone acetate, which are contained in certain contraceptive pills. However, low-dose gonadotropin stimulation or, if pathological insulin resistance is present, the use of substances with an anti-diabetic effect , such as metformin , are possible. If all of these measures are insufficient to fulfill the desire to have children, so-called in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) or adoption can be considered.

Treatment of hyperthecosis ovarii is very difficult. By giving long-acting GnRH analogues, the hormone with which the hypothalamus drives the ovaries, the amount of testosterone and androstenedione in the blood can be significantly reduced, but the production of dehydroepiandrosterone sulfate (DHEAS) in the ovaries is not affected.

forecast

The prognosis in the presence of ovarian failure depends on the form and cause of the ovarian failure. In the case of primary ovarian failure due to premature menopause, those affected should be informed that spontaneous healing will occur and that despite primary ovarian failure, ten percent of those affected will become pregnant within a period of ten years without treatment. Egg donation can increase their chances of conceiving, although the laws governing egg donation vary around the world. In the case of primary ovarian failure due to gonadal dysgenesis or after surgical removal of the ovaries, natural conception is no longer possible. In these cases, egg donation or adoption alone can help achieve a desire to have children.

In secondary ovarian insufficiency, treatment of the cause and replacement of the missing gonadotropins, if these do not normalize through treatment of the cause, or artificial insemination such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) can be used. to become pregnant.

literature

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