Functional hypothalamic amenorrhea

Introduction to functional hypothalamic amenorrhea The hypothalamus is an important organ of reproduction. The hypothalamus regulates the function of the pituitary gland through nerve conduction and the pituitary-portal system, so that the pituitary gland secretes corresponding hormones. These hormones act on the ovaries and produce steroid hormones to ensure the normal maintenance of reproductive function. On the one hand, the function of the hypothalamus is stimulated by central nervous cells to regulate the secretion of pituitary hormones; on the other hand, it is regulated by the negative feedback of hormones secreted by the pituitary gland. Neuroendocrine cells in the arcuate nucleus of the central hypothalamic nucleus release GnRH in a pulsed manner. Mental stress, strenuous exercise, and hypothalamic tumors can cause abnormal GnRH secretion, leading to anovulation and amenorrhea. basic knowledge The proportion of sickness: 0.004% - 0.005% Susceptible people: women Mode of infection: non-infectious Complications: malnutrition

Functional hypothalamic amenorrhea

(1) Causes of the disease

Refers to the disorder in the hypothalamus or hypothalamus, due to hypothalamic hormone GnRH deficiency or secretion disorder, resulting in amenorrhea, including hypothalamic-pituitary unit dysfunction, central nervous system-hypothalamic dysfunction, and other endocrine abnormalities caused by hypothalamic Amenorrhea due to appropriate feedback adjustment.

(two) pathogenesis

1. Hypothalamic-pituitary unit dysfunction

It may be a congenital hypothalamic-pituitary function defect, or a hypothalamic hormone GnRH synthesis and secretion disorder secondary to injury, tumor, inflammation and radiation. The most common hypothalamic-pituitary unit dysfunction in clinical practice. The resulting amenorrhea is hyperprolactinemia, which is due to the lack of prolactin inhibitory factor (mainly dopamine) in the hypothalamus, which causes the pituitary to secrete excessive prolactin. In addition, any other reason hinders the inhibition of prolactin secretion by dopamine. Hyperprolactinemia can occur, such as tumor compression of the pituitary stalk will block the inhibition of prolactin secretion by dopamine; some drugs can increase the secretion of prolactin due to the consumption of dopamine storage or blocking dopamine receptors, such as Metoclopramide, chlorpromazine and other drugs, other pituitary adenomas, hypothyroidism, sucking nipples and chest stimulation can also cause increased prolactin secretion, elevated prolactin levels can also act on the hypothalamus, inhibit GnRH Synthesis and release; acting on the pituitary, reducing the sensitivity of the pituitary to GnRH; acting on the ovary, interfering with the synthesis of ovarian steroid hormones, in addition to amenorrhea, lactation is also often It is often one of the important manifestations of hyperprolactinemia. However, many patients cannot find lactation by themselves. About half of them are found in physical examinations due to amenorrhea or irregular menstruation. Laboratory tests will find elevated levels of serum prolactin. 30ng/ml, FSH, LH is equivalent to or lower than the normal early follicular phase, estrogen levels are low, except for pituitary tumors, imaging should be performed in the sellar region, and if necessary, the visual field should be checked to alert the tumor to oppression of the optic nerve. Visual field defect.

2. Central-hypothalamic dysfunction

Mental factors, changes in the external or internal environment can lead to amenorrhea through the central nervous system through the neuroendocrine pathways of the cerebral cortex, thalamus and hypothalamus, or through the limbic system to influence hypothalamic function. In young women, the more common typical cases Such as mental stimulation, emotional stress or sudden amenorrhea after changing the environment, FSH, LH and E2 levels can be in the normal range, because the rhythm of GnRH pulse secretion is disturbed, resulting in anovulation, resulting in amenorrhea, due to deliberate weight loss, the pursuit of slim body Anorexia nervosa is common in adolescent girls. They go from dieting to anorexia or quirks eating habits, severe weight loss, amenorrhea, and even the dysfunction of multiple organs such as the thyroid gland, adrenal gland, gonads and pancreas, and even water and electrolyte disturbances. Extreme malnutrition is life-threatening. Most of these patients can be asked for a history related to mental and psychological factors. Generally, FSH, LH and E2 levels are low. In addition, pseudopregnancy is also a central hypothalamic dysfunction caused by mental and psychological factors. Infertile women who are eager to see.

3. Other endocrine abnormalities cause inappropriate feedback regulation

(1) Too much androgen: Excessive androgen can be derived from the ovary and/or adrenal gland. The most common clinical phenomenon among adolescent women is polycystic ovary syndrome. The main pathophysiological feature is excessive androgen. And continuous anovulation, manifested as amenorrhea or menstrual disorders, hairy and obese, and a series of symptoms and signs of ovarian polycystic enlargement, excessive androgen mainly from the ovary, partly from the adrenal gland, increased androgen around Intra-tissue conversion to estrogen, this continuous non-cyclical estrogen conversion increases the sensitivity of the pituitary to GnRH, leading to increased LH secretion and loss of periodicity, while FSH is relatively insufficient, blood circulation in patients with polycystic ovary syndrome The level of androgen in the diet is about 50% to 100% higher than that of normal women. If the androgen is abnormally elevated, it should be distinguished from other conditions, such as ovarian or adrenal gland secretion of androgen tumor, congenital adrenal hyperplasia caused by enzyme deficiency. And other sexual developmental abnormalities.

Congenital adrenal hyperplasia is another common androgenic condition in girls. It is due to the lack of an enzyme in the adrenal cortex during the synthesis of steroids to produce excessive androgen, making the hypothalamic-pituitary-gonadal axis In addition to irregular menstruation or amenorrhea, the patient often has varying degrees of masculinization and even genital malformations.

(2) abnormal thyroid hormone: thyroid hormone participates in the metabolism of various substances in the body. Therefore, excessive or too little thyroid hormone can directly affect reproductive hormone and reproductive function. For example, some patients with hyperthyroidism may have less menstruation or amenorrhea.

(3) secretory sex hormone tumors: more common in ovarian and adrenal tumors, excessive secretion of sex hormones by the tumor can inhibit the secretion regulation of the hypothalamus and pituitary by feedback mechanism, destroying its periodicity, leading to no ovulation or amenorrhea, according to the blood female The abnormal increase in hormone or androgen levels can determine the nature of the hormone secreted by the tumor. Careful pelvic examination, imaging examination of the corresponding parts, such as pelvic and adrenal B-ultrasound, CT scan, MRI, etc. can help the diagnosis of the tumor.

(4) Exercise and amenorrhea: athletes, ballerinas, etc., due to engaging in large-volume activities, too little fat in the body, exercise amenorrhea, energy consumption, and mental stress in training and competition can affect neuroendocrine and metabolic functions. Abnormal secretion of GnRH in the thalamus leads to amenorrhea.

(5) drug-induced amenorrhea: some drugs can affect hypothalamic function and cause amenorrhea, especially thiazide sedatives, high-dose applications can often cause amenorrhea lactation, menstruation can be restored after stopping the drug, a few women inject long-acting injectables or Long-term oral high-dose contraceptives lead to secondary amenorrhea, which is caused by the drug's persistent inhibition of the hypothalamic-pituitary axis.

(6) Obesity: Obesity is sometimes accompanied by other endocrine abnormalities. Here, it refers to simple obesity. The body weight is closely related to the hypothalamic-pituitary-gonadal axis. Adipose tissue is the place where estrogen accumulates and is the main part of androgen conversion to estrogen. Excessive adipose tissue leads to an increase in estrogen. This non-periodic estrogen produces a continuous inhibition of the hypothalamic-pituitary body through a feedback mechanism, resulting in anovulation or amenorrhea.

Functional hypothalamic amenorrhea prevention

1. Do not ignore hunger and others to comfort, pursue slim, refuse to eat and cause hypokalemia, arrhythmia, secondary amenorrhea.

2. Avoid prolonged participation in intense physical training and overload exercise.

Functional hypothalamic amenorrhea complications Complications malnutrition

It is characterized by secondary amenorrhea with weight loss, weight loss, malnutrition, and even multiple system complications, which are life-threatening.

Functional hypothalamic amenorrhea symptoms Common symptoms Loss of appetite Anorexia nervosa menopause transition period and absolute... Pregnancy secondary amenorrhea prepubertal amenorrhea

Mental amenorrhea

These patients often have a history of mental stimulation, only menstrual thinning and amenorrhea, may have infertility and weight loss, the relevant tests show higher blood cortisol levels, but no relevant clinical symptoms; gonadotropin-releasing hormone stimulation test shows pituitary Reactive or exogenous GnRH is unresponsive.

2. pseudopregnancy (pseudocyesis)

Patients are eager to have birth and depression, amenorrhea, milk secretion, nausea and vomiting, loss of appetite and other early pregnancy-like reactions, is a typical neuroendocrine disease, when the patient thinks that pregnancy can be seen BBT continuous high temperature phase, blood PRL and LH The secretion pulse amplitude is increased, and the E2 and P levels are maintained in the luteal phase, but the patient knows that he is not pregnant, and the above hormone levels can be drastically decreased, and the menstruation can come.

3. Anorexia nervosa (anorexia nervosa)

Clinical manifestations: common in adolescents or young women, age range 15 to 30 years old, from the upper middle class, obsessed with weight loss, excessive restriction of diet, induced vomiting, or even almost no food, weight loss is obvious, at least 25% lower than the original weight 40% or less, patients with anorexia, refractory food or other symptoms of dietary dysfunction, may be accompanied by vomiting or abdominal distension, abdominal pain, nausea, hiccups and other abdominal symptoms, may be complicated by esophagitis or ulcers, pancreatitis, etc., often accompanied by skin Dry, yellow, hair loss, soft, low blood pressure, hypothermia, constipation, diarrhea, chills, bradycardia, emotional excitement, introversion, depression, bulimia or other neurological symptoms, patients Sexual weight loss, weight loss, amenorrhea is the most important manifestation (primary or secondary), with varying degrees of sexual regression, sexual dysfunction, menstrual disorders or complete amenorrhea, in addition to the above performance, there may also be urinary system, Endocrine system, skeletal system, blood system and metabolic complications, and finally serious cachexia.

4. exercise-related amenorrhea (exercise-related amenorrhea)

This disease is common in female athletes. Due to long-term participation in intense physical training or competition activities, the hypothalamic-pituitary function is abnormal, causing delayed menarche or normal menstrual menstrual disorders and amenorrhea. The occurrence of amenorrhea in long-distance runners The rate can be as high as 59%, while ballerinas are up to 79%.

Functional hypothalamic amenorrhea

Examination of ovarian function:

Vaginal exfoliative cell examination

It is a commonly used method to understand the level of estrogen. After immersing the saline in a cotton stick, take the exfoliated cells on the side wall of the upper vagina and apply it on the slide. After fixation and staining, observe the percentage of cells in the table, middle and bottom layers. The higher the percentage of cells, the higher the level of estrogen.

2. Cervical mucus

If the cervical mucus of amenorrhea patients is found to be transparent, the thin mucus with good pulling force, after drying on the glass piece, can be seen under the microscope, which indicates that the patient's ovary has the function of secreting estrogen.

3. Drug test

This is a clinically commonly used diagnostic test for amenorrhea, especially in experimental equipment lacking hormone assays. Drug trials are important for assessing ovarian function and endometrial function.

(1) Progesterone test: application of progesterone to amenorrhea patients, intramuscular injection 20mg / d, for 3 to 5 days; or medroxyprogesterone 5 ~ 10mg / d, even for 5 to 7 days, after stopping 3 to 7 Days (generally no longer than 2 weeks), withdrawal of drug withdrawal is positive, suggesting that the endometrium has function, can exclude uterine amenorrhea, the ovary has the function of secreting estrogen, the endometrium is affected by a certain level of estrogen After the reaction to progesterone, shedding bleeding, indicating that amenorrhea is not a lack of estrogen, but due to a variety of progesterone deficiency caused by anovulation; if the progesterone test is negative, there is no bleeding after stopping the drug, suggesting the following possibilities: First, the ovarian function is low, there is no proper estrogen on the endometrium; the second is normal ovarian function, but the endometrial defect or damage, can not respond to estrogen, that is, does not rule out uterine amenorrhea; the third is not excluded Pregnancy.

(2) Estrogen test: amenorrhea patients with negative progesterone test oral administration of diethylstilbestrol 1 mg / d, or ethinyl estradiol 10 g / d, or other biological estrogen for 20 days, the last 3 to 5 days plus progesterone 20mg / d, intramuscular injection, 3 to 7 days after stopping the drug to observe whether there is withdrawal of blood, if there is still no bleeding, suggesting that the lesion may be in the uterus, that is, uterine amenorrhea, with the above test withdrawal of blood, indicating endometrium to female The role of progesterone is reactive, and normal growth and shedding changes can occur. The cause of amenorrhea should be in the ovary or higher, and the level of sex hormones should be further tested to confirm the diagnosis.

4. Determination of sex hormone levels

The determination of pituitary hormone is particularly important for the diagnosis of amenorrhea. Patients with amenorrhea and low estrogen should further measure the levels of blood FSH, LH and prolactin (PRL). If FSH and LH are elevated, it suggests ovarian amenorrhea; If FSH, LH is low, the cause may be in the pituitary or hypothalamus; FSH, LH is equivalent to the normal follicular phase, amenorrhea is due to hypothalamic secretion dysfunction; if LH is elevated and FSH is relatively insufficient, polycystic ovary syndrome The diagnosis should be considered; if the abnormal PRL is elevated, amenorrhea is caused by hyperprolactinemia, and the cause of hyperprolactinemia should be further examined, especially the possibility of pituitary tumors.

When FSH and LH levels are low, the pituitary stimulation test can further distinguish the lesion in the pituitary or in the hypothalamus. The pituitary stimulation test is to dissolve 100 g of LHRH in saline 5 ml, intravenously, and inject it within 30 s before and after injection. At 30, 60, 120min, blood was taken for LH. If the LH value increased to more than 3 times before injection 30 to 60 minutes after injection, the pituitary function was good, and the hypothalamic hormone LHRH responded normally. The cause of amenorrhea was in the lower part of the thalamus or higher. If the LH does not increase or increase after injection, it is not obvious, indicating that the pituitary is not responding, and the cause of amenorrhea may be in the pituitary.

5. Basal body temperature measurement

Indirect understanding of ovulation function (see gynecological endocrine examination method), luteal secretion of progesterone after ovulation, progesterone has the effect of increasing body temperature, the normal menstrual cycle during the follicular phase, the body temperature is relatively stable, generally fluctuating below 36.5 ° C, after ovulation The body temperature rises by 0.3 to 0.5 °C, and is maintained for 12 to 16 days. It falls to the follicular phase on the day before menstruation or on the day of menstrual cramps. The basal body temperature which is low in the first half cycle and increases in the second half cycle is called biphasic body temperature, which generally indicates ovulation. Or corpus luteum formation, the body temperature without this change is called single-phase body temperature, indicating no ovulation, the basal body temperature of amenorrhea patients is mostly single-phase, but uterine amenorrhea is normal because of its ovarian function, therefore, it can show biphasic basal body temperature.

Pelvic B-ultrasound can help diagnose whether there is a congenital uterus deficiency or deformity. The imaging examination in the sellar area can diagnose the presence of pituitary tumors, diagnostic curettage, uterine lipiodol angiography and endoscopy to understand the uterine cavity and endometrium. In addition, if other endocrine abnormalities or developmental abnormalities are to be excluded, other hormone levels such as thyroid gland, adrenal gland, biochemical, pathophysiological examination and chromosome examination should be examined.

Functional diagnosis of functional hypothalamic amenorrhea

Diagnostic criteria

The process of diagnosis is the process of finding the cause of amenorrhea, which determines where the amenorrhea occurs.

History

Mainly menstrual history, age of menarche, menstrual cycle, etc., judging whether primary amenorrhea or secondary amenorrhea is helpful for analyzing the cause of amenorrhea, to understand whether there are congenital defects or other diseases, medication history and response to drug treatment Etc. Also ask if there are any predisposing factors that cause amenorrhea such as mental factors, environmental changes or other diseases.

2. Physical examination

Should pay attention to the general condition, whether the development is normal, whether there is deformity, whether the height and weight are in the normal range, the limbs, the proportion of the trunk, intelligence, nutrition and health, check the development of the second sexual characteristics such as breast development, hair distribution, presence or absence Milk secretion, etc., gynecological examination should pay attention to the development of internal and external genitalia, with or without defects, deformities and tumors.

3. Examination of ovarian function.

4. Pelvic B-ultrasound iodine oil angiography and endoscopy.

5. Saddle area imaging examination, pathological examination and chromosome examination.

Differential diagnosis <br /> Hypothalamic functional amenorrhea occurs mostly in mental workers, long-distance runners, ballerinas or sudden mental stimuli. It can occur after extreme fatigue or strenuous exercise. Young unmarried women are more common, before and after puberty. Good hair, manifested as secondary amenorrhea with weight loss, weight loss, malnutrition and so on.

Firstly, the hypothalamic and organic lesions of the pituitary must be excluded. The cause of the disease, the development of the disease, clinical manifestations and auxiliary examinations, combined with the determination of hormones, and analysis, typical hypothalamic functional amenorrhea patients, blood FSH, LH partial Low or near normal, ovarian dysfunction or a certain function, atypical hypothalamic functional amenorrhea patients, high blood LSH and low TSH, similar to PCOS, a small number of patients with FSH, high LH close to premature ovarian failure.

Ultrasound examination showed that the size of the double ovary was normal, and there were small vesicles in the ovary, but less than 10, the diameter of 2 ~ 8 mm can be distributed throughout the ovary, the interstitial echo is not enhanced, and can be differentiated from PCOS.

1. Diagnosis and differential diagnosis of mental amenorrhea These patients often have a history of mental stimulation, only menstrual thinning and amenorrhea, may have infertility and weight loss, the relevant tests show higher blood cortisol levels, but no relevant clinical symptoms; Gonadotropin-releasing hormone stimulation tests indicate that the pituitary is reactive or unresponsive to exogenous GnRH.

2. Anorexia nervosa, also known as Anorexia nervosa syndrome, rickets-induced digestive cessation syndrome, is a neuroendocrine disorder that has been in the West for nearly 20 years. The national incidence rate is high, which is common in young women aged 15 to 24 years old, generally less than 25 years old. The prevalence of the disease in adult women is 1% to 2%, and the ratio of male to female is 1:20. The trend of increasing year by year.

The following differential diagnosis must also be performed prior to diagnosis: primary endocrine diseases such as hypopituitarism, Addison disease, hyperthyroidism and diabetes; gastrointestinal diseases; chronic infections such as tuberculosis; neoplastic diseases such as lymph Tumor; other diseases such as AIDS, cerebral vascular malformations, and hypothalamic tumors.

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