Prepubertal amenorrhea

Introduction In the early stage of puberty, in the second or third year of the first menstrual period, because the ovarian function is still unstable, the menstrual cycle is often irregular. This amenorrhea that occurs during development is called physiological amenorrhea, which is a normal phenomenon. Amenorrhea has physiological and pathological points. Pre-puberty, pregnancy, lactation, and menstruation after menopause are all physiological amenorrhea. What is discussed here is only the problem of pathological amenorrhea. Menstruation is caused by the periodic regulation of the hypothalamic-pituitary-ovarian axis, resulting in the endometrial cycle shedding, so any organic or functional appearance in the hypothalamus, pituitary, ovary and reproductive tract, especially the uterus. Changes can cause amenorrhea. Organic and functional abnormalities in other endocrine glands may also affect menstruation and cause amenorrhea.

Cause

Girls 6 to 9 years old can detect dehydroepiandrosterone (DHEA) and its sulfate from the urine, which rises rapidly at the age of 10, which is the initial manifestation of adrenal function. The androgen from the adrenal gland causes the pubic hair to appear. The body grows rapidly and rapidly, because the hypothalamic-pituitary-ovarian axis has yet to be further developed, the estrogen level is still low, the endometrial proliferation is poor, and it does not cause bleeding, so menstruation is delayed. At this stage before menarche, there is no physiological phenomenon in menstrual cramps. Some girls have a menstrual flow for a period of one and a half years after menarche, and it is normal for anovulatory menstruation.

(1) Causes of the disease

Amenorrhea has physiological and pathological points. Pre-puberty, pregnancy, lactation, and menstruation after menopause are all physiological amenorrhea. What is discussed here is only the problem of pathological amenorrhea. Menstruation is caused by the periodic regulation of the hypothalamic-pituitary-ovarian axis, resulting in the endometrial cycle shedding, so any organic or functional appearance in the hypothalamus, pituitary, ovary and reproductive tract, especially the uterus. Changes can cause amenorrhea. Organic and functional abnormalities in other endocrine glands may also affect menstruation and cause amenorrhea.

(two) pathogenesis

Organs associated with menstruation include the uterus, ovaries, pituitary glands, and hypothalamus, and amenorrhea may occur in any of the links. According to the site where the disorder occurs, it can be divided into four types: uterus, ovarian, pituitary and hypothalamic.

Uterine amenorrhea

The cause of amenorrhea is in the uterus. Although the ovarian function is normal, the endometrium does not produce a normal response and therefore does not come to menstruation. Diseases that cause uterine closure are common:

(1) Congenital uterine hypoplasia or lack of: due to hypoplasia or non-development of the secondary renal tube. Expressed as the primary amenorrhea. After puberty, secondary sexual characteristics such as breast, external genitalia, yin and mane are all normal. If the basal body temperature can sometimes show ovulation, it can also show periodic breast tenderness and abdominal discomfort. Chromosomes and gonads are normal women. Various ovarian hormones and pituitary gonadotropins FSH, LH, etc. are at the normal female level. Pelvic examination and B-ultrasound confirmed no uterus. If the primary amenorrhea with periodic abdominal pain should be considered congenital uterus or vaginal deformity, such as vaginal septum or hymen atresia. Due to poor reproductive tract, menstrual blood cannot be discharged. B-ultrasound can be found in uterine hemorrhage and vaginal blood. Opening the channel by surgery will restore normal menstruation. And congenital uterine hypoplasia or lack of menstruation will never occur.

(2) endometrial damage or adhesion: often occurs after artificial abortion, postpartum or abortion curettage, due to excessive scratching injury to the endometrium, or postoperative infection caused by intrauterine adhesions, amenorrhea. When the uterine cavity partially adheres, the menstrual blood can not flow out, which is characterized by amenorrhea accompanied by periodic abdominal pain and falling feeling. The diagnosis can be confirmed by comparing the symptoms with the basal body temperature or by detecting B-ultrasound uterus. Some infections such as tuberculous endometritis, abortion or severe postpartum endometritis can cause destruction of the endometrium leading to amenorrhea, usually secondary amenorrhea. If a girl infected with endometrial tuberculosis before puberty, she presented with primary amenorrhea.

(3) uterine treatment: uterine amenorrhea can occur after uterus or endometrial resection or intrauterine radiation therapy.

(4) Androgen insensitivity syndrome: also known as testicular feminization. This is a special form of uterine amenorrhea. The patient's karyotype is 46, XY, and the gonad is the testis. Since the target organ lacks androgen receptors or receptors and cannot undergo normal biological functions, it fails to develop into a normal male. The feminine appearance of the complete testis is very similar to that of a woman with breast development, but the uterus is absent, such as the upper end of the vagina. Patients often have a primary amenorrhea after puberty.

2. Ovarian amenorrhea

Refers to amenorrhea caused by abnormalities or functional abnormalities in the ovaries themselves. It can be innate or acquired. The two main endocrine indicators for ovarian amenorrhea diagnosis are low estrogen levels and elevated levels of gonadotropins.

(1) Congenital ovarian hypoplasia: also known as Turner syndrome. It is the most common type of adolescent girls with amenorrhea. This is a disease with abnormal sex chromosomes. Most of them are abnormal X chromosome numbers. The basic karyotype is 45, X, and it can also be abnormal for sex chromosome structure, such as X chromosome and other arms, long or short arm missing, circular X Chromosome, etc. Still others are chimeras of a variety of karyotypes. In addition to the primary amenorrhea and secondary sexual characteristics, the patient has a group of abnormal physical manifestations, such as short stature, neck-shaped hernia, multi-faceted hernia, barrel chest, elbow valgus and other deformities. A small number of cases with 46, XX chimerism may appear as secondary amenorrhea or occasional normal menstruation.

(2) simple gonadal dysplasia: including 46, XX simple gonadal dysplasia and 46, XY simple gonadal dysplasia. The clinical manifestations were similar except for the karyotype. Both manifestations of primary amenorrhea, secondary sexual characteristics are not developed. It is tall, long in limbs, and has a cast shape. The gonads are mostly cord-like. The gonads with karyotype XY are prone to tumors. Peking Union Medical College Hospital has reported 5 cases of XY simple gonadal dysplasia, resection of the gonads, pathologically confirmed 4 cases of tumors, including 2 cases of gonadal cell tumor, 1 case of sexomyma and supporting cell tumor. Therefore, XY simple gonadal dysplasia should be surgically removed as soon as possible.

(3) premature ovarian failure: also known as early menopause, that is, menopause occurs before the age of 40. Occasionally seen in young women under the age of 20. Most are secondary amenorrhea, rarely primary amenorrhea. Ovarian atrophy, estrogen levels are low, and FSH rises to the level of menopause. The true mechanism of premature ovarian failure is not well understood. It has been observed that premature ovarian failure is related to the autoimmune system. It is often found that premature ovarian failure is associated with a variety of autoimmune diseases, such as Addison disease, thyroiditis, hypoparathyroidism, myasthenia gravis, diabetes, etc. Tissue antibodies, which have been observed to have anti-gonadotrophin receptor antibodies on the ovary, prevent FSH from binding to receptors on the cell membrane. It has also been reported that there are family factors in premature ovarian failure, and early menopause in the mother or sister of the patient.

(4) ovarian insensitivity syndrome: clinical manifestations with premature ovarian failure, can be primary amenorrhea or early menopause. Unlike premature ovarian failure, there are many normal follicles in the ovary of such patients, but they are in a state of rest and cannot mature and ovulate. The pathogenesis of ovarian insensitivity syndrome is also not well understood. More explanation is the presence of anti-gonadotrophin receptor antibodies or receptors in the ovaries. The reproductive hormone changes of the disease are the same as premature ovarian failure. If B-ultrasound or laparoscopic ovarian atrophy and small follicles are present, it can be differentiated from premature ovarian failure.

(5) Ovariectomy syndrome: oophorectomy or tissue destruction. Mostly due to surgical removal of bilateral ovaries or bilateral ovaries after radiation therapy, ovarian tissue is destroyed and loss of function, manifested as primary or secondary amenorrhea. Severe ovarian inflammation can also destroy ovarian tissue and cause amenorrhea.

3. Pituitary amenorrhea

Pituitary lesions cause gonadotropin synthesis and secretion disorders, which affect ovarian function leading to amenorrhea.

(1) Primary pituitary gonadotropin: It is a rare genetic disease characterized by isolated gonadotropin deficiency, patients often have primary amenorrhea, sexual signs are not developed, and some are accompanied by olfactory disorders. Pituitary gonadotropin FSH and LH and ovarian sex hormones are low levels.

(2) secondary anterior pituitary dysfunction: due to pituitary damage, hemorrhage, inflammation, radiation and surgery, etc., disrupting the function of the anterior pituitary, causing gonadotropins and other hormones in the anterior pituitary, such as thyroid stimulating hormone and adrenal cortex Lack of hormones, etc. Therefore, in addition to hypogonadism, there are sometimes hypothyroidism and adrenal insufficiency, showing amenorrhea, weight loss, fatigue, cold, hypoglycemia, hypotension, low basal metabolism and loss of libido. Sheehan syndrome, which occurs due to postpartum hemorrhage and shock-induced ischemic necrosis of anterior pituitary tissue, is a typical condition of secondary hypopituitarism.

(3) pituitary tumors: also a common cause of pituitary amenorrhea, can directly disrupt the function of the anterior pituitary or destroy the regulation channel between the hypothalamus and the pituitary, interfere with the secretion and regulation of reproductive hormones, leading to amenorrhea. There are many types of pituitary tumors, such as growth hormone tumors, prolactinomas, thyroid stimulating hormone adenomas, adrenocortical adenomas, mixed tumors of gonadotropin adenomas, and non-functional pituitary adenomas. The most common pituitary tumor associated with amenorrhea is prolactinoma.

4. Hypothalamic amenorrhea

Refers to the disorder above the hypothalamus or hypothalamus. Amenorrhea is caused by a deficiency or a disordered form of hypothalamic gonadotropin releasing hormone (GnRH). Including hypothalamic-pituitary dysfunction, central nervous system-hypothalamic dysfunction, and other endocrine abnormalities caused by inappropriate feedback regulation of hypothalamic inappropriate amenorrhea.

(1) hypothalamic-pituitary unit dysfunction: may be congenital hypothalamic-pituitary dysfunction, may also be secondary to injury, tumor, inflammation and radiation caused by hypothalamic hormone GnRH synthesis and secretion disorders. The most common clinically common hypothalamic-pituitary unit dysfunction is amenorrhea. This is due to the lack of prolactin inhibitory factor (mainly dopamine) in the hypothalamus, which causes excessive secretion of prolactin from the pituitary gland.

In addition, any other cause of the inhibition of prolactin secretion by dopamine may cause hyperprolactinemia. For example, tumor compression of the pituitary stalk will block the inhibition of prolactin secretion by dopamine; some drugs may increase prolactin secretion due to consumption of dopamine storage or blocking dopamine receptors, such as metoclopramide (metaclopramide) , chlorpromazine (hibernation) and other drugs. Other pituitary adenomas, hypothyroidism, sucking nipples, and chest irritation can also cause an increase in prolactin secretion. Elevated prolactin levels can also act on the hypothalamus, inhibit the synthesis and release of GnRH; act on the pituitary, reduce the sensitivity of the pituitary to GnRH; act on the ovary and interfere with the synthesis of ovarian steroid hormones. In addition to amenorrhea, lactation is often one of the important manifestations of hyperprolactinemia. However, many patients cannot find lactation by themselves, and about half of them are found by physical examination at the time of amenorrhea or irregular menstruation. Laboratory tests will find elevated levels of blood prolactin, >30 ng / ml, follicle stimulating hormone (FSH), luteinizing hormone (LH) is comparable to or lower than normal early follicular phase, and estrogen levels are low. In order to exclude pituitary tumors, imaging studies in the saddle area should be performed. If necessary, the visual field should also be checked to alert the tumor to the visual field defect caused by oppression of the optic nerve.

(2) Central-hypothalamic dysfunction: mental factors, changes in the external or internal environment can cause 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. Among young women, the more common typical conditions are mental stimulation, emotional stress or sudden amenorrhea after changing the environment. FSH, LH and estradiol (E2) levels can be in the normal range, and amenorrhea occurs due to interference with the rhythm of GnRH pulse secretion leading to anovulation. Because of deliberate weight loss, the anorexia caused by the pursuit of slim body is not uncommon among young girls. They range from dieting to anorexia or quirky eating habits, severe weight loss, amenorrhea, resulting in hypofunction of multiple organs such as the thyroid gland, adrenal gland, gonads and pancreas, and even water and electrolyte imbalances and extreme malnutrition endangering life. A medical history related to mental and psychological factors can be pursued. Generally, FSH, LH and E2 levels are low. In addition, pseudopregnancy is also a central hypothalamic dysfunction caused by mental and psychological factors. Often occurs in infertile women who are eager to see.

(3) Other endocrine abnormalities cause inappropriate feedback adjustment:

1 Androgen excess: Excess androgen can come from the ovary and / or adrenal gland. The most common clinically among adolescent women is polycystic ovary syndrome. Its main pathophysiological characteristics are excessive androgen and persistent anovulation, which are characterized by amenorrhea or menstrual disorders, hirsutism and obesity, and a series of symptoms and signs of ovarian polycystic enlargement. Excessive androgen is mainly derived from the ovary and partly from the adrenal gland. Increased androgen is converted to estrogen in surrounding tissues. This sustained, non-periodic estrogen conversion increases the sensitivity of the pituitary to Gn-RH, resulting in increased LH secretion and loss of periodicity, while FSH is relatively insufficient. The level of androgen in the blood circulation of patients with polycystic ovary syndrome is about 50% to 100% higher than that of normal women. If the androgen is abnormally elevated, attention should be paid to the identification of other conditions, such as ovarian or adrenal gland secretion of androgen tumors, congenital adrenal hyperplasia and other sexual dysplasia caused by enzyme deficiency.

Congenital adrenal hyperplasia is another common form of androgen in girls. It is because the adrenal cortex lacks an enzyme in the process of synthesizing steroid hormones to produce excessive androgen, which causes disturbance of hypothalamic-pituitary-gonadal axis function and irregular menstruation or amenorrhea. In addition, patients often have varying degrees of masculinization and even genital malformations.

2 thyroid hormone abnormalities: thyroid hormones participate in the metabolism of various substances in the body. Therefore, too much or too little thyroid hormone can directly affect reproductive hormone and reproductive function, such as some patients with hyperthyroidism can show less menstruation or amenorrhea.

3 secretory sex hormone tumor: more common in ovarian and adrenal tumors. Excessive secretion of sex hormones by the tumor can inhibit the secretion regulation function of the hypothalamus and pituitary gland through a feedback mechanism, destroying its periodicity, leading to anovulation or amenorrhea. According to the abnormal increase of estrogen or androgen levels in the blood, the nature of the hormone secreted by the tumor can be judged. Careful pelvic examination, imaging examination of the corresponding parts, such as pelvic and adrenal B-ultrasound, CT scan, MRI, etc. contribute to 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, there will be exercise amenorrhea. Energy consumption and mental stress during training and competition can affect neuroendocrine and metabolic functions, causing abnormal secretion of GnRH in the hypothalamus, leading to amenorrhea.

5 drug-induced amenorrhea: some drugs can affect the function of the hypothalamus and cause amenorrhea, especially thiazide sedatives, high-dose applications can often cause amenorrhea lactation, menstruation can be restored after stopping the drug. A small number of women who inject long-acting injectables or long-term oral high-dose contraceptives cause 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. This refers to simple obesity. 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 the extrahormonal gland to be converted into estrogen. Excessive adipose tissue leads to an increase in estrogen. This non-periodic estrogen produces a sustained inhibition of the hypothalamic-pituitary body through a feedback mechanism, resulting in anovulation or amenorrhea.

[Type Description]

According to the location of the pathology, the pathogen of amenorrhea can be divided into four areas:

Zone 1: Lower genital tract or uterine lesions.

Second area: ovarian lesions.

The third area: pituitary lesions.

Fourth area: hypothalamic and central neuropathy.

Other: Adrenal or thyroid lesions.

an examination

Related inspection

Gynecological ultrasound examination of brain CT for six tests of sex hormones

General examination: The general examination of amenorrhea is mainly to conduct a comprehensive examination and analysis of mental, physical and developmental conditions, such as normal body type, finger distance, skin, hair and chest development, whether there is galactorrhea, groin and other abnormalities Phenomenon and so on.

Inspection of gynecological diseases : The examination of gynecological diseases mainly depends on the regularity of the reproductive organs inside and outside and the phenomenon of tumors. If it is a patient with primary menopause, it is necessary to pay attention to the examination of the genitourinary tract and the examination of the clitoris.

Laboratory examination: The laboratory examination is mainly to check the hormones of the hypothalamus, pituitary and uterine axis of the patient to see if there is any abnormality.

Inspection of the device:

1. Chest X-ray examination: This mainly determines whether there is a lesion of tuberculosis in the patient.

2, the measurement of basal body temperature: the measurement of basal body temperature is mainly to check the ovulation of the patient and the determination of the basal body temperature curve during the physiological period. If the basal body temperature of the ovulation-free physiological period is not present, if there is no progesterone, it will be a single Phase-type, so after the detection of no ovulation, there is a case of corpus luteum development.

3, medical imaging examination: medical imaging examination is mainly through B-mode ultrasound, CT, hysterosalpingography, and ventricle, cerebral angiography after peritoneal inflation.

4, endoscopy: endoscopy examination mainly includes hysteroscopy and laparoscopy, you can understand the ovulation and hormone secretion in the ovary.

5, cesarean exploration and gonadal biopsy: This cesarean section and gonadal biopsy is mainly for the examination of the secretion of gonads in women to judge.

Differential diagnosis

Differential diagnosis of prepubertal amenorrhea :

1, secondary amenorrhea: the case of menstruation but later menopause is called secondary amenorrhea. Secondary amenorrhea refers to those who have menopause for more than 6 months after menstrual cramps, or those who have menopause in menstrual thinning to reach 3 normal intervals.

2, sports amenorrhea: light female athletes, amenorrhea in the sports competition or intense training process, called "sports amenorrhea." Some young women may also have amenorrhea during their travels or intense work and study. The pathogenesis is similar to this disease, and can also be treated with reference to exercise amenorrhea. The disease is often associated with excessive mental stress, leading to endocrine dysfunction. Chinese medicine believes that due to excessive mental stress, the movement of air-conditioners is reversed, and the dysfunction of the rushing function is caused by the bloody sea.

3, pituitary amenorrhea: pituitary amenorrhea: the closure of the pituitary tumor can be accompanied by headache, blurred vision, or lactation; uterine necrosis before the pituitary, occurs in postpartum hemorrhage, manifested as loss of libido, genital atrophy, fatigue Fear of cold, hair loss.

4, uterine amenorrhea: the endometrium is stimulated by the ovarian secretion of sex hormones and periodic changes, when the endometrial peeling off there is menstrual cramps, therefore, in congenital absence of uterus or uterine dysplasia, endometrial damage Or hysterectomy cases, even if the ovarian function is sound, the secretion of sex hormones is normal, there is no menstrual cramps, the cause of this amenorrhea is in the uterus, it is also called uterine amenorrhea.

5, ovarian amenorrhea: If the ovary is absent or dysplastic, ovarian damage or premature aging, so that the body does not produce sex hormones, the endometrium can not grow, can not occur cyclical changes and exfoliation, menstruation can not come, this amenorrhea, Known as ovarian amenorrhea.

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