闭 经 诊 治Closed consultation转载2008-05-04
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什么是闭经?What is amenorrhea? 闭经是就是不来月经或者停径,原因可能在于基因、染色体、下丘脑、垂体、卵巢和子宫各个层面。首先,要详问病史,包括病人的饮食习惯、锻炼水平和主要症状,如溢乳和潮热。应行彻底的体格检查,尤为注意第二性征是否缺乏,有
什么是闭经?What is amenorrhea?
闭经是就是不来月经或者停径,原因可能在于基因、染色体、下丘脑、垂体、卵巢和子宫各个层面。首先,要详问病史,包括病人的饮食习惯、锻炼水平和主要症状,如溢乳和潮热。应行彻底的体格检查,尤为注意第二性征是否缺乏,有无多毛和生殖道的异常。首先应取血检查血清绒毛膜促性腺激素(human chorionic gonadotropin, hCG)、促甲状腺激素(thyrotropic stimulating hormone, TSH)、卵泡刺激素(follicle stimulating hormone, FSH)、黄体生成素(luteotropic hormone, LH)、雌二醇(Estrodial, E2)和泌乳素(prolactin, PRL)水平是合理的。hCG用于除外妊娠相关的闭经,TSH除外由于甲状腺功能紊乱而继发的闭经。但应注意的是,进行激素检查应在停用各种激素或含激素的药物1~3个月之后方能进行。
The reason why amenorrhea is not menstruating or stopping is probably due to various levels of genes, chromosomes, hypothalamus, pituitary gland, ovary and uterus. First, ask about your medical history, including your diet, level of exercise, and major symptoms such as milk spillage and hot flashes. A thorough physical examination should be carried out, paying particular attention to the lack of secondary sexual characteristics, the presence of multiple hairs and abnormal reproductive tract. Blood should first be taken to check the serum chorionic gonadotropin(hCG), thyrotropising hormone(TSH), follicular stinger hormone(FSH), Huangtishengchengsu(LH), LH(LH). E2) and prolactin(PRL) levels are reasonable. HCG is used to exclude pregnancy-related amenorrhea, except TSH for secondary amenorrhea due to thyroid dysfunction. However, it should be noted that hormone screening should be carried out after 1 to 3 months of deactivation of various hormones or hormone containing drugs.
闭经的诊断和鉴别诊断Diagnosis and differential diagnosis of amenorrhea
原来贯用的孕激素撤退试验和人工周期方法已经被淘汰,不但周期长,而且病因也无法确定。取而代之的是详尽病史,阴道四维彩超,电化学发光法内分泌检测、垂体兴奋试验&全垂体兴奋试验,宫腹腔镜检查和MIR等;
The original progesterone withdrawal test and artificial cycle method have been eliminated, not only for a long period, but also for a determined cause. Instead, it is a detailed history, vaginal four-dimensional color ultrasound, electrochemical luminescence endocrine detection, pituitary excitement test & amp; Total pituitary excitement test, uterine laparoscopy and MIR;
分析电化学发光法内分泌和垂体兴奋结果事半功倍,如子宫、宫颈和阴道闭锁造成的闭经FSH、LH和E2都正常;FSH和LH高,E2低,则说明卵巢早衰(premature ovarian failure, POF);若FSH、LH和E2都低,是垂体或下丘脑闭经,进一步地,可以进行全垂体兴奋试验,如果FSH、LH和E2能够被刺激起来,说明问题出在下丘脑,反之则是垂体问题。
Analysis of electrochemiluminescent endocrine and pituitary stimulation results in half the effort, such as amenorrhea FSH, LH, and E2 caused by uterus, cervix, and vaginal atresia are normal; FSH and LH are high, and E2 is low, indicating premature ovarian premature failure(POF); If FSH, LH, and E2 are all low, they are pituitary or hypothalamus amenorrhoea. Further, full pituitary stimulation tests can be conducted. If FSH, LH, and E2 can be stimulated, the problem is in the hypothalamus, and vice versa. pituitary problem.
1、下丘脑1, hypothalamus
(1) 下丘脑功能性闭经(1) Functional amenorrhea of the hypothalamus
下丘脑性闭经是由于GnRH脉冲式分泌缺陷而致性腺机能减退并且不排卵状态。大约占继发闭经的15%,是原发闭经的一较罕见的原因。这些病人的特点:Hypothalamic amenorrhea is caused by gonadal hypoplasia and ovulatory state due to GnRH pulsed secretion defects. About 15 % of secondary amenorrhea is a relatively rare cause of primary amenorrhea. Characteristics of these patients:
①促性腺激素水平低或正常
1 Low or normal gonadotropin levels
②泌乳素水平正常
2 The lactoid level is normal
③垂体影像正常
The pituitary image is normal
④病人中,低体重和精神紧张比率高
Among the patients, there is a high rate of low weight and mental stress
⑤在明显闭经前有月经紊乱病史
There is a history of menstrual disorders before apparent amenorrhoea
⑥大部分有长期下丘脑功能紊乱
Most of them have long-term hypothalamus disorders
下丘脑性闭经者有升高的皮质醇。在灵长类动物上的研究表明促肾上腺皮质激素释放激素在紧张时,抑制促性腺激素的分泌,同时促使皮质醇的释放。Berga 等人分析了10名患有功能性下丘脑性闭经病人的垂体前叶的一些激素昼夜分泌的方式。24小时皮质醇有17%的增高,而泌乳素和T3,T4水平显著减少。并且发现在GnRH的基因水平和FSH及LH的b亚单位均没有异常。
People with hypothalamic amenorrhea have elevated cortisol. Studies in primates have shown that corticosteroid release hormones inhibit the secretion of gonadotropin when they are tense and promote cortisol release. Berga et al. analyzed the way in which some hormones in the anterior pituitary lobe of 10 patients with functional hypothalamic amenorrhea were secreted day and night. There was a 17 % increase in 24-hour cortisol and a significant decrease in prolactin and T3 levels. It was found that there were no abnormalities in the gene level of GnRH and B subunits of FSH and LH.
安太治疗:
Antai treatment:
1、安装脉冲式电子泵静脉给予外源性GnRH,它能按要求定时定量的供给GnRH,从而恢复垂体和卵巢功能,达到规律排卵,规律月经、妊娠的目的。1, the installation of pulsed electronic pump veins to give exogenous GnRH, which can supply GnRH on a regular basis as required, so as to restore pituitary and ovarian functions, to achieve regular ovulation, regular menstruation, pregnancy.
2、腹腔镜下卵巢唤醒术 + FSH + 生长激素 + HCG 序贯疗法,促使卵泡发育,排卵,妊娠。
2, laparoscopic ovarian awakening + FSH + growth hormone + HCG sequential therapy, promote follicular development, ovulation, pregnancy.
3、无生育要求者行性激素替代疗法。对经垂体兴奋试验确诊的下丘脑功能性闭经。
3, no reproductive requirements for sex hormone replacement therapy. Functional amenorrhea of the hypothalamus confirmed by the hypophysis stimulation test.
注意:克罗米酚是没有效的。无论是这种药物或激素替代治疗,均没有显示自然GnRH脉冲的恢复。
Note: cromidol is not effective. Neither this drug nor hormone replacement therapy showed the recovery of natural GnRH pulses.
(2) 体重下降和厌食性闭经
(2) Weight loss and anorexia amenorrhea
临床上,存在多种表现形式,可从一次突然饮食紊乱而致一次停经到由于衰弱厌食而致长期闭经。神经性厌食常发生在围青春期的妇女,这些妇女往往有一定的心理问题,想表现吸引人的和成功的外表。心理学对此解释为,此类病人不能对付初步形成的性特征,并且有着家庭压力。通常对身体形象抱有误解的否定态度。
Clinically, there are many forms of expression, from a sudden eating disorder and lead to a period of menopause to chronic amenorrhea due to anorexia. Neuroanorexia often occurs in periadolescent women. These women often have certain psychological problems and want to show attractive and successful appearance. Psychology explains that such patients can not cope with initial sexual characteristics and have family pressure. There is usually a negative attitude toward the body image that is misunderstood.
厌食的特点为体重下降25%(或体重低于年龄和身高的15%),伴有闭经。病人可能具有下列一些或全部特点:心动过缓,便秘,柔毛(lanugo),运动狂(exercise fanaticism),高胡萝卜素血症(hypercarotenemia)和尿崩症(diabetes insipidus)。通常遇见这些病人的医生注意闭经的主诉而不注意与体重联系起来。Burgeoning 厌食的诊断是重要的,因为这不是一良性病症,其死亡率在5-15%。Anorexia is characterized by a loss of 25 per cent of body weight(or less than 15 per cent of age and height), accompanied by amenorrhea. The patient may have some or all of the following characteristics: bradycardia, constipation, lanugo, exercise madness, hypercarotendemia, and uria. Diabets collapse. Doctors who usually meet these patients pay attention to the main complaint of amenorrhea and do not pay attention to the connection with weight. The diagnosis of Burgeoning anorexia is important because it is not a benign condition and its mortality rate is 5-15 %.
大约50%的病人有贪食倾向。贪食后,又开始倾泻通过戒食,自己诱导呕吐,或使用泻药。现在显示,在年轻妇女中贪食倾向日趋流行。
About 50 % of patients are prone to gluttony. After gluttony, he began to pour through abstinence, induce vomiting, or use laxatives. It now appears that gluttony is becoming more popular among young women.
厌食的临床症状表现在下丘脑功能的衰退,体现在食欲,激素分泌,水代谢,体温,睡眠和自身平衡的紊乱。在这些病人中,促性腺激素水平低,而泌乳素,TSH,和甲状腺素水平正常。皮质醇和生长激素升高。有趣的是T3下降而反向T3升高。这反常现象解释这些病人表现甲状腺功能低下样症状如便秘,不耐冷,心动过缓,低血压,粗糙的皮肤和代谢率降低。这显示甲状腺素成分代偿性的反向T3转换来帮助对抗严重的营养不良。
The clinical symptoms of anorexia are manifested in the decline of hypothalamus function, manifested in the disorders of appetite, hormone secretion, water metabolism, body temperature, sleep and self-balance. In these patients, gonadotropin levels were low, while prolactin, TSH, and thyroxine levels were normal. Cortisol and growth hormone elevated. What is interesting is that T3 drops and reverse T3 rises. This anomaly explains why these patients showed hypothyroidism such as constipation, cold intolerance, bradycardia, low blood pressure, rough skin and reduced metabolic rates. This shows the reverse T3 conversion of thyroxine components to help combat severe malnutrition.
安太治疗:
Antai treatment:
1、心理呵护、医学教育,效果不好时给抗抑郁药,如选择性五羟色胺重吸收抑制剂(SSRI)治疗有一定效果,但可能需较大剂量。
1, psychological care, medical education, when the effect of antidepressants, such as selective serotonin reabsorption inhibitors(SSRI) treatment has a certain effect, but may require a larger dose.
2、腹腔镜下卵巢唤醒术 + FSH + 雌激素 + HCG 序贯疗法,促使卵泡发育,排卵,妊娠。
2, laparoscopic ovarian awakening + FSH + estrogen + HCG sequential therapy, promote follicular development, ovulation, pregnancy.
3、鼓励提高性交频率,改变性观念(这些人多有认为性交不洁和猥亵)。
3, encourage to increase the frequency of sexual intercourse, change sexual attitudes(these people think that sexual intercourse is unclean and obscene).
(3) 运动诱发闭经
(3) Exercise induced amenorrhea
由于从事体力活动的现代妇女数量的增加,有月经紊乱和闭经的症状也很容易出现。这体现另一种下丘脑性抑制的疾病。有66%的赛跑运动员有不排卵或黄体期短。在青春期前开始锻炼的人,初潮可延迟3年。
As the number of modern women engaged in physical activity increases, symptoms of menstrual disorders and amenorrhea are also likely to occur. This reflects another type of hypothalamus inhibition. 66 % of runners have no ovulation or short luteal periods. People who start exercising before puberty can delay the first wave by 3 years.
影响这种疾病的两种因素是运动本身的强度和身体脂肪水平的危机。
The two factors that affect the disease are the strength of the exercise itself and the crisis in body fat levels.
①身体脂肪水平。正常周期的月经需要体重的保持,因此身体的脂肪水平应在一定水平上。月经初潮需要身体内17%的脂肪,而维持正常周期需要身体22%的脂肪。应该指出由于脂肪组织转换为肌肉组织而体重没有明显变换时,身体的脂肪已经发生了变化。另外,身体脂肪的作用,紧张和长期艰苦训练能量的消耗也各自独立的影响月经的功能。
1 Body fat level. The normal period of menstruation needs to maintain weight, so the body's fat level should be at a certain level. Menstruation requires 17 % of the body's fat, while maintaining the normal cycle requires 22 % of the body's fat. It should be pointed out that the body's fat has changed since the fat tissue has not changed significantly due to the conversion of muscle tissue into muscle tissue. In addition, the role of body fat, stress and long-term hard training energy consumption also independently affect the function of menstruation.
②激烈的运动明显影响妇女的内分泌环境。促性腺激素下降,但泌乳素,生长激素,睾酮,ACTH,肾上腺的类固醇激素和内啡肽(endorphins)是升高的。由于闭经,女性运动员经常有低雌激素状态,因此,骨骼疾病的危险性增加。Drinkwater等人指出与正常月经的人比较,在闭经赛跑运动员中,其脊椎骨的骨密度有着显著降低。
The fierce movement obviously affects the endocrine environment of women. Gonadotropin decreased, but prolactin, growth hormone, testosterone, ACTH, adrenal steroid hormone and endorphins were elevated. Due to amenorrhea, female athletes often have low estrogen status, so the risk of bone disease increases. Drinkwater et al. pointed out that there was a significant decrease in the bone density of the vertebrae in the amenorrhea runners compared to the normal menstrual period.
安太治疗:
Antai treatment:
1、FSH + 小量雌激素 + HCG 序贯疗法,促使卵泡发育,排卵,妊娠。大量吃动物脂肪也有助育恢复。
1, FSH + small amount estrogen + HCG sequential therapy, promote follicular development, ovulation, pregnancy. Eating large amounts of animal fat also helps recovery.
(4) Kallmann’s综合征
(4) Kallmann's syndrome
在1944年由Kallmann所描述的罕见情况,为低促性腺激素性性腺机能低下伴随嗅觉功能丧失或低下(Kallmann’s综合征)。也可伴随其他一些症状如色盲,神经性耳聋,智力发育迟缓等。此病症是由于GnRH神经元和嗅觉神经元及它们从胚胎的发源地嗅基板到下丘脑终止的神经的异常。
The rare case described by Kallmann in 1944 was the loss or low olfactory function of hypogonadal gonadal hypotropy(Kallmann's syndrome). It can also be accompanied by other symptoms such as color blindness, neurological deafness, and mental retardation. This condition is due to the abnormalities of GnRH neurons and olfactory neurons and their nerve termination from the olfactory substrate where the embryo originated to the hypothalamus.
安太治疗:同下丘脑性闭经。
Antai therapy: hypothalamic amenorrhea.
2、垂体疾病2, pituitary disease
(1) 垂体低促性腺激素性闭经(1) pituitary hypogonadal hormone amenorrhea
临床表现除闭经外,主要为促性腺激素缺乏的症状,卵巢内有始基卵泡和初级卵泡,性器官与性征不发育,血LH、FSH及E2水平低下。
In addition to amenorrhea, clinical manifestations are mainly symptoms of gonadotropin deficiency. There are primal follicles and primary follicles in the ovary, sexual organs and sexual characteristics are not developed, and blood LL, FSH, and E2 levels are low.
安太治疗:腹腔镜下卵巢唤醒术 + FSH + 雌激素 + HCG 序贯疗法,促使卵泡发育,排卵,妊娠。Antai therapy: laparoscopic ovarian arousal + FSH + estrogen + HCG sequential therapy, promoting follicular development, ovulation, pregnancy.
(2) 高泌乳血症(2) Hyperlactation
大多数病人是由于垂体瘤所至的泌乳素的分泌。其中1/3的继发闭经是由于垂体瘤造成。其特点为闭经,溢乳,如果瘤体大,压迫视交叉时,出现视野缺损。多巴胺是泌乳素的主要抑制因子。它是通过上升的泌乳素经过一短反馈的刺激释放的。多巴胺通过内源性β内啡肽的刺激来抑制GnRH脉冲式分泌。Most patients are due to the secretion of prolactin from pituitary tumors. One third of the secondary amenorrhea is caused by pituitary tumors. It is characterized by amenorrhea, milking, if the tumor body is large, when the compression cross, there is a visual field defect. Dopamine is the main Suppressor of prolactin. It is released through a short feedback stimulus of elevated prolactin. Dopamine inhibits GnRH pulsed secretion through the stimulation of endogenous beta-endorphins.
安太治疗:Antai treatment:
1、嗅隐停 标准化治疗。1, smell stop standardized treatment.
2、注意的是垂体无功能肿瘤也可以引起高泌乳素血症,这是因为虽然垂体瘤本身并不产生泌乳素但可以压迫垂体和下丘脑之间的连接处,使得下丘脑分泌的垂体泌乳素抑制因子(如多巴胺)不能到达垂体,垂体泌乳素分泌细胞失去控制而分泌大量泌乳素。这种情况的特点是垂体瘤较大而泌乳素相对来说不太高,用溴隐亭也可以使泌乳素水平下降,但肿瘤体积不缩小,对这种情况应采用手术治疗。分泌泌乳素的肿瘤,无论大小,都无需手术,使用溴隐亭即可有效治疗。
2, note that pituitary non-functional tumors can also cause hyperlactoemia, because although pituitary tumors themselves do not produce prolactin, they can oppress the connection between the pituitary gland and the hypothalamus, making the hypothalamus secreted pituitary prolactin inhibition factor(such as dopamine) can not reach the pituitary gland. The pituitary prolactin secretion cells lose control and secrete a large amount of prolactin. This situation is characterized by large pituitary tumors and relatively low prolactin levels. The use of bromine occultation can also reduce prolactin levels, but the tumor size does not shrink, and surgical treatment should be used in this case. The tumor that secretes prolactin, regardless of size, does not require surgery, and bromine occultation can be effectively treated.
注意:伽马刀是万万使不得,因为它能够摧毁下丘脑功能,术后月经正常2-3年后多转化成下丘脑性闭经。Note: The gamma knife is impossible because it can destroy the hypothalamus function. After normal menstruation 2 to 3 years after surgery, it is converted into hypothalamus amenorrhea.
(3) 甲状腺功能性疾病
(3) Functional thyroid disease
甲状腺功能的紊乱可导致月经不规律。随着正常甲状腺功能的恢复,正常的月经周期也随着恢复。Graves’疾病是最常见的甲状腺毒症的病因,女性的发病率是男性的7倍。甲状腺毒症妇女的月经间期可长可短,在严重的病人,会出现闭经。现在已知甲状腺素可升高SHBG水平, 但不知甲状腺素是否对卵巢、垂体、下丘脑和肝脏有影响。这些病人的体重下降,焦虑会单一对下丘脑产生抑制。虽然闭经,但仍可能有排卵。因此,这些病人在治疗前尤其放射碘治疗前首先应该排除妊娠。Disorders in thyroid function can lead to irregular menstruation. With the recovery of normal thyroid function, normal menstrual cycle is also restored. S disease is the most common cause of thyrotoxicosis. Women have seven times the incidence rate of men. The menstrual period of women with thyroid poisoning can be long or short, and amenorrhea can occur in severe patients. Thyroxine is now known to increase SHBG levels, but it is not known whether thyroxine affects the ovary, pituitary gland, hypothalamus, and liver. When these patients lose weight, anxiety can be suppressed by a single pair of hypothalamus. Although amenorrhea, there may still be ovulation. Therefore, these patients should first exclude pregnancy before treatment, especially before radiation iodine treatment.
安太治疗:甲状腺机能亢进的月经不调很容易治疗。通常采用抗甲状腺药物 (如他巴唑methimazole) 使其甲状腺功能恢复正常后。再可接受放射碘治疗,治疗中必须严密监护以防甲状腺功能低下。甲状腺功能低下者也存在月经不调,其1/3者伴随高泌乳血征症。大约1%的继发闭经病人是由于甲状腺功能低下,然而45%的病人出现月经过多,其原因是由于不排卵而致功能性子宫出血,这些病人可用甲状腺素替代治疗。Antai treatment: hyperthyroidism menstruation is easy to treat. Anti-thyroid drugs(such as traprazole methimazole) are usually used to restore normal thyroid function. The treatment of radioactive iodine can be accepted. The treatment must be closely monitored to prevent hypothyroidism. People with hypothyroidism also have irregular menstruation, and one-third of them are accompanied by high lactation symptoms. About 1 % of secondary amenorrhea patients are due to hypothyroidism, but 45 % of patients have excessive menstruation due to functional uterine bleeding due to non-ovulation. These patients can be treated with thyroxine instead.
(4) 席汉氏综合征(4) Sheehan's syndrome
因Sheehan首先描述此征而命名,是由于产后大出血与休克导致垂体功能低下的典型的垂体性闭经(席汉氏综合征)。垂体功能低下可累及性腺、甲状腺、肾上腺等靶腺的功能,导致促性腺激素、促肾上腺激素、促甲状腺激素和泌乳素分泌减少,偶见生长激素低落。Named after Sheehan's first description of this sign, it is a typical pituitary amenorrhea(Scheehan's syndrome) due to postpartum hemorrhage and shock. Low pituitary function can affect the function of target glands such as the gonad, thyroid, and adrenal glands, resulting in reduced secretion of gonadotropin, adrenal hormone, thyroid hormone, and prolactin, and occasionally low growth hormone.
①席汉综合征的临床表现主要依据其累及的腺体。若累及性腺可导致促性腺激素分泌不足,临床表现为无卵泡发育、雌激素低落、闭经、乳房与生殖器萎缩等;若累及肾上腺可出现促肾上腺皮质激素分泌不足的症状,如:全身虚弱无力、生活无力自理、免疫力低下、食欲差、浮肿、消瘦、无性欲等。若累及甲状腺则表现为促甲状腺激素分泌不足,如:畏寒、面色苍白、皮肤粗糙、毛发脱落、表情淡漠迟钝、心率慢等;泌乳素不足则表现为产后乳汁少或缺乏;生长激素不足则易发生低血糖等。The clinical manifestation of Sihan syndrome is mainly based on the glands it involves. If gonadal involvement can lead to insufficient gonadotropin secretion, clinical manifestations are no follicular development, low estrogen, amenorrhea, breast and genital atrophy; If the adrenal gland is involved, there can be symptoms of insufficient secretion of adrenal corticosteroids, such as: weakness of the body, inability to take care of oneself, low immunity, poor appetite, edema, wasting, and lack of libido. If the thyroid gland is involved, it is characterized by insufficient secretion of thyroid hormone, such as: fear of cold, pale, rough skin, hair loss, indifferent expression, slow heart rate, etc.; The deficiency of prolactin shows that there is less milk or lack of postpartum milk. Insufficient growth hormone is prone to hypoglycemia and so on.
安太治疗:同下丘脑-垂体功能性闭经,但要注意的是,本病往往存在甲状腺和肾上腺功能的低下,需同时予以检查并治疗。Antai treatment: functional amenorrhea with hypothalamus-pituitary, but it should be noted that the disease often has a low thyroid and adrenal function, need to be examined and treated at the same time.
(5) 药物引起闭经(5) Drug induced amenorrhea
服用抗精神病药物可出现闭经泌乳,如氯丙嗪、奋乃静等;长期服用避孕药,停药后出现闭经;长期服用如棉酚、雷公藤等亦可引起闭经。当年轻患者生殖功能旺盛时,停药后能自然恢复。年龄40岁以上近绝经过渡期时,停药后可能不能自然恢复。如早绝经时应予治疗,不能恢复者为预防绝经后并发症应予性激素替代治疗或卵巢移植、唤醒等等。Taking antipsychotic drugs can produce amenorrhea lactation, such as chlorpromazine, perphenazine, etc.; Take the contraceptive pill for a long time, after stopping the drug, amenorrhea occurs; Long-term use such as gossypol, Lei Gong Teng, etc. can also cause amenorrhea. When young patients have strong reproductive function, they can naturally recover after stopping the drug. When the age of 40 or older is near the transition period, it may not be able to recover naturally after stopping the drug. If early menopause should be treated, those who can not recover should be sex hormone replacement therapy or ovarian transplantation, awakening, etc. to prevent postmenopausal complications.
3、卵巢早衰3, ovarian premature failure
卵巢早衰是在40岁以前,伴随持续的促性腺激水平升高的闭经(卵巢早衰)。其发生率大约1%。卵巢的状态与正常绝经后的相似。卵巢皮质萎缩而髓质增生。The premature failure of the ovary is a amenorrhea(premature failure of the ovary) before the age of 40, accompanied by a continuous increase in the level of gonadal stimulation. Its incidence is about 1 %. The state of the ovary is similar to that of normal postmenopausal. Ovary cortex atrophy and medullary hyperplasia.
(1) 卵巢早衰与激素的关系。(1) The relationship between ovarian premature failure and hormones.
通过低雌激素和高促性腺激素状态即可确诊。上升的FSH与卵巢衰竭有一定程度上的联系,不论衰竭是自然的,人工诱导的或病理性早衰,可认为病人没有生育能力,有报道约2%~3%的患者可能短期或长期恢复排卵。The diagnosis can be made by low estrogen and high gonadotropin status. The rising FSH is related to ovarian failure to some extent. Whether the failure is natural, artificially induced or pathological premature failure, the patient can be considered to have no fertility. About 2 % to 3 % of patients may report short-term or Long-term recovery of ovulation.
然而,某些有上升FSH病人并不意味卵巢衰竭,如分泌促性腺激素的垂体肿瘤和围绝经期状态(perimenopausal)等。在后者,通常为月经周期停止前,FSH就有显著上升。在这期间,仍存在一些具有的抵抗性的卵泡,它能抵抗内源性激素刺激而不成熟。这些卵泡内的颗粒细胞产生抑制素减少,FSH的抑制被解除,因此FSH水平升高。
However, some patients with elevated FSH do not mean ovarian failure, such as pituitary tumors that secrete gonadotropins and perimenopausal conditions. In the latter, FSH has a significant increase before the menstrual cycle stops. During this period, there are still some resistant follicles that can resist endogenous hormone stimulation and are immature. The granulocyte production in these follicles decreased, and the inhibition of FSH was removed, so the FSH level increased.
(2) 卵巢早衰的病因包括以下几个方面:The causes of premature ovarian failure include the following:
①自身免疫:有许多文献支持这一观点。由自身免疫疾病影响的卵巢有组织学的认定,组织学认为卵巢有正常的始基卵泡,但其颗粒细胞和卵泡膜细胞有淋巴细胞和浆细胞侵润。自身免疫性疾病常与卵巢早衰并存。Belvisi 等人指出,28个卵巢早衰者有18个病人(40%)肯定存在至少一种特异器官的自身抗体,而对照组仅有1%,抗甲状腺抗体最常见(20%)。与卵巢早衰关联的多腺体综合征(The polyglandular syndromes)包括甲状旁腺功能低下,肾上腺功能不足,甲状腺炎。自身免疫性卵巢炎也与卵巢早衰有着联系。卵巢早衰者15%有着肾上腺功能衰竭,所以定期评估肾上腺功能是必要的。There is a lot of literature to support this view. The ovaries affected by autoimmune diseases have histological findings. Histology believes that the ovaries have normal basal follicles, but their granular cells and follicular membrane cells have lymphocytes and plasma cells. Autoimmune diseases often coexist with premature ovarian failure. Belvisi et al. noted that 18 patients(40 per cent) of 28 premature ovarian failure had ascertainable autoantibodies to at least one specific organ, compared with only 1 per cent in the control group, with anti-thyroid antibodies being the most common(20 per cent). The polyglandular syndromes associated with ovarian premature failure include low parathyroid function, insufficient adrenal function, and thyroiditis. Autoimmune ovaries are also associated with premature ovarian failure. With 15 % of premature ovarian failure having adrenal failure, it is necessary to regularly assess adrenal function.
② 卵巢不敏感综合征:尽管卵巢内有卵泡存在,但也存在闭经和促性腺激素水平升高。病理学显示卵巢皮质厚并且纤维化,另存在许多始基卵泡和少量初级卵泡。大部分始基卵泡没有发育的迹象。目前,考虑是卵泡的促性腺激素受体的缺乏或由于涉及FSH受体与有活性的腺苷酸环化酶(adenylate cyclase)结合障碍而致受体后信号缺失。伴有卵巢早衰的SLE和重症肌无力的病人,血中各自存在FSH与其受体结合的抑制物和FSH受体的自身抗体。必须有足够的卵巢组织进行活检才能确诊此疾病。因为此疾病很少见并且对大剂量外源性刺激物反应率很低,所以,行侵害性的诊断不可取,经阴道超声检查其卵泡是可以考虑的。
Ovary insensitivity syndrome: Although there are follicles in the ovary, there is also an increase in amenorrhea and gonadotropin levels. Pathology shows that the ovarian cortex is thick and fibrosis, and there are many primary follicles and a small number of primary follicles. Most of the basal follicles do not show signs of development. At present, it is considered that the deficiency of gonadotropin receptors in follicles or the loss of post-receptor signals due to the binding of FSH receptors to active adenylate cyclase. SLE with premature ovarian failure and patients with myasthenia Gravis have their own FSH binding inhibitors and FSH receptor autoantibodies in the blood. There must be enough ovarian tissue for a biopsy to confirm the disease. Because this disease is rare and the response rate to large doses of exogenous stimulants is very low, it is not advisable to perform invasive diagnosis. Vaginal ultrasound examination of the follicles can be considered.
③ X染色体的部分缺失:Krauss等人在1987年曾报道一家庭4姐妹有Xq缺失,其中3个人出现卵巢早衰,另一人在其31岁出现月经不规则。3 Part of the X chromosome is missing: Krauss et al. reported in 1987 that a family of 4 sisters had Xq loss. Three of them had premature ovarian failure and the other had irregular menstruation at the age of 31.
④ 医源性:由于手术切除卵巢、放射治疗和化学治疗引起。4 Iatrogenic: Due to surgical removal of ovaries, radiotherapy and chemotherapy.
⑤ 感染:任何感染均可损伤卵巢,如生殖系统结核或继发于流行性腮腺炎的卵巢炎。5 Infection: Any infection can damage the ovary, such as reproductive tuberculosis or ovarian inflammation secondary to mumps.
⑥ 特发性:有些病人有家族史,说明有遗传学倾向。Idiopathic: Some patients have a family history, indicating a genetic tendency.
安太治疗:Antai treatment:
1、卵巢组织嫁接术是最好的方法,这是安太医院的发明创造,就是把同型组织的卵巢嫁接到患者卵巢残基上。术前需要组织配型,术前术后要吃抗排异药物。卵巢组织来源分为亲体供者和非亲体供者,亲体供者如母亲,姊妹,堂姊妹或表姊妹,这些人就不需要配型了。1, ovarian tissue grafting is the best method. This is the invention and creation of Antai Hospital, that is, grafting the ovaries of the same type of tissue to the remains of the patient's ovaries.
2、激素替代疗法:根据内分泌结果,依据缺什么补什么,缺多少不多少的原则进行终生。特别是等待卵巢嫁接者也不可停药。
Tissue matching is required before and after surgery to take antirejection drugs. The source of ovarian tissue is divided into parental donors and non-parental donors, and parental donors such as mothers, sisters, cousins, or cousins, these people do not need matching.
Hormone replacement therapy: According to endocrine results, according to what is missing, what is missing is not much. Especially waiting for the ovary grafts also can not stop the medicine.
4、性腺发育不全4, gonadal hypoplasia
由于胚胎时期卵巢发育异常而致卵巢没有其功能,称性腺发育不全(Gonadal dysgenesis),这些病人主要是存在染色体数量的异常,性腺发育异常可致原发性闭经或卵巢早衰。大约35%的原发性闭经病人由于不正常的发育,性腺为条索样,50%的病人患turner’s综合征(X单体)。这些病人有着明显的特征:身材低矮,无第二性征发育,肘外翻,眼距宽,后发际低,黑痣,第4掌及第4趾骨短。她们的卵泡通常在青春期前就耗竭了,但有3%的病人(X单体)存有足够的卵子,有着短期正常的性腺功能。而在X/XX嵌合体病人,12%有短期正常的卵巢功能。Due to abnormal ovarian development during the embryonic period, the ovary has no function, and it is called Gonadal dysgenesis. These patients are mainly abnormal in the number of chromosomes, and abnormal gonad development can cause primary amenorrhea or premature ovarian failure. About 35 % of primary amenorrhea patients have striated gonads due to abnormal development, and 50 % of patients have Turner's syndrome(X monomer). These patients have obvious characteristics: low body size, no secondary sexual development, elbow roll, wide eye distance, low posterior hairline, black mole, fourth palm and fourth phalange. Their follicles are usually depleted before puberty, but 3 % of patients(X monomers) have enough eggs to have
安太治疗:同卵巢早衰。short-term normal gonad function. In the X/XX chimera patient, 12 % had short-term normal ovarian function.
5、多囊卵巢综合征Antai treatment: premature ovarian failure.
5, polycystic ovary syndrome
是以排卵障碍为特征,伴有糖脂代谢紊乱的征候群。是高雄激素和/或高胰岛素引起卵巢分泌功能异常。诊北京安太医院陈凤林院长的断标准被多数学者采用,即除外其他原因引起的高雄激素血症后,下列3项中的2项符合即可诊断:It is a symptom group characterized by ovulation disorders and accompanied by glycolipids metabolic disorders. It is Kaohsiung hormone and/or high insulin that causes abnormal ovarian secretion. After the diagnosis of Chenfenglin, the director of Beijing Antai Hospital, was adopted by most scholars, that is, except for Kaohsiung hormone anaemia caused by other reasons, two of the following three items can be diagnosed:
(1)月经改变如稀发,反复功血或闭经;(1) Menstruation changes such as rare hair, repeated blood work or amenorrhea;
(2)基础内分泌表现高雄血症, LH/FSH大于等于1;(2) Basic endocrine performance Kaohsiung, LL/FSH is greater than or equal to 1;
(3)B超声可显示双侧卵巢各有多个小卵泡,每侧最大切面>8-10个,或出现典型的“项链征”“蜂窝征”。(3) B ultrasound can show that there are multiple follicles on each side of the ovary, with a maximum cut surface on each side & GT; 8-10, or a typical "necklace sign" or "hive sign."安太治疗:分为15个亚型,治疗都以腹腔镜卵巢打孔为主,然后依据亚型给预不同的药物辅助治疗,脂肪代谢紊乱严重的肥胖者同时吸脂手术,治疗后妊娠率99%。Antai treatment: divided into 15 subtypes, the treatment is mainly laparoscopic ovarian perforation, and then according to the subtype to give different drug assisted treatment, fat metabolism disorders of the obese at the same time liposuction surgery, after the treatment pregnancy rate of 99 %.
注意:PCOS多并发子宫纵隔和黄体功能不建,导致流产,治疗时要一并考虑。Note: PCOS has multiple concurrent uterine mediastinal and luteal functions that do not build, resulting in miscarriage, and should be considered together with treatment.
6, reproductive tract
6、生殖道
(1) 单纯生殖道畸形:严重的问题如处女膜闭锁、阴道和子宫横隔。因为经血不能排出,临床上有周期性腹痛,妇科检查可触及压痛性包块。手术治疗是唯一方法。(1) Pure genital deformities: serious problems such as hymen atresia, vaginal and uterine septum. Because the menstrual blood can not be discharged, there is periodic abdominal pain in the clinic, gynecologic examination can touch the painful bag block. Surgical treatment is the only way.
(2) 苗勒氏管发育不全(the Mayer-Rokitansky-Kuster-Hauser syndrome):先天发育异常导致无阴道或阴道发育不全。病人可有始基子宫,具有正常功能的卵巢并能产生正常的类固醇激素。病人的核型为女性,放射学检查提示大约1/3的病人有泌尿系统畸形和12%的骨骼系统畸形,通常是脊椎骨。(2) The Mayer-Rokitansk-Kuster-Hauser syndrome: congenital dysplasia leads to no vagina or vaginal hypoplasia. The patient can have a primal uterus, have normal functioning ovaries and can produce normal steroid hormones. The patient's nuclear type is female. Radiological tests indicate that about one-third of patients have urinary system deformities and 12 % of skeletal system deformities, usually vertebrae.
安太治疗:腹腔镜下墙角阴道复位术,术后达到以假乱真高潮迭起的效果,可通过代孕实现生儿育女的目的。Antai treatment: laparoscopic vaginal reduction of the corner, after surgery to achieve the effect of false orgasm, can achieve the purpose of childbearing through surrogacy.
(3) 完全性雄激素不敏感或睾丸女性化:其特点为女性特征,男性核型。对雄激素先天不敏感,为X染色体上雄激素受体基因缺陷造成。因为不缺乏苗勒氏抑制因子,因此没有子宫和输卵管。睾丸通常下降腹股沟环内,阴道下1/3是存在的。有乳房发育,原发闭经,阴毛和腋毛缺乏或稀少,阴道较短,子宫和宫颈缺失。病人有升高的促性腺激素,尤其LH,中度升高的睾酮,雌二醇水平较高。没有精子的产生,因此不能妊娠。(3) Complete androgen insensitivity or testicular feminisation: It is characterized by female characteristics and male nuclear type. Innate insensitivity to androgen is caused by androgen receptor gene defects on the X chromosome. Because there is no lack of Myrtle inhibition factors, there is no uterus and fallopian tubes. The testicles usually drop within the groin ring, and 1/3 of the vagina is present. There is breast development, primary amenorrhea, lack or scarcity of pubic and axillary hair, short vagina, and lack of uterus and cervix. Patients had elevated gonadotropins, especially LH, moderately elevated testosterone, and higher estradiol levels. There is no sperm production and therefore no pregnancy.
安太治疗:切除睾丸,用双膜法进行阴道成型,术后进行激素替代治疗。Antai treatment: testicular resection, the use of double membrane method for vaginal formation, postoperative hormone replacement treatment.
(4) Asherman’s综合征:由于宫腔粘连而致子宫腔部分或全部梗阻(Asherman’s综合征)。可表现为月经不规则、月经过少或闭经和不育,传统认为是医源性的,由于过度的刮宫引起基底层裸露,其实真正的原因是瘢痕体质,这种体质的人正常宫腔操作后即可形成不同程度的粘连。另外,也可能与感染有关,可由于产后子宫内膜炎,生殖系统结核,或宫内环所至。用雌孕激素后没有撤血,或通过子宫输卵管造影或宫腔镜检查。(4) Asherman's syndrome: partial or total obstruction of the uterine cavity due to uterine adhesion(Ashman's syndrome). It can be manifested as irregular menstruation, menarche or amenorrhoea and infertility. Traditionally, it is considered to be iatrogenic. Due to excessive curettage, the ground floor is exposed. In fact, the real reason is scar Constitution. This kind of constitution can form different degrees of adhesion after normal cavity operation. In addition, it may also be related to infection, which can be due to postpartum endometritis, reproductive system tuberculosis, or intrauterine ring. There was no withdrawal of blood after using estrogen, or through hysterectomy or hysteroscopy.
安太治疗:宫腔镜下冷剪分解粘连,切除瘢痕,生物防粘膜处理。 但不能期望一次手术成功,术后妊娠成功率在85%左右。(2)
Antai treatment: cold shear decomposition adhesion under hysteroscopy, scar removal, biological anti-mucosal treatment. However, one operation can not be expected to succeed. The success rate of postoperative pregnancy is about 85 %. (2)
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