Etiology and Pathology

The earliest recorded mention of this condition can be found in Zhang Zhongjing's "Jin Gui Yao Lue · Women's Pregnancy Diseases: Pulse Diagnosis and Treatment": "A woman who has a pre-existing illness, whose menstruation has been absent for less than three months, yet experiences continuous vaginal bleeding..." The "Zhu Bing Yuan Hou Lun" first listed the "Vaginal Bleeding Syndrome," "Uterine Bleeding Syndrome," and "Combined Uterine Bleeding and Vaginal Bleeding Syndrome," and observed that uterine bleeding and vaginal bleeding could occur simultaneously and transform into one another. The "Ji Sheng Fang · General Discussion on Diagnosis and Treatment" states: "The disease of uterine bleeding and vaginal bleeding is essentially one single syndrome; when mild, it is called vaginal bleeding, and when severe, it is called uterine bleeding." The "Jing Yue Quan Shu" explicitly classifies uterine bleeding and vaginal bleeding as part of menstrual disorders, pointing out that they are "menstrual diseases" and "blood diseases." The "Mai Jing" mentions the "Five Types of Uterine Bleeding": blue, yellow, red, white, and black. During the Song Dynasty, the physician Qi Zhongfu, in his "Hundred Questions on Gynecology," distinguished between "Yin Bleeding" and "Yang Bleeding." As for the etiology and pathogenesis, different physicians have slightly different focuses, but most emphasize the close relationship with the internal organs, meridians, and qi and blood. In the Sui Dynasty, Chao Yuanfang's "Zhu Bing Yuan Hou Lun" stated: "The manifestation of uterine bleeding is damage to the Chong and Ren meridians," and "excessive fatigue and overwork lead to qi deficiency in the Chong and Ren meridians, which can no longer control the menstrual blood," thus considering damage to the Chong and Ren meridians as the key cause of uterine bleeding and vaginal bleeding. In the Jin Dynasty, Cheng Wuji, in his "Shang Han Ming Li Lun," said: "When the Chong meridian is heated, the blood will inevitably flow abnormally," believing that blood heat can lead to damage to the Chong and Ren meridians, forcing the blood to flow abnormally. The "Bei Ji Qian Jin Yao Fang" states: "Stagnant blood occupies the blood chamber, causing the blood to fail to return to the meridians." "The blood in the uterus changes every month—old blood is replaced by new blood, and old blood becomes stagnant blood. If this stagnant blood is not removed, it will obstruct the body's functions." It considers stagnant blood as the key factor leading to uterine bleeding and vaginal bleeding. The "Lan Ting Shi Mi Cang · Volume Four" says: "In women, uterine bleeding is caused by kidney yin deficiency, which cannot restrain the fire of the yang, so the blood flows out and causes uterine bleeding." The "Zhu Lin Nü Ke Zheng Zhi" also points out that persistent uterine bleeding is due to kidney yin deficiency, inability to control the yang fire, and resulting blood heat and abnormal blood flow. In the Ming Dynasty, Fang Guang, in his "Dan Xi Xin Fa Fu Yu · Women's Section," wrote: "When the five passions become excessively intense, the menstrual blood suddenly flows out, arrives irregularly, and continues for a long time without stopping—this is called uterine bleeding." He believed that emotional disturbances could also trigger uterine bleeding. Later, Zhang Jiebin further proposed: "The disease of uterine bleeding and vaginal bleeding...is invariably caused by excessive worry, contemplation, depression, and anger, which first damage the spleen and stomach, then affect the Chong and Ren meridians." He considered damage to the spleen and stomach as an important cause of uterine bleeding and vaginal bleeding. In the Qing Dynasty, Shen Jin'ao, in his "Gynecological Jade Ruler," wrote: "Worry damages the spleen, preventing it from controlling the blood, leading to abnormal blood flow." He believed that uterine bleeding and vaginal bleeding are caused by spleen deficiency, which fails to regulate the blood, causing it to flow abnormally. The "Nü Ke Cuo Yao" records: "Because there is fire in the liver meridian, the blood gets hot and flows downward—blood heat leads to uterine bleeding and vaginal bleeding—or because anger stirs up the liver fire, the blood heats up and boils," suggesting that liver stagnation turning into fire, and failure to release it properly, can lead to uterine bleeding and vaginal bleeding. Modern medical scholars' understanding of uterine bleeding and vaginal bleeding: Zheng Jianben and others argue that based on the mechanism of menstruation and their clinical experience, although the causes of uterine bleeding and vaginal bleeding are complex, the root cause lies in the kidneys—kidney qi deficiency, loss of containment function, instability of the Chong and Ren meridians, and inability to control the menstrual blood. Li Yanhong and others believe that during adolescence and perimenopause, women often have insufficient kidney qi and essence, inadequate kidney water, making them highly susceptible to internal and external environmental factors or various other influences, which can cause heat to accumulate in the Chong and Ren meridians, leading to yin deficiency and blood heat, forcing the blood to flow abnormally and resulting in uterine bleeding and vaginal bleeding. Li Zhengsheng believes that spleen deficiency and loss of regulation are the fundamental causes of uterine bleeding and vaginal bleeding, with the main pathogenesis being spleen and stomach weakness, qi deficiency and blood depletion; the causes are mostly irregular diet, excessive worry, overwork, or prolonged illness without recovery, leading to spleen and stomach damage, insufficient middle qi, and consequently, loss of blood regulation, qi sinking with blood, instability of the Chong and Ren meridians, and ultimately uterine bleeding and vaginal bleeding. Long Yuan and others believe that although there are many causes of uterine bleeding and vaginal bleeding, stagnant blood is one of the most common causes, appearing at different stages in various types. Cold accumulation, heat scorching, qi deficiency, exposure to the six pathogenic factors during menstruation, obstruction—all these can lead to stagnation. Stagnant blood that remains unremoved can actually become the cause, preventing new blood from being produced and causing the blood to fail to return to the meridians, resulting in continuous bleeding. Xia Yang and others believe that if the spleen and kidneys are deficient and the Chong and Ren meridians are unstable, it can lead to uterine bleeding and vaginal bleeding; if qi deficiency makes it difficult to transport blood or prolonged bleeding leads to stagnation, it can further cause stagnant blood to remain, preventing new blood from returning to the meridians and exacerbating the bleeding. Cause and effect are interconnected, qi and blood are both affected, and multiple organs are involved. Chen Yunean believes that during the menopausal transition, or after the first menstruation in young girls, as well as some middle-aged women, due to physiological and psychological imbalances, they often become overly sentimental, emotionally tense, or depressed, which can lead to liver qi stagnation, transformation into fire, and forced blood flow, resulting in uterine bleeding and vaginal bleeding. Yan Ying and others believe that the main mechanism of adolescent dysfunctional uterine bleeding is that adolescents are in a period when their bodies easily generate heat, coupled with heavy academic work or emotional frustration, leading to liver qi stagnation and transformation into fire, with excessive internal heat damaging the Chong and Ren meridians and forcing the blood to flow abnormally, thus causing uterine bleeding and vaginal bleeding. Additionally, during adolescence, the kidney's yin-yang transformation function is not yet fully developed, often resulting in insufficient kidney essence and blood source, making the meridians dry and brittle, leading to stagnation due to deficiency; or prolonged bleeding leading to stagnation; or indulgence in pampering and spoiled habits, resulting in unfulfilled desires, liver qi stagnation, and qi-stagnant blood stasis. Stagnant blood blocks the channels, preventing new blood from returning to the meridians, further exacerbating the bleeding. Jing Guoqing believes that the mechanism of menopausal uterine bleeding is that the heavenly癸 gradually runs out during menopause, resulting in kidney yin deficiency, insufficient essence and blood, and imbalance in the Chong and Ren meridians. Sun Hao and others believe that women of childbearing age often suffer qi and blood injuries due to childbirth, breastfeeding, or labor, damaging the spleen and stomach, causing spleen qi to sink and lose its ability to regulate the blood, leading to instability of the Chong and Ren meridians and abnormal accumulation of blood in the uterus, resulting in uterine bleeding and vaginal bleeding. Section 2: Amenorrhea
Amenorrhea manifests as the absence of menstruation or the cessation of menstruation, which is a common gynecological symptom. It is divided into primary amenorrhea and secondary amenorrhea. Primary amenorrhea refers to individuals over the age of 15 whose secondary sexual characteristics have already developed but who still have not experienced menstruation, or those over the age of 13 whose secondary sexual characteristics have not yet developed. Secondary amenorrhea refers to individuals who had established normal menstrual cycles but then stopped menstruating for more than six months, or who stopped menstruating for more than three menstrual cycles according to their original cycle. Classified by the reproductive axis and the site of dysfunction, it can be divided into hypothalamic amenorrhea, pituitary amenorrhea, ovarian amenorrhea, uterine amenorrhea, and lower genital tract amenorrhea. The World Health Organization (WHO) classifies amenorrhea into three types: Type I is characterized by no endogenous estrogen production, normal or low FSH levels, normal prolactin (PRL) levels, and no evidence of organic lesions in the hypothalamus or pituitary gland; Type II is characterized by endogenous estrogen production, normal FSH and PRL levels; Type III is characterized by elevated FSH levels and ovarian failure.
Etiology and Pathology
The establishment of a normal menstrual cycle depends on the maturation of the reproductive tract, the neuroendocrine regulation of the hypothalamus-pituitary-ovarian axis, the cyclical response of the target organ—the endometrium—to sex hormones, and the patency of the lower genital tract. Any disruption in any of these links can potentially lead to amenorrhea.

1. Primary Amenorrhea
   Most cases are caused by genetic factors or congenital developmental defects, which are relatively rare. Based on the presence or absence of secondary sexual characteristics, it is further divided into two categories: with secondary sexual characteristics and without secondary sexual characteristics. Primary amenorrhea with secondary sexual characteristics includes conditions such as Müllerian duct agenesis, complete androgen insensitivity syndrome (also known as complete testicular feminization), resistant ovary syndrome (also known as ovarian insensitivity syndrome), genital tract atresia, and true hermaphroditism. Primary amenorrhea without secondary sexual characteristics includes hypogonadotropic hypogonadism (constitutional delay in gonadal development and anosmia syndrome) and hypergonadotropic hypogonadism (Turner syndrome, 46XX gonadal dysgenesis, and 46XY gonadal dysgenesis).
2. Secondary Amenorrhea
   Its incidence is significantly higher than that of primary amenorrhea. It is divided into hypothalamic amenorrhea, pituitary amenorrhea, ovarian amenorrhea, uterine amenorrhea, and amenorrhea caused by abnormalities in the development of the lower genital tract, among which hypothalamic amenorrhea is the most common.
   II. Clinical Manifestations
3. Symptoms
   The absence of menstruation or the cessation of menstruation may be accompanied by symptoms related to the underlying cause. For example, pituitary tumors may present with galactorrhea; Sheehan's syndrome may present with hair loss, fatigue, drowsiness, cold extremities, and poor appetite; polycystic ovary syndrome may present with acne and hirsutism; premature ovarian failure may present with hot flashes, insomnia, frequent dreams, irritability, and other symptoms.
4. Signs
   Physical appearance may be thin or obese, secondary sexual characteristics may be underdeveloped, and there may be excessive hair growth, facial hair, galactorrhea, dry skin, and hair loss.
   III. Diagnosis
5. Diagnostic Points
   (1) Medical History: For patients with primary amenorrhea, a detailed history of congenital physical condition and postnatal growth and development should be obtained. For patients with secondary amenorrhea, attention should be paid to whether there was a late onset of menstruation or a history of infrequent menstruation; or a history of postpartum hemorrhage or postpartum infection; or a history of hormone therapy or radiation therapy; malnutrition or psychological trauma; a history of acute or chronic diseases, such as anemia, tuberculosis, diabetes, pituitary tumors, etc.; or a history of induced abortion, dilation and curettage, or surgical removal of the uterus or ovaries; abuse of contraceptive pills or long-term breastfeeding; or a history of thyroid or adrenal gland diseases.
   (2) Clinical Manifestations: Same as mentioned above.
   (3) Physical Examination: Examine overall development, check for deformities, measure weight, height, and the ratio of limbs to trunk, observe mental state, intellectual development, nutrition, and health status, examine secondary sexual characteristics such as hair distribution and breast development to see if they are normal, check for milk secretion, and check for goiter.
   During gynecological examination, pay attention to the development of internal and external genitalia, check for congenital defects or deformities. Also check for masses in the pelvic cavity.
   (4) Laboratory and Other Examinations
   ① Drug Withdrawal Test: To understand the level of endogenous estrogen and the function of the endometrium, thereby determining the degree of amenorrhea.
   ② Pituitary Stimulation Test: Also known as the GnRH stimulation test, it involves intravenous injection of GnRH to measure FSH and LH before and after, to assess the pituitary gland's responsiveness to GnRH.
   ③ Blood Steroid Hormone Measurement: Includes measurement of estradiol, progesterone, and testosterone. Elevated progesterone levels suggest ovulation; low estrogen levels suggest abnormal or failing ovarian function; high testosterone levels suggest possible polycystic ovary syndrome or ovarian supporting stromal cell tumor, etc.
   ④ Prolactin and Pituitary Gonadotropin Measurement: When PRL exceeds 25 ng/L, it is considered hyperprolactinemia. For those with elevated PRL, TSH should be measured; elevated TSH indicates hypothyroidism; if TSH is normal but PRL exceeds 100 ng/L, a cranial MRI or CT scan should be performed to rule out pituitary tumors. For those with normal PRL, pituitary gonadotropins should be measured. If FSH is greater than 40 U/L in two measurements, it suggests ovarian failure; if LH is greater than 25 U/L or LH/FSH ratio exceeds 3, polycystic ovary syndrome is highly suspected; if both FSH and LH are less than 5 U/L, it suggests pituitary dysfunction, with possible lesions in the pituitary gland or hypothalamus.
   Ultrasound Examination: To observe whether there is a uterus in the pelvic cavity, the shape, size, and thickness of the endometrium, the size and shape of the ovaries, and the number of follicles.
   CT or MRI: Used for examining the pelvic cavity and the sella turcica area of the head, to understand the nature of pelvic masses and central nervous system lesions, diagnose ovarian tumors, hypothalamic lesions, pituitary microadenomas, empty sella turcica, etc.
   Hysteroscopy: Used to diagnose intrauterine adhesions.
   Chromosome Examination:
   Those with hypergonadotropic amenorrhea and sex differentiation abnormalities should undergo this examination.
   9 Other Examinations: Such as target organ response tests, including basal body temperature measurement and diagnostic curettage; for those suspected of PCS, check lipid levels, blood sugar, insulin; for pituitary amenorrhea, check triiodothyronine (T3), total thyroxine (T4), TSH, and 24-hour urinary free cortisol, etc.
   IV. Western Medical Treatment
6. Systemic Treatment: Treat systemic diseases, improve physical condition, eat a balanced diet, maintain standard weight, provide psychological comfort, and eliminate mental tension and anxiety.
7. Etiological Treatment
   (1) Uterine Amenorrhea
   For those born without a vagina, vaginoplasty can be performed at an appropriate time. For endometrial tuberculosis, anti-tuberculosis treatment should be administered. For those with intrauterine adhesions, the adhesions should be separated, followed by placement of an intrauterine device, and sequential estrogen and progesterone therapy for a certain period to prevent re-adhesion.
   (2) Ovarian Amenorrhea
   For those with tumors, the tumors should be removed. For patients with chromosome 46XY, the gonads and underdeveloped uterus should be removed to prevent pituitary amenorrhea and pituitary prolactin tumors, with Moxibustion as the preferred treatment. For larger tumors that cause visual field loss, surgical decompression may be considered, followed by Moxibustion.
   (3) Hypothalamic Amenorrhea
   Hypothalamic tumors should be treated surgically. For those caused by excessive exercise, mental stimulation, environmental changes, or low body weight, exercise should be reduced, mindset adjusted, work-rest balance maintained, and weight increased. For those with nervous anorexia, eating habits should be changed, and if necessary, high-nutrition food should be administered via nasogastric tube to increase weight, but it will take a long time for menstruation to resume. For those caused by birth control pills, the pills should be discontinued and observation made.
8. Sex Hormone Replacement
   The purpose of treatment is to maintain women's overall health and reproductive health, including the cardiovascular system, bones and bone metabolism, nervous system, etc.; to promote and maintain secondary sexual characteristics and menstruation.
   V. Professor Pei Zhengxue's Clinical Experience
   Amenorrhea was historically referred to as "women not having periods," "periods not coming," "menstrual closure," etc. The "Su Wen" first recorded "women not having periods," "periods not coming," and "blood drying up." The "Jin Gui Yao Lue" called it "the cessation of menstrual flow"; the "Women's Comprehensive Good Prescription" called it "menstrual closure," "periods not flowing," "closed periods," and "blood division"; the "Fu Qingzhu Women's Gynecology" recorded "periods shortening before reaching old age," while the "Women's Essential Gynecology" called it "menstrual closure."
   Professor Pei Zhengxue believes that the causes and mechanisms of amenorrhea can be mainly divided into two aspects: on the one hand, excess pathogenic factors (such as the six pathogenic factors, seven emotions, phlegm-dampness, stagnant blood, etc.) lead to dysfunction of the internal organs and imbalance of qi, blood, and body fluids, thereby causing amenorrhea; on the other hand, deficiency of vital energy (such as spleen-kidney qi deficiency, liver-blood deficiency, yang deficiency, etc.) prevents nourishment of the uterus, leading to amenorrhea.
   The phenomenon of ovarian function decline and amenorrhea in women before the age of 40 due to various factors is a common gynecological endocrine disease. The average age of menopause for normal women is 51, and ovarian function begins to decline around ages 45 to 55. If menstrual irregularities or amenorrhea and signs of ovarian function decline appear before the age of 40, it is medically termed premature ovarian failure. Its main manifestations include estrogen deficiency, elevated gonadotropin levels, and accompanying symptoms such as facial flushing, hot flashes and excessive sweating, decreased libido, osteoporosis, and other varying degrees of menopausal symptoms or infertility. The "Su Wen · Ancient Heavenly Truth Theory" states: "When a woman reaches the age of 27, the heavenly癸 arrives, the Ren meridian is unblocked, the Tai Chong meridian is strong, and menstruation comes on time... ... By the age of 77, the Ren meridian becomes weak, the Tai Chong meridian declines, and the heavenly癸 is exhausted." This shows that the period from 14 to 49 years old is the fertile age when menstruation flows normally, and if menstruation gradually decreases or stops during this period, it is premature ovarian failure. Usually, when women pass the age of 40, menstruation gradually decreases, and people often do not consider it premature failure, calling it menopause instead. However, in recent years, due to factors such as induced abortion, medication-induced abortion, late marriage, late childbearing, and many other influences, many women of childbearing age before the age of 40 have seen their menstruation gradually decrease, even stopping altogether. These women should be regarded as the key group for premature ovarian failure and must receive treatment.
   Professor Pei Zhengxue believes that premature ovarian failure is caused by excessive sexual activity and frequent pregnancies, or repeated abortions, or long-term illness without proper care, or extreme exhaustion from labor, leading to insufficient kidney qi and kidney essence, resulting in weakened qi and blood in the Chong and Ren meridians, empty uterine vessels, and lack of nourishment, hence the absence of menstruation and infertility. The "Fu Qingzhu Women's Gynecology" states: "Ultimately, all water comes from the kidneys... If kidney qi is inherently weak, how can it be full enough to produce menstrual fluid and let it flow out?" The "Medical Correct Transmission" says: "Menstruation entirely relies on kidney water for transformation; if kidney water is lacking, menstrual blood will gradually dry up." Women naturally rely on the liver, and the liver and kidneys share the same origin, mutually regulating storage and excretion, favoring smoothness and disliking depression. Modern women face great pressure, often leading to mental tension and other negative emotions, which can cause liver qi stagnation, poor blood circulation, and blockage of the uterine vessels; or uncontrollable anger, leading to liver qi turning into fire, consuming qi and blood, leaving the uterine vessels empty, which can result in early cessation of menstruation and infertility. The heart controls blood storage and spirit, and the uterus is the continuation of the kidneys. When the heart and kidneys interact smoothly, menstruation flows normally; but if the five passions become too intense and harm the heart, the heart and kidneys will not communicate, leading to the absence of menstruation. The lungs control qi, sending it to hundreds of meridians and delivering fine qi to the uterus, participating in the production and regulation of menstruation; if the lungs fail to diffuse and deliver, the fine qi will not reach the uterus. Therefore, dysfunction of the liver, spleen, and lungs should not be ignored. Emotional distress can lead to liver qi stagnation, poor qi circulation, qi-stagnant blood stasis, blocking the uterine vessels, or kidney essence deficiency, spleen qi deficiency, and lack of qi and blood, slowing down blood circulation, blocking the Chong and Ren meridians, and preventing menstruation. Obese people often have excessive phlegm and dampness, or the spleen loses its ability to transport, leading to internal phlegm and dampness, or the liver and kidneys have yin deficiency and fire excess, burning the body fluids into phlegm, which obstructs the Chong and Ren meridians, closing the uterine vessels and preventing menstruation. Therefore, Professor Pei Zhengxue believes that kidney deficiency is the main pathogenesis of premature ovarian failure, possibly accompanied by liver-spleen-blood deficiency, stagnant blood and phlegm-dampness, while the six pathogenic factors, emotional distress, sexual activity, surgery, and medication are the triggers for this disease. Professor Pei Zhengxue believes that the etiology and pathogenesis of this disease should be considered from the perspectives of deficiency, stagnation, and stasis.
   VI. Professor Pei Zhengxue's Differential Diagnosis and Treatment
9. Qi Stagnation and Blood Stasis Type