As one of the more complex of the endocrine disorders, both diagnosis and treatment of amenorrhea require a detailed history and a thorough and careful evaluation by the physician. Today I will share with you the diagnosis and treatment of amenorrhea.
In clinical work, after encountering patients who visit the clinic for amenorrhea and determining primary or secondary amenorrhea, physiological amenorrhea, such as pregnancy, lactation, menopause, contraceptive pills, and exogenous androgen use, should be ruled out first. The main causes of pathologic amenorrhea include outflow tract abnormalities, ovarian, pituitary, hypothalamic, and other endocrine gland dysfunctions. Based on the analysis of medical history data (Table 1), combined with physical and ancillary examinations, emphasis is placed on thyroid, height, weight, development of secondary sexual characteristics, hirsutism, acne, hairline, blood pressure, and development of uterus, vagina, and hymen in pelvic examination; examinations include routine blood, sex hormones, and thyroid function (Table 2), especially cranial MRI and pelvic ultrasound.
Based on the history and ancillary tests, it is generally not difficult to make a diagnosis of the etiology of amenorrhea, and the corresponding treatment varies among etiologies.
Anatomical abnormalities
Müllerian duct hypoplasia syndrome – normal karyotype, mainly presenting with an initiating uterus or no uterus, no vagina, normal breast development; hymenal atresia and transverse vaginal septum (often accompanied by acute pelvic pain with menstrual blood accumulation).
Surgical treatment is recommended.
Androgen insensitivity syndrome – often normal breasts, scant pubic and axillary hair, presence of male genitalia, serum androgen levels in the male range, and a karyotype of 46XY.
Testicular excision is recommended to avoid malignancy.
Uterine adhesions – decreased menstrual flow with abdominal pain in severe cases.
Treatment with hysteroscopic dissection of adhesions.
Primary ovarian hypofunction
Premature ovarian failure: folliculopoietin is in the menopausal range and amenorrhea or scanty menstruation occurs before the age of 40. The incidence is about 1%, 90% of which is caused by acquired factors such as radiation, radiotherapy, and autoimmune processes that can also cause infertility.
Hormone replacement therapy is recommended to reduce the incidence of osteoporosis, ischemic heart disease and menopausal symptoms, combined with exercise and calcium supplementation.
Turner syndrome: The karyotype is 45X or its variants, with specific phenotypes such as webbed neck, low hairline, heart defects, and lymphedema. Some patients present only with short stature, and their defects in ovarian function are variable (even with the possibility of fertility).
Hormone replacement and growth hormone are used to treat this. Such patients need to be screened for aortic stenosis, renal malformations, hearing loss or hypothyroidism.
Hypothalamic factors
Functional hypothalamic amenorrhea is often secondary to weight loss, excessive exercise, stress, eating disorders or malabsorption syndromes, and presents with low estrogen and gonadotropin levels, but no organic disease.
Treatment involves finding the causative factors, correcting the energy imbalance, and assessing bone density and supplementing with calcium and vitamin D. After correction, menstruation may resume and osteoporosis is gradually reversed. Current studies also confirm the effectiveness of leptin in the treatment of functional hypothalamic amenorrhea.
Serum prolactin levels
Elevated levels are often due to drug effects, pituitary adenoma, hypothyroidism or impaired hypothalamic inhibition.
MRI of the pituitary gland is routinely recommended, but may be dispensed with if drug effects or PRL <100 ng/mL are clearly identified. prolactinomas are treated with dopamine agonists when found, and surgical excision is considered in severe cases.
Lesions of the central nervous system
Infection or injury to the central nervous system or autoimmune destruction of the pituitary gland can lead to amenorrhea. Note the distinction between primary delayed puberty and functional hypothalamic amenorrhea, both of which are hypogonadotropic hypogonadism, the former being a lack of secondary sexual characteristics and the latter often being secondary amenorrhea. Hypothalamic congenital gonadotropin-releasing hormone deficiency should also be considered, as in the case of olfactory deficiency syndrome.
Polycystic ovary syndrome (PCOS)
A multifactorial endocrine disorder characterized by hyperandrogenism, polycystic ovaries and anovulation. Androgen levels are usually no more than 2 times the upper limit of normal, and when they are too high, other causes need to be considered. Fasting blood glucose and insulin release tests need to be checked in such patients, and prolonged anovulation will increase the risk of endometrial cancer.
Patients are advised to be treated aggressively and guided to assist in pregnancy. First-line treatment is weight control and exercise, and medications are low-dose contraceptives to regulate menstruation and lower androgens, and metformin to improve insulin resistance and ovulation.
Pregnancy and contraception
Pregnancy should be ruled out first and ectopic pregnancy should be ruled out in case of abdominal pain. It is worth noting that long-cycle contraceptives such as levonorgestrel intrauterine delayed-release system (Mannorrhea) can also cause amenorrhea.
Thyroid and adrenal gland disorders
Severe hyperthyroidism is likely to cause amenorrhea; late-onset congenital adrenocortical hyperplasia, androgen-secreting tumors, and Cushing’s syndrome should be distinguished from hyperandrogenic amenorrhea in PCOS. Meaningful elevation of androgen levels or rapid onset of symptoms requires consideration of adrenal or ovarian tumors. Increased cortisol due to Cushing’s syndrome rarely leads to amenorrhea.
In summary, all patients with amenorrhea should be treated by excluding pregnancy and making a clear etiologic diagnosis to avoid misdiagnosis.