Introduction to late-onset hypogonadism

  As early as the 1930s, Western scholars found that some middle-aged and elderly men would experience physical decline, sexual dysfunction, psychological disorders, hot flashes, poor concentration, memory loss and emotional instability, and first adopted the term “male menopause syndrome” to name the disease. “In the 1970s, some scholars called it “menopause”, which corresponds to “menopause”, but in the following half century, many scholars considered its name inappropriate. In 1994, the Austrian Urological Society proposed for the first time to rename the “male menopause syndrome” as “partial androgen deficiency syndrome in middle-aged and older men (PADAM)” at the European Male Science Symposium, which was widely recognized. After the 1990s, American scholars proposed the name “androgen deficiency syndrome in middle-aged and older men” (ADAM) until 2002, when the International Society for the Study of Aging Men (ISSAM) renamed the syndrome as late-onset hypogonadism (LOH), the reason why it was called “late-onset “The reason for this name is that there are many causes of hypogonadism, including primary hypogonadism if the lesion is in the gonads themselves, secondary hypogonadism if the lesion is in the pituitary and hypothalamus, and LOH, also known as age-related testosterone deficiency syndrome (TDS), is a clinical and biochemical syndrome associated with aging, characterized by certain clinical symptoms and It is characterized by certain clinical symptoms and reduced serum testosterone levels (below the normal reference range for young healthy adult males), which seriously affects the quality of life and adversely affects the function of various organs and systems of the body.  Clinical manifestations and auxiliary examinations I. Clinical manifestations LOH prevalent age is generally older than 40 years old, mainly has four symptoms, such as sexual dysfunction, physical decline, mental and psychological disorders and vasodilatation, among which the most common clinical symptom is loss of libido.  1, sexual dysfunction: loss of interest in matters involving sex, loss of libido, erectile dysfunction, decrease in the number of erections and erectile hardness at night.  2, physical decline: easy fatigue, general weakness, can not engage in heavy physical labor, serious cases of independent living ability decreased.  3, mental and psychological disorders: poor mental state, inattention, forgetfulness; depressed mood, irritability or indifference, irritability, anxiety and even panic, intellectual and spatial skill activity disorders; sleep disorders, insomnia and depressive symptoms, etc.  4. Vasodilatory symptoms: hot flashes (non-exertional), excessive sweating (unintended and sudden) and flushing, as well as panic and shortness of breath, chest tightness and blood pressure fluctuations.  5.Other symptoms: centripetal obesity, low back pain, limb and joint pain may occur. Due to osteoporosis, minor trauma can lead to fracture. Patients with LOH often show insulin resistance and can develop many symptoms of type II diabetes and metabolic syndrome.  Physical examination There may be an increase in blood pressure, a slight decrease in height, weight gain, increase in abdominal circumference and skin atrophy, etc. Due to the decrease in testosterone level, there may be a weakening of male secondary sexual characteristics, hair thinning, a slight decrease in testicular volume and a slight softening of texture, etc.  (1) Physical examination: height, weight, blood pressure, body mass index (BMI), abdominal circumference, external genitalia, breast, etc.  (2) Blood biochemical examination: liver and kidney function, blood glucose, blood lipids, etc.  (3) Other examinations: blood and urine routine examination, etc.  (4) Prostate assessment tests: serum prostate-specific antigen test (PSA), prostate rectal examination (DRE), prostate ultrasound.  Serum sex hormones include FSH, LH, PRL, T, E2, etc. Testosterone in human blood circulation exists in the form of free testosterone (FT) and protein-bound testosterone, with only 2% being FT and 98% being protein-bound testosterone. Of the protein-bound testosterone, about 43% is bound to the higher affinity sex hormone binding globulin (SHBG) and about 55% is bound to the weaker affinity albumin. Free testosterone and albumin-bound testosterone are called bioavailable testosterone (Bio-T or non-SHBG-bound testosterone). Young men differ from older men in that there is a distinct circadian rhythm of testosterone, peaking between 6:00 and 8:00 am and dropping to a minimum between 17:00 and 18:00 pm, with a trough value of about 50% of the peak. [1][28] Middle-aged and older men show elevated serum SHBG concentrations with increasing age, resulting in normal or decreasing total testosterone (TT), while free testosterone decreases very significantly, with its decline far exceeding that of serum TT [28] (level 2b, level A).  (1) Detection methods of serum sex hormones: serum sex hormones can be detected by immunological principle-based detection methods (radioimmunoassay, enzyme-linked immunoassay, etc.) and supporting commercial kits, which can basically meet the needs of clinical diagnosis of LOH, and chemiluminescence and mass spectrometry are more precise and accurate, and currently, chemiluminescence is mostly used in tertiary hospitals in larger cities in China. When the serum total testosterone level cannot accurately diagnose LOH, free testosterone (FT) and bioactive testosterone (Bio-T) levels should be measured. There is no universally accepted low limit of normal free testosterone criteria for the diagnosis of LOH; however, when free testosterone is below 225 pmol/L (65 pg/ml), it is a strong basis for testosterone therapy. The threshold for bioactive testosterone varies depending on the assay method used and is not currently widely used clinically. The gold standard method for free testosterone is the equilibrium dialysis method, but this method is expensive, time-consuming and lacks a normal range of reference values based on population data. Therefore, serum sex hormone-binding globulin (SHBG) is measured along with total serum testosterone, and free testosterone (cFT) is then calculated. There is a good correlation between the calculated value of free testosterone and the measured value of equilibrium dialysis method. Obtaining a stable constant of testosterone binding to SHBG and albumin level will greatly improve the accuracy of the calculated value of free testosterone.  (2) Judgment of test results: At present, there is no uniform cut-off value at home and abroad, and the lower value of the 95% confidence limit of the age group of 30~39 years old or the 10% median is generally used as the cut-off value. The recommended cut-off values for low serum T levels are: TT≤11,5nmol/L, TSI≤2,8nmol/IU (TSI testosterone secretion index TT/LH), cFT≤0,3nmol/L, FTI≤0,42nmol/nmol (FTI free androgen index, TT/SHBG).  (3) The following issues should be noted regarding the determination of serum sex hormones: ① Since there is no unified test method and standard, each laboratory should establish its own test method and undergo clinical validation; it should also establish the reference range and quality control system for laboratory determination of various hormone parameters for normal population of different age groups in the laboratory; ② At least two times, the patient’s blood should be drawn between 7:00 and 9:00 in the morning for serum sex hormone levels. ③The measurement of total serum testosterone is currently the accepted standard for the diagnosis of LOH, and if total serum testosterone is greater than 11,5 nmol/L, testosterone supplementation is generally not required; ④If total serum testosterone is less than 8 nmol/L, patients can benefit from testosterone supplementation; ⑤If total serum testosterone is between 8 and 11,5 nmol/L, further testing is required (6) When total serum testosterone is less than 5 or 2 nmol/L or when secondary hypogonadism is suspected, LH and serum prolactin (PRL) should be tested to make a comprehensive judgment on the function of the hypothalamic-pituitary-gonadal axis; (7) When other endocrine disorders are suspected in clinical symptoms, E2, thyroid hormone, cortisol, growth hormone, etc. should be tested; (8) When total testosterone is less than 8 nmol/L, testosterone supplementation can benefit patients. (8) In addition to the interpretation of the test results in the context of clinical symptoms, the influence of the hypothalamic-pituitary-gonadal axis should be taken into account, as well as the influence of the metabolites of androgens on the body (the activity of AR, aromatase activity and 5α-reductase activity should be taken into account).