male hypogonadism
Introduction
Introduction to male hypogonadism Male hypogonadism is a series of manifestations of testicular dysfunction caused by various causes. The clinical manifestations of male gonad function reduction vary with age at onset. If the gestational age is 2 to 3 months, androgen deficiency occurs, causing pseudohermaphroditism. Insufficient androgen deficiency during puberty, manifested as a lack of secondary sexual characteristics and ecstasy, penis is child-type, testicles are small, scrotum is smooth and wrinkle-free, pubic hair and mane are sparse, face, chest and abdomen and back hair are scarce or rare, The voice is thin, the muscles are underdeveloped, and the physical strength is lower than normal. If adult males lack androgen, manifested as loss of libido, impotence, poor physical strength, decreased hair and beard, accompanied by infertility. basic knowledge The proportion of illness: 0.005% Susceptible people: male Mode of infection: non-infectious Complications: impotence, erectile dysfunction, premature ejaculation, male infertility
Cause
Causes of male hypogonadism
(a) hypothalamic pituitary disease
1. Hypothalamic-pituitary tumor
Inflammation, trauma, surgery, granuloma, etc., affect the production and release of GnRH, insufficient secretion of pituitary gonadotropin, thereby affecting testicular development, reduced androgen production and spermatogenesis defects, male testicular softening, genital atrophy, impotence, libido Decreased, infertile, may be associated with hypothalamic syndrome or other manifestations of anterior pituitary dysfunction.
2. Gonadotropin-secreting hypogonadism (Kallmann syndrome)
Also known as olfactory loss-like testis syndrome: the intrinsic is congenital, the karyotype is 46XY, the cause may be autosomal dominant, recessive or X-linked inheritance, due to incomplete formation of the olfactory bulb during embryonic development, can cause Hypothalamic GnRH secretion is low, leading to hypogonadal function, decreased testosterone secretion, testicular spermatogenic disorder, manifested as lack of smell, secondary sexual dysplasia, similar to no testicular state.
3. Simple LH deficiency: The patient has the characteristics of no testicular disease, with male breast development, low serum LH and testosterone, FSH can be normal, seminiferous tubules can produce fertility, and HCG can cause testicular maturation.
4. Simple FSH deficiency: less common, interstitial cells can normally secrete testosterone, male sexual characteristics are normal, due to FSH deficiency affects spermatogenesis, causing infertility.
5. Low muscle tone - mental retardation - sexual development - obesity syndrome (Prader-Willi syndrome)
The cause is unknown, may be autosomal recessive inheritance, low muscle tone after birth, lethargy, sucking and swallowing reflex disappeared, feeding difficulties, muscle tone improved after several months, polyphagia, obesity, mental retardation, gonadal development defects, Secondary sexual dysplasia, may have cryptorchidism, male breast development, mild diabetes, short jaw, eyelid skin, auricular deformity and other congenital anomalies.
6. Sexual naive-retinal retinitis-multi-finger (toe) malformation syndrome (Laurence-Moon-Biedl syndrome)
For autosomal recessive inheritance, due to congenital defects of hypothalamic-pituitary, causing insufficient secretion of gonadotropin, secondary hypotesty function, patients with mental retardation, growth retardation, secondary sexual characteristics do not appear during puberty, penis and testicles None of them develop, obesity, retinitis pigmentus causes vision loss or blindness, and there are multiple fingers (toes) or fingers (toe) deformities.
7. Alstrams syndrome
For the pathogenesis of autosomal recessive genes, this disease is rare, clinically and Laurence-Moon Biedl syndrome has many similarities, such as retinitis pigmentosa, obesity, sexual naive, but this disease has no mental retardation and multi-finger (toe) malformation .
8. Obesity reproductive incompetence syndrome (Froehlish syndrome)
Any cause (such as craniopharyngioma) caused by hypothalamic-pituitary damage can cause this disease, which is characterized by rapid obesity, drowsiness, polyphagia, delayed bone development, and male breast development or diabetes insipidus in a short period of time. External genital and secondary sexual dysplasia, blood LH, FSH is lower than normal.
9. Cortisol
The adrenal cortex secretes a large amount of cortisol and androgen, and both feedback inhibit the release of gonadotropin from the pituitary gland, which reduces testosterone secretion and hypogonadism.
10. Congenital adrenal hyperplasia
It refers to the congenital deficiency of certain enzymes in the synthesis of adrenocortical steroid hormones, resulting in decreased cortisol synthesis, decreased feedback inhibition, increased ACTH secretion in the pituitary gland, resulting in adrenal hyperplasia, and the need for five enzymes in the process of cholesterol synthesis of testosterone. Participation (Figure 15-56), in which cholesterol carbon chain enzyme (20,22-carbon chain lyase), 3-hydroxysteroid dehydrogenase, 17-hydroxylase are present in both the adrenal gland and testicular tissue, their Defects lead to the synthesis of glucocorticoids and mineralocorticoid disorders in the adrenal gland, leading to testicular synthesis of testosterone. In the early stage of male embryos, if there is a serious defect in testosterone synthesis, it affects the male differentiation of the fetus, which may occur in the vagina, hypospadias, cryptorchidism. But no uterus and fallopian tubes, cholesterol carbon chain enzyme deficiency, cholesterol can not be converted to pregnenolone, cortisol, aldosterone and sex hormone synthesis have barriers, a large amount of cholesterol deposition, causing lipid adrenal hyperplasia, clinically showed adrenal insufficiency Symptoms, male pseudo-sexual malformation, patients with early early loss, 3-hydroxysteroid dehydrogenase deficiency Causing leads to chronic adrenal insufficiency, ACTH increase, adrenal hyperplasia; male reproductive organ differentiation and development, hypospadias, cryptorchidism, breast development, etc., 17-ketosteroids in the urine, 17-hydroxylase deficiency, cortex Alcohol secretion is reduced, ACTH is elevated, 11-deoxycorticosterone is increased, male genitalia is female or pseudo-sexual malformation, vas deferens can have different degrees of development, and elevated plasma pregnenolone is helpful for diagnosis.
11. Hyperprolactinemia
PRL can inhibit the secretion of LH and FSH, so that the testicular secretion of testosterone and seminiferous tubules can reduce spermatogenesis, which can be associated with male breast development and galactorrhea.
12. Familial cerebellar ataxia
It is a familial disease, characterized by sexual naiveness, small external genitalia, small and soft testicles, less mane, female pubic hair, high pitch, high body and no testicular shape, low mental retardation, even dementia, slow cerebellum Axia, can be associated with neurological deafness, optic atrophy.
13. Hemochromatosis
Autosomal recessive inheritance, due to excessive absorption of iron in the intestinal mucosa and iron barrier of reticuloendothelial cells, excessive iron deposition in the hypothalamic pituitary, decreased gonadotropin secretion, hypogonadism, testicular atrophy, male breast development.
(B) testicular dysfunction
1. Testicular development and structural abnormalities
(1) Congenital testicular hypoplasia syndrome (Klinefelter syndrome): is a more common genetic disease of sex chromosome aberration, see Klinefelter syndrome.
(2) 46, XX male syndrome: the intrinsic sex chromosome is XX, no Y chromosome, HY antigen can be detected in serum, suggesting that there is a small amount of Y embedded in X or autosome, which can not be found in vitro culture, and its phenotype is In males, the incidence rate is 1:20,000 to 24,000. The patient lacks all female genitalia and has male psychological characteristics. The clinical manifestations are similar to Klinefelter syndrome: the testicles are small and hard (generally less than 2 cm). There are often male breast development, penis size is normal or slightly smaller than normal adults, usually with sperm deficiency and glassy changes of seminiferous tubules, blood testosterone levels are reduced, estradiol levels are elevated, gonadotropin levels are elevated, clinically This type is similar to the XXY/XY chimeric type, with short stature, mental retardation and personality changes are very light, and relatively rare, the incidence of hypospadias is increased.
(3) Male Turner syndrome: autosomal dominant inheritance, nucleus shape 46, XY, clinical manifestations of typical Turner syndrome: short stature, neck brace, elbow eversion, congenital heart disease, male phenotype, Often there are cryptorchidism, testicular shrinkage, seminiferous tubule dysplasia, sexual naive, blood testosterone decreased, serum gonadotropin levels increased, a small number of patients with normal testes, and fertile.
(4) Adult seminiferous tubules can be reduced: causes include orchitis, cryptorchidism, radiation damage, uremia, alcoholism, anti-tumor drugs, etc., without clear cause, impaired light, testicular biopsy can be seen in various stages of germ cells The number is reduced, and the growth of germ cells is stopped at the stage of spermatogonial cells or primary spermatocytes. In severe cases, there are no germ cells, only intact support cells, and the most severe cases are fibrosis and transparency. Deformation, clinical manifestations of infertility, testicular mild to moderate atrophy, interstitial cells secrete testosterone function, secondary sexual characteristics developed well, no breast development, semen examination showed less sperm or no sperm, blood testosterone or LH concentration normal The basal blood FSH is normal or increased, and the FSH is excessively increased after stimulation with GnRH.
(5) Interstitial cell hypoplasia: fetal interstitial cells secrete testosterone disorder, produce male pseudohermaphroditism, testicular but spermatogenic disorder, vulvar deformity, female phenotype, penis similar to clitoris, blind end vagina, but no uterus , fallopian tube, to adolescence only found primary amenorrhea, pubic hair, scarce hair, patients FSH, LH base value increased, GnRH test gonadotropin response, blood testosterone is significantly lower, HCG stimulation does not increase.
(6) There is no testicular disease: the embryonic stage causes complete atrophy of the testicle due to infection, trauma, vascular embolism or testicular torsion. The phenotype is male. The second sex of adolescent male is not developed, and the external genitalia remains immature. Without testicles, if you do not give androgen treatment as early as possible, there will be a lieutenant body type. If residual or ectopic stromal cells secrete androgen, moderate second sexual characteristics may occur, blood testosterone levels are low, and gonadotropin is significantly elevated. High, testosterone does not increase after HCG stimulation.
(7) cryptorchidism: can be unilateral or bilateral, with the most common in the groin, because the intra-abdominal temperature is higher than the temperature inside the scrotum, so the spermatogenic function of the cryptorchidism is inhibited, and easy to cancer, cryptorchidism is generally no Symptoms, can not touch the testis on one or both sides, no androgen deficiency, often accompanied by infertility, and no testicular disease, cryptorchidism patients with HCG stimulation, testosterone significantly increased.
(8) Atrophic myotonia: adult onset, face, neck, hand and lower extremity muscle tonic atrophy, ptosis, frontal muscle compensatory contraction, increased frontal ridge, 80% with primary testicular function Decreased, serum FSH is significantly elevated, is a familial disease, autosomal dominant inheritance.
(9) Adult interstitial cell hypofunction: also known as male menopausal syndrome, males gradually appear sexual dysfunction after age 50, may have personality and mood changes, blood testosterone gradually reduced, gonadotropin increased, sperm decreased Or lack.
(10) Immotile cilia syndrome: an autosomal recessive genetic defect characterized by respiratory tract and sperm cilia activity disorders, such as Kartagener syn-drome, expressed as Visceral reversal ectopic, chronic sinusitis and bronchiectasis triad, infertility due to sperm cilia movement disorders.
2. Acquired testicular abnormalities
(1) testicular infection: can be divided into non-specific, viral, fungal, spirochete, parasitic and other types, mumps virus-induced viral orchitis is the most common, clinical manifestations of affected testicular swelling, scrotal skin edema , hydrocele effusion, often with chills and high fever, abdominal pain, testicular ulcers can have varying degrees of atrophy after the disease, some patients can cause infertility.
(2) Trauma: The testicles are vulnerable to external violence, and the disappearance of spermatogonial cells in the seminiferous tubules leads to infertility. If there is a hematoma, destroying blood supply can also lead to testicular atrophy.
(3) Radiation damage: Spermatogonia is very sensitive to radiation damage. If it is damaged, oligozoospermia or azoospermia may occur.
(4) Drugs: spironolactone and ketoconazole can inhibit testosterone synthesis. Spironolactone and cimetidine compete with androgen for cytoplasmic receptor protein and interfere with the role of testosterone in target cells. Taking mediostatin, digitalis can make plasma estradiol. Increased testosterone decreased, long-term alcohol abuse, can cause plasma testosterone reduction, anti-tumor and chemotherapy drugs, insecticides, dibromochloropropane, cadmium and lead, can inhibit spermatogenesis, leading to infertility.
(5) Autoimmunity: Schmidt syndrome has anti-testicular basement membrane antibody. If the blood-testis barrier is destroyed, semen acts as an antigen and produces an autoimmune reaction, producing anti-sperm antibodies, male prostatitis or epididymitis, especially E. coli infection. When anti-sperm antibodies are produced, sperm granuloma can be formed after vas deferens obstruction or severance. Sperm destroys and absorbs in sperm granuloma to form antigen, and produces anti-sperm antibodies. Currently, two types of anti-sperm antibodies, spermatozoa, can be detected. Agglutination antibodies and sperm-braking antibodies, anti-sperm antibody, can reduce sperm motility and sperm agglutination or non-liquefaction, in addition, anti-sperm antibodies can promote immune orchitis, produce antigen-antibody complex deposition in testicular germ cells On, affecting the occurrence of normal sperm.
3. Testicular abnormalities associated with systemic diseases
Systemic diseases such as chronic liver disease, renal insufficiency, severe malnutrition, metabolic disorders, diabetes, etc. can lead to testicular dysfunction and infertility.
(3) Androgen synthesis or its deficiency
The karyotype of the patient is 46, XY, and the gonad is the testis. Due to the deficiency of androgen, the development of sexual organs in the embryo is not completely masculine, and the formation of male pseudohermaphroditism can be divided into three categories according to the cause:
1. Androgen synthesis defect
In the testosterone production pathway, there are five different enzymes involved, and any one of the enzyme defects can cause testosterone synthesis disorder, which leads to male pseudohermaphroditism, in which cholesterol carbon chain enzyme (20, 22 carbon chain lyase), 3-hydroxysteroid dehydrogenase, 17 hydroxylase is present in the testis and adrenal gland, if these three defects, not only cause male pseudohermaphroditism, but also cause congenital adrenal hyperplasia; two other enzymes (17, 20 carbon chain lyase, and 17-hydroxysteroid dehydrogenase) are only present in the testis, and if it is defective, it only causes male pseudohermaphroditism.
2. Secondary renal tubular degeneration
It is also a rare autosomal recessive or X-linked recessive hereditary disease. In the fetal period, it supports the secretion of paramyroidal inhibitory factor (MIF) in the cell, or binds to the receptor, making 46, XY male patients retain Some female reproductive ducts (fallopian tubes, uterus, 1/3 of the vagina), due to MIF and testicular drop substances are secreted by the supporting cells, so the degeneration of the secondary renal tube may be accompanied by ipsilateral cryptorchidism, testicular hypoplasia, but also Mixed with hypogonadism with high cancer rate.
3. Androgen insensitivity
(1) testicular feminizaation syndrome: male pseudohermaphroditism, the patient is caused by androgen insensitivity due to the androgen receptor and post-receptor defects in the target organ, and belongs to X-linked recessive genetic disorder. Intrinsic scores are complete and incomplete, 1 complete androgen insensitive - testicular feminization, also known as complete male pseudohermaphroditism, karyotype 46, XY, in the embryonic period, in the abdominal or genital The developmental testis, because the middle kidney tube is not sensitive to androgen, can not further differentiate into vas deferens, seminal vesicle, prostate and ejaculatory duct, the vulva can not differentiate into male direction, but the fetal testicular support cells can still secrete MIF, so the deputy kidney Tube degeneration, no fallopian tube, uterus and upper vaginal segment, the external genitalia is completely female when born, has a shallow blind end vagina, can touch the testicle in the groin or genital area of the child, in the adolescence, because the target organ is not sensitive to androgen , causing increased secretion of LH, thus increasing testosterone, testosterone conversion to produce estradiol, so that women's secondary sexual characteristics, such as breast development, but primary After a few patients, the clitoris increased and there was mild masculinity. After puberty, the testes were easily malignant and should be removed. 2 Incomplete androgen-insensitive, also known as incomplete male pseudo-sexual deformity type I, Reifenstein Syndrome, karyotype 46, XY, due to partial orrogen receptor defects or post-receptor defects, phenotype biased to men, but the degree of masculinity is very different, severe genital hermaphroditism, blind end Vagina, perineal scrotum-type hypospadias, mild manifestations of dysplastic male external genitalia, small penis, hypospadias and scrotal bifurcation, puberty, poor male development, male breast development, more fertility, Testosterone, LH and estradiol were elevated.
(2) 5a-reductase deficiency: also known as incomplete male pseudohermaphroditism type II, is autosomal recessive, nucleus is 46, XY, due to lack of 5a-reductase, testosterone is converted to dihydrotestosterone deficiency Male external genital development disorder, manifested as small penis, perineal hypospadias, scrotum is bilobal, patients have testes, epididymis, vas deferens and seminal vesicles, no uterus, fallopian tubes and ovaries, puberty, masculinity, no male breast development The sperm count is normal, the plasma testosterone level is normal or increased, the dihydrotestosterone is lowered, and the LH is increased.
The clinical manifestations of male gonad function decline vary with age at onset, such as hormonal deficiency at 2 to 3 months, causing pseudohermaphroditism, androgen deficiency during puberty, and a lack of secondary sexual characteristics. The shape of the stagnation disease, the penis is child-type, the testicle is small, the scrotum is smooth and wrinkle-free, the pubic hair and the mane are sparse, the face, chest, abdomen and back are lacking or very rare, the voice is thin, the muscle is underdeveloped, and the physical strength is lower than normal. Male androgen deficiency, manifested as loss of libido, impotence, poor physical strength, decreased hair and beard, accompanied by infertility.
Prevention
Male hypogonadism prevention
The key to the prevention and treatment of this disease is early detection, early diagnosis, early treatment, symptomatic treatment, male hypogonadism caused by hypothalamic-pituitary secretion of gonadotropin deficiency, using gonadotropin treatment, which helps to recover Spermatogenic function and promote the development of secondary sexual characteristics, cryptorchidism should use HCG in 2 to 9 years old, stimulate the secretion of endogenous testosterone, it is possible to correct cryptorchidism, the external genitalia have gender deformity, the choice of gender is very important, requires The selected gender enables the patient to better adapt to social life and have better sexual development during adolescence.
Complication
Male genital hypofunction complications Complications, impotence, erectile dysfunction, premature ejaculation, male infertility
Mainly complicated by impotence (erectile dysfunction), premature ejaculation, male infertility and other symptoms.
Symptom
Male hypogonadism symptoms common symptoms testicular hypoplasia testicular microsecond secondary changes recurrent genital ulcer
Determination of gonadotropin in the blood can distinguish between hypogonadal dysfunction as primary or secondary. The former has elevated gonadotropin base values; the latter is reduced, and the LRH excitatory test and the chloramphenicol test can determine the pituitary gland. The reserve capacity, the hypogonadal hypogonadism is weak, the hypothalamic is weak or delayed, the primary hypogonadism is active, the chorionic gonadotropin (HCG) stimulation test, normal male or child Plasma testosterone is at least doubled, plasma testosterone is also elevated after cryptorchidism injection, and no testosterone has no such reaction, secondary sexual development, testicular location, size, texture, and plasma testosterone levels, semen routine Examination helps to establish the presence and extent of testicular dysfunction, karyotyping, and detection of plasma dihydrotestosterone for further classification.
Examine
Examination of male gonads hypofunction
(1) Determination of blood and urine related hormones
1. Testosterone determination: Male blood testosterone 90% from the testis, which reflects the function of interstitial cells, normal adult male blood testosterone levels of 10 ~ 35nmol / L (3 ~ 10mg / L, RIA method).
2. The plasma dihydrotestosterone level in normal young men with dihydrotestosterone (DHT) is about 10% of testosterone, about 2 nmol/L (0.5 mg/L) (RIA method).
3.24-hour urinary 17-ketosteroid determination: urinary 17-ketosteroids mainly from the adrenal weak androgen or its metabolites, only 40% of testosterone metabolites, can not accurately reflect the testicular function, so the results should be combined with clinical analysis .
4. Determination of plasma LH: The normal value of LH in adult males is 5-10 IU/L (RIA method). Testosterone should be measured simultaneously when measuring LH. If both levels are low, it indicates hypothalamic and pituitary diseases; if plasma testosterone levels are low, LH levels If elevated, it suggests primary testicular insufficiency.
5. Determination of plasma FSH: The normal adult male FSH range is 5-20 IU/L, and the hypothalamic-pituitary axis is normal. If the spermatogenic epithelial destruction is severe, the FSH level is increased.
6. Chorionic gonadotropin (HCG) stimulation test: HCG biological activity is similar to LH by intramuscular injection of HCG 4000IU once a day for 4 days, blood test for testosterone on day 5, normal response to blood testosterone levels doubled from normal If the ground value is low, the absolute value of the increase should be calculated. The primary hypogonadism is reduced. After HCG stimulation, the blood testosterone is not significantly increased. The testicular interstitial cell function secondary to the lower pituitary function is reduced. Testosterone was significantly increased.
7. Clomethene test (100-200mg/d orally), LH and FSH increased after 6 days in normal people, and the response of pituitary or hypothalamic lesions was significantly reduced.
8. LRH excitatory test: can reflect the reserve of pituitary gonadotropin by intravenous injection of LRH 50g, blood LH and FSH at 0', 15', 30', 120', normal male peaks appear in 15' ~ 30', LH increased about 2 to 5 times, FSH increased about 2 times, patients with impaired pituitary function showed low weak response, LH and FSH did not increase; hypothalamic lesions showed delayed response, intravenous drip LRH714 After a day, the response of the pituitary to LRH stimulation can return to normal, primary testicular disease, LH and FSH secretion is too high, such as lesions confined in the seminiferous tubules, FSH can be abnormally elevated, but LH response is normal.
(2) Chromosome sex analysis
1. Sex chromosome: The peripheral blood venous lymphocytes were analyzed by fluorochromatography for karyotype analysis. The normal male karyotype was 46, XY, and the normal female karyotype was 46, XX. The C-band analysis can identify the presence or absence of mitosis in the middle. The Y chromosome, G band analysis is useful for finding the type of chromosomal malformation.
2. Sexual chromatin: also known as Barr's body (Barr: body), can be detected by oral mucosa smear, female chromatin is positive, male is negative.
(three) semen examination
Normal males have a fine volume of 2 to 6 ml, the total number of sperm exceeds 60 million, the density is more than 20 million/ml, and the sperm with normal vitality and morphology should be more than 60%.
(4) Sperm penetration of cervical mucus test
Sperm can pass through the cervical mucus, fertility, or infertility.
(5) Anti-sperm antibody and anti-serum serum antibody
If positive, it indicates that the presence of these antibodies in the reproductive tract of women causes sperm to aggregate or inhibit sperm activity, causing infertility.
(6) Testicular biopsy
It can identify vas deferens obstruction and spermatogenic failure.
(7) seminal vesicle, vas deferens angiography
You can understand the blockage of the insemination pipeline.
(8) Histocompatibility Y antigen (HY antigen)
Unique to men, it is a more gender-specific marker than sex chromosomes. It does not exist in women and contributes to the analysis of the causes of hermaphroditism. The most common form of true hermaphroditism is 46,XX males, which cannot be found in cytogenetics. Shifted Y chromosome fragment, but HY antigen expression indicates that the patient has Y chromosome gene. Male pseudohermaphroditism has normal male karyotype and bilateral testicular differentiation, HY antigen is positive, female pseudohermaphroditism is normal female nucleus, and there are double Lateral ovaries, HY antigen negative.
(9) Other auxiliary diagnosis:
X-ray bone age determination, pelvic B-ultrasound, CT, MRI for gonads, pipeline exploration, etc.
Diagnosis
Diagnosis and differentiation of male gonads hypofunction
The disease is mainly primary or secondary identification, the former gonadotropin base value increased; the latter decreased, LRH stimulation test and chloralamine test can determine the pituitary reserve capacity, pituitary gland function Attenuation is weak, weak hypothalamic response or delayed response, primary hypogonadal dysfunction is active, chorionic gonadotropin (HCG) stimulation test, normal male or child plasma testosterone is at least doubled, Plasma testosterone is also elevated after cryptorchidism, but no testicular symptoms, secondary sexual development, testicular location, size, texture, and plasma testosterone levels, routine semen examination helps establish testicular insufficiency The presence and extent, karyotype analysis, and detection of plasma dihydrotestosterone contribute to further classification.
