hypogonadism

definition  The clinical manifestations of androgen deficiency depend on the time of onset and the degree of deficiency. Either testosterone deficiency or defective spermatogenesis constitutes hypogonadism.

 Testosterone: -wolffian duct development into the epididymis, vas deferens, seminal vesicles, and ejaculatory ducts -virilization of the external genitalia  early prenatal androgen deficiency : ambiguous genitalia and pseudohermaphroditism. - Androgen deficiency later during gestation: micropenis or cryptorchidism, the unilateral or bilateral absence of testes in the scrotum resulting from the failure of normal testicular descent.

 During puberty, androgens are responsible for male sexual differentiation, which includes growth of the scrotum, epididymis, vas deferens, seminal vesicles, prostate, penis, skeletal muscle, and larynx  androgens stimulate the growth of axillary, pubic, facial, and body hair, as well as increased sebaceous gland activity *Postpubertal androgen deficiency may result in a decrease in libido impotence, low energy, fine wrinkling around the corners of the eyes and mouth, and diminished facial and body hair.

Male hypogonadism may be classified into three categories 1 -primary or hypergonadotropic hypogonadism, 2- secondary or hypogonadotropic hypogonadism 3-Defects in Androgen Action

HYPOTHALAMIC-PITUITARY DISORDERS  Panhypopituitarism occurs congenitally from structural defects or from inadequate production or the release of the hypothalamic-releasing factors. -tumors -infarction from vascular insufficiency -infiltrative disorders - Autoimmune diseases - trauma - infections

 Kallmann syndrome : hypogonadotropic hypogonadismassociated with problems in the ability to discriminate odors, either incompletely (hyposmia) or completely (anosmia)  Hyperprolactinemia : hypogonadotropic hypogonadism because prolactin elevation inhibits normal GnRH release, decreases the effectiveness of LH at the Leydig cell level, and also inhibits some of the action of testosterone at the target organ level.  Weight loss or systemic illness in male patients can cause another form of secondary hypogonadism, hypothalamic dysfunction.

PRIMARY GONADAL ABNORMALITIES  Klinefelter syndrome  occurs in about 1 of every 600 live male births  XXYgenotype.  At puberty, clinical findings include :  degrees of hypogonadism; gynecomastia; small, firm testes measuring less than 2 cm in the longest axis azoospermia; and elevations of FSH and LH

 myotonic dystrophy,  Cryptorchidism : which spontaneously corrects during the first year of life incidence of this condition is about 0.75%.  When the testes are maintained in the intra-abdominal position, the increased temperature leads to defective spermatogenesis and oligospermia.  Leydig cell function generally remains normal, and therefore adult testosterone levels are normal  Bilateral anorchia,( vanishing testicle syndrome): external genitalia are fully formed. However, the testicular tissue disappears before or shortly after birth, and the result is an empty scrotum.

 Acquired gonadal failure * infections: mumps, gonococcal or lepromatous orchitis, irradiation, vascular injury, trauma, alcohol ingestion, chemotherapeutic drugs,  The serum FSH concentrations may be normal or elevated,  The Leydig cell compartment may also be damaged by these same conditions. some men experience a gradual decline in testicular function as they age, possibly because of microvascular insufficiency.  The decreased testosterone production may clinically exhibit lowered libido and potency, emotional lability, fatigue, and vasomotor symptoms such as hot flushes. The serum LH concentration is usually elevated in this situation

DEFECTS IN ANDROGEN ACTION  androgen action:  When either testosterone or its metabolite, dihydrotestosterone, binds to the androgen receptor in target cells, the receptoris activated and binds DNA with resulting stimulation of transcription, protein synthesis, and cell growth,  An absence of androgen receptors causes the syndrome of testicular feminization,a form of male pseudohermaphroditism

testicular feminization  cryptorchid testes but appear to be phenotypic females.  the labial-scrotal folds fail to fuse, and a short vagina results.  The fallopian tubes, uterus, and upper portion of the vagina are absent because the testes secrete müllerian duct inhibitory factor  At puberty, these patients have breast enlargement because the testes secrete a small amount of estradiol, and the peripheral tissues convert testosterone and adrenal androgens to estrogens.  Axillary and pubic hair does not grow.  The serum testosterone concentrations are elevated as a result of continuous stimulation by LH  may have incomplete forms of androgen insensitivity and clinically these patients show varying degrees of male pseudohermaphroditism.

Treatment  Treatment of androgen deficiency in patients who have hypothalamic- pituitary or primary testicular abnormalities is exogenous testosterone  Testosterone therapy increases libido, potency, muscle mass, strength, athletic endurance,and hair growth on the face and body.  Side effects include : acne, fluid retention, erythrocytosis, BPH, and, rarely, sleep apnea. This therapy is contraindicated in patients with cancer of the prostate.  GnRH: If fertility is desired, patients with hypothalamic abnormalities may develop virilization and spermatogenesis

MALE INFERTILITY  Infertility affects about 15% of couples, and male factors responsible in 40% of cases. Female factors for another 40%, couple factor is present in about 20% of cases.  defects in spermatogenesis that occur in patients with hypothalamic, pituitary, testicular, or androgen action disorders, hyperthyroidism, hypothyroidism, adrenal abnormalities, and systemic illnesses  retrograde ejaculation :Disorders of the vas deferens, seminal vesicles, and prostate may also lead to infertility, as can diseases affecting the bladder sphincter sperm passes into the bladder rather than through the penis