Male Reproductive Disorders Flashcards
What is the basic physiology of the Hypothalamic-Pituitary-Testicular axis and how does this affect hypogonadism?
The reproductive axis is comprised of a series of interconnecting feedback loops between the hypothalamus (GnRH), the anterior pituitary (FSH, LH) and the testes. Hypogonadism can result from a defect at any level of the HPG axis.
What sorts of disorders may result in hypogonadism?
Disorders may be mechanical:
congenital absence of the testes
damage to the testes
Hormonal defect:
GnRH
LH and/or FSH
Testosterone production.
The defect can be congenital or acquired.
What are the two classes of hypogonadism?
Hypogonadotropic
Hypergonadotropic
What are the lab values and clinical signs of hypogonadotropic hypogonadism?
low LH and FSH and low testosterone, and impotence
What is the cause of congenital hypogonadotropic hypogonadism?
Congenital – This defect is termed GnRH deficiency (or Kallman’s syndrome when associated with anosmia,(loss of smell) or normosmic hypogonadotropiv hypogonadism ).
Due to a failure of migration of GnRH neurons to migrate to the hypothalamus. GnRH neurons are born in the olfactory placode in the nose. In utero, the neurons migrate with the olfactory neurons across the cribiform plate into the forebrain, to the hypothalamus. The signals for neuronal migration and gene expression are under intensive investigation. These patients have an “intact hardware, but the software program is missing”.
What are the common pathways for acquired hypogonadotropic hypogonadism?
a. Acquired defects are the most common cause of low Testosterone: observed after severe illness, surgery, or stress, or with obstructive sleep apnea, narcotics or repeated glucocorticoid injections.
b. A deficiency in LH and FSH can be seen with an INFILTRATIVE DISEASE (eg. hemochromatosis) that block production and or release of the pituitary gonadotropins. In hemachromatosis, iron deposition is selectively in gonadotropes. Patients also have liver disease, diabetes, and congestive heart failure.
c. In addition, some PITUITARY TUMORS make hormones that block the GnRH-induced LH and FSH signal such as prolactin, growth hormone, and ACTH. Prolactinomas are the most common pituitary tumor.
What additional hormone level should be examined in patients with hypogonadotropic hypogonadism and low LH, FSH, and testosterone levels?
prolactin levels
What are the lab values and clinical signs of hypergonadotropic hypogonadism?
High FSH &/or LH, and impotence
What are some causes of congenital hypergonadotropic hypogonadism?
congenital anorchia and vanishing testes syndrome
Klinefelter’s syndrome
mutations in the androgen receptor
What occurs in congenital hypergonadotropic hypogonadism caused by congenital anorchia and vanishing testes syndrome
An insult to the fetus (before 10-12 weeks of gestation) interrupts testicular development. The GnRH-induced gonadotropin signal is high in an attempt to stimulate the failing gonad.
HIGH LH and FSH levels and LOW testosterone levels.
How does Klinefelter’s syndrome result in hypergonadotropic hypogonadism?
A genetic defect of XXY is associated with a failing testes, with no spermatogenic elements, no Sertoli cells, but intact Leydig cells.
Small testes and delayed or incomplete puberty, gynecomastia, eunuchoid body habitus and infertility.
Often elevated FSH levels (due to lack of inhibin B), normal LH and low normal testosterone.
With time there is progressive tubular fibrosis and destruction of the Leydig cells; testosterone levels drop and LH levels rise. Risk for these men include increase in breast cancer (they need mammograms) and need for androgen replacement. Fertility is not possible.
What can happen if an XY person has a defect in the androgen receptor?
If mild they present with hypospadias, or ambiguous genitalia
If complete they present as females with inguinal gonads and a blind vaginal pouch and the disorder is called testicular feminization.
The estrogenization is excellent and the patients with complete defects are raised successfully as women after gonadectomy and estrogen replacement.
What do labs look like for someone with an androgen receptor mutation?
HIGH LH, FSH, Testosterone and Estradiol, but no clinical effects of the androgen because of the steroid receptor mutation.
What can cause acquired hypergonadotropic hypogonadism
mechanical and cytotoxic trauma to the testes such as torsion, mumps orchitis, alcohol, chemotherapy or radiation, infiltrative diseases, diabetes
What do lab values show in acquired hypergonadotropic hypogonadism
Early rise in FSH,(due to loss of inhibin) followed later by increase in LH and decline in testosterone. These patients eventually require androgen replacement.
