GnRH

Gonadotropin-releasing hormone (GnRH) is a neurohormone consisting of ten amino acids which is produced by the arcuate nuclei of the hypothalamus. It is integral for starting the reproductive hormone cascade.

GnRH is secreted in the hypothalamus which is part of the brain. The hypothalamus is part of the 'Hypothalamus - Pituitary - Gonad' axis which regulates the reproductive system in men and women. Secretion of GnRH by the hypothalamus is delivered through a direct pathway between the hypothalamus and pituitary. GnRH stimulates the synthesis and secretion of two gonadotrophins namely, lutenizing hormone (LH) and follicle stimulating hormone (FSH) by the anterior pituitary gland. Controlled by internal and external factors, GnRH acts in a negative feedback loop. For instance, if there is excess FSH, LH or testosterone, then these hormones will inhibit GnRH production.

Lifestyles can also affect GnRH secretion. Lack of exercise, poor diet, opiad drugs and excessive stress can negatively affect GnRH production. What is so striking in GnRH is that under normal circumstances, GnRH is released at intervals of 90 to 120 minutes. Hence, in patients with GnRH deficiency, the releasing hormone should be administered in pulses. Constant administration of GnRH also suppresses gonadotropin secretion especially in children in puberty stage and in men with prostate cancer.

Why is GnRH treatment used?

This hormone is produced by the hypothalamus and it stimulates the pituitary gland to produce LH and FSH. Lack of GnRH in the hypothalamus can halt testosterone production in the testicles of men. In women, abnormal GnRH levels can be responsible for ovulatory disorders.

This is commonly used when Clomid treatment has not stimulated egg follicles to develop on the ovaries. GnRH works effectively to replace the natural GnRH in women and men who do not produce enough of it. Failure of release of GnRH can result in deficiency that can be partial or complete.

In a woman who is not ovulating because of lack of stimulation from hypothalamus.

In a man who is not producing sperm because his hypothalamus is not stimulating the hormones that trigger sperm production.

The use of GnRH can result in multiple pregnancies.

Some studies report that the pregnancy rate after treatment with GnRH is about 20%.

Side effects

Some side effects include:

• Breathing trouble
  
• Swelling of face, lips, tongue and throat
  
• Itching and redness at the site of the intravenous catheter
  
• Infection at the site of the IV catheter
  
• Ovarian hyper stimulation syndrome - GnRH poses less risk of this syndrome than does human menopausal Gonadotropin and other treatments for ovulation.

The small pump that is used for GnRH may bother some people and treatment requires daily monitoring by a doctor.

Although clinicians and scientists have observed the findings of olfactory disturbances and reproductive dysfunction, the syndrome comprising complete GnRH deficiency and lack of olfactory senses is named Kallmann Syndrome after the American geneticist Kallmann who identified this disorder in 1944.

Treatment

The choice of therapy depends upon the patient's desire to achieve one or more of the following options:

• Secondary sexual characteristics
  
• Fertility
  
• Bone and muscle mass

In males, treatment is decided to provide androgen replacement. The patient's age, potential adverse effects of therapy, patient's desire for fertility are considered. In the prepubertal male, GnRH stimulates penile growth, body and facial hair growth, bone and muscle development and voice changes. Androgens also stimulate growth hormone production, contributing to the adolescent growth spurt. Male androgen deficiency can result in social ridicule and therefore starting androgen therapy around age 14-15 is prudent.

Oral, injectable and transdermal and implantable pellets formulation are available for treatment of males with Kallmann syndrome. Oral androgen preparations should not be used due to their toxic effects on the liver and adverse effects on lipids. Injectable long-acting testosterone are low-cost, relatively safe and effective. The disadvantages include intramuscular injection and non physiologic pattern of testosterone over the dosing interval. There could be wide swings in libido in some men.

Transdermal patches and gel preparation of testosterone are currently available - adverse effect with these formulations include skin reactions at the application. In females as in males, treatment depends upon age and fertility desires. Estrogen replacement is a must to prevent osteoporosis.

Oral preparations, transdermal patches, vaginal cream and rings are available for standard hormone replacement therapy. Transdermally administered 17 beta estradiol has been shown as an effective regimen for preventing bone loss in normal menopausal women.

Women with intact uterus receive a cyclical progestin to accompany estradiol treatment. Optimal hormone therapy depends upon whether the patient has primary or secondary amenorrhea. Gradual dose escalation results in optimal breast development and allows time for young woman to adjust psychologically to her physical maturation.

AFP Test

AFP Test or Alpha-fetoprotein test is conducted on pregnant women to check the AFP level in the blood. The liver in the fetus produces AFP naturally. Determining the amount of AFP in the mother's blood will help identify any neural tube defect in the fetus. Neural tube defects arise in 2 out of every 1,000 pregnancies. AFP test also helps check for Down's syndrome. There are 60% chances for detecting Down's syndrome when the AFP levels are low in the blood. AFP can also be calculated from the sample of amniotic fluid of a pregnant woman. This screening test is generally performed between 16 and 18 weeks of pregnancy and is very sensitive between 15 and 17 weeks. The accuracy of the AFP test result lies in the exact age of the fetus. The AFT test is also referred to as maternal serum alpha-fetoprotein (MSAFP). AFP test is done on men and non-pregnant women too to confirm cancer in the testicles, stomach, pancreas, liver and the ovaries. High levels of AFP can indicate renal cell cancer.

Interpretation of AFP test results: In men and non-pregnant women, the values of the AFP test is 0-6.4 IU/mL (international units per milliliter), 0-20 nanograms per milliliter (ng/mL) or 0-20 micrograms per liter. In pregnant women of about 15 - 22 weeks gestation, the AFP results usually show 19-75 IU/mL, 7-124 ng/mL or 7-124 microgram per liter. AFP test values vary depending on the weight of the woman and race. Black women have higher values than white women and white women have higher values than Asian women. High AFP can suggest multiple pregnancies, fetus with neural tube defects, and abdominal wall defect in the fetus or fetal death. In non-pregnant adults, high AFP values mean cancer in the testicles or ovaries. High AFP can also indicate liver disease and bowel inflammation.

ELISA test

ELISA is an abbreviation for 'enzyme-linked immunosorbent assay'. ELISA tests are relatively accurate tests, highly sensitive and specific. They compare favorably with other methods used to detect substances in the body such as Radio immune assay (RIA) tests. ELISA tests have an added advantage in that there is no need for radioisotopes or costly radiation counter. An HIV ELISA test is also called HIV enzyme immunoassay (EIA). It is the first and basic test to determine if an individual is positive for a selected pathogen such as HIV. The test is performed in a plastic plate of 8 cm x 12 cm which contains 8 x 12 matrix of 96 wells, each of which is about 1 cm high and 0.7 cm in diameter.

A patient's serum contains certain antibodies. If the patient is HIV positive, then the serum will contain antibodies to HIV. Those antibodies will bind to the HIV antigens on the plate. Sometimes, even in some individuals not infected with HIV antibodies, positive result is given in HIV ELISA. This is called false positive. One reason for false positive is that in women who have had multiple pregnancies, may possess the antibodies directed against human leukocyte antigens (HLA) which are present in host cells used to propagate HIV. As HIV buds from the surface of the host cell, it incorporates some of the host cell HLA into its envelope. False negatives can also occur during the window between infection and an antibody response to the virus called seroconversion. A person will be retested if the serum gives positive result. If the ELISA retests are also positive, then the patient will be retested by western blot analysis.