How Do Gonadotropin Releasing Hormone Agonists Work?

Gonadotropin-releasing hormone (GnRH) agonists are medications used to relieve the symptoms of endometriosis in adult women and delay the onset of central precocious puberty in children. GnRH agonists work by desensitizing the stimulatory effect of GnRH on the pituitary gland which secretes reproductive hormones in response.

GnRH agonist is a synthetic form of the natural GnRH secreted by the hypothalamus. GnRH stimulates the pituitary gland to release follicular stimulating hormone (FSH) and luteinizing hormone (LH), which are responsible for the development and functioning of the reproductive glands (gonads), ovaries in females, and testes in males.

Gonadotropin-releasing hormone agonists initially stimulate the pituitary gland which results in a temporary increase in the gonadotropins FSH and LH. Continued administration of GnRH desensitizes the pituitary gland, subsequently leading to a decrease in the secretion of gonadotropins and the production of sex hormones by the ovaries and testes.

Endometriosis is a condition in which endometrial tissue that normally lines the inside of the uterus gets implanted outside the uterus, most commonly on the ovaries, fallopian tubes, outer surface of the uterus, intestines, or the pelvic lining. These tissues go through the same cyclic changes which result in internal bleeding, inflammation, and scarring.

Central precocious puberty is a condition caused by premature secretion of gonadotropins due to conditions such as congenital brain anomalies, brain tumors, or injuries, which leads to abnormally early onset of puberty and development of secondary sexual characteristics in children, before ages eight in girls and nine in boys. In most cases of central precocious puberty, the cause cannot be identified.

By suppressing the secretion of FSH and LH, gonadotropin-releasing hormone agonists reduce estrogen production by the ovaries, which helps shrink the endometrial tissue and relieve endometriosis symptoms. Reduction in FSH and LH to prepubertal levels slows down the rate of sexual maturation and skeletal growth in children.

Gonadotropin releasing hormone agonist is a nasal spray approved by the FDA for use in the following conditions:

• Management of endometriosis in adult women including pain relief and reduction of endometrial lesions. The spray is administered twice a day, once in the morning in one nostril and once in the evening in the other nostril, starting between days 2-4 of the menstrual cycle. The maximum treatment duration is six months.
• To delay the onset of central precocious puberty in both boys and girls (age two years and above). A total of eight sprays are administered per day, two sprays in each nostril once in the morning and once in the evening. The treatment is continued until puberty onset is desired.

Side effects of gonadotropin-releasing hormone agonists may include the following:

• Acne
• Breast enlargement
• Vaginal bleeding
• Seborrhea (a skin condition that causes an itchy rash and dandruff)
• Emotional lability (mood swings)
• Crying
• Irritability
• Impatience
• Anger
• Aggression
• Depression
• Suicidal ideation and attempt, in children, treated for central precocious puberty (rare)
• Vaginal discharge
• Rhinitis (inflammation of the nasal passage)
• Body odor
• Increase in pubic hair
• Arthralgia (joint pain)
• Breast engorgement
• Chloasma (facial skin pigmentation disorder)
• Maculopapular rash (flat and raised skin lesions)
• Paresthesia (abnormal skin sensation)
• Weakness
• Palpitations
• Eye pain
• Liver injury
• Pituitary apoplexy (hemorrhage or impaired blood flow into the pituitary gland)
• Pituitary gland changes
• Seizures
• Ovarian hyperstimulation syndrome

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with travel medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of the FDA-approved gonadotropin-releasing hormone agonist drug are:

• nafarelin
• Synarel