Gonadotropin-releasing hormone analog

A gonadotropin-releasing hormone analog, also known as a GnRH analog, is a class of synthetic peptide drugs modeled on the human hypothalamic gonadotropin-releasing hormone (GnRH) and designed to mimic or antagonize the physiological effects of GnRH for therapeutic purposes.

Agonist versus antagonist

Drugs that stimulate GnRH receptors are called GnRH agonists and drugs that block such receptors are GnRH antagonists. Paradoxically an agonist can have an antagonist effect through downregulation of receptors. Commonly long-term agonists are used to "shut-down" the reproductive system. Thus after a brief agonistic effect with realease of FSH and LH of the pituitary, after about 10 days a phase hypogonadism is entered due to the downregulation effect. While this phase is reversible it can be maintained with further medication for a long time.

Indications

In clinical practice, these drugs are most commonly used to suppress the sex steroids produced by the reproductive system. Among the conditions in which suppression of reproductive hormones is sometimes desirable:

1. estrogen-dependent cancers, such as breast cancer
2. testosterone-dependent cancers, such as prostate cancer
3. precocious puberty
4. endometriosis
5. severe catamenial (i.e., dependent on the menstrual cycle) disorders

There are far fewer conditions in which a GnRH analog is used as an agonist:

1. as a substitute for GnRH (now unavailable) for endocrine diagnostic testing
2. cryptorchidism
3. a mature graafian follicle can be ovulated by use of GnRH or its agonistic analog.

In the stimulation process for IVF gonadotropin drugs are usually supplemented with a GnRH analog to prevent endogenous ovulation. This allows for better control of the stimulation cycle; typically exgenous human chorionic gonadotropins (HCG) are used to trigger ovulation.

Current medications

The most common drugs of the agonists are leuprolide, nafarelin, and buserelin. Leuprolide is by far the most commonly used in North America. A currently available antagonist is cetrorelix.