Gonadotropin Releasing Hormones Agonists Overview

Doctor holding injection

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Gonadotropin releasing hormone agonists (GnRH) are a type of medication that suppresses ovulation by stopping the production of estrogen and progesterone.

Gonadatropin releasing hormone is a naturally occurring hormone in the body. It is released by the hypothalamus and it controls the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. These hormones FSH and LH then stimulate the production of estrogen and progesterone in the ovaries. It is this relationship known as the hypothalamic pituitary ovarian axis that controls your menstrual cycle.

In order for this axis to function properly and result in ovulation, GnRH has to be released in a pulsatile fashion. If this axis is functioning properly you will have regular periods if you didn’t get pregnant when you ovulated.

GnRH Agonist Medications

The class of medications known as GnRH agonists exploits this need for pulsatile secretion of GnRH. The medication results in a continuous stimulation of the pituitary gland. At first, there can be a brief surge of FSH and LH release but then the non pulsatile concentration of GnRH causes the pituitary gland to stop producing FSH and LH, which ultimately turns off hormone production in the ovary.

The three GnRH agonists commonly used in clinical practice are:

  • Lupron - leuprolide
  • Zoladex - goserelin
  • Synarel - nafarelin

Leuprolide and goserelin are administered by injection in doses for every 4 weeks or 12 weeks while nafarelin is administered by a nasal spray 1-2 times daily. Most women will experience suppression of their ovaries by 4 weeks and almost all women will after 8 weeks of treatment.


Because GnRH agonists temporarily turn off your ovaries production of estrogen and progesterone this class of medications is used to treat certain conditions in women that are estrogen and progesterone dependent. These include:

There is also some evidence to suggest that GnRH agonists may also help preserve ovarian function in women undergoing chemotherapy for breast cancer.

Side Effects

These medications are very effective treatment options. Unfortunately, they have some significant side effects. Because they suppress your ovaries production of hormones, the side effects of GnRH agonists mimic the symptoms of menopause. These side effects include:

  • Hot flashes - most common, reported in 80% of women
  • Vaginal dryness
  • Decreased libido
  • Headache
  • Fatigue
  • Mood disturbances
  • Decreased bone mineral density

Obviously, the menopausal symptoms are unpleasant but the most concerning side effect is the loss of bone mineral density. In general, the bone loss is reversed after treatment has stopped but in a small number of women, this bone loss may never be fully recovered.

To prevent the loss of bone associated with GnRH treatment your doctor will likely prescribe a progestin or a combination of estrogen and a progestin. This is known as add-back therapy and it has been shown to be effective in preventing the bone loss associated with extended use of GnRH agonists. It also may help reduce the severity of the hot flashes as well.

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