Medical Health Encyclopedia

GnRH Analogs. Potent hormonal drugs called gonadotropin-releasing hormone (GnRH) agonists suppress ovulation and, thereby, the hormonal fluctuations that produce PMS. They are sometimes used for very severe PMS symptoms and to improve breast tenderness, fatigue, and irritability. (These drugs, in fact, are sometimes used to rule out or confirm a diagnosis of PMS. If symptoms persist while the drug is being taken, then PMS is unlikely to be their cause.) GnRH analogs, however, appear to have little effect on depression.

They include nafarelin (Synarel), goserelin (Zoladex), leuprolide (Lupron Depot), and histrelin (Supprelin). Some experts believe that GnRH analogs may be useful as first line therapy in some women with menstrual pain and irregular periods. These drugs are also effective for relieving symptoms of severe PMS, endometriosis, fibroids, and menorrhagia.

Commonly reported side effects (which can be severe in some women) include menopausal-like symptoms that include hot flashes, night sweat, and changes in the vagina, weight change, and depression. The side effects vary in intensity depending on the GnRH agonist. They may be more intense with leuprolide and persist after the drug has been stopped.

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The most important concern is possible osteoporosis from estrogen loss. Women ordinarily should not take them for more than six months. Certain approaches may preserve enough estrogen to protect bones and still effectively relieve endometriosis symptoms:

Click the icon to see an image of osteoporosis.

• Add-back therapy, which provides doses of estrogen and progestin that are high enough to maintain bone density, but are too low to offset the beneficial effects of the GnRH agonist.
• Intermittent leuprolide, which uses repeated six-month courses of GnRH agonists followed by an average of nine months of symptom control only.
• Taking GnRH agonists in very low doses is an alternate approach, but is still largely untested.
• Adding a bone-protective agent called a bisphosphonate (alendronate or etidronate) may also be helpful.
• Other drugs are being tested in combination with a GnRH agonist to preserve bone. They include parathyroid hormone or tibolone (available in Europe). Tibolone is known as a selective estrogen-receptor modulator (SERM), which means it has some, but not all, effects of estrogen.