Applications of Gonadotropin-Releasing Hormone Analogues in the Treatment of Premenstrual Syndrome

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Abstract
A regimen in which a GnRH agonist is used with estrogen-progestin replacement provides a significant potential advance in the treatment of PMS. Substantial evidence indicates that the pathophysiology of PMS is dependent on cyclic progesterone changes which, after a time delay, influence central neurotransmitter systems and peripheral tissues. Because of the myriad neurotransmitter changes induced by progesterone, the most comprehensive treatment of the complex array of symptoms in severe PMS may require pharmacologic agents that reduce circulating progesterone levels. The most effective agent in this regard in a GnRH analogue. Until recently, use of these analogues has been limited to short-term courses as a result of the deleterious effects of hypoestrogenism. Based on newer information, a regimen in which a GnRH agonist is used concomitantly with CEE and MPA replacement appears to ameliorate PMS symptoms substantially while providing a proven estrogen-progestin replacement therapy to protect against the side effects of hypoestrogenism. Before treatment, an accurate diagnosis must be made that rests on exclusion of concomitant psychiatric and/or medical diagnoses and prospective symptom recording. In addition, before use of the GnRH agonist and estrogen-progestin add-back treatment, consideration should be given to agents, such as fluoxetine and alprazolam, which target specific neurotransmitter alterations. Currently, the superiority of one agent over others has not been tested in controlled trials. Nonetheless, in patients who cannot tolerate or do not respond to fluoxetine and alprazolam, a GnRH agonist plus estrogen and progestin appears the indicated treatment of choice.

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