Successful Treatment of Severe Premenstrual Syndrome by Combined Use of Gonadotropin-Releasing Hormone Agonist and Estrogen/Progestin*

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Abstract
Although abolishment of ovarian cyclicity by the use of a long-acting GnRH agonist (GnRH-a) provides effective treatment for premenstrual syndrome (PMS), its use is limited by sequellae of the resultant hypoestrogenism. In this study the effects of estrogen/progestin replacement on the symptomatic improvement afforded by GnRH-a were evaluated in eight women with severe PMS. The 8-month study design included 2 months of control, 2 months of GnRH-a alone, and 4 further months in which the exogenous steroids were replaced in randomized, double blind, placebo-controlled cross-over fashion using 1 month each of 1) conjugated equine estrogen (CEE) on days 1–25, 2) 10 mg medroxyprogesterone acetate (MPA) on days 16–25, 3) CEE (days 1–25) plus MPA (days 16–25), and 4) placebo alone. Mood and physical symptoms were measured daily on a valid and reliable instrument, the Calendar of Premenstrual Experiences. As expected, administration of GnRH-a alone resulted in a 75% improvement in luteal phass symptom scores (17.8 ± 4.8 vs. 4.2 ± 1.6; P < 0.01). Combined sequential administration of CEE and MPA in addition to GnRH-a was effective in maintaining the reduced symptom scores seen after GnRH-a alone and was superior to the addition of CEE alone, MPA alone, or placebo. This combination of CEE and MPA resulted in a 60% improvement (P < 0.05) compared to the luteal phase of control months in both behavioral (14.1 ± 3.9 vs. 4.2 ± 0.8) and total (17.8 ± 4.8 vs. 6.5 ± 1.8) symptoms. We conclude that the undesirable consequence of ovarian steroid deficiency in the treatment of PMS by GnRH-a can be overcome by the addition of sequential estrogen and progsstogen replacements without significantly reducing the effectiveness of GnRH-a in this disorder.

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