Successful treatment of severe premenstrual syndrome by combined use of gonadotropin-releasing hormone agonist and estrogen/progestin.
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 phase symptom scores (17.8 +/- 4.8 vs. 4.2 +/- 1.6; P less than 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 less than 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 progestogen replacements without significantly reducing the effectiveness of GnRH-a in this disorder.
Mortola
J F
JF
Department of Reproductive Medicine, University of California, San Diego School of Medicine, La Jolla 92093.
Girton
L
L
Fischer
U
U
D000328:Adult; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008525:Medroxyprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017258:Medroxyprogesterone Acetate; D010919:Placebos; D011293:Premenstrual Syndrome / Q000188:drug therapy* / Q000503:physiopathology
D004966:Estrogens, Conjugated (USP); D010919:Placebos; D007987:Gonadotropin-Releasing Hormone; D017258:Medroxyprogesterone Acetate; C029256:histrelin; D008525:Medroxyprogesterone