Successful treatment of severe premenstrual syndrome by combined use of gonadotropin-releasing hormone agonist and estrogen/progestin.

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 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.

• Authors: J F Mortola, L Girton, U Fischer
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 72 Issue 2 Pg. 252A-252F (Feb 1991) ISSN: 0021-972X [Print] United States
• PMID: 1846868 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Estrogens, Conjugated (USP)
• Placebos
• Gonadotropin-Releasing Hormone
• Medroxyprogesterone Acetate
• histrelin
• Medroxyprogesterone

Topics

• Adult
• Double-Blind Method
• Drug Therapy, Combination
• Estrogens, Conjugated (USP) (administration & dosage, therapeutic use)
• Female
• Gonadotropin-Releasing Hormone (administration & dosage, analogs & derivatives, therapeutic use)
• Humans
• Medroxyprogesterone (administration & dosage, analogs & derivatives, therapeutic use)
• Medroxyprogesterone Acetate
• Placebos
• Premenstrual Syndrome (drug therapy, physiopathology)