A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin "add-back" regimens for women with leiomyomata uteri.
Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen-progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen-progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed.
Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
A J
AJ
Friedman
M
M
Daly
M
M
Juneau-Norcross
M S
MS
Rein
C
C
Fine
R
R
Gleason
M
M
Leboff
D000328:Adult; D015519:Bone Density / Q000187:drug effects; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism; D016729:Leuprolide / Q000627:therapeutic use; D008875:Middle Aged; D011372:Progestins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D013131:Spine / Q000378:metabolism; D017329:Triptorelin Pamoate / Q000031:analogs & derivatives*; D014463:Ultrasonography; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014599:Uterus / Q000000981:diagnostic imaging
D004338:Drug Combinations; D004967:Estrogens; D011372:Progestins; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; C019176:Tryptal; D016729:Leuprolide