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 mon ths will result in profound hypoestrogenism, a significant but tempora ry 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 symptom s. 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 acetat e depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or proges tin-only add-back regimen for an additional 92 weeks. Efficacy paramet ers assessed included serial uterine volumes, hemoglobin concentration s, and hematocrits; safety parameters evaluated included serial bone m ineral density measurements, lipid profiles, and medication-related sy mptoms. This report analyzes the first 52 weeks of study data. Mean ut erine 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 wee k 52. Both groups demonstrated significant improvements in mean hemogl obin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol con centration, which was not seen in the estrogen-progestin add-back grou p. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regime n 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 prog estin add-back regimen in all efficacy and safety parameters assessed.