Estriol add-back therapy in the long-acting gonadotropin-releasing hormoneagonist treatment of uterine leiomyomata

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyo mas but to induce bone loss. Estriol has been described to be a weak and sh ort-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatmen t of uterine leiomyomata with GnRHa plus oral estriol add-back therapy coul d prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomi zed to receive either leuprolide acetate depot alone at a dose of 3.75 mg s c every month for 6 months (non add-back group; n = 6), or GnRHa for 6 Mont hs plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the rema ining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bon e-specific alkaline phosphatase, increased significantly throughout the tre atment in the non and-back group, whereas they were suppressed by the add-b ack therapy. The bone mineral density of lumbar. spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the iron add-back group, but did not change significant ly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.