title: Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata.
abstract: The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized 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 months 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 remaining 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 bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back 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 non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.forename: Y
authors.initials: Y
authors.lastname: Sagara
authors.forename: A
authors.initials: A
authors.lastname: Kikuchi
authors.forename: K
authors.initials: K
authors.lastname: Ando
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Matsumi
authors.forename: Y
authors.initials: Y
authors.lastname: Osuga
authors.forename: M
authors.initials: M
authors.lastname: Momoeda
authors.forename: Y
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015519:Bone Density; D003692:Delayed-Action Preparations; D004964:Estriol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy*; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use*; D008159:Lumbar Vertebrae; D008875:Middle Aged; D010024:Osteoporosis / Q000517:prevention & control; D014594:Uterine Neoplasms / Q000188:drug therapy*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D016729:Leuprolide; D004964:Estriol