Medroxyprogesterone acetate with Zoladex for long-term treatment of fibroids: effects on bone density and patient acceptability

A randomized trial was carried out to investigate the effect of 12 monthsadministration of the gonadotrophin-releasing hormone agonist (GnRHa)Zoladex in combination with either placebo or medroxyprogesterone acetate(MPA) from the third month. Bone density, markers of bone resorption,symptoms and uterine volume were monitored in 24 women with symptomaticfibroids or menstrual problems. A total of 21 women were recruited to actas controls for the assessment of bone parameters. Vasomotor side-effectswere reduced significantly in the MPA-treated group. The reduction inuterine volume in women with fibroids was not impaired by the addition ofMPA. The bone markers osteocalcin and alkaline phosphatase were assessed inplasma, and the cross-links pyridinoline and deoxypyridinoline measured inurine. Changes in these markers are reported which suggest increases inbone resorption during the period of observation. Bone mineral density(BMD) was assessed by dual energy X-ray absorptiometry at the spine andforearm. The net reduction in BMD at the spine in the treated groups was4.30 +/- 0.59% at 6 months and 7.50 +/- 0.78% at 1 year, with no change inthe control group. No change was seen in forearm BMD. No protective effectwas observed when MPA was added. At 1 year after the completion oftreatment, BMD remained significantly below baseline, and this hasimplications for the prolonged use of GnRHa.