title: Long-term continuous combined hormone replacement therapy in the prevention of postmenopausal bone loss: a comparison of high- and low-dose estrogen-progestin regimens.
abstract: We studied the effect of four continuous combined estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) dose combinations in six treatment groups (n = 70 per group) receiving regimens containing 1 mg or 2 mg E2V combined to 2.5 mg or 5 mg MPA, on bone mineral density (BMD) and endometrium in 419 healthy postmenopausal women over 4 treatment years. In two groups the 1 mg dose of E2V was increased to 2 mg after the first 6 months, while the MPA doses remained constant (2.5 mg or 5 mg). The remaining four groups received 1 E2V + 2.5 mg MPA, 1 mg E2V + 5 mg MPA, 2 mg E2V + 2.5 mg MPA, or 2 mg E2V + 5 mg MPA throughout the study. BMD at the spine and hip was measured by dual-energy X-ray absorptiometry and endometrial biopsy samples were taken at 6, 12, 24, 36 and 48 month follow-ups. Combinations containing the low dose of 1 mg of E2V (with 2.5 mg or 5 mg MPA) resulted in a mean BMD increase of 6.2% at the spine and 2.9% at the femoral neck after 4 years of treatment. With 2 mg E2V the corresponding increases were 7.4% and 2.9%, respectively. The largest increases in BMD were seen in women for whom the E2V dose was doubled after the initial 6 months of treatment: 8.9% at the spine and 4.2% in the femoral neck. Both MPA doses (2.5 mg and 5 mg) effectively prevented estrogen-induced stimulation of the endometrium. No endometrial hyperplasia was observed in any of the treatment groups. Lower-dose combinations of continuous combined estrogen-progestin regimens are effective in increasing and maintaining BMD and provide a good endometrial safety profile for the long-term prevention of osteoporosis in postmenopausal women.
authors.affiliation: The Deaconess Institute of Oulu, Isokatu, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Heikkinen
authors.forename: R
authors.initials: R
authors.lastname: Vaheri
authors.forename: P
authors.initials: P
authors.lastname: Kainulainen
authors.forename: U
authors.initials: U
authors.lastname: Timonen
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015519:Bone Density / Q000187:drug effects*; D004311:Double-Blind Method; D004338:Drug Combinations; D004717:Endometrium / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage*; D045166:Estradiol Congeners / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D045167:Progesterone Congeners / Q000008:administration & dosage*; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D045166:Estradiol Congeners; D045167:Progesterone Congeners; D004958:Estradiol; D017258:Medroxyprogesterone Acetate