Original Article

Osteoporosis International

, Volume 11, Issue 11, pp 929-937

First online:

Long-Term Continuous Combined Hormone Replacement Therapy in the Prevention of Postmenopausal Bone Loss: A Comparison of High- and Low-Dose Estrogen–Progestin Regimens

  • J. HeikkinenAffiliated withThe Deaconess Institute of Oulu, Isokatu, Oulu
  • , R. VaheriAffiliated withOrion Pharma, Espoo, Finland
  • , P. KainulainenAffiliated withOrion Pharma, Espoo, Finland
  • , U. TimonenAffiliated withOrion Pharma, Espoo, Finland

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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.

Key words:Bone mineral density – Continuous combined hormone replacement therapy – Estradiol valerate – Medroxyprogesterone acetate – Postmenopausal osteoporosis