Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women

Robert Lindsay, Christopher Gallagher, Michael Kleerekoper, James H. Pickar

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Context: Lower-than-commonly-prescribed doses of conjugated equine estrogens (CEEs) with medroxyprogesterone acetate (MPA) improve vasomotor symptoms and vaginal atrophy, provide acceptable bleeding and lipid profiles, and afford endometrial protection. This lower-dose therapy's protection against loss of bone mineral density (BMD) associated with menopause has not been thoroughly investigated. Objective: To determine the effects of lower doses of CEEs only or CEEs-MPA on spine and hip BMD, total body bone mineral content (BMC), and biochemical markers of bone turnover in postmenopausal women. Design and Setting: Two-year randomized, double-blind, placebo-controlled substudy of the Women's Health, Osteoporosis, Progestin, Estrogen trial, conducted at 19 US centers between August 1995 and October 2000. Participants: Eight hundred twenty-two healthy postmenopausal women aged 40 to 65 years who were within 4 years of their last menstrual period. Interventions: Patients were randomly assigned to receive CEEs, 0.625; CEEs, 0.625 and MPA, 2.5; CEEs, 0.45; CEEs, 0.45 and MPA, 2.5; CEEs, 0.45 and MPA, 1.5; CEEs, 0.3; CEEs 0.3 and MPA, 1.5 (all doses in mg/d); or placebo for 2 years. All participants also received elemental calcium at 600 mg/d. Main Outcome Measures: Changes from baseline in spine and total hip BMD, total body BMC, and biochemical markers of bone turnover (serum osteocalcin and urinary cross-linked N-telopeptides of type I collagen), assessed at 6-month intervals and compared among treatment groups with a modified intention-to-treat approach. Results: At 24 months, women assigned to all of the active treatment groups had significant gains from baseline (P

Original languageEnglish (US)
Pages (from-to)2668-2676
Number of pages9
JournalJournal of the American Medical Association
Issue number20
StatePublished - May 22 2002


All Science Journal Classification (ASJC) codes

  • Medicine(all)

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