Review Article

Revisiting Estrogen: Efficacy and Safety for Postmenopausal Bone Health

Table 2

Selected studies on the effect of lower doses of hormone therapy on bone metabolism in postmenopausal women.

Study NameStudy TypeSample Size, Mean Age in Years (Range), and
Years since Menopause
Type of TherapyDoseTreatment DurationResults for BMD, BMC, or Fracture Risk

ULTRA Trial [39]RCT417,
67 (60–80),
5 years
E2 patch or placebo patch*E2: 0.014 mg/day2 years2.1% greater LV BMD versus placebo.

HOPE Trial [40]RCT822,
51.6 (40–65),
1 to 4 years
CEE,
CEE + MPA, or placebo*
CEE: 0.625, 0.45, or 0.3 mg/d
MPA: 2.5 or 1.5 mg/d
2 years1.33–3.46% increase in LV BMD;
Approximately 1.5–3% increase in hip BMD;
1.03–1.74% increase in total BMC, with these doses.

Gambacciani et al, 2008 [41]Open TrialSample size not provided,
57 (range not provided),
1 year
E2 + NA (oral) or no treatment*1 mg E2 + 0.5 mg NA for 28 d or 0.5 mg E2 + 0.25 mg NA per day2 years2–5% increase in LV BMD;
1.8–2.8% increase in femur neck BMD, with these doses.

Garcia-Pérez et al, 2006 [42]Transversal Study136, 53 for 0.05 mg/d and placebo groups to 56 for 0.025 mg/d group (range not provided),
1 year
E2 patch + micronized progesterone, or placebo*E2: 0.05 or 0.025 mg/d progesterone: 100 mg/d18 months0.73–0.92% increase in femur neck BMD;
-0.35–0.87% change in LV BMD, with these doses.

Gambacciani et al, 2001 [43]Open Trial38,54 (45–56),
1 year
CEE + MPA*CEE: 0.3 mg/d
MPA: 2.5 mg/d
2 years2.7% increase in LV BMD.

CEE: Conjugated Equine Estrogen, MPA: Medroxyprogesterone Acetate, NA: Norethisterone Acetate, E2: 17β-estradiol, BMD: Bone Mineral Density, BMC: Bone Mineral Content, and LV: Lumbar Vertebrae. *All subjects received additional supplementation with calcium alone or with vitamin D.