The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial.
BACKGROUND
Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women.


OBJECTIVE
To determine the bone-sparing effect of continuous low-dose HRT in elderly women.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
University osteoporosis research and clinical center.


METHODS
128 healthy white women (age > 65 years) with low bone mass recruited by word of mouth and by local advertisement. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less.


METHODS
Continuous therapy with conjugated equine estrogen, 0.3 mg/d, and medroxyprogesterone, 2.5 mg/d, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups.


METHODS
Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months.


RESULTS
During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant increases were seen in total-body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived.


CONCLUSIONS
Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well tolerated by most patients.
Recker
R R
RR
Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska 68131, USA.
Davies
K M
KM
Dowd
R M
RM
Heaney
R P
RP
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density; D002118:Calcium / Q000008:administration & dosage*; D003404:Creatinine / Q000652:urine; D019587:Dietary Supplements; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008525:Medroxyprogesterone / Q000008:administration & dosage* / Q000009:adverse effects; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives*
D015415:Biomarkers; D004966:Estrogens, Conjugated (USP); D015675:Osteocalcin; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D003404:Creatinine; D000469:Alkaline Phosphatase; D008525:Medroxyprogesterone; D006909:Hydroxyproline; D002118:Calcium