PEPI: Bone Mineral Density
The Postmenopausal Estrogen/Progestin Interventions
(PEPI) Trial. Effects of hormone therapy on bone
mineral density: results from the postmenopausal
estrogen/progestin interventions (PEPI) trial.
Objective: To assess the effects of hormone therapy
on bone mineral density (BMD) in the spine and hip of
Design: A 3-year, multicenter, randomized, double-blinded,
placebo-controlled clinical trial.
Participants: A total of 875 healthy women aged
45 to 64 years recruited at 7 clinical centers.
Interventions: Treatments were
(2) conjugated equine estrogens [Premarin] (CEE), 0.625
(3) CEE, 0.625 mg/day plus medroxyprogesterone acetate
(MPA), 10 mg/day for 12 days/mo;
(4) CEE, 0.625 mg/day plus MPA, 2.5 mg/d daily; or
(5) CEE, 0.625 mg/day plus micronized progesterone (MP),
200 mg/day for 12 d/mo.
Main Outcome Measures: Bone mineral density at
baseline, 12 months, and 36 months.
Results: Participants assigned to the placebo group
lost an average of 1.8% of spine BMD and 1.7% of hip
BMD by the 36-month visit, while those assigned to active
regimens gained BMD at both sites, ranging from 3.5%
to 5.0% mean total increases in spinal BMD and a mean
total increase of 1.7% of BMD in the hip.
Changes in BMD for women assigned to active regimens were
significantly greater than those assigned to placebo.
Women assigned to CEE plus continuous MPA had significantly
greater increases in spinal BMD (increase of 5%) than
those assigned to the other 3 active regimens (average
Findings were similar among those adhering to assigned
therapy, although, among adherent participants, there
were no significant differences in BMD changes among
the 4 active treatment groups. Older women, women with
low initial BMD, and those with no previous hormone
use gained significantly more bone than younger women,
women with higher initial BMD, and those who had used
Conclusions: Postmenopausal women assigned to placebo
demonstrated decreased BMD at the spine and hip, whereas
women assigned to estrogen therapy increased BMD during
a 36-month period. These findings demonstrate that estrogen
replacement therapy increases BMD at clinically important
--The Writing Group for the PEPI
Comment in: JAMA 1996 Nov 6;276(17):1430-2
Comment in: JAMA 1997 May 21;277(19):1515; discussion
Journal of the American
Medical Association (JAMA)