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Bone Mass Response to Discontinuation of Long-term Hormone Replacement Therapy
Results From the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study
Gail A. Greendale, MD;
Mark Espeland, PhD;
Stacey Slone, MS;
Robert Marcus, MD;
Elizabeth Barrett-Connor, MD;
for the PEPI Safety Follow-up Study (PSFS) Investigators
Arch Intern Med. 2002;162:665-672.
Background Accelerated bone loss after stopping hormone therapy (HRT) is postulated
to explain the lack of hip-fracture protection conferred by former HRT use.
The abbreviation HRT (traditionally standing for "hormone replacement therapy")
is used herein because of its wide recognition in the field. However, the
pharmacological doses of estrogens and progestins used are not truly "replacement"
in nature.
Objectives To determine whether women lose bone mineral density (BMD) after stopping
HRT; to assess whether their rate of loss is significantly greater than that
of women not undergoing HRT; and to determine whether long-term HRT is associated
with continued gains in BMD.
Methods A total of 495 women who were adherent to assigned treatment in the
3-year Postmenopausal Estrogen/Progestin Interventions randomized controlled
trial (PEPI-RCT) and who had an additional BMD measurement during the PEPI
Safety Follow-up Study were observed for an average of 3 years during and
4 years after the PEPI-RCT.
Results Women who stopped HRT after 1 year during the PEPI-RCT had annual rates
of BMD change of -0.54% (hip) and -0.81% (spine) during the following
2 years. Those who underwent HRT for 3 years during the PEPI-RCT and then
discontinued it had annual changes of -1.01% (hip) and -1.04%
(spine). Rates of BMD loss among women who stopped HRT during or after the
PEPI-RCT did not differ significantly from those of women who did not undergo
HRT, who lost bone at a rate of approximately 1% yearly during the first year
of the PEPI-RCT and about half that rate afterward. Women who continued HRT
after the PEPI-RCT did not show additional BMD gains.
Conclusions Our results do not support the hypothesis that bone is lost at an unusually
fast rate after discontinuation of HRT, nor do they suggest that longer-term
HRT leads to additional BMD gain beyond that evident after 3 years.
From the Division of Geriatrics, University of California at Los Angeles
School of Medicine, Los Angeles (Dr Greendale); the Department of Public Health
Sciences, Wake Forest School of Medicine, Winston-Salem, NC (Dr Espeland and
Ms Slone) the Department of Medicine, Stanford University and the Geriatrics
Research, Education and Clinical Center, Veterans Affairs Medical Center,
Palo Alto (Dr Marcus); and the Department of Family and Preventive Medicine,
University of California at San Diego, San Diego, Calif (Dr Barrett-Connor).
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