Bone mass response to discontinuation of long-term hormone replacement therapy: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) Safety Follow-up Study.
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.


OBJECTIVE
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.
Greendale
Gail A
GA
University of California at Los Angeles School of Medicine, 10945 Le Conte Ave, Suite 2339, Los Angeles, CA 90095-1687, USA.
Espeland
Mark
M
Slone
Stacey
S
Marcus
Robert
R
Barrett-Connor
Elizabeth
E
D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000503:physiopathology* / Q000517:prevention & control*; D045167:Progesterone Congeners / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors; D028761:Withholding Treatment
D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; D017258:Medroxyprogesterone Acetate