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Bone Loss Resumes When Hormone Replacement Therapy Stops, But At Normal Rate

WINSTON-SALEM, N.C. – Stopping hormone replacement therapy does not appear to accelerate loss of bone in postmenopausal women, according to a long-term follow-up of the national Postmenopausal Estrogen/Progestin Intervention (PEPI) study.

Writing in Monday''s (March 25, 2002) edition of Archives of Internal Medicine, the research team said, "Our results suggest that women who stop hormone replacement therapy may resume bone loss, but it will be at a rate similar to women who never took these drugs."

The seven-year study also showed that while bone mass increased substantially in the first 36 months after starting hormone replacement therapy, there was little gain in bone mass after that. Among women who remain on hormone replacement therapy for up to five more years; bone mass remains stable at a higher level.

The PEPI study involved more than 800 women at seven academic medical centers. The national coordinating center was at Wake Forest University School of Medicine.

Mark Espeland, Ph.D., one of the authors and professor of public health sciences (biostatistics) at Wake Forest, said the current results stem from a safety follow-up study lasting up to five years after the end of the initial three-year PEPI study. "We wanted to follow these women to see if there were any long-term health consequences."

During the follow-up, investigators monitored both occurrence of fractures and changes in bone density as measured by bone scans. Declining bone density increases the risk of fractures and leads to osteoporosis. It is a natural process of aging that occurs in women who do not start hormone replacement therapy, and was confirmed in the placebo arm of the PEPI study.

"PEPI helped establish that estrogen can lead to short term increases in bone mineral density in postmenopausal women," Espeland said. But several other studies had raised questions whether bone loss may accelerate when hormone replacement therapy stops. Instead, the PEPI results showed that when hormone replacement therapy stops, the rate of bone loss is about the same as the natural process.

Espeland said the long-term follow-up "gave us a chance to examine the consequences of remaining on estrogen or stopping estrogen after three years."

He pointed out that the increase in bone mass following initiation of hormone replacement therapy gives women who stop a higher starting point; it is several years before their bone loss declines to the point where they would have been had they never started treatment.

Sustained use of hormone replacement over many years may increase a woman’s risk of breast cancer. Results from PEPI allow doctors to consider other strategies, such as prescribing hormone replacement therapy for a period of time, then stopping it, then resuming in a few years.

"Our paper indicates this could have some benefits in increasing bone mineral density and preventing fractures," Espeland said. ###

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