Giving lower doses of estrogen and progesterone during hormone replacement therapy (HRT), in combination with calcium and vitamin D, spares older women significant osteoporotic bone mass loss while limiting HRT's significant side effects, according to a new NIAMS-supported study.

The randomized, controlled clinical trial (Ann Intern Med. 1999;130:897-904), carried out by Robert R. Recker, M.D., and his colleagues at the NIAMS-sponsored Specialized Center of Research on Osteoporosis at Creighton University, tested a continuous daily regimen of 0.3 milligrams of estrogen (and 2.5 milligrams of progesterone) in women over 65 with low bone mass. The test dosage was less than half the HRT estrogen dosage most commonly prescribed to prevent osteoporosis. Calcium and vitamin D were added to ensure adequate levels. Over the course of the 3.5-year study, patients showed a 3.5 percent increase in spinal bone mineral density and significant increases in total body and forearm bone density--effects similar or better than with higher dose regimens. Perhaps even more importantly, the women's experience of HRT side effects--such as breast tenderness, pelvic discomfort, mood changes, and bleeding--was mild and short lived.

"HRT has long been the bedrock of osteoporosis prevention, but for many women, its side effects have been intolerable," says Dr. Recker. "Our results could mean that many more postmenopausal women who could benefit from the therapy would be willing to be treated, and with a higher compliance rate."

Dr. Recker believes that part of the trial's success might have been due to the close attention the scientists paid to calcium and vitamin D levels. "The vitamin D levels we induced in our patients," he says, "were higher than in other studies of HRT."

Osteoporosis, a largely preventable disease, is characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures--especially of the hip, spine, and wrist. In the United States today, 10 million individuals already have osteoporosis and 18 million more have low bone mass, placing them at increased risk. The burden of health care costs from osteoporotic fractures is estimated to be $13.8 billion per year.

Joan McGowan, Ph.D., director of the NIAMS' Musculoskeletal Diseases Branch, sees great potential benefits in the study's results. "Since estrogen is the first line of defense against osteoporosis," she says, "it's critical to use the lowest effective dose that will preserve and even add bone. This study provides important proof that low-dose estrogen can be an effective preventive and therapeutic option in older women with adequate calcium and vitamin D intake."

Surprisingly few dosing studies of estrogen have been carried out, and those that tested lower doses yielded inconsistent results. The present study shows the efficacy of low-dose estrogen for women who are well past menopause; its effect in younger women closer to menopause is uncertain, however.

NIAMS-supported specialized centers of research (SCORs), including the osteoporosis SCOR that performed this study, bring together basic and clinical researchers in a single setting to study human disease. Their goal is to advance basic research on disease causes and to expedite transfer of basic science advances into clinical applications and improved patient care.

Recker RR, Davies KM, Dowd RM, Heaney RP. The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. Annals of Internal Medicine 1999;130:897-904.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH), leads the Federal medical research effort in arthritis and musculoskeletal and skin diseases. The NIAMS supports research and research training throughout the United States, as well as on the NIH campus in Bethesda, MD, and disseminates health and research information. The National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse (NAMSIC) is a public service sponsored by the NIAMS that provides health information and information sources. Additional information can be found on the NIAMS Web site at

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