Effects of Estrogen-Progestin on Risk of Fracture and Bone Mineral Density

Author: Jane A. Cauley, John Robbins, Zao Chen, Steven R. Cummings, Rebecca D. Jackson, Andrea Z. LaCroix, Meryl LeBoff, Cora E. Lewis, Joan McGowan, Joan Neuner, Mary Pettinger, Marcia L. Stefanick, Jean Wactawski-Wende, Nelson B. Watts
Publication: JAMA. 2003;290:1729-1738

This study involded 16608 postmenopausal women who were tested for the influence of estrogen-progestin therapy on the risk of hip fractures. The estrogen-progestin formulation was at the time of the study the most common prescribed postmenopausal hormone replacement therapy regimen in the US. The test was a randomized, controlled and double blind trail, which followed the women during a period of 5.2 years. The women, aged between 50 and 79 years, received either a placebo or a treatment with estrogen (0.625 mg estrogen daily)-progestin (2.5 mg medroxyprogesteron acetate). During the trial the number of fractures and bone mineral density were measured at the baseline, and after 1, 3 and 6 years.

At the start of the study, the risk factors were collected with a questionnaire and women using tomaxifen were excluded. During the study other health problems were recorded such as coronary heart disease, invasive breast cancer, stroke, pulmonary embolus, endometrial cancer, hip fractures, colorectal cancer and other diseases which are life threatening. A global health index was calculated to determine the overall balance of risks and benefits.

The women in the estrogen group experienced significantly less fractures (8.6 percent) compared to the placebo group (11.1 percent). Estrogen-progestin reduced the risk of hip fracture by 33 percent. There was no influence of race and ethnicity on total fractures. The reduction of hip fractures caused by estrogen and progestin were also not influenced age, smoking, fracture history, past use of hormone replacement therapy and years of menopause. The bone mass density improved by 3.7 percent in de estrogen group and remained nearly unchanged (+0.14 percent) in the placebo group. Although the estrogen-progestin therapy reduced the risk of fractures, the overall global index showed a 15 percent increase for the estrogen-progestin group. This means that the estrogen-progestin therapy causes more harm than benefits. The main risks were cardiovascular disease and breast cancer. There were no subgroups of women where the treatment with estrogen-progestin had an overall benefit.

Because of the unfavourable risk-benefit ratio and the availability of other treatments of osteoporosis, the investigators concluded that the estrogen-progestin therapy should not be recommended for the prevention of osteoporosis in women without vasomotor symptoms.