Health Initiative Randomized Trial Research Articles

Effects of Conjugated Equine Estrogen on Risk of Fractures and BMD in Postmenopausal Women With Hysterectomy: Results From the Women's Health Initiative Randomized Trial

Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture. The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented. Postmenopausal women 50-79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk. CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45-0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44-0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47-0.72), and total fracture (HR, 0.71; 95% CI, 0.64-0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68-1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62-1.05; mid risk: HR, 1.09; 95% CI, 0.92-1.30; highest risk: HR, 1.04; 95% CI, 0.88-1.23; interaction, p = 0.42). CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit.

Estrogen-Plus-Progestin Use and Mammographic Density in Postmenopausal Women: Women's Health Initiative Randomized Trial

Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P < .001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P < .001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P < .001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.

385: Cardiovascular Disease and Hormone Therapy: Can we Agree on what the Women's Health Initiative Randomized Trial Teaches us?

385: Cardiovascular Disease and Hormone Therapy: Can we Agree on what the Women's Health Initiative Randomized Trial Teaches us?

Guidelines for the hormone treatment of women in the menopausal transition and beyond: Position Statement by the Executive Committee of the International Menopause Society

Guidelines for the hormone treatment of women in the menopausal transition and beyond: Position Statement by the Executive Committee of the International Menopause Society

Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women’s Health Initiative Randomized Trial

The large-scale Women's Health Initiative has confirmed that, in postmenopausal women, combined estrogen/ progestin therapy entails an increased risk of invasive breast cancer. The investigators have now explored this relationship in detail, characterizing the cancers that developed and seeking to learn whether hormonal effects on the mammogram can influence diagnosis. A total of 16,608 postmenopausal women 50 to 79 years of age, all with an intact uterus, were randomly assigned to receive active treatment (0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate daily in a single tablet) or placebo. The participants, seen at 40 clinical centers, were to be followed from 1993 to 1998 by annual clinical breast examinations and mammograms, but the trial was ended after a mean interval of 5.2 years. Intent-to-treat analyses demonstrated a hazard ratio of 1.24 for both total cancers and invasive cancers in women given hormone therapy compared with the placebo group. There was some suggestion of an increased risk for in situ breast cancer in hormone-treated women. An increased risk of breast cancer in treated women emerged after 3 years in those not receiving hormones previously and after 2 years in previously treated women. The findings were similar when women in specific risk categories were analyzed, and race and ethnicity were not significant factors. Invasive cancers associated with combined hormone therapy were larger than those in placebo recipients, more likely to be node-positive, and diagnosed when more advanced. There was, however, no difference in tumor grade or in the distribution of histologic types of breast cancer. After the first year, hormone-treated women more often had abnormal or highly suspicious mammograms than did those given placebo. In this prospective, randomized trial, combined estrogen/progestin treatment of postmenopausal women increased both breast cancer risk and the frequency of abnormal mammograms requiring medical assessment. In addition, cancers in treated women were more advanced when diagnosed than was the case for placebo recipients.

Oestrogen plus progestogen increased risk of breast cancer in postmenopausal women

(2003) JAMA 289, 3243. Chlebowski RT, Hendrix SL, Langer RD, et al. . Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health...