Greater mammographic density was associated with the use of estrogen/progestin combination therapy, regardless of how the progestin was given, but not with the use of estrogen only.

Further study of the magnitude and meaning of increased mammographic density due to use of estrogen and estrogen-progestins is warranted because mammographic density may be a marker for risk for breast cancer.

We assessed the associations of eight bone turnover markers (BTMs) with baseline and 1-year percentage changes in lumbar spine and hip bone mineral density (BMD) of 293 postmenopausal women undergoing treatment with hormone replacement therapy (HRT) or placebo using squared correlation coefficients (R 2 ). In 239 women assigned to treatment with estrogen alone or with with estrogen plus progestins (active treatment), mean percentage changes for all markers decreased significantly and remained below baseline values through 3 years of study, whereas mean percentage changes for 54 women assigned to the placebo group showed no significant change from baseline in any marker. At baseline, age and body mass index (BMI) together accounted for 16% and 25% of the variance in spine and hip BMD, respectively. The telopeptide resorption marker, cross-linked N-telopeptide of type I collagen (NTX), alone accounted for 12% and 8% of variance, respectively. Another telopeptide, carboxyterminal telopeptide of type I collagen (Crosslaps), accounted for 8% and 7% of variance, respectively. A bonespecific alkaline phosphatase (BALP-2) accounted for 8% of variance at the spine and 5% at the hip. No other marker accounted for more than 5% of total variance at either site; adding either baseline NTX, Crosslaps, or BAP-2 to regressions containing age and BMI increased R 2 values at the spine and hip to about 22% and 28%, respectively. In the placebo group, baseline spine BMD accounted for 4% of the variance in 1-year spine BMD percentage change, whereas baseline values for age and BMI accounted for 1% and 0% of the variance, respectively; none of the three accounted for more than 0% of hip BMD percentage change; Crosslaps and NTX contributed 5% and 4% to the variance in 1-year spine BMD percentage change, but other markers accounted for < 2% of variance at the spine. At the hip, another BALP (BALP-1) accounted for 4% of variance, but no other baseline marker except NTX accounted for more than 1% of variance. In the active treatment group, baseline values for age, BMI, and spine BMD together accounted for 13% of the percentage change in spine BMD and for 4% of the BMD change at the hip. No individual or pair of baseline markers significantly enhanced these R 2 values, but addition of 1-year percentage changes in some individual markers did significantly increase it. The largest R relationships between quartile and change in spine BMD, and these did not reach significance at the hip. When the 1-year change in markers was stratified into quartiles, significant relationships with percentage change in spine BMD were observed only for BALP phosphatases. We conclude that BTMs are not a surrogate for BMD to identify women with low bone mass and that they offer little useful information for predicting BMD changes for individual untreated or HRT-treated postmenopausal women. (J Bone Miner Res 1999;14:1583-1595)

Background-Postmenopausal hormone therapy has been reported to decrease levels of lipoprotein (Lp)(a) in cross-sectional studies and small or short-term longitudinal studies. We report findings from a large, prospective, placebo-controlled clinical trial that allows a broad characterization of these effects for four regimens of hormone therapy. Methods and Results-The Postmenopausal Estrogen/Progestin Interventions study was a 3-year, placebo-controlled, randomized clinical trial to assess the effect of hormone regimens on cardiovascular disease risk factors in postmenopausal women 45 to 65 years of age. The active regimens were conjugated equine estrogens therapy at 0.625 mg daily, alone or in combination with each of three regimens of progestational agents: medroxyprogesterone acetate (MPA) at 2.5 mg daily (ie, continuous MPA), MPA at 10 mg days 1 to 12 (ie, cyclical MPA), and micronized progesterone at 200 mg days 1 to 12. Plasma levels of Lp(a) were measured at baseline (nϭ366), 12 months (nϭ354), and 36 months (nϭ342). Assignment to hormone therapy resulted in a 17% to 23% average drop in Lp(a) concentrations relative to placebo (PϽ.0001), which was maintained across 3 years of follow-up. No significant differences were observed among the four active arms. Changes in Lp(a) associated with hormone therapy were positively correlated with changes in LDL cholesterol, total cholesterol, apolipoprotein B, and fibrinogen levels and were similar across subgroups defined by age, weight, ethnicity, and prior hormone use. Conclusions-Postmenopausal estrogen therapy, with or without concomitant progestin regimens, produces consistent and sustained reductions in plasma Lp(a) concentrations. (Circulation. 1998;97:979-986.)

Greater increase in serum estrone level as a function of treatment is a significant predictor of increase in mammographic percent density in women randomly assigned to the combination of estrogen and progestin.