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We evaluated potential associations between single nucleotide polymorphism (SNP) variants in estrogen receptor (ERalpha and ERbeta) genes, high-density lipoprotein (HDL) cholesterol, and apolipoprotein A-1 (apoA-1) concentrations in women of 4 races/ethnicities. Participants included 1,520 African American, Caucasian, Chinese, and Japanese women from the Study of Women's Health Across the Nation (SWAN) who were premenopausal or perimenopausal and who were also enrolled in the SWAN Genetics Study, which collected blood for lipid analyses and carried out lymphocyte transformation from which DNA was extracted and genotyped. We evaluated SNPs from ERalpha and ERbeta genes (ESR1 and ESR2, respectively), including ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, ESR1 rs3798577, ESR2 rs1255998, ESR2 rs1256065, and ESR2 rs1256030. The mean HDL cholesterol and apoA-1 values for these women were 1.47 mmol/L and 1.51 g/L, respectively. Japanese women with the ESR1 rs3798577 TC genotype had significantly lower apoA-1 (P=0.02) and HDL cholesterol levels (P=0.03) than did those with the TT genotype. African American women with the ESR1 rs728524 GG genotype had higher HDL cholesterol levels than did women with the AA or AG genotypes (P=0.05). ESR2 rs1256030 and ESR2 rs1256065 genotypes were associated with HDL cholesterol concentrations in Chinese women (P=0.05). Although associations were identified between the ESR1 and ESR2 SNP variants and lipids in these women, these associations were not consistently observed across the 4 racial/ethnic groups, nor were the associations consistently inclusive of both HDL cholesterol and apoA-1. These genetic variants provide limited evidence of associations with lipids that may help explain the cardioprotective effect of premenopausal status in women.

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OBJECTIVE: The purpose of this study was to determine the incidence of endometrial hyperplasia in subjects who receive continuous norethindrone acetate and ethinyl estradiol combinations versus unopposed ethinyl estradiol. STUDY DESIGN: Nine hundred forty-five postmenopausal women were randomly selected for 12 months of treatment with one of six blinded norethindrone acetate/ethinyl estradiol combinations (milligrams of norethindrone acetate/micrograms of ethinyl estradiol: 0/5, 0.25/5, 1/5, 0/10, 0.5/10, or 1/10) or to open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate. Endometrial hyperplasia and endometrial proliferation were assessed by biopsy at screening, months 6 and 12. RESULTS: Endometrial hyperplasia developed in 26 subjects: Placebo, 0/5 and 0.25/5 (1 subject each) and 0/10 (23 subjects). Significantly less endometrial proliferation was measured in the 1/5 norethindrone acetate/ethinyl estradiol and other norethindrone acetate/ethinyl estradiol combination groups and in the 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate group, than in unopposed ethinyl estradiol groups (6 months: P <.004; 12 months: P <.001). Treatment with 1/5 norethindrone acetate/ethinyl estradiol and with other norethindrone acetate/ethinyl estradiol combinations significantly reduced endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (6 and 12 months: P <.02). CONCLUSION: Norethindrone acetate protects the endometrium from estrogen-induced hyperplasia and changes in proliferative status. In addition, norethindrone acetate/ethinyl estradiol-treated subjects had significantly less endometrial proliferation compared with 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate-treated subjects.

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OBJECTIVE: The purpose of this study was to compare the effects on vaginal bleeding patterns of continuous combined hormone replacement therapy with norethindrone acetate and ethinyl estradiol versus conjugated equine estrogens and medroxyprogesterone acetate. STUDY DESIGN: Three hundred fifty-seven postmenopausal women were selected randomly (in a blinded manner) to 12 months of treatment with 1 mg norethindrone acetate/5 microg ethinyl estradiol, placebo, or open-label 0.625 mg conjugated equine estrogens/2.5 mg medroxyprogesterone acetate (conjugated equine estrogens/medroxyprogesterone acetate [CEE/MPA]; Prempro). The incidence and duration of vaginal bleeding were assessed throughout the study. Statistical analyses used Cochran-Mantel-Haenszel methodology and analysis of variance. RESULTS: At 3 months, 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy reduced the incidence of bleeding (12% vs 23%; P <.029) and bleeding and/or spotting (22% vs 44%; P <.001), compared with conjugated equine estrogens/medroxyprogesterone acetate therapy. The mean duration of bleeding and bleeding and/or spotting were also reduced with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate (P =.004 and P <.001, respectively). The incidence of cumulative amenorrhea at every monthly interval was significantly better with 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy versus conjugated equine estrogens/medroxyprogesterone acetate therapy (P <.05). Associated adverse event (ie, headache, breast pain) incidence rates were similar in the 2 active treatment groups. CONCLUSION: The 1 mg norethindrone acetate/5 microg ethinyl estradiol therapy provides significantly better control of vaginal bleeding than conjugated equine estrogens/medroxyprogesterone acetate therapy at all time points investigated in this 12-month study.

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