Effects of oral conjugated equine estrogens with or without medroxyprogesterone acetate on incident hypertension in the Women's Health Initiative hormone therapy trials.

OBJECTIVE: The aim of the study was to determine the effect of menopausal hormone therapy on incident hypertension in the two Women's Health Initiative hormone therapy trials and in extended postintervention follow-up. METHODS: A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. This analysis includes the subsample of 18,015 women who did not report hypertension at baseline and were not taking antihypertensive medication. Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 5,994) or placebo (n = 5,679). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 3,108) or placebo (n = 3,234). The intervention lasted a median of 5.6 years in the CEE plus MPA trial and 7.2 years in the CEE-alone trial with 13 years of cumulative follow-up until September 30, 2010. The primary outcome for these analyses was self-report of a new diagnosis of hypertension and/or high blood pressure requiring treatment with medication. RESULTS: During the CEE and CEE plus MPA intervention phase, the rate of incident hypertension was 18% higher for intervention than for placebo (CEE: hazard ratio [HR], 1.18; 95% CI, 1.09-1.29; CEE plus MPA: HR, 1.18; 95% CI, 1.09-1.27). This effect dissipated postintervention in both trials (CEE: HR, 1.06; 95% CI, 0.94-1.20; CEE plus MPA: HR, 1.02; 95% CI, 0.94-1.10). CONCLUSIONS: CEE (0.625 mg/d) administered orally, with or without MPA, is associated with an increased risk of hypertension in older postmenopausal women. Whether lower doses, different estrogen formulations, or transdermal route of administration offer lower risks warrant further study.

The effect of hormone therapy on mean blood pressure and visit-to-visit blood pressure variability in postmenopausal women: results from the Women's Health Initiative randomized controlled trials.

OBJECTIVES: Mean and visit-to-visit variability (VVV) of blood pressure (BP) are associated with an increased cardiovascular disease risk. We examined the effect of hormone therapy on mean and VVV of BP in postmenopausal women from the Women's Health Initiative (WHI) randomized controlled trials. METHODS: BP was measured at baseline and annually in the two WHI hormone therapy trials, in which 10 739 and 16 608 postmenopausal women were randomized to conjugated equine estrogens (CEEs, 0.625 mg/day) or placebo, and CEEs and medroxyprogesterone acetate (MPA, 2.5 mg/day) or placebo, respectively. RESULTS: At the first annual visit (year 1), mean SBP was 1.04 mmHg [95% confidence interval (CI) 0.58, 1.50] and 1.35 mmHg (95% CI 0.99, 1.72) higher in the CEEs and CEEs and MPA arms, respectively, compared with the corresponding placebos. These effects remained stable after year 1. CEEs also increased the VVV of SBP (ratio of VVV in CEEs vs. placebo, 1.03; P < 0.001), whereas CEEs and MPA did not (ratio of VVV in CEEs and MPA vs. placebo, 1.01; P = 0.20). After accounting for study drug adherence, the effects of CEEs and CEEs and MPA on mean SBP increased at year 1, and the differences in the CEEs and CEEs and MPA arms vs. placebos also continued to increase after year 1. Further, both CEEs and CEEs and MPA significantly increased the VVV of SBP (ratio of VVV in CEEs vs. placebo, 1.04; P < 0.001; ratio of VVV in CEEs and MPA vs. placebo, 1.05; P < 0.001). CONCLUSION: Among postmenopausal women, CEEs and CEEs and MPA at conventional doses increased mean and VVV of SBP.

Quality of life and hypertension after hormone therapy withdrawal in New York City.

OBJECTIVE: Many women stopped hormone therapy (HT) or estrogen therapy (ET) after the Women's Health Initiative results were published in 2002. This study assessed the incidence of hypertension, weight gain, and dyslipidemia; conditions that predispose to chronic diseases; medication use; and quality of life in women who used HT/ET for at least 5 years and subsequently stopped its use compared with those who continued its use. METHODS: A retrospective study was conducted. All consenting eligible women (aged 56-73 y) in physicians' offices were interviewed, and measurements of weight, height, waist-to-hip ratio, and body fat were performed. Standardized quality-of-life and menopausal and medical questionnaires were administered. Three groups were compared: group 1, women who have remained on HT/ET; group 2, women who have resumed HT/ET after stopping for at least 6 months; and group 3, women who have stopped HT/ET and have not resumed. RESULTS: One hundred fifty-nine women were enrolled in group 1, 43 women were enrolled in group 2, and 108 women were enrolled in group 3. Women's characteristics were similar, except that group 3 was 1.5 (0.5) years older and had 4.4 (0.7) years less HT/ET use than groups 1 and 2. Utian Quality of Life scores were significantly lower in group 3 (83.4 [12.5]) than in groups 1 and 2 (87.6 [13.3], P < 0.02), particularly in the occupational satisfaction scale. About 16.6% and 16.3% of women in groups 1 and 2 were on antihypertensive medication, respectively, compared with 27.4% in group 3 (P < 0.04). CONCLUSIONS: Discontinuation of HT/ET may predispose some women to the risk of hypertension and may affect their quality of life.

Acceptability of home use of mifepristone for medical abortion.

BACKGROUND: Most medical abortion protocols require women to take mifepristone in the doctor's office. We assessed the acceptability of home use of mifepristone among women and their providers. STUDY DESIGN: In this multicenter trial, eligible women requesting termination of early pregnancy (n=301) chose whether to take mifepristone in the office or at home. Data on safety, efficacy, acceptability and disability were collected. RESULTS: One hundred thirty-nine women (46%) chose to take mifepristone at home, and 162 (54%) chose office administration. Ninety-five percent of home users said that they would take the mifepristone in the same place in the future. Home users were not more likely to call the doctor's office or make an unplanned visit, and providers would recommend home use again for 95% of patients who chose home use. CONCLUSIONS: Home administration of mifepristone was safe and acceptable to women and providers in our study. Women should be offered this choice to allow more flexibility, comfort and privacy in their abortion experiences.

Extending outpatient medical abortion services through 70 days of gestational age.

OBJECTIVE: To estimate the efficacy and acceptability of medical abortion at 64-70 days from last menstrual period (LMP) and to compare it with the already proven 57-63 days from LMP gestational age range. METHODS: This prospective, comparative, open-label trial enrolled 729 women with pregnancies 57-70 days from LMP requesting abortion at six U.S. clinics. Medical abortions were managed with 200 mg mifepristone and 800 micrograms buccal misoprostol and sites' service delivery protocols. Follow-up visits occurred 7-14 days after mifepristone, with an abortion considered complete if surgical intervention was not performed. Success, ongoing pregnancy, and acceptability rates were compared. RESULTS: A total of 629 cases were analyzable for efficacy. Success rates were similar in the two groups (57-63 days group: 93.5%, 95% confidence interval [CI] 90-96; 64-70 days group: 92.8%, 95% CI 89-95). Ongoing pregnancy rates also did not differ significantly (57-63 days: 3.1%, 95% CI 1.6-5.8; 64-70 days: 3.0%, 95% CI 1.5-5.7). Acceptability was high and similar in both arms, with most women (57-63 days: 87.4%; 64-70 days: 88.3%) reporting that their experience was either very satisfactory or satisfactory. CONCLUSION: Medical abortion with mifepristone and misoprostol in current outpatient settings is an efficacious and acceptable method of ending pregnancies 64-70 days from LMP and can be offered without alteration of existing services. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, www.clinicaltrials.gov, NCT00997347. LEVEL OF EVIDENCE: II.

Comparison of serum markers for thrombophilia and autoimmune disease in reproductive age women with and without false positive rapid plasma reagin tests.

PROBLEM: The rapid plasma reagin test (RPR) is performed frequently in clinical practice, particularly among reproductive age women. The phenomenon of the biologic false positive RPR is well-recognized, but its clinical significance is poorly characterized. Our objective was to assess the relationship between the false positive RPR and several established clinical and biological markers for thrombophilia and/or autoimmune disease. METHOD OF STUDY: We conducted a clinic-based, case-control study of 41 healthy, reproductive age women with history of a biologic false positive RPR and 30 control women with a negative RPR to assess the relationship between the false positive RPR and several established clinical and biological markers for thrombophilia and/or autoimmune disease. We used t-tests and constructed frequency tables for case-control comparisons. RESULTS: Cases were significantly more likely than controls to have lupus anticoagulant present in serum, have a positive ANA, and a positive ANA with a titer of 1:320 or greater. Cases were also more likely to be positive for anticardiolipin antibodies and have a prolonged activated partial thromboplastin time, but the CIs for those point estimates included the null value. Eight participants tested positive for both lupus anticoagulant and ANA. All eight were in the case group. CONCLUSION: These results suggest that the RPR test might be used to identify a subset of women who warrant further testing for autoimmune and/or thromboembolic disease.

Non-physician clinicians can safely provide first trimester medical abortion.

Mid-level clinicians are integral to provision of pregnancy-related care in many settings. Yet midwives and other non-physician clinicians are excluded from training and from providing medical abortion. A substantial body of evidence exists demonstrating that mid-level providers, including nurses and midwives specialized in pregnancy-related care for women, are either already competently involved in providing medical abortions or have the requisite skills to expand their scope of practice to include medical abortion with a short course of additional training. While additional evidence may be needed to show that second trimester medical abortion can be safely and effectively provided by trained mid-level providers, we argue that for first trimester medical abortion the evidence is sufficient for governments to implement, monitor and evaluate programmes that allow mid-level clinicians to offer first trimester medical abortion independently. Because mid-level clinicians often work in rural or remote areas where physicians are scarce or where there are few surgical facilities or equipment, the expansion of the medical abortion provider pool has the potential to greatly improve the reproductive health of women worldwide.

The transdermal patch and the vaginal ring: two novel methods of combined hormonal contraception.

This article reviews two novel contraceptive methods that have become recently available in the United States: the transdermal patch and the vaginal ring. In general, newer methods of contraception are designed to make adherence easier for patients. The two contraceptive methods discussed in this article may help patients achieve this goal.