Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women's Health Initiative Randomized Trials.
ABSTRACT IMPORTANCE Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention. OBJECTIVE To report a comprehensive, integrated overview of findings from the 2 Women's Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up. DESIGN, SETTING, AND PARTICIPANTS A total of 27 347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers. INTERVENTIONS Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506) or placebo (n = 8102). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 5310) or placebo (n = 5429). The intervention lasted a median of 5.6 years in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of cumulative follow-up until September 30, 2010. MAIN OUTCOMES AND MEASURES Primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death. RESULTS During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10 000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years. Quality-of-life outcomes had mixed results in both trials. CONCLUSIONS AND RELEVANCE Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000611.
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ABSTRACT: The Women's Health Initiative (WHI) Estrogen-Alone Trial randomized postmenopausal women, 50 to 79 years of age, with prior hysterectomy, to conjugated equine estrogens (CEE) or placebo with a 5.9-year median duration of CEE use. In 2013, the WHI published outcomes for additional extended follow-up. Reported here for the first time is an analysis of the number needed to treat with CEE rather than placebo for younger women (50-59 years) to prevent an adverse long-term outcome. For every 76 women randomized to CEE at 50-59 years, one less myocardial infarction occurred during the 13-year cumulative long-term follow-up. For every 37 women randomized to CEE at 50-59 years, one less woman experienced a global index endpoint (including coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, hip fracture, and death) during the 13-year follow-up. Younger women (50-59 years), compared to older women, had more favorable cumulative long-term outcomes for MI and global index. Though a subgroup analysis is not an adequate basis for making primary prevention guideline recommendations, the WHI Estrogen-Alone Trial outcomes strongly suggest that a similar course of estrogen initiated at 50-59 years in postmenopausal women with prior hysterectomy results in significant long-term health benefit.
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ABSTRACT: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels.Clinics (São Paulo, Brazil) 02/2015; 70(2):107-13. DOI:10.6061/clinics/2015(02)07 · 1.42 Impact Factor
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ABSTRACT: To evaluate safety and efficacy of gabapentin in management of psychosexual symptoms in postmenopausal women. Fifty symptomatic postmenopausal females were randomly allocated into two groups; Group I received gabapentin 900 mg/day along with calcium 500 mg and Group II was given only calcium for 6 months and followed-up at 1,3, and 6 months. Data was analyzed in terms of percentage reduction of psychosomatic and sexual symptoms. Change in lipid profile and other blood parameters by the end of study were measured. Maximum improvement was seen in insomnia (90-98%) in gabapentin group. Improvement in anxiety was noted by 40.5, 49.5, and 53.8% at 1, 3, and 6 months, respectively, in Group I. While in Group II, maximum improvement noted was 18.6, 19.7, and 20% at 1, 3, and 6 months, respectively. Similarly for depression, improvement was 40.4,47, and 49.5%at 1, 3, and 6 months, respectively, in Group I; while it was 15.4, 16.6, and 17% at 1, 3, and 6 months, respectively, in Group II. No significant improvement in vaginal dryness and dyspareunia noted at all follow-ups in either group. Somatic symptoms reduced by 33, 36.8, and 40% at 1, 3, and 6 months, respectively, in Group I compared to 18% improvement at all follow-up in Group II. Low density lipoprotein (LDL) was raised in Group I significantly more than Group II. Other blood parameters were comparable in both groups. Gabapentin can lead to improvement in postmenopausal psychosomatic symptoms, while sexual symptoms show no improvement. Gabapentin can lead to increase in serum LDL, hence, precaution should be taken in patients with deranged lipid profile before starting therapy and it should be monitored during course of therapy. This drug can cause minor side effects like somnolence and dizziness.01/2015; 6(1):10-15. DOI:10.4103/0976-7800.153605