No 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 PARTICIPANTSA 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. RESULTSDuring 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 Ն65 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 n...

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.).

In this study, women with dysmenorrhea of at least 6 months' duration were recruited to a randomized, double-blind, controlled trial, which compared the effectiveness of conservative surgical treatment with treatment with presacral neurectomy. One hundred twenty-six women with a diagnosis of dysmenorrhea caused by endometriosis who had been unresponsive to medical treatment formed the study subjects. A preoperative evaluation established a baseline for frequency and severity of dysmenorrhea, dyspareunia, and chronic pelvic pain. Similar measurements were made at 6 and 12 months. Pain severity was rated using a 100-point visual analog scale with 100 being the most severe pain. Patients were randomized to 1 of 2 treatment groups. Group A (n ϭ 63) received electrocautery ablation or excision of visible pelvic endometriotic lesions, enucleation of endometriomas, and lysis of pelvic adhesions. Group B (n ϭ 63) underwent presacral neurectomy after conservative treatment. Presacral neurectomy was performed after retraction of the sigmoid colon and vasopressin infiltration of the sacral promontory area. The presacral area was exposed and underlying tissue layers cauterized. At the periosteum, a semilunar piece of retroperitoneal tissue was dissected. Neurectomy was confirmed with pathologic examination of this tissue for evidence of nerve fiber presence. The 2 treatment groups were similar in demographic and clinical data. All laparoscopies were successfully completed with no surgical complications in either group. The length of surgery was significantly greater for those in group B (mean 123 minutes vs. 110 minutes; P Յ.05), but otherwise all operative parameters were similar. Short-term complications were minimal in both groups. No patient in group A had long-term complications. In group B, 21 and 9 women, at the 6-and 12-month visits, respectively, reported constipation. Medical therapy was successful in 15 of the 21 women at 6 months. Three patients reported urinary urgency at both the 6-and 12-month follow up. At the 6-month and 12-month visits, 83.2% and 85.6%, respectively, of the patients in group B reported either no dysmenorrhea or only light discomfort and were considered cured. In comparison, 60.3% and 57% of the women in group A were cured at 6 and 12 months, respectively (P Յ.05 for both). At each stage of endometriosis, and in women with deep rectovaginal septum endometriosis, the cure rate in group B was significantly higher compared with those in group A. Women in group A who had deep rectovaginal septum endometriosis were less likely to be cured compared with all stages of endometriosis in the same group. The severity of dysmenorrhea and dyspareunia was significantly improved at the 6-and 12-month visit in group B compared with group A, but the frequency of symptoms was similar in both groups after treatment. ABSTRACTTwo hundred nulliparous women were enrolled in a prospective observational study to investigate the influence of childbirth on pelvic organ mobility. The mobility of the urethra, bladder, c...