Objective: The purpose of this study was to describe the prevalence of and correlates for pelvic organ prolapse. Study Design: This was a cross-sectional analysis of women who enrolled in the Women's ...Health Initiative Hormone Replacement Therapy Clinical Trial (n = 27,342 women). Baseline questionnaires ascertained demographics and personal habits. A baseline pelvic examination assessed uterine prolapse, cystocele, and rectocele. Descriptive statistics and logistic regression models were used to investigate factors that were associated with pelvic organ prolapse. Results: In the 16,616 women with a uterus, the rate of uterine prolapse was 14.2%; the rate of cystocele was 34.3%; and the rate of rectocele was 18.6%. For the 10,727 women who had undergone hysterectomy, the prevalence of cystocele was 32.9% and of rectocele was 18.3%. After controlling for age, body mass index, and other health/physical variables, African American women demonstrated the lowest risk for prolapse. Hispanic women had the highest risk for uterine prolapse. Parity and obesity were strongly associated with increased risk for uterine prolapse, cystocele, and rectocele. Conclusion: Pelvic organ prolapse is a common condition in older women. The risk for prolapse differs between ethnic groups, which suggests that the approaches to risk-factor modification and prevention may also differ. These data will help address the gynecologic needs of diverse populations. (Am J Obstet Gynecol 2002;186:1160-6.)
The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens ...(CEE) plus medroxyprogesterone acetate (MPA).
To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women.
Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers.
In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos.
Probable dementia and MCI.
In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio HR, 1.49; 95% confidence interval CI, 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04).
Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.
In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of ...7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported.
To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009.
A total of 16,608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12,788 (83%) of the surviving participants.
Invasive breast cancer incidence and breast cancer mortality.
In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases 0.42% per year vs 293 cases 0.34% per year; hazard ratio HR, 1.25; 95% confidence interval CI, 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 23.7% vs 43 16.2%, respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths 0.03% per year vs 12 deaths 0.01% per year; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths 0.05% per year vs 31 deaths 0.03% per year; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group.
Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.
clinicaltrials.gov Identifier: NCT00000611.
HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have ...sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance.
The Women's Health Initiative (WHI) trial of estrogen plus progestin was stopped early because of adverse effects, including an increased risk of stroke in the estrogen plus progestin group.
To ...assess the effect of estrogen plus progestin on ischemic and hemorrhagic stroke and in subgroups, and to determine whether the effect of estrogen plus progestin was modified by baseline levels of blood biomarkers.
Multicenter double-blind, placebo-controlled, randomized clinical trial involving 16 608 women aged 50 through 79 years with an average follow-up of 5.6 years. Baseline levels of blood-based markers of inflammation, thrombosis, and lipid levels were measured in the first 140 centrally confirmed stroke cases and 513 controls.
Participants received 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).
Overall strokes and stroke subtype and severity were centrally adjudicated by stroke neurologists.
One hundred fifty-one patients (1.8%) in the estrogen plus progestin and 107 (1.3%) in the placebo groups had strokes. Overall 79.8% of strokes were ischemic. For combined ischemic and hemorrhagic strokes, the intention-to-treat hazard ratio (HR) for estrogen plus progestin vs placebo was 1.31 (95% confidence interval CI, 1.02-1.68); with adjustment for adherence, the HR was 1.50 (95% CI, 1.08-2.08). The HR for ischemic stroke was 1.44 (95% CI, 1.09-1.90) and for hemorrhagic stroke, 0.82 (95% CI, 0.43-1.56). Point estimates of the HRs indicate that excess risk of all stroke was apparent in all age groups, in all categories of baseline stroke risk, and in women with and without hypertension, prior history of cardiovascular disease, use of hormones, statins, or aspirin. Other risk factors for stroke, including smoking, blood pressure, diabetes, lower use of vitamin C supplements, blood-based biomarkers of inflammation, higher white blood cell count, and higher hematocrit levels did not modify the effect of estrogen plus progestin on stroke risk.
Estrogen plus progestin increases the risk of ischemic stroke in generally healthy postmenopausal women. Excess risk for all strokes attributed to estrogen plus progestin appeared to be present in all subgroups of women examined.
Emerging clinical evidence suggests intravenous bisphosphonates may inhibit breast cancer while oral bisphosphonates have received limited evaluation regarding breast cancer influence.
The ...association between oral bisphosphonate use and invasive breast cancer was examined in postmenopausal women enrolled onto the Women's Health Initiative (WHI). We compared a published hip fracture prediction model, which did not incorporate bone mineral density (BMD), with total hip BMD in 10,418 WHI participants who had both determinations. To adjust for potential BMD difference based on bisphosphonate use, the hip fracture prediction score was included in multivariant analyses as a BMD surrogate.
Of the 154,768 participants, 2,816 were oral bisphosphonate users at entry (90% alendronate, 10% etidronate). As calculated hip fracture risk score was significantly associated with both BMD (regression line = 0.79 to 0.0478 log predicted fracture; P < .001; r = 0.43) and breast cancer incidence (P = .03), this variable was incorporated into regression analyses to adjust for BMD difference between users and nonusers of bisphopshonate. After 7.8 mean years of follow-up (standard deviation, 1.7), invasive breast cancer incidence was lower in bisphosphonate users (hazard ratio HR, 0.68; 95% CI, 0.52 to 0.88; P < .01) as was incidence of estrogen receptor (ER) -positive invasive cancers (HR, 0.70; 95% CI, 0.52 to 0.94, P = .02). A similar but not significant trend was seen for ER-negative invasive cancers. The incidence of ductal carcinoma in situ was higher in bisphosphonate users (HR, 1.58; 95% CI, 1.08 to 2.31; P = .02).
Oral bisphosphonate use was associated with significantly lower invasive breast cancer incidence, suggesting bisphosphonates may have inhibiting effects on breast cancer.
The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of ...coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis.
To determine the effects of CEE on breast cancers and mammographic findings.
Following breast cancer risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included.
A dose of 0.625 mg/d of CEE or an identical-appearing placebo.
Breast cancer incidence, tumor characteristics, and mammogram findings.
After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval CI, 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up.
Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits.
clinicaltrials.gov Identifier: NCT00000611.
Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. ...Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial.
We analyzed the results of the WHI randomized clinical trial--in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo--and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use.
In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged.
The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.
Postmenopausal women have a greater risk than men of developing Alzheimer disease, but studies of the effects of estrogen therapy on Alzheimer disease have been inconsistent. On July 8, 2002, the ...study drugs, estrogen plus progestin, in the Women's Health Initiative (WHI) trial were discontinued because of certain increased health risks in women receiving combined hormone therapy.
To evaluate the effect of estrogen plus progestin on the incidence of dementia and mild cognitive impairment compared with placebo.
The Women's Health Initiative Memory Study (WHIMS), a randomized, double-blind, placebo-controlled clinical trial, began enrolling participants from the Women's Health Initiative (WHI) estrogen plus progestin trial in May 1996. Of the 4894 eligible participants of the WHI study, 4532 (92.6%) postmenopausal women free of probable dementia, aged 65 years or older, and recruited from 39 of 40 WHI clinical centers were enrolled in the WHIMS.
Participants received either 1 daily tablet of 0.625 mg of conjugated equine estrogen plus 2.5 mg of medroxyprogesterone acetate (n = 2229), or a matching placebo (n = 2303).
Incidence of probable dementia (primary outcome) and mild cognitive impairment (secondary outcome) were identified through a structured clinical assessment.
The mean (SD) time between the date of randomization into WHI and the last Modified Mini-Mental State Examination (3MSE) for all WHIMS participants was 4.05 (1.19) years. Overall, 61 women were diagnosed with probable dementia, 40 (66%) in the estrogen plus progestin group compared with 21 (34%) in the placebo group. The hazard ratio (HR) for probable dementia was 2.05 (95% confidence interval CI, 1.21-3.48; 45 vs 22 per 10 000 person-years; P =.01). This increased risk would result in an additional 23 cases of dementia per 10 000 women per year. Alzheimer disease was the most common classification of dementia in both study groups. Treatment effects on mild cognitive impairment did not differ between groups (HR, 1.07; 95% CI, 0.74-1.55; 63 vs 59 cases per 10 000 person-years; P =.72).
Estrogen plus progestin therapy increased the risk for probable dementia in postmenopausal women aged 65 years or older. In addition, estrogen plus progestin therapy did not prevent mild cognitive impairment in these women. These findings, coupled with previously reported WHI data, support the conclusion that the risks of estrogen plus progestin outweigh the benefits.
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