Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial.
ABSTRACT The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a randomized trial setting.
To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures.
Randomized, double-blind, placebo-controlled trial of 16 608 postmenopausal women, who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 (average follow-up, 5.6 years).
One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).
Incident invasive cancer of the ovary and endometrium.
In 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer, 58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24). The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable differences were found in the distributions of tumor histology, stage, or grade for either cancer site. The incidence of other gynecologic cancers was low and did not differ by randomization assignment. More women taking estrogen plus progestin required endometrial biopsies (33% vs 6%; P<.001).
This randomized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo. The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen. These data provide additional support for caution in the use of continuous combined hormones.
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ABSTRACT: Menopausal symptoms affect a significant portion of women. Traditional treatment with manufactured hormone therapy can alleviate these symptoms, but many women and their health care providers are concerned about the risks, such as venous thromboembolism and certain types of cancer, demonstrated with manufactured hormone therapy. Compounded bioidentical hormone therapy has been proposed and is often used as a solution for these concerns. Despite this use, no data are currently available to support the claims that compounded bioidentical hormone therapy is a safer or more efficacious option compared with manufactured hormone therapy. A common misperception is that all manufactured products consist of synthetic hormones and all compounded medications consist of natural hormones; however, in fact, significant overlap exists. Several key stakeholder organizations have issued statements expressing concern about the lack of evidence regarding the efficacy and safety of compounded bioidentical hormone therapy, in addition to concerns regarding prescribing patterns. The Women's Health Practice and Research Network of the American College of Clinical Pharmacy recommends against the consistent use of compounded bioidentical hormones as a safer option compared with manufactured therapy and supports the statements of other key organizations, acknowledging the need for more robust clinical studies to evaluate the potential advantages and disadvantages of compounded bioidentical products compared with manufactured products.Pharmacotherapy 01/2014; · 2.31 Impact Factor
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ABSTRACT: Endometrial carcinoma (EC) is the leading female genital tract malignancy in industrialized countries. It will become an important public health problem in the coming years in the USA and Europe, where its incidence is increasing, and next-generation interventions should include periodical screening in high-risk women. In this review, we discuss the importance to gynaecologists of detecting women at high risk and offering an adequate screening programme. Screening for EC is particularly challenging and there is currently no proven programme for the surveillance of women estimated to be at an increased risk of developing this form of cancer. The data in the literature, including this and previous issues of Cytopathology, and personal experience suggest that endometrial liquid-based cytology (LBC) might play an essential role in a screening policy for EC. LBC may enable practitioners to reduce age-adjusted mortality for women at high risk for EC.Cytopathology 01/2014; · 1.71 Impact Factor
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ABSTRACT: As ovarian tumors progress, they undergo a process of dedifferentiation, allowing adaptive changes in growth and morphology that promote metastasis and chemoresistance. Herein, we outline a hypothesis that TATA-box binding protein associated factors (TAFs), which compose the RNA Polymerase II initiation factor, TFIID, contribute to regulation of dedifferentiation states in ovarian cancer. Numerous studies demonstrate that TAFs regulate differentiation and proliferation states; their expression is typically high in pluripotent cells and reduced upon differentiation. Strikingly, TAF2 exhibits copy number increases or mRNA overexpression in 73% of high-grade serous ovarian cancers (HGSC). At the biochemical level, TAF2 directs TFIID to TATA-less promoters by contact with an Initiator element, which may lead to the deregulation of the transcriptional output of these tumor cells. TAF4, which is altered in 66% of HGSC, is crucial for the stability of the TFIID complex and helps drive dedifferentiation of mouse embryonic fibroblasts to induced pluripotent stem cells. Its ovary-enriched paralog, TAF4B, is altered in 26% of HGSC. Here, we show that TAF4B mRNA correlates with Cyclin D2 mRNA expression in human granulosa cell tumors. TAF4B may also contribute to regulation of tumor microenvironment due to its estrogen-responsiveness and ability to act as a cofactor for NFκB. Conversely, TAF9, a cofactor for p53 in regulating apoptosis, may act as a tumor suppressor in ovarian cancer, since it is downregulated or deleted in 98% of HGSC. We conclude that a greater understanding of mechanisms of transcriptional regulation that execute signals from oncogenic signaling cascades is needed in order to expand our understanding of the etiology and progression of ovarian cancer, and most importantly to identify novel targets for therapeutic intervention.Frontiers in Oncology 01/2014; 4:45.