Effects of Estrogen Plus Progestin on Gynecologic Cancers and Associated Diagnostic Procedures: The Women's Health Initiative Randomized Trial

University of Washington Seattle, Seattle, Washington, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 10/2003; 290(13):1739-48. DOI: 10.1001/jama.290.13.1739
Source: PubMed


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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    • "Supplementary estrogen can improve bladder function which may be due to inhibition of collagen hyperplasia and increased smooth muscle density (Yang et al., 2009). However, ERT is associated with a higher risk of hormone-related cancer (Anderson et al., 2003) and other unfavorable adverse events (Morabito et al., 2002). Consequently, it is necessary to develop safer and natural alternatives to ERT. "
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    ABSTRACT: Background: Postmenopausal period is associated with a high incidence of symptoms in the lower urinary tract. Aim: to investigate the beneficial effect of defatted flaxseed (FS), as a natural alternative to hormonal therapy, on the deterioration of urinary bladder in experimentally menopaused albino rats in view of the health risks associated with hormones. Methods: Thirty 3-month old non pregnant female albino rats were randomized into five equal groups: Group I (Sham-operated), Group II (Sham-operated with FS), Group III (ovariectomized), Group IV (ovariectomized + estrogen) and Group V (ovariectomized + FS). The experimental period lasted for 12 weeks. Animals' bladders were processed for light and scanning electron microscopic examination. In addition, quantitative assessments of collagen fiber content as well as estrogen receptor α (ER-α), estrogen receptor ß (ER-ß) and desmin immunoexpression were performed. Results: Our results revealed a significant protective effect of defatted flaxseed on the urinary bladder of ovariectomized rats. These beneficial effects of flaxseed were mainly due to its estrogenic action, upregulating ER-ß expression. Conclusion: Defatted flaxseed has promising effects on improvement of altered structure of the urinary bladder in ovariectomized rats. This may provide a potential therapeutic approach for lower urinary symptoms among menopaused women. © 2014 AENSI Publisher All rights reserved. To Cite This Article: Abeer E. El-Mehi and Neveen M. El-Sherif., Protective effect of defatted flaxseed on urinary bladder of ovariectomized albino rats. Aust. J. Basic & Appl. Sci., 8(18): 686-698, 2014
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    • "The cessation of the ovarian function accounts for several complaints in postmenopausal women like vaginal dryness, depression, anxiety, hot flushes, insomnia and osteoporosis [1]. But the classical treatment of choice to alleviate these medical conditions, hormone replacement therapy (HRT) has been linked with an increased risk of breast and endometrial cancer and also stroke and pulmonary embolism [2] [3] [4]. As a consequence, consumer's interest in effective and preferably safe alternative treatment options are being developed. "
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    ABSTRACT: The potential utilization of plant secondary metabolites possessing estrogenic properties as alternatives to the classical Hormone Replacement Therapy (HRT) for the relief of postmenopausal complaints asks for an evaluation regarding the safety in reproductive organs. In order to contribute to the estimation of the safety profile of the flavanones naringenin (Nar), 8-prenylnaringenin (8PN) and 6-(1,1-dimethylally)naringenin (6DMAN), we investigated uterus and vagina derived from a three-day uterotrophic assay in rats. Also, we investigated the metabolite profile resulting from the incubation of the three substances with liver microsomes. While no metabolites were detectable for naringenin, hydroxylation products were observed for 8PN and 6DMAN after incubation with human as well as rat liver microsomes. The parent compound naringenin did not evoke any estrogenic responses in the investigated parameters. A significant increase of the uterine wet weight, uterine epithelial thickness and proliferating vaginal cells was observed in response to 8PN, questioning the safety of 8PN if applied in the human situation. In contrast, no estrogenic effects on the reproductive organs were observed for 6DMAN in the conducted study, rendering it the compound with a more promising safety profile, therefore justifying further investigations into its efficacy to alleviate postmenopausal discomforts.
    The Journal of Steroid Biochemistry and Molecular Biology 10/2014; 145. DOI:10.1016/j.jsbmb.2014.10.001 · 3.63 Impact Factor
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    • "However, compared to post-menopausal women who were not using HRT at the time of surgery, those who were on such therapy had larger numbers of ALDH+ cells in tissue at basal (p = 0.025) and non-basal (p = 0.03) levels (Figure 5 and Table 2), and this difference was independent of other risk factors. In the post-menopausal group, HRT was the only hormone intake parameter that showed a statistically significant correlation with a high frequency of ALDH+ cells, which agrees with evidence that HRT postpones TDLU involution and increases the risk of cancer [18-21]. This finding also suggests that ongoing HRT may be one of the factors that influence the number of ALDH+ cells. "
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    ABSTRACT: Knowledge is limited regarding the association between stem cells in histologically benign breast tissue and risk factors for breast cancer, and hence we addressed this issue in the present study. Recently, we assessed the histology of benign breast tissue from cancer and non-cancer patients for cells positive for the putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH), and the findings indicated an association between expression of ALDH and the hormonal factors menopause and hormone therapy. The current investigation examined possible associations between various known clinical and genetic risk factors for breast cancer and cellular expression of ALDH in ductules in benign human breast tissue. The study included breast surgery patients that were BRCA1/2 mutation carriers without breast cancer (n = 23), had BRCA1/2 (n = 28) or sporadic (n = 21) breast cancer, or required non-cancer-related mammoplasty (n = 34). The distribution and frequency of ALDH-immunolabelled cells were correlated to patient subgroups with different risk factors, using mammoplasty patients as a control group. Statistical analyses comprised linear and logistic regression, Spearman's rank test, Pearson's test, and Fisher's exact test. In two-tailed tests, p < 0.05 was considered significant. A strong association was found between family history of breast cancer and a high frequency of ALDH+ cells (p = 0.001) at all ductular levels in all groups, regardless of BRCA status, age, parity, or occurrence of cancer. In pre-menopausal non-BRCA cancer patients, the frequency of ALDH+ cells increased with age (p < 0.01) but decreased with increasing parity (p < 0.03). High frequencies of ALDH+ cells were found in the non-basal ductular levels in BRCA1 mutation carriers (p = 0.03), but in the basal ductular level inBRCA2 cancer patients (p = 0.02). Among post-menopausal patients, only on-going hormone replacement therapy was correlated with a high number of ALDH+ cells (p < 0.03). In histologically normal breast tissue, we found a positive association between the frequency of ductular ALDH+ cells and several breast cancer risk factors, particularly family history of this disease, which supports previous evidence that ALDH plays a role in breast cancer.
    BMC Clinical Pathology 11/2013; 13(1):28. DOI:10.1186/1472-6890-13-28
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