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.
"Progesterone therapy for endometrial neoplasia has been reported to commonly cause hyperglycemia, hypertension, nausea, vomiting, weight gain, and sexual dysfunction, but can also cause more serious reactions including pulmonary embolus, diabetes, adrenal suppression and cardiomyopathy (Thigpen et al., 1999). Progesterone is also known to increase the risk of breast cancer in women undergoing hormonal replacement therapy (Manson et al., 2013; Beral and Million Women Study Collaborators, 2003), however, breast cancer in a woman undergoing hormonal treatment for endometrial cancer has not been described . Here we report a case of advanced breast cancer in a 32 year old woman who had undergone hormonal therapy for fertility sparing treatment of endometrial cancer. "
[Show abstract][Hide abstract] ABSTRACT: •Progesterone therapy is a commonly used alternative to surgical management for women with endometrial cancer who desire fertility preservation.•Prior research suggests that progestins may contribute to breast tumorigenesis.•We report a patient diagnosed with progesterone receptor positive breast cancer during hormonal treatment of endometrial cancer.
"Figure displaying absolute risks of chronic disease outcomes by age group, Women_s Health Initiative Hormone Therapy Trials: data from Manson JE, et al. JAMA 2013; 310:1353-1368 (reference 4 above). NAMS Practice Pearl on Extended Duration Use of Hormone Therapy: Kaunitz A. (available online at: http://www. menopause.org/docs/default-source/2013/nams-practice-pearl- extended-ht-duration.pdf)"
"The cessation of the ovarian function accounts for several complaints in postmenopausal women like vaginal dryness, depression, anxiety, hot flushes, insomnia and osteoporosis . 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   . As a consequence, consumer's interest in effective and preferably safe alternative treatment options are being developed. "
[Show abstract][Hide abstract] 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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