Compounded HRT and the Sunday Newspapers.(part 2)
The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years.
- Departments of Obstetrics and Gynecology and Psychiatry, Yale University School of Medicine, New Haven, CT, USA. firstname.lastname@example.org
We examined the effect of estrogen avoidance on mortality rates among hysterectomized women aged 50 to 59 years.
We derived a formula to relate the excess mortality among hysterectomized women aged 50 to 59 years assigned to placebo in the Women’s Health Initiative randomized controlled trial to the entire population of comparable women in the United States, incorporating the decline in estrogen use observed between 2002 and 2011.
Over a 10-year span, starting in 2002, a minimum of 18 601 and as many as 91 610 postmenopausal women died prematurely because of the avoidance of estrogen therapy (ET).
ET in younger postmenopausal women is associated with a decisive reduction in all-cause mortality, but estrogen use in this population is low and continuing to fall. Our data indicate an associated annual mortality toll in the thousands of women aged 50 to 59 years. Informed discussion between these women and their health care providers about the effects of ET is a matter of considerable urgency.
Progesterone inhibits endometrial cancer invasiveness by inhibiting the TGFβ pathway.
- Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
- Division of Gynecologic Oncology, and Gynecologic Cancer Translational Research Center of Excellence, Walter Reed National Military Medical Center, Bethesda, Maryland.
- Department of Obstetrics and Gynecology and Women’s Health Integrated Research Center, Inova Fairfax Hospital, Falls Church, Virginia.
- Division of Gynecologic Oncology, North Shore University Health System, University of Chicago, Evanston, Illinois.
- Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Department of Molecular and Cell Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland. email@example.com.
Increased expression of TGFβ isoforms in human endometrial cancer correlates with decreased survival and poor prognosis. Progesterone has been shown to exert a chemoprotective effect against endometrial cancer, and previous animal models have suggested that these effects are accompanied by changes in TGFβ. The goal of this study was to characterize the effect of progesterone on TGFβ signaling pathway components and on TGFβ-induced protumorigenic activities in endometrial cancer cell lines. Progesterone significantly decreased expression of three TGFβ isoforms at 72 hours after treatment except for TGFβ2 in HEC-1B and TGFβ3 in Ishikawa cells. Progesterone treatment for 120 hours attenuated expression of the three isoforms in all cell lines. Progesterone exposure for 72 hours reduced expression of TGFβ receptors in HEC-1B cells and all but TGFβR1 in Ishikawa cells. Progesterone reduced TGFβR3 expression in RL-95 cells at 72 hours, but TGFβR1 and βR2 expression levels were not affected by progesterone at any time point. SMAD2/3 and pSMAD2/3 were substantially reduced at 72 hours in all cell lines. SMAD4 expression was reduced in RL-95 cells at 24 hours and in HEC-1B and Ishikawa cells at 72 hours following progesterone treatment. Furthermore, progesterone effectively inhibited basal and TGFβ1-induced cancer cell viability and invasion, which was accompanied by increased E-cadherin and decreased vimentin expression. An inhibitor of TGFβRI blocked TGFβ1-induced effects on cell viability and invasion and attenuated antitumor effects of progesterone. These results suggest that downregulation of TGFβ signaling is a key mechanism underlying progesterone inhibition of endometrial cancer growth.