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Frederick Naftolin

Publications and source records attributed to Frederick Naftolin.

27 records · Page 2Linked to original sources
PubMed2004

Is the WHI relevant to HRT started in the perimenopause?

The Women's Health Initiative (WHI) hormone replacement therapy (HRT) estrogen plus progestin (E+P) and estrogen-only arms are part of a large NIH-sponsored randomized controlled trial (RCT). Both arms were terminated prematurely after 5 and 8 yr, respectively. The E+P arm showed non-statistically significant increased incidences of cardiovascular events and breast cancer, whereas the E-only arm did not. Both arms showed an increased rate of thromboembolic events and stroke. Both arms showed protection against fractures and with protection against colon cancer only in the E+P arm. These results have been widely generalized as indicating a negative risk/benefit ratio for HRT in menopausal women. The WHI results are at odds with results of large epidemiological studies that showed protection against cardiovascular disease. Although the latter data are, in part, confounded by a "healthy user bias," much of the inconsistency may be explained by the fact that women in the latter studies initiated HRT at the menopausal transition, whereas the WHI trial was conducted in older women (mean age 63.3), who were, on average, approx 12 yr postmenopausal. In addition, older trials included women on either unopposed estrogen therapy (ERT) or cyclic HRT regimens. Whatever other forces may have been at work, observational and experimental evidence supports the conclusion that estrogen's atheropreventive effects predominate early, in the absence of vulnerable plaque to be ruptured or thrombotic episodes propagated by narrowed lumens and intravascular turbulence. On the contrary, age-related adverse effects of HRT may prevail once complex atheromas and luminal narrowing/irregularity are established. It is known that prevalence of subclinical "at-risk" atherosclerotic lesions increases in women during the first 5-10 yr after menopause. Furthermore, animal and clinical evidence supports the use of lower doses of estrogen than were employed in the WHI in older/longer postmenopausal women.

Arteriosclerosis↗
PubMed2002

Ezrin, a membrane-cytoskeletal linking protein, is highly expressed in atypical endometrial hyperplasia and uterine endometrioid adenocarcinoma.

We previously demonstrated that ezrin transcription was required for in vitro invasion and was involved in the acquisition of metastatic potential in endometrial cancer cells. In order to determine the functional role of ezrin in endometrial cancer, we examined ezrin protein expression in 20 cancerous and 33 non-cancerous tissues by immunohistochemistry and Western blot analysis. The specimens included 20 uterine endometrioid adenocarcinomas (UEC), seven simple endometrial hyperplasias (sH), seven complex endometrial hyperplasias (cH), seven atypical endometrial hyperplasias (aH), and 12 samples of normal endometrium (NE). Tissues of primary (P) and metastatic (M) lesions of endometrial cancers were obtained from five patients. Ezrin was specifically expressed in UEC and its precursor lesions. Ezrin expression was significantly higher in aH (P<0.05) and UEC (P<0.001) compared with NE, sH, and cH. In addition, ezrin was significantly highly expressed in M compared with P (P<0.05). Ezrin expression was associated with neither clinical stage nor histopathologic grade of UEC. In immunohistochemistry, ezrin was localized in the membrane of metastasized cancer cells, although ezrin was mainly distributed in the cytoplasm of most cancer cells and some endometrial hyperplastic cells. On Western blot analysis, ezrin was also detected in both cytosolic and membrane fractions in aH and UEC, whereas ezrin was detected in only cytosolic fraction in sH and cH. These data suggest that expression and subcellular distribution of ezrin protein play an important role in development and progression of UEC.

Adult↗
PubMed2002

Hormonal regulation of apoptosis and the Fas and Fas ligand system in human endometrial cells.

The process of apoptosis is responsible for normal cellular turnover in numerous tissues throughout the body. The endometrial layer of the uterus shows steroid-dependent cyclic changes in structure and function. After a proliferative and secretory phase, steroid support is withdrawn and the uterine epithelium is shed. We hypothesize that the apoptosis observed in endometrial cells following hormonal withdrawal is mediated by the Fas/Fas ligand (FasL) system. Normal endometrial cells and endometrial cancer cells were cultured in the presence of estrogen and progesterone. In order to mimic physiological hormonal changes, estrogen and progesterone were removed from the media. Apoptosis was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-dephenyl tetrazolium bromide (MTT) assay and propidium iodide staining, while Fas and FasL expression were evaluated by Western blot analysis. The endometrial cells expressed Fas and low levels of FasL. Withdrawal of estrogen and/or progesterone from the culture induced apoptosis causing an approximately 50% decrease in cell viability. This coincided with increased Fas and FasL expression. Treatment of the cells with anti-FasL antibody prevented cell death following hormonal withdrawal. Estrogen and progesterone therefore represent survival factors which hamper cell death by impeding the expression of apoptotic factors. Our results indicate that Fas-mediated apoptosis is important for endometrial cycling and suggest that dysregulation of the Fas/FasL interactions may have an important role in the development of endometrial cancer.

Adult↗
PubMedDate not supplied

Better oral reading and short-term memory in midlife, postmenopausal women taking estrogen.

OBJECTIVE: Considerable controversy surrounds the issue of whether estrogen influences cognitive function in postmenopausal women, and the results are far from consistent. For the most part, the cognitive processes studied have involved memory; to our knowledge, no previous studies have specifically examined the effects of estrogen on women's reading ability. DESIGN: To investigate reading and short-term memory in postmenopausal women treated with conjugated equine estrogens, we carried out a randomized, double-blind, placebo-controlled trial of 21 days in 60 midlife, postmenopausal women aged 32.8 to 64.9 years (mean 51.2 years, SD 5.0 years). Women were evaluated for oral reading measured by Gray Oral Reading Tests (third edition) and for verbal memory using immediate and delayed recall on the Logical Memory and Paired Associate Learning subtests of the Wechsler Memory Scale and by a Sentence Span task. RESULTS: The group receiving daily treatment with conjugated equine estrogens (Premarin, 1.25 mg; Wyeth-Ayerst Labs, Philadelphia, PA, USA) showed better oral reading and verbal memory performance than the placebo group. CONCLUSION: Estrogen may have positive effects on oral reading and verbal memory in midlife, postmenopausal women.

Adult↗
PubMedDate not supplied

Postmenopausal hormone therapy: new questions and the case for new clinical trials.

Observational studies suggest that postmenopausal hormone therapy (HT) prevents coronary heart disease, whereas randomized clinical trials have not confirmed a cardioprotective effect. Although observational studies may have overestimated the coronary benefit conferred by postmenopausal hormone use, there are other plausible explanations for the apparent discrepancy between previous results and the less favorable findings from clinical trials such as the large Women's Health Initiative. There is now a critical mass of data to support the hypothesis that age or time since menopause may importantly influence the benefit-risk ratio associated with HT, especially with respect to cardiovascular outcomes, and that the method of administration, dose, and formulation of exogenous hormones may also be relevant. Although the weight of the evidence indicates that older women and those with subclinical or overt coronary heart disease should not take HT, estrogen remains the most effective treatment currently available for vasomotor symptoms, and its effects on the development of coronary disease in newly postmenopausal women remain unclear. Moreover, effects of HT on quality of life and cognitive function in recently postmenopausal women merit further study. These unresolved clinical issues provide the rationale for the design of the Kronos Early Estrogen Prevention Study, a 5-year randomized trial that will evaluate the effectiveness of low-dose oral estrogen and transdermal estradiol in preventing progression of atherosclerosis in recently postmenopausal women.

Administration, Cutaneous↗
PubMedDate not supplied

Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy.

The risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy. Low-dose transdermal estrogen monotherapy can preserve bone density while relieving vasomotor symptoms. Transdermal administration may offer advantages, including lack of first-pass liver metabolism, which permits the use of lower doses and avoids a negative impact on the lipid profile. Moreover, a recently published 2-year study of ultra-low-dose transdermal estrogen monotherapy in an older population similar to that of the WHI reported significant increases in bone mineral density, accompanied by significant reductions in markers of bone turnover, with no increased risk of endometrial hyperplasia or other side effects. Additional studies are warranted to shed further light on the possible benefits of low-dose estrogen monotherapy for the prevention of bone loss in postmenopausal women.

Administration, Cutaneous↗