1.
Hormonal carcinogenesis and socio-biological development factors in endometrial cancer: a clinical review.
Tinelli, A, Vergara, D, Martignago, R, Leo, G, Malvasi, A, Tinelli, R
Acta obstetricia et gynecologica Scandinavica. 2008;(11):1101-13
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Abstract
OBJECTIVE Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries and the eighth leading cause of cancer death in women; it typically arises in the sixth or seventh decade of life. The aim of this review was to evaluate possible roles of genetic and socio-biological factors in type I endometrial cancer, largely confined to pre- and perimenopausal women, with a history of estrogen exposure and/or endometrial hyperplasia. METHODS An extensive literature review, from 1990 to 2007 was performed on modifiable risk factors for type I endometrial cancer. Additionally, carcinogenesis mechanisms, biomarker and hormonal and biomolecular approaches to cancer detection, progression and monitoring and socio-biological factors were reviewed. RESULTS Several socio-biological and lifestyle characteristics, such as hormone replacement therapy, glycemic index, obesity, alcohol use, antipsychotic medication, melatonin, physical activity and variants in hormone metabolism genes have been identified as risk factors for developing endometrial cancer of type I, the majority of which are associated with excess estrogens causing continued stimulation of the endometrium. There is a genetic link to non-polyposis colorectal cancer syndrome, but association of endometrial cancer risk to other genetic polymorphisms has yielded conflicting results. CONCLUSIONS Many factors linked to hormonal imbalance, such as obesity, weight change, body size, alcohol, hyper-androgenic states, glycemic index and antidepressant agents, influence the endometrial cancer risk, central to which are endogenous and exogenous estrogen hyperstimulation of the endometrium. Conversely, smoking cigarettes, diet, physical activity and melatonin production seem to reduce the risk of cancer development. Other external factors fit well with the unopposed estrogen theory, but more studies are needed to investigate modifiable and added risk factors for endometrial cancer.
2.
A comparison of oral and transdermal short-term estrogen therapy in postmenopausal women with metabolic syndrome.
Chu, MC, Cosper, P, Nakhuda, GS, Lobo, RA
Fertility and sterility. 2006;(6):1669-75
Abstract
OBJECTIVE To determine whether it would be preferable to prescribe oral or transdermal estrogen to symptomatic postmenopausal women with metabolic syndrome (MBS). DESIGN Prospective, randomized study. SETTING Academic medical center. PATIENT(S): Fifty obese postmenopausal women with MBS. INTERVENTION(S): Women were randomized to receive either oral E(2) (oE(2), 1 mg/d) or transdermal E(2) (tE(2), 0.05 mg/d) for 3 months. Fasting blood was obtained before and after treatment for glucose, insulin, lipid profiles, the adipocytokines (adiponectin, leptin, and resistin), and a gastric peptide (ghrelin). In addition, a 75-g 2-hour oral glucose-tolerance and intravenous insulin-tolerance tests were performed before and after E(2). MAIN OUTCOME MEASURE(S): Changes in parameters of insulin resistance (IR), lipid profiles, and adipocytokine levels. RESULT(S): Mean serum concentrations of E(2) in women using oE(2) and tE(2) were 39.1 +/- 5.6 and 49.2 +/- 28.6 pg/mL, respectively. After oE(2), there was a statistically significant worsening of IR markers, including an increase in baseline insulin (15.28 +/- 1.27 to 22.02 +/- 2.40 microU/mL), a reduction in quantitative insulin-sensitivity check index (0.3177 +/- 0.0043 to 0.2977 +/- 0.0057), and an increase in homeostasis model assessment (3.96 +/- 0.38 to 8.59 +/- 2.08). The only significant change in the lipid profile was an increase in high-density-lipoprotein cholesterol (50.46 +/- 2.34 vs. 55.08 +/- 2.51 mg/dL). Leptin levels increased (81.43 +/- 7.87 ng/mL to 94.10 +/- 6.56 ng/mL), and adiponectin decreased nonsignificantly, resulting in an increased leptin-adiponectin ratio (12.56 +/- 1.70 to 15.86 +/- 2.24); resistin levels increased (9.37 +/- 1.09 ng/mL to 11.72 +/- 1.10 ng/mL); and baseline ghrelin levels decreased (701.64 +/- 59.79 pg/mL to 581.72 +/- 36.07 pg/mL). After tE(2), no significant changes in IR parameters occurred, except for a decrease in glucose-insulin ratio. There were no changes in lipid parameters. Leptin did not change (72.7 +/- 9.3 ng/mL to 78.8 +/- 7.9 ng/mL), whereas adiponectin levels showed statistically significant increase (7.97 +/- 0.7 microg/mL vs. 9.96 +/- 1.1 microg/mL), with no change in the leptin-adiponectin ratio. Resistin levels did not change significantly, and ghrelin levels decreased (888.52 +/- 109.98 pg/mL vs. 579.04 +/- 39.30 pg/mL). CONCLUSION(S): This short-term study suggests that oral E(2) may worsen IR and adipocytokine parameters, worsening cardiovascular risk. Transdermal E(2) had minimal effects on IR and resulted in higher adiponectin. Although these data may not reflect alterations that occur with estrogen therapy in more metabolically normal postmenopausal women or with longer term therapy, the findings suggest that tE(2) may be a preferable treatment for obese women with MBS. Long-term studies are needed to make any recommendations.
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Hormones and cardiovascular health in women.
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Human reproduction update. 2006;(5):483-97
Abstract
Cardiovascular diseases (CVDs) may have their origin before birth: the combination of being small at birth and having an overly rich post-natal diet increases the likelihood of obesity and of acquiring a specific metabolic syndrome in adulthood that carries an increased risk of CVD. The incidence of CVD and mortality is very low in women of reproductive age but rises to a significant level in older women. In this article, we discuss CVD in relation to hormonal contraception, pregnancy and polycystic ovarian syndrome (PCOS) in younger women and menopause in older women. Women with PCOS have a higher risk of diabetes and hypertension, but studies to date have not shown an effect on CVD events. Use of combined hormonal contraception has only small effects on CVD because of the low baseline incidence of myocardial infarction (MI), stroke and venous thromboembolism (VTE) among young women. Women with existing risk factors or existing CVD, however, should consider alternative contraception. In pregnancy, CVD is rare, although, in the West, it now accounts for a significant proportion of maternal mortality as the frequency of obstetrical causes of mortality has substantially declined. The frequency of VTE is 15 per 10,000 during pregnancy and the post-partum period. In older women, menopause causes a slightly higher risk of MI after allowing for age, although there is substantial heterogeneity in the results of studies on menopause and age at menopause and MI. A larger effect might have been expected, because estrogen reduces the risk of developing atherosclerosis in premenopausal women, whereas in post-menopausal women who may have established atherosclerotic disease, estrogen increases the risk of myocardial disease through the effects on plaque stability and clot formation. Recent trial results indicate that hormone treatment in menopause does not favourably affect the risk of MI, stroke or other vascular disease. Thus, prevention of CVD should rely on diet and fitness, low-dose aspirin and treatment of hypertension, hyperglycaemia and hyperlipidaemia.