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Resveratrol: Promising Promotion in Cardioprotection against Coronary Heart Disease
Wednesday November 25, 2009
Resveratrol: Promising Promotion in Cardioprotection against Coronary Heart Disease
Jaime
Urdinola MD Medical Association Andes CS AK 9116 20 326 Bogotá DC Colombia - Tel 571/215 23 00 Ext 13 80
e-mail: jaimeurdinolamd@gmail.com blogger: http://www . urdinola.blogspot.com www.urdinolamenopausia2.blogspot.com
Symposium / Luncheon on Women's Health Menopause Medical Association and the Andes - Board Room - Wednesday November 25, 2009

The chemical structure of t-RESV is resveratrol (trans-3, 4 ',5-trihydroxystilbene).

Resveratrol is a phytoalexin (antibiotic compounds produced by plants in response to microbial growth and as inhibitors of food). Manufacturing


Resveratrol is used to make resveratrate from the root of Polygonum cuspidatum , a plant that comes from China. Once harvested the plant is sent to a laboratory in Belgium, where resveratrol is extracted through a process lasts 14 days. Resveratrol then passed through an advanced process of desalination to increase its potency. Thus begins the manipulation of resveratrol to make it resveratrate: three phosphate groups are added to each molecule in a process called phosphorylation. Once you become resveratrate, resveratrol becomes stable and compatible with the skin, allowing scientists to multiply by 5 its concentration to act on the longevity gene SIRT1.


Introduction In September 2009 at Harvard University in Boston, a conference on aging, with the participation of both the 120 Club (people trying to live up to that age) to the devotees of low-calorie diets. The heavy weight of the participants was Sirtris Pharmaceuticals. This company develops drugs that mimic resveratrol, a chemical found in some red wines. Resveratrol activates a class of proteins called sirtuins, of which the company derives its name. It is thought that activation of sirtuins help the body cope with hunger. If placed in mice and rats on a diet with 30% fewer calories, they can live up to 40% longer.

it seems that it managed to avoid the common degenerative diseases, thus obtaining not only a vida más larga, sino más tiempo con buena salud.

Sirtuínas
Las sirtuínas son una clase de enzimas, unas deacetilasas de histona, NAD-dependientes, que se
encuentran tanto en las células procariotas como en las eucariotas. Afectan al metabolismo celular, regulando la expresión de ciertos genes ( o epigenética ) dentro de las células eucariotas de vegetales y animales. El nombre proviene de S ilent mating type I nformation R egulation two , el gen responsable de la regulación celular en el interior de las levaduras, e -ina , terminación o conventional suffix for proteins.

The company Sirtris researchers believe that drugs that activate sirtuins, could mimic the process of making the body stronger and more resistant to disease and aging. It has been shown that in mice, the activators of sirtuins are effective against lung cancer or colon cancer, melanoma, lymphoma, Type 2 diabetes, cardiovascular disease and Alzheimer's. These drugs reduce inflammation, which suggests that humans could remedy problems such as irritable bowel syndrome or glaucoma.

Several clinical studies are in Phase 1 and 2 research. No
have shown that resveratrol increased lifespan in mice as it does in normal mice
obesity, as well as worms and flies.

Resveratrol red wine has long been associated with called "French Paradox
" reflecting the low incidence of heart disease (CHD) among the French despite the consumption of a diet high in saturated fat. It is a polyphenolic compound found in the skin of some red fruit such as grapes and plums, the red skin of peanuts and even peanut butter.

The interest stems from numerous epidemiological studies que demostraron una asociación entre el
consumo moderado de alcohol y la reducción en las cifras de la enfermedad coronaria, así como la reducción en la EC en bebedores especialmente de vino, en comparación con otro tipo de bebidas 1 . Frankel 2 demostró que los polifenoles del vino rojo inhibían la oxidación del colesterol LDL más que el antioxidante establecido, el α-tocoferol. Esto, por supuesto y como era de esperarse, llevó a los científicos a enfocarse en investigaciones que aclararan el efecto cardioprotector del vino rojo. Además, protege las células de la acumulación de lípidos and oxidative stress induced by hydrogen peroxide 3.

myocardial angiogenesis mediated by hypoxia / reoxygenation depends on a mechanism dependent on nuclear factor kB by increasing its DNA binding activity. Resveratrol synthase increased phosphorylated endothelial nitric oxide, by regulating the growth of endothelial cells. The Vascular Endothelial Growth Factor is a proangiogenic factor and a cardioprotective molecule that induces hemodynamic changes and microvascular permeability. You can see that the beneficial effects of resveratrol may have anti-ischemic basis multifactorial, increasing also the production of nitric oxide in endothelial cells 4 . Conclusions


This brief review demonstrates that resveratrol means great promise in the treatment of pathophysiological complications such as myocardial ischemia as well as hypercholesterolemia and diabetes by regulating several target molecules that protect the myocardium against injury disease, and to reduce ventricular remodeling. Thus treatment with resveratrol may be used for and development of therapeutic angiogenesis in patients with coronary artery disease
. References

1- Grønbaek M, Deis A, Sørensen TI, Becker U, Schnohr P, Jensen G. Mortality associated with moderate intakes of wine, beer, or spirits. BMJ. 1995; 310: 1165-9.
2- Frankel EN, Kanner J, German JB, Parks E, Kinsella JE. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine. Lancet. 1993;341:454-7.
3- Dani C, Oliboni LS, Vanderlinde R, Pra D, Dias JF, Yoneama ML, Bonatto D, Salvador M, Henriques JA. Antioxidant activity and phenolic and mineral content of rose grape juice. J Med Food. 2009;12:188-92.
4- Penumathsa SV, Maulik N. Resveratrol: a promising agent in promoting cardioprotection against coronary heart disease. Can J Physiol Pharmacol. 2009, 87: 275-286.

If you have any comments, questions or concerns, you can "click" in comments and send your message. Or if you prefer, you can send your comments, questions or concerns e-mail jaimeurdinolamd@gmail.com

Make Herbal Cigarettes

E l A screw

Wednesday October 28, 2009

E l A screw

Jaime MD Urdinola.

Medical Association Andes CS AK 9116 20 326 Bogotá DC Colombia

Phone 571/215 23 00 Ext 13 80 e-mail: jaimeurdinolamd@gmail.com

blogger: http://www.urdinola.blogspot.com www. urdinolamenopausia2.blogspot.com

Symposium / Luncheon on Women's Health and Menopause Medical Association

Andes Boardroom - Wednesday, October 28, 2009

Summary NuvaRing ® is

a novel contraceptive vaginal ring that has recently come to Colombia.

is a combined hormonal contraceptive for administration parenteral at long intervals, so that is expected to improve the continuity and compliance with treatment.

contains progestin and ethinyl estradiol and etonogestrel as its estrogen, released in small amounts (120 mcg and 15 mcg / day, respectively), from a soft, transparent ring with a diameter of 54 mm and a thickness of 4 mm.

Women in other parts of the world have accepted without reservation, since it is easy to use.

common side effects with combined oral contraceptives are less with the ring, contraceptive efficacy is very good and draws attention to the hormonal serum levels obtained are very low, which implies that its metabolic impact is reduced. These benefits are ideal for healthy women and those with overweight and metabolic syndrome. Introduction


contraceptive vaginal ring NuvaRing ®, developed by Organon company that is now part of Schering Plough Corporation, which in turn has recently merged with Merck Sharp & Dohme, was approved from 2 001 in the Netherlands and by the U.S. FDA and is available from 2 002 in these countries.

just arrived to Colombia in recent months as a real novelty and as a method that actually increases the options in contraception, as it is a method to manage rather than daily as oral contraceptives (COCs), but with intervals of 4 weeks. This feature can improve compliance and continuity of this contraceptive method, as these are no greater than 40% in COCs after 6 months of use.

universal requirements
contraception contraception should be effective, easy to use, have almost no side effects and safe.

Security is an important prerequisite for hormonal contraception in relation to its metabolic impact and long-term consequences on the cardiovascular system. Cardiovascular risk is increased in women with Metabolic syndrome, especially in these times of global epidemic of obesity, underlying disorder which is represented in the reduced insulin sensitivity (SI). Precisely the SI is decreased with the use of hormonal contraceptives currently in use, an effect that can be seen in those containing levonorgestrel (LNG).

vaginal route for the administration of contraceptives, as the case of contraceptive vaginal ring NuvaRing ®, appears to offer an explanation pharmacokinetic advantages later. Acceptance


Contrary to what one might expect, in the studies to date, Most women report that the ring is easy to insert and remove. The proportion of women who report feeling the ring during intercourse was only 18%. For its part, the percentage of sex partners they felt the ring during intercourse was 32%. However, 94% of the companions did not object to the use of the ring. In turn, 85% of participants were satisfied or very satisfied at the end of the study and 90% and indicated they would recommend their familiar ring 1-4. Benefits

long interval for the administration of contraceptive doses
Half the hormonal contraceptive failures are due to incorrect use of contraception. During the first 2 months of method use, 47% of women forget to take a pill and 22% forget 2 of them. The contraceptive ring provides a significant advantage, and to be inserted only once every 4 weeks, using it 3 weeks and resting.

Another advantage is that hormonal fluctuations are much lower with the vaginal route, compared with administration of oral tablets or even against the contraceptive skin patch, and thus a reduced systemic exposure to ethinyl estradiol (EE) 5 . Therefore, vaginal route seems the best route for low doses, constant and accurate control hormones, which results in stable serum concentrations and low exposure to EE.

Comparison with the contraceptive patch and contraceptive efficacy
In 2 002 hit the market the contraceptive patch and vaginal ring. In 2005 the FDA modified the prescribing information for the patch, and that serum levels of EE obtained with the patch can be up to 60% higher than those obtained with the AOC. This could lead to more side effects occur and possible thromboembolic complications. Women who switched to the patch AOC compared with the contraceptive ring users experienced longer periods (38% vs. 9%), increased dysmenorrhea (29% vs. 16%), frequent nausea (8% vs. 1%), mood swings (14% vs. 8%) and frequent skin rash (12% vs. 2%). The contraceptive vaginal ring users preferred it compared to COCs (p <0.001) color="#3366ff"> 6. There were 6 pregnancies in 12 109 cycles studied, for a Pearl Index of 0.65 (CI = confidence interval 95%, 0.24- 1.41). In the international study on the patch 7 15 pregnancies occurred during 22 160 cycles studied, Pearl Index of 0.88 (95% CI, 0.44-1.33).

cycle control and body weight compared with the AOC
The results obtained after observation for 6 cycles, indicate that withdrawal bleeding (obtained by removing the method) is presented as equal in both groups. The incidence of irregular bleeding in all cycles with NuvaRing ® was <5> 8, compared with COCs.

weight changes observed were very small, in one study ranged from -0.1 to + 0.1 kg 9-10.

NuvaRing ® and lipids
total cholesterol and cholesterol HDL did not change with the contraceptive vaginal ring use, whereas in the group of AOC levels of HDL cholesterol, HDL2 and HDL3 decreased. The levels of apolipoprotein A-1 increased with NuvaRing ®, but decreased with the AOC. In both groups, nievels of apolipoprotein B and triglycerides were increased and lipoprotein (a) decreased. These changes reflect the low androgenicity of etonogestrel versus. levonorgestrel and show that NuvaRing has minimal effects on lipid profile 11.

The contraceptive vaginal ring and insulin sensitivity (SI)
A prospective randomized study using AOC (30 or 20 mcg EE and desogestrel [DSG] 150 mg) and NuvaRing ® 12 for 6 months, analyzed via oral or vaginal administration of hormonal contraceptives, to assess whether the route has a similar effect on the SI. The SI decreased with AOC regardless of high or low dose COCs. But the SI did not decrease with the use of contraceptive vaginal ring. These data indicate that in contrast to the AOC, the vaginal contraceptive SI deteriorates. NuvaRing ® thus represents an appropriate choice for long-term contraception in women who are at risk for developing diabetes mellitus or metabolic syndrome, Known risk factors for cardiovascular disease.


Conclusions It was concluded according to the data, which is characterized by NuvaRing ®:

high
● ● Acceptance Better adherence to treatment, greater continuity and compliance
● No interference
● Very sexuality ● With
effectively reduced exposure to ethinyl estradiol
● Good cycle control side effects

● ● Reduced metabolic neutrality

For the foregoing reasons NuvaRing ® can be considered as

● A birth de primera línea
● Un anticonceptivo para usar a largo plazo debido a su neutralidad metabólica

Referencias

1- Roumen FJME, Apter D, Mulders TMT, Dieben ThOM. Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethynil oestradiol. Hum Reprod. 2001;16:469-75.
2- Dieben ThOM, Roumen FJME, Apter D. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol. 2002; 100: 585-93.
3- Novák A, de la Loge C, Abetz L, van der Meulen EA. The combined contraceptive vaginal ring, NuvaRing®: an international study of user acceptability. Contraception. 2003; 67:187-194.
4- Novák A, de la Loge C, Abetz L. Development and validation of an acceptability and satisfaction questionnaire for a contraceptive vaginal ring, NuvaRing®. Pharmacoeconomics. 2004; 22:245-256.
5- van den Heuvel MW, van Bragt AJM, Alnabawy AKM, Kaptein MCJ . Comparison of ethynilestradiol pharmacokinetics in three hormonal contraceptive forrulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception .2005; 72: 168-174.
6- Creinin MD, Meyn LA, Borgatta L, Barnhart K, Jensen J, Burke AE, Westhoff C, Gilliam M, Dutton C, Ballagh SA. Multicenter comparison of the contraceptive ring and patch. Obstet Gynecol. 2008; 111: 267-77.
7- Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertil Steril. 2002;77( Suppl 2):S13-8.
8- Bjarnadóttir RI, Tuppurainem M, Killick SR. Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethynil estradiol. Am J Obstet Gynecol. 2002; 186: 389-95.
9- Merki-Feld GS, Hund M. Clinical experience with NuvaRing® in daily practice in Switzerland: Cycle control and acceptability among women of all reproductive ages. Eur J Contracept Reprod Health Care. 2007;12:240-7.
10- Milsom I, Lete I, Bjertnaes A, Rokstad K, Lindh I, Gruber CJ, Birkhäuser MH, Aubeny E, Knudsen T, Bastianelli C. Effects of cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 μg ethynil estradiol and 3 mg drospirenone. Hum Reprod. 2006; 21: 2304-11.
11- Tuppurainen M, Klimscheffskij R, Venhola M, Dieben ThOM. The combined contraceptive vaginal ring (NuvaRing®) and lipid metabolism: a comparative study. Contraception. 2004; 69: 389-94.
12- Cagnacci A, Ferrari S, Tirelli A, Zanin R, Volpe A. Route of administration of contraceptives containing desogestrel / etonogestrel and insulin sensitivity: a prospective randomized study. Contraception. 2009, 80:34-9.

.


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Abreva Instructions For Use

Ring Menopause Hormone Therapy: Concerns True and False Alarms - Part II: Cardiovascular

Hormone Therapy in Menopause: True and False Alarms Concerns

Wednesday August 26, 2009

Menopause Hormone Therapy: Concerns Real and False Alarms - Part II: Cardiovascular

Jaime MD Urdinola.
Andes Medical Association - AK 9116 20 CS 326 - Bogotá DC Colombia

Phone 571/215 23 00 Ext 13 80
e-mail: jaimeurdinolamd@gmail.com

blogger: http://www.urdinola.blogspot.com - www.urdinolamenopausia2.blogspot.com

Symposium / Luncheon on Women's Health and Menopause - Medical Association of the Andes - Prime Boardroom Floor

Wednesday August 26, 2009

Summary

from 2 002-2 008 reports of the WHI (Women's Health Initiative = Initiative Women's Health) said the Menopausal Hormone Therapy (HT) significantly increased risk for developing breast cancer, cardiac events, Alzheimer's disease and stroke. These statements have alarmed the public and to health professionals, immediately causing a sharp decrease in the number of women who are taking prescribed or TH.
However, current data published in the articles on the WHI show that the findings reported in the press releases and interviews with principal investigators, were often distorted, oversimplified or wrong.
This second part of the review examines the findings on cardiovascular disease, most of which are weak or not statistically significant. On these complicated matters, therefore, physicians and the public should be very cautious in accepting the "findings of press releases" to determine on their part, doctors if they prescribe o las pacientes si toman la TH formulada. (Cancer J. 2009; 15:93-104) 1

Introducción

La Enfermedad Cardiovascular (ECV) y especialmente la Enfermedad Coronaria (EC) son las principales causas de muerte en la mujer, no sólo en los países desarrollados sino también en Colombia.

Según datos del DANE ( Departamento Administrativo Nacional de Estadística) 2 ,

en el año 2 005 la tasa de mortalidad en mujeres mayores de 50 años por enfermedades cerebrovasculares was of 50.7 per 1 000 women and 67.1 per 1 000 women the rate of ischemic heart disease.
Of the 75 891 deaths that occurred that year in women, 25 441 = 33.5% were caused by CVD.
If we compare with deaths from breast cancer, a woman in Colombia is almost 14 times more likely to die from CVD than from breast cancer. In the U.S. the same proportion is 5 to 1.

It is therefore crucial to understand the role of TH in the possible development and progression of cardiovascular disease as well as it could provide protection against this entity HT. Recommendations

U.S. scientific societies on TH

● 1992 - American College of Obstetricians and Gynecologists - Probable beneficial effects of estrogen on heart disease, "
● 1992 - American College of Physicians - " Women with Coronary Heart Disease or who have increased risk for it, could benefit from hormonal therapy "
● 1996 - American Heart Association - " Estrogen therapy seems promising as long-term protection against a heart attack "

These recommendations were based in various publications of the eighties, on the cardiovascular benefit obtained from taking HRT, reporting that the reduction of CHD with estrogen therapy (ET) could be 30%, consistent finding in 90% of the cohort, 63% of Case-control studies and one randomized, double-masked study to date 3.

In 1991 an editorial in the New England Journal of Medicine reported that the consensus of epidemiological studies on the reduction was 40-50%, compared to women not receiving HRT. In Study 2 000 Nurses reported that HT decreased the early development of primary CVD by about 40%.

It should be noted however that despite the plausible evidence obtained from observational studies that point on the cardiovascular benefit, this indication was never approved by any regulatory authorities of the globe.

And despite these data, the large randomized HERS 4 found a statistically significant increase in cardiac events in women with known CAD who had received HRT, but only during the first year of uso4 ("effect of thrombophilia?).

2 002 In the WHI study 9 reported that women taking combined HRT, but not women with ET, showed a slight increase in the relative risk of "cardiac events" (EC which included acute myocardial infarction requiring hospitalization or silent myocardial infarction), CVD death, angina or indications for bypass surgery. But as in the case of the HERS study, this increased risk occurred only among women during the first year of taking combined HT.

2 007 In the WHI researchers reviewed the findings of 2 002, concluding that women who started HT during the first 10 years following menopause reduced their risk of CHD, while those who started HRT after this period slightly increase your risk 5.

-Observational Study - the Nurses 6 reached the same conclusions.

These data supported the theory of Opportunity for the Initiation of HT 7 although in July this year 2009 a new analysis of WHI study appears to rebut August, which could be discussed further in another symposium. KEEPS and ELITE studies currently underway, trying to test the theory. Why

TH increases cardiovascular risk only during the first year and only among women ancianas ?

Se sabe de datos obtenidos en primates, que el estrógeno administrado en forma continua mantiene saludables los vasos sanguíneos. También conocemos, que la TE después de un intervalo libre de hormonas no revierte el daño vascular. Los estudios HERS y Estrogen Prevention of Atherosclerosis Trial and Estrogen Replacement son consistentes con los datos obtenidos de animales.

Una de las explicaciones es que entre las mujeres sin ECV, la TH reduce la oxidación del colesterol LDL y produce dilatación en los vasos sanguíneos, inhibiendo de esta manera la aterosclerosis. Sin embargo, en las mujeres con ECV, la TH puede ser potencialmente dañina, causando que la placa stable atherosclerotic breaks induced by inflammation and in turn you have bleeding within the plaque, leading to block both phenomena critically affected coronary artery.

This analysis may explain why studies have enrolled older women younger, the Nurses Study, found that HRT provides a protective effect, because these women probably have less arterial atherosclerotic plaques.

But in the WHI study only 10% of the women were between 50 and 54 years of age, age at which TH can probably have a beneficial role. 70% of the women were between 60 to 79 years of age range in which we expect to find pre-formed plates 9. TH Although the latter age may be effective in reducing total cholesterol, LDL cholesterol and glucose as well as raise HDL cholesterol levels, these benefits do not result in a reduction in the incidence of stroke in elderly women, it which is consistent taking into account pre-existing atherosclerosis in this population.

The WHI is likely that atherosclerosis was present in the population, as well as the average age of 63 years, 70% of women were overweight and half of them were obese. About 50% were or had been smokers and 35% were treated for hypertension. Women with these risk factors were not excluded from the analysis of HT and cardiovascular events, although the WHI investigators had established that all women who were recruited were healthy, a prerequisite for participation in this course study of primary prevention . However, it is difficult to reconcile these statements with the records of this large number of women 10 .

What conclusions can you go?

- HT may have beneficial effects on the heart of women who start taking HRT early after menopause (around 50 years old), since estrogen promotes healthy blood vessels and may help delay the formation of atherosclerotic plaque

- HT may not have a protective effect in women who start HT use later in the decade of their 60

- HT is potentially risky for women who start during the decade of their 60's, at least during the first year of use, especially if they have EC
existing
Finally, you can share the opinion of the majority of cardiologists, there is no reason to prevent CVD only by TH, as there are other ways to reduce cardiovascular risk.

But something can be clear. It is time to cease calls to cite security concerns about the TH, based on the publication of the WHI study 2 002 9 because their findings have been superseded and its conclusions have been reinterpreted.



References

1 - Bluming AZ, Tavris C. Hormone Replacement Therapy: Real Concerns and False Alarms. J. Cancer 2009, 15: 93-104.
2 - DANE: Table of Deaths by Age and Sex Grouped Causes According List - Preliminary 2005 to 6187 ICD-10.
3 - Barrett-Connor E, Bush TL. Estrogen replacement and coronary heart disease. Cardiovasc Clin. 1989; 19:159-172.
4- Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998; 280: 605-613.
5- Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007; 297: 1465 – 1477.
6- Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menoapuse and aged at hormone initiation. J Womens Health. 2006; 15: 35 – 44.
7- Barrett-Connor E. Hormones and Heart Disease in Women: The Timing Hypothesis. Am J Epidemiol. 2007; 166: 506-510.
8- Prentice RL, Manson JE, Langer RD, et al. Benefits and risks of postmenopausal hormone therapy when it is initiated son after menopause. Am J Epidemiol. 2009;170:12–23.
9- Rossouw JE, Anderson GL, Prentice RL, et al. Writing Group for the Women’s Health Initiative investigators. Risks and benefits os estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Helath initiative Randomized Controlled Trial. JAMA. 2002; 288: 321 – 333.
10- Bhavnani BR, Strickler RC. Menopausal hormone therapy. J Obstet Gynaecol Can. 2005; 27: 137 – 162.

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Hormone Therapy in Menopause: True and False Alarms Concerns

Menopause Hormone Therapy: Concerns and Interests False Alarms
Wednesday July 29, 2009
Menopause Hormone Therapy: Concerns Real and False Alarms-First Party: Breast Cancer

Jaime Urdinola
MD Medical Association Andes CS AK 9116 20 326 Bogotá DC Colombia - Tel 571/215 23 00 Ext 13 80 e-mail: jaimeurdinolamd@gmail.com blogger: http://www.urdinola . blogspot.com http://www.urdinolamenopausia2.blogspot.com/

Symposium / Luncheon on Women's Health and Menopause Medical Association Andes

First Floor - Board Room - Wednesday, July 29 , 2 009

Summary from 2 002-2 008 reports of the WHI (Women's Health Initiative = Women's Health Initiative) stated that the Menopausal Hormone Therapy (HT) significantly increased risk for developing breast cancer, cardiac events, Alzheimer's disease and stroke. These statements have alarmed the public and to health professionals, immediately causing a sharp decrease in the number of women who are prescribed or taken HT.
However, current data published in the articles on the WHI show that the findings reported in the press releases and interviews with principal investigators, were often distorted, oversimplified or wrong.
This review examines the findings on breast cancer in this first part, most of which are weak or not statistically significant. On these complicated issues, physicians and the public should be very cautious in accepting the "findings of press releases" to determine on their part if they prescribe or take HT. (Cancer J. 2009, 15: 93-104) 1

Introduction
Most women in the U.S. or Colombia does not take any form of HT after menopause and those who do, not take more than 5 years 2 . Only a minority of women take HRT for the rest of his life.

As is known, the TH is very effective to relieve common menopausal symptoms like hot flashes, night sweats, emotional lability, palpitations, insomnia, increased urination frequency and discomfort and painful intercourse. Some women who are at high risk for osteoporosis also are prescribed HRT, and that estrogens reduce the incidence of osteoporotic hip fracture in 25 to 50%. As currently there are alternative drugs-bisphosphonates such as alendronate, risedronate and ibandronate, which offer a similar protective benefit, most Doctors are not recommending the use of hormones to prevent hip fracture, although the former may have adverse effects such as gastric and esophageal irritation and in rare cases, osteonecrosis of the jaw.

has been debated for decades about the risks and benefits of estrogen combined with or without progestin. Since the 50 and 60 of the last century, when at that time Ayerst Laboratories began to aggressively market its estrogen preparation, Premarin, hormone supplements or as they were called "replacement" was presented as a panacea, that seductive words New York gynecologist, Robert Wilson, remain women "feminine forever." Since the 80's many critics argued that this treatment was a serious and unnecessary risk to the health of women. The biggest concern of these critics was breast cancer, a disease dreaded by women and heart disease causes more deaths than breast cancer occurs.

In July 2002, the first publication of the WHI study findings announced with fanfare and bold headlines in the media, that the damage of HT included not only breast cancer but also heart disease and accident cerebrovascular 3 . The news was alarming, since this study was a prospective, randomized study in which women took hormones or placebo, the largest to date and with a considerable time tracking. The cost is now approaching one trillion dollars. As a result of initial claims, not surprising that attention generated worldwide has led to the rate of prescription for HRT has fallen more than 50%.

A previous study, prospective, randomized, double-masked found no risk for breast cancer in women even up after 22 years who took the TH 4 , but this research has never made headlines in the media.

data extraction, reporting risk and other problems in research
be denied HT short or long term to women with menopausal symptoms, because they are afraid of breast cancer, heart disease or stroke? Their concerns are justified by the data available?
If analyzed closely to findings published in the articles on the WHI and placed in the context of research on HT over the past decades, no big surprises for the huge discrepancies found between the belief that hormones are dangerous and lack of data to support these beliefs.

Science is a process and therefore, a simple, single study does not provide a definitive answer. Two statistical errors have contributed to research on TH is unclear, one has to do with the way it reports on the risks, the other with the "extraction" inappropriate data, ie, when researchers are looking for something or thing about their findings, which may come to be regarded as a significant risk factor.

There are differences between absolute risk and relative risk. Media and researchers tend to report the relative risks, which are expressed in percentages may seem more important than they are. Not the same 300%, the increase that occurs when switching between the incidence of 1 in 10 000 women to 3 in 10 000 women, mean 300% increase, but it is very likely to be a random artifact.
But if the risk is clear that 100 was passed to 300 cases in 10 000, can be reasonably worried. In large epidemiological studies, which generally include tens of thousands of people, you may find a small link that might be considered "significant" statistically, but in practical terms means little or nothing, according to the low absolute numbers. The recommendation of various projects of consensus on the way they should report the findings of clinical studies, is that it must provide not only absolute numbers and percentage changes.

Risk Factors Associated with Breast Cancer
Risk Factor Risk 95% Reference Interval
Relative Confidence (IC) *
-
Conjugated equine estrogens 0.77-0.59 - 1.01 5
- Consumption of fish 1.14-1.03 - 1.26 6
- Premarin / gestagen 1.24-1.01 - 1.54 3
- Premarin / gestagen 1.26-1.00 - 1.59
7 - Consumer-A
fries extra serving per week 1.27-1.12 - 1.44
8 - 1.3 Grapefruit Juice - 1.06 - 1.58 9
- Night work 1.51-1.36 - 1.68 10
- Hostess (Finland) 1.87-1.15 - 2.23 11
- Dutch Famine 2.01-0.92 - 4.41 12
- Use antibiotics 7.2-1.48 - 2.89
13 - Hostess (Iceland) 4.1- 1.70 - 8.50 14
- Using electric blanket 4.9-1.50 - 15.6
15 - smoking / lung Ca 7.26-6.58 - 103.3 16

As shown in the table above, many studies of HT and breast cancer risk have produced inconclusive results or statistically really modest, which has tried to give the appearance of imposing the report as relative risks. At first glance you can see the weakness of these associations when compared with the actual discovery of the association at the end of the table, cigarette to lung cancer. In any case the relative risks are low, with virtually the lowest TH, compared with consumption of fish or grapefruit juice, the use of antibiotics or the fact of being a flight attendant.

extraction research data, in turn, can lead to bias, that when there are significant associations that led to the hypothesis of the study to a possible risk factor and disease or problem, returns to the data, "probe", looking at other factors that can establish a statistical connection with the dependent variable in question. This effort may result in interesting questions or hypotheses for future research but the problem is that in the data set of thousands of people could find any relationship discovered in retrospect, which may become significant only by chance. The contrast is that despite numerous investigations, the relationship between HRT and breast cancer is not yet clear.

there a link between HRT and breast cancer?
In the press release from the National Institutes of Health U.S. 9 July 2002, it was reported that he had interrupted a very important clinical trial (of the WHI) by relative risk (RR) increased (1.26) for breast cancer in healthy women who had received a combination of estrogen plus progestin compared to women who they had been randomly assigned placebo. What few noticed was this sentence in the publication "26% increase in the incidence of breast cancer among HT group compared with the placebo group almost reached nominal statistical significance." But the word "almost" means that did not reach statistical significance. Neither showed a marked increase in cases of noninvasive breast cancer, which precedes the invasive type cancer. There was, however, the difference between the 2 groups in the incidence of this cancer early, nor in cases of death from breast cancer. In terms absolute, this would mean that HRT increased the risk of 5 women in 100 to 6 100.

2 003 In the WHI published a follow up to 2 002 17, confirming that the use of combined estrogen with progestin increased the risk of invasive breast cancer significantly during a period of 5 years. The reported RR was 1.24, lower than the finding of 1.26 in 2 002 and that "only" reached statistical significance.

2 006 In another update from the same cohort of patients 18, the WHI reported no increased risk for breast cancer in women randomized to combination therapy. Significant relative risk was gone. This news did not make the headlines.

Nor Nurses Study found increased risk for breast cancer among women taking HT 19 , researchers compared women who had used HT previously with women who had never taken. No increased risk was found for breast cancer, even among those who had taken HT for more than 10 years, compared with those who never users. Then they subestratificaron again shown in a) current users and b) women who had used TH in the past and had been suspended. In this way the researchers found an increased risk for breast cancer, but only those who were taking combined HRT or estrogen alone for at least 5 years. But what is the explanation for that risk is increased in the group of women who take HRT for 5 years but not for those who have taken over 10 years?

In contrast, if the TH represents a risk factor will be for women with BRCA1 and BRCA2 gene mutation, which predisposes them to develop the disease. If they do oophorectomy, the risk of developing cancer breast halves. But the surgery induced menopause and some women take HT to relieve menopausal symptoms, which evokes questions as they are in danger? Taking estrogen denied the benefits of surgery? The study 20 of 236 patients with breast cancer and 236 controls who were all carriers of BRCA1 (no women with BRCA2 that may be included), found no increased risk among women taking hormones, whether natural menopause had been presented by age or surgery. It seems a contradiction, because if the decrease of estrogen to practice oophorectomy is the reason for the decline risk for breast cancer in carriers of BRCA1, estrogen administration would be irrational sumplementarios for relief of symptoms.

Estrogen does cause cancer?
The hypothesis that hormones are related to breast cancer is derived from two well-documented facts: the incidence of breast cancer is 100 times greater in women than in men, and the earlier presentation of menarche and the latest of the menopause, the greater the risk of women for breast cancer.

reasonably
These observations suggested that estrogen may be the culprit, the circular for more years. In the scientific process, the first step is to establish a reliable association, which according to previous data has become very weak or nonexistent. The second step is to demonstrate a mechanism responsible for the phenomenon, which in the case of breast cancer is contradictory according to the following lines of evidence:

- Birth control pills contain more estrogen than those of TH. Therefore, should increase the risk for breast cancer. Although the controversy continues, most studies in this field are not at increased risk 21.

- Women who take estrogen only should have a greater risk for breast cancer, but do not. So I checked the WHI study, after an average of 6.8 years follow 22.

- The incidence of breast cancer increases as women get older. If you take estrogen were part of the reason, the rate of breast cancer in women not taking HT should decrease with age, consistent with the natural decline in estrogen levels, but this does not happen.

- Estrogens do not act directly as carcinogens on mammary cells. But estrogen can induce cell proliferation. WHI investigators have modified their hypothesis, stating that agents that induce mutations are around us and to the extent that the rate of cell proliferation is high, the greater the probability that a cell is exposed to the mutagen and malignice. Endometrial cells are very sensitive to estrogen because women account for only taking estrogen have a risk 5 to 6 times higher for endometrial cancer, but not at higher risk for breast cancer. Term stimulation by estrogen in the case of early menarche and menopause should predispose late endometrial cancer, which does not appreciate 23.

As can be inferred from the above, the relationship between HRT and breast cancer has not yet been clarified despite the vast amount of research has been done 24.





References 1 - Bluming AZ, Tavris C. Hormone Replacement Therapy: Real Concerns and False Alarms. J. Cancer 2009, 15: 93-104.
2 - Pilon D, Castilloux AM, Lelorier J. Estrogen replacement therapy: Determinants of persistence with steam treatment. Obstet Gynecol. 2001, 97:97-100.
3 - Rossouw JE, Anderson GL, Prentice RL, et al. Writing Group for the Women’s Health Initiative investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative Randomized Controlled Trial. JAMA.2002; 288: 321.333.
4- Nachtigall MJ, Smilen SW, Nachtigall RD, et al. Incidence of breast cancer in a 22-year study of women receiving estrogen-progestin replacement therapy. Obstet Gynecol. 1992;80: 827– 830.
5- The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2004; 291:1701–1712.
6- Stripp C, Overvad K, Christensen J, et al. Fish intake is positively associated with breast cancer incidence rate. J Nutr. 2003;133:3664 –3669.
7- Chlebowski RT, Hendrix SL, Langer RD, et al; for the WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA. 2003; 289:3243–3253.
8- Michels KB, Rosner BA, Chumlea WC, et al. Preschool diet and adult risk of breast cancer. Int J Cancer. 2006; 118:749 –754.
9- Monroe KR, Murphy SP, Kolonel LN, et al. Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study. Br J Cancer. 2007; 97:440–445.
10- Megdal SP, Kroenke CH, Laden F, et al. Night work and breast cancer risk:a systemic review and meta-analysis. Eur J Cancer. 2005; 41:2023–2032.
11- Pukkala F, Auvinen A, Wahlberg G. Incidence of cancer among Finnish airline cabin attendants, 1967–1992. BMJ. 1995; 311:649–652.
12- Elias SG, Peeters PH, Grobbee DE, et al. Breast cancer risk after caloric restriction during the 1944–1945 Dutch famine. J Natl Cancer Inst. 2004; 96:539 –546.
13- Velicer CM, Heckbert SR, Lampe JW, et al. Antibiotic use in relation to the risk of breast cancer. JAMA. 2004; 291:827– 835.
14- Rafnsson V, Tulinius H, Jo´nasson JG, et al. Risk of breast cancer in female flight attendants: a population-based study (Iceland). Cancer Causes Control. 2001;12:95–101.
15- Kangmin Z, Hunter S, Payne-Wiks K, et al. Use of electric bedding devices and risk of breast cancer in African-American women. Am J Epidemiol. 2003; 158:798–806.
16- Sasco AJ, Merrill RM, Dari I, et al. A case-control study of lung cancer in Casablanca, Morocco. Cancer Causes Control. 2002; 13:609–616.
17- Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A; WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA. 2003. 25; 289:3243-53.
18- Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, Aggerwal A, David Curb J, Hendrix SL, Allan Hubbell F, Khandekar J, Lane DS, Lasser N, Lopez AM, Potter J, Ritenbaugh C. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas. 2006. 20;55:103-15.
19- Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ, Hennekens C, Rosner B, Speizer FE. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332:1589-93.
20- Eisen A, Lubinski J, Gronwald J, Moller P, Lynch HT, Klijn J, Kim-Sing C, Neuhausen SL, Gilbert L, Ghadirian P, Manoukian S, Rennert G, Friedman E, Isaacs C, Rosen E, Rosen B, Daly M, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst. 2008; 100:1361-7.
21- Casey PM, Cerhan JR, Pruthi S. Oral contraceptive use and risk of breast cancer. Mayo Clin Proc. 2008;83: 86-90.
22- Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE, Schenken RS, Yasmeen S, Lessin L, Chlebowski RT; WHI Investigators Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA. 2006, 295:1647-57.
23 - Thomas DB. Do hormones cause breast cancer? Cancer.1984, 53: 595-604.
24 - spied M, Daura JP, Chevallier T, Mares P, Micheletti MC, De Reilhac P. Breast cancer incidence, and hormone replacement therapy: results from the MISSION study, prospective phase. Gynecol Endocrinol. 2007; 23:391-7.


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VIBE Study Analysis

Study VIBE: First comparison head to head "on fracture risk in women treated with monthly oral ibandronate [Bonviva (R)] or weekly bisphosphonates

Wednesday April 30, 2009

VIBE Study: First compared head to head "on fracture risk in women treated with monthly oral ibandronate [Bonviva (R)] or weekly bisphosphonates

Urdinola Jaime MD

Andes Medical Association 9116 AK 20 CS 326 Bogotá DC Colombia

Phone 571/215 23 00 e-mail: jaimeurdinolamd@gmail.com

blogger: http://www.urdinola.blogspot.com/ www.urdinolamenopausia2.blogspot.com

Symposium / Luncheon on Women's Health and Medical MenopausiaAsociación

Andes

Board Room - Wednesday April 30, 2009

VIBE study a is important and topical, as it is the first to establish a comparison head to head "between the rates of monthly ibandronate fracture and weekly bisphosphonates administered orally. This is a large study of older women or 45aňos of age, who were given first monthly ibandronate or weekly bisphosphonates - alendronate or risedronate - orally, they did not display any type of malignancy or Paget's disease of bone.

The primary analysis included patients who had adherence to treatment during the first 90 days after the index date. The risk of hip fracture, no spinal cord and any clinical fracture were compared using risk models and adjusted Cox proportional to factors that could potentially lead to confusion.

A secondary analysis of "intention to treat including all patients who received at least one prescription of bisphosphonates.

sensitivity analysis based on the primary analysis compared patients who received ibandronate to patients who had received weekly alendronate or risedronate separately and explored the effect of excluding patients with factors that potentially could lead to confusion analysis. Further analysis of sensitivity varied the requirement of adherence during the first 90 days after the index date.

The primary analysis population included patients 7 345 56 837 monthly ibandronate with weekly bisphosphonate . Fracture rates after 12 months of observation period were < 2% y el riesgo de fractura no fué significativamente diferente entre pacientes que recibieron Ibandronato mensual o bisfosfonatos semanales, para fractura de cadera, fractura no vertebral o cualquier tipo de fractura clínica (riesgo relativo ajustado: cadera= 1.06, p=0.84; no vertebral=0.88, p=0.255; cualquier fractura clínica=0.82, p= 0.052).

But patients receiving ibandronate had a significantly lower risk of vertebral fracture than those who received weekly bisphosphonates (adjusted relative risk 0.36, confidence interval 95% 0.18 to 0.75, p = 0.006).

In the secondary analysis of "intent to treat" fractrura relative risks were not significantly different between treatment groups for any type of fracture. The results of sensitivity analysis were generally consistent with the primary analysis.

This retrospective cohort study found that patients treated with bisphosphonates ibandronate monthly or - alendronate, risedronate - weekly orally, had a similar and reduced risk of hip fracture, vertebral fracture and any fracture clinic.

But ibandronate patients had a significantly lower relative risk of vertebral fracture than patients who received weekly bisphosphonates. The clinical implications of these findings require further exploration and validation. In the beginning

bisphosphonates were marketed for daily administration and its efficacy in reducing vertebral and nonvertebral fractures was evaluated in clinical trials. The efficacy and regulatory approval of new dosage regimens (weekly monthly or quarterly), checking anti-fracture efficacy was established on the basis of changes in bone mineral density (BMD) compared to those seen with daily dosing.

But until now no study had been made "head to head" between bisphosphonates administered daily or the new extended dosing regimens. The monthly oral ibandronate 150 mg provides approx. twice the cumulative annual dose oral formulation of 2.5 mg daily. The effectiveness of this dose was examined in the study MOBILE 2, as well as in meta-analysis comparing monthly dose of 150 mg doses with quarterly 2 and 3 mg IV, which showed a significant reduction in nonvertebral fractures compared with placebo 3.

had not been studied head to head "comparison of the aforementioned anti-fracture efficacy, taking into account the large sample size needed to reliably detect differences in fracture risk and high costs associated. For this reason, databases used for analysis, which may allow sufficient sample sizes for the comparison of marketed doses in routine clinical practice. But as it is not randomized, it is possible that the study groups are different analysis of databases. To avoid the impact of these differences, is used to reduce the statistical adjustment, although the factors that potentially lead to confusion and biases may persist.

should also note the limitation that implies that this cohort study was based on data from patients seeking financial reimbursement for their medication, not research. Among other things, for example, there is no guarantee that the medication has been ingested properly or that the diagnosis of osteoporosis or fracture can not be wrong. But by chance, this could have occurred similarly in the 2 comparison groups. Neither fractures were evaluated so morphometrically. As non-randomized study may be significant differences between groups of patients, although this is not clinically important. Nor were adjusted p values \u200b\u200bfor multiple comparisons.

can conclude, therefore, that the observational analysis of the databases provide additional information to information obtained from randomized trials.


Summary of Important
● This study includes a fairly large sample, more diverse and the real world, that would allow a randomized trial with inclusion and exclusion criteria ●
stricter patient populations, treatment patterns and outcomes in routine clinical practice may differ from those we see in randomized trials. It is important and it is also necessary to assess outcomes in real world scenarios
● This study demonstrates, in real life, the risk of vertebral fracture in general or of hip fracture in particular women received up to one year of treatment with monthly ibandronate or bisphosphonates - alendronate, risedronate - orally, was similar
● But it also notes the study, vertebral fracture risk is lower in patients with adequate adhesion and receiving monthly ibandronate, compared with those receiving a weekly bisphosphonates
● Obviously, the clinical implications for the findings in reducing fractures need further exploration / research and validation of the data found

References
1 - Harris ST, et al. Risk of fracture in Women Treated with weekly or monthly oral bisphosphonates ibandronate: The Evaluation of Ibandronate Efficacy (VIBE) database fracture study. Bone. 2009, doi: 10.1016/j.bone.2009.01.002.
2 - Reginster JY, Adamis, Lakatos P, Greenwald M, Stepan JJ, Silverman SL, et al. Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study. Ann Rheum Dis. 2006, 65: 654-61.
3 - Harris ST, Blumentals WA, Miller PD. Ibandronate and the Risk of non-vertebral fractures in postmenopausal Women with osteoporosis: results of a meta-analysis of phase III studies. Curr Med Res Opin 2008, 24: 237-45.


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