Posted 18 October 2006 - 10:36 PM
Posted 19 October 2006 - 12:21 AM
Posted 19 October 2006 - 03:47 AM
Posted 19 October 2006 - 04:49 AM
No harmful side effects were detected. That is good news, but it does not mean the supplements are altogether safe, said Simon Yeung, manager of the Web site on supplements and integrative medicine at the Memorial Sloan-Kettering Cancer Center in New York
...
Dr. Paul Stewart of England's University of Birmingham said in an accompanying editorial that more research should be done on DHEA, and if it proves safe and effective, it should be regulated as a drug.
"Without a reversal of the current U.S. legislation, DHEA is likely to continue to be used inappropriately, and quackery will prevail," Stewart wrote.
.
Volume 355:1647-1659 October 19, 2006 Number 16
DHEA in Elderly Women and DHEA or Testosterone in Elderly Men
K. Sreekumaran Nair, M.D., Ph.D., Robert A. Rizza, M.D., Peter O'Brien, Ph.D., Ketan Dhatariya, M.D., M.R.C.P., Kevin R. Short, Ph.D., Ajay Nehra, M.D., Janet L. Vittone, M.D., George G. Klee, M.D., Ananda Basu, M.D., Rita Basu, M.D., Claudio Cobelli, Ph.D., Gianna Toffolo, Ph.D., Chiara Dalla Man, Ph.D., Donald J. Tindall, Ph.D., L. Joseph Melton, III, M.D., Ph.D., Glenn E. Smith, Ph.D., Sundeep Khosla, M.D., and Michael D. Jensen, M.D.
ABSTRACT
Background Dehydroepiandrosterone (DHEA) and testosterone are widely promoted as antiaging supplements, but the long-term benefits, as compared with potential harm, are unknown.
Methods We performed a 2-year, placebo-controlled, randomized, double-blind study involving 87 elderly men with low levels of the sulfated form of DHEA and bioavailable testosterone and 57 elderly women with low levels of sulfated DHEA. Among the men, 29 received DHEA, 27 received testosterone, and 31 received placebo. Among the women, 27 received DHEA and 30 received placebo. Outcome measures included physical performance, body composition, bone mineral density (BMD), glucose tolerance, and quality of life.
Results As compared with the change from baseline to 24 months in the placebo group, subjects who received DHEA for 2 years had an increase in plasma levels of sulfated DHEA by a median of 3.4 µg per milliliter (9.2 µmol per liter) in men and by 3.8 µg per milliliter (10.3 µmol per liter) in women. Among men who received testosterone, the level of bioavailable testosterone increased by a median of 30.4 ng per deciliter (1.1 nmol per liter), as compared with the change in the placebo group. A separate analysis of men and women showed no significant effect of DHEA on body-composition measurements. Neither hormone altered the peak volume of oxygen consumed per minute, muscle strength, or insulin sensitivity. Men who received testosterone had a slight increase in fat-free mass, and men in both treatment groups had an increase in BMD at the femoral neck. Women who received DHEA had an increase in BMD at the ultradistal radius. Neither treatment improved the quality of life or had major adverse effects.
Conclusions Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life. (ClinicalTrials.gov number, NCT00254371 [ClinicalTrials.gov] .)
Source Information
From the Division of Endocrinology (K.S.N., R.A.R., K.D., K.R.S., A.B., R.B., S.K., M.D.J.) and the Departments of Health Sciences Research (P.O., L.J.M.), Urology (A.N., D.J.T.), Medicine (J.L.V.), Laboratory Medicine and Pathology (G.G.K.), and Psychology (G.E.S.), Mayo Clinic, Rochester, MN; and the Department of Information Engineering, University of Padua, Padua, Italy (C.C., G.T., C.D.M.).
Drs. Khosla and Jensen contributed equally to this article.
Address reprint requests to Dr. Nair at the Division of Endocrinology, Mayo Clinic, 200 First St. SW, 5-194 Joseph, Rochester, MN 55905, or at nair.sree@mayo.edu.
Methods
Subjects
Subjects were eligible to participate in the study if they were at least 60 years of age. Eligibility criteria included, for men, a level of bioavailable testosterone that was less than 103 ng per deciliter (3.6 nmol per liter) and a sulfated DHEA level that was less than 1.57 µg per milliliter (4.3 µmol per liter), and for women, a sulfated DHEA level that was less than 0.95 µg per milliliter (2.6 µmol per liter). These cutoff values, which represented the 15th percentile of levels for normal young men and women,2 were chosen to ensure that a sufficient number of healthy elderly people could participate in the study. All volunteers underwent a medical history taking and physical examination and were excluded if there was evidence of clinically important coexisting illnesses or conditions that could have an effect on outcome measures.
In addition, we evaluated 38 healthy young women and 37 healthy young men between the ages of 18 and 31 years once in order to obtain a baseline for a comparison of outcome measures. Elderly men underwent a digital rectal examination and ultrasonography to quantify the size of the prostate and to detect any nodules, and all elderly men with a level of prostate-specific antigen (PSA) above the age-adjusted normal level were excluded.
Edited by nootropikamil, 19 October 2006 - 05:02 AM.
Posted 19 October 2006 - 09:26 AM
Here's what's important for anyone who started an anti aging program using the compounds tested:
1. No harmful side effects were detected. So at worst, this study infers that all you are doing (possibly if you are about 60 y.o.) is burning a hole in your pocket with these compounds.
2. The drug companies are going to want to regulate "natural" anti aging therapies if they prove to be effective. Great. It better be my pharmaceutical company selling it, dude.
3. All of the sudden anyone taking testosterone or DHEA is a victim of "quackery" according to "Stewart." That's bullshit. What about folks under 60 who have been monitoring their blood testosterone or DHEA levels and are correcting for deficiency?
And indeed,
some therapies currently promoted as “anti-aging”
medicine may actually be pro-aging. The most notable
example of this is hormone replacement therapy with
human growth hormone (hGH) or sex hormones such as
testosterone or estrogen (including even natural estrogen,
such as TriEst). These hormones actually appear to
accelerate aging in animal models,18-20 and are associated
with an increased risk of cancer21,22 and total mortality23-25 in
humans. And on the other hand, a lifetime of low exposure
to growth hormone (or its mediator, insulin-like growth
factor-1 (IGF-1)) along with prolactin and triiodothyronine
extends longevity in several animal models18 and
apparently in humans.26 Ironically, in fact, it now appears
that “topping up” declining levels of hGH or testosterone
don’t even deliver the promised improvements in frailty or
quality of life,27-29 let alone longevity.
Posted 19 October 2006 - 09:45 AM
It's really this simple: After the age of 40-ish, your hormones purposely decline. You lose energy, libido, and a substantial layer of protection against age-related illnesses. Therefore -- hang with me on this! -- doesn't in make sense to restore your hormones to more youthful levels?
Oddly enough, many people don't get this. Then again, oddly enough, many people think death is okay. It takes all types...
Posted 19 October 2006 - 12:52 PM
And you don't just start administering testosterone and DHEA to patients (under 60 too!) without running the tests to make sure they need to be adjusted to correct for deficiency.
Eligibility criteria included, for men, a level of bioavailable testosterone that was less than 103 ng per deciliter (3.6 nmol per liter) and a sulfated DHEA level that was less than 1.57 µg per milliliter (4.3 µmol per liter), and for women, a sulfated DHEA level that was less than 0.95 µg per milliliter (2.6 µmol per liter). These cutoff values, which represented the 15th percentile of levels for normal young men and women ...
Posted 19 October 2006 - 01:22 PM
http://news.yahoo.co...DltBHNlYwM3MTY-
I really hate that news is more about entertainment than fact.
When you actually read the article, the study only say's DHEA and testosterone patches don't work. It says NOTHING about other anti-aging supplements. sigh.
Posted 19 October 2006 - 02:09 PM
Posted 19 October 2006 - 04:49 PM
Posted 19 October 2006 - 06:27 PM
About the side-effects, it was only a two year trial so the theoretically likely pro-aging effects of hormonal replacement (based on antagonist pleiotropy and corroborating evidence in animals and even on humans) therapies do not yet appear in that short a time frame. On the other hand, the putative health promoting effects should appear almost immediately. Earlier on I thought the "silent" pro-aging effects of these hormones might be offset by radical health improving effects, making the overall contribution positive perhaps even from survival point-of-view and especially so from quality of life point of view. Now the positive effects appear non-existant or mild at best, so I do not see why one should risk it with them.
People over 60 are "deficient" in both hormones, I actually view this as a "natural defense" againts various age-related ailments as opposed to it being causal factor.
From AOR, note that these results corroborate earlier findings about mild to existent positive effects of hormonal replacement (27-29):
http://www.aor.ca/ma...2003_Spring.pdf
And indeed,
some therapies currently promoted as “anti-aging”
medicine may actually be pro-aging. The most notable
example of this is hormone replacement therapy with
human growth hormone (hGH) or sex hormones such as
testosterone or estrogen (including even natural estrogen,
such as TriEst). These hormones actually appear to
accelerate aging in animal models,18-20 and are associated
with an increased risk of cancer21,22 and total mortality23-25 in
humans. And on the other hand, a lifetime of low exposure
to growth hormone (or its mediator, insulin-like growth
factor-1 (IGF-1)) along with prolactin and triiodothyronine
extends longevity in several animal models18 and
apparently in humans.26 Ironically, in fact, it now appears
that “topping up” declining levels of hGH or testosterone
don’t even deliver the promised improvements in frailty or
quality of life,27-29 let alone longevity.
18 Carter CS, Ramsey MM, Sonntag WE. A critical analysis of the role of growth hormone and IGF-
1 in aging and lifespan. Trends Genet. 2002 Jun;18(6):295-301.
19 Patronek GJ, Waters DJ, Glickman LT. Comparative longevity of pet dogs and humans: implications
for gerontology research. J Gerontol A Biol Sci Med Sci. 1997 May;52(3):B171-8.
20 Asdell SA, Doornenbal H, Joshi SR, Sperling GA. The effects of sex steroid hormones upon
longevity in rats. J Reprod Fertil. 1967 Aug;14(1):113-20.
21 Swerdlow AJ, Higgins CD, Adlard P, Preece MA. Risk of cancer in patients treated with human
pituitary growth hormone in the UK, 1959-85: a cohort study. Lancet. 2002 Jul
27;360(9329):273-7.
22 Greaves M. Cancer causation: the Darwinian downside of past success? Lancet Oncol. 2002
Apr;3(4):244-51.
23 Maison P, Balkau B, Simon D, Chanson P, Rosselin G, Eschwege E. Growth hormone as a risk for
premature mortality in healthy subjects: data from the Paris prospective study. BMJ. 1998 Apr
11;316(7138):1132-3.
24 Waters DJ, Shen S, Glickman LT. Life expectancy, antagonistic pleiotropy, and the testis of dogs
and men. Prostate. 2000 Jun 1;43(4):272-7.
25 Hamilton JB, Mestler GE. Mortality and survival: comparison of eunuchs with intact men and
women in a
mentally retarded population. J Gerontol. 1969 Oct;24(4):395-411.
26 Krzisnik C, Kolacio Z, Battelino T, Brown M, Parks JS, Laron Z. The “little people” of Krk – revisited.
Etiology of hypopituitarism revealed. J Endocr Genet. 1999:9-19.
27 Blackman MR, Sorkin JD, Munzer T, et al. Growth hormone and sex steroid administration in
healthy aged women and men: a randomized controlled trial. JAMA. 2002 Nov 13;288(18):2282-
92.
28 Janssens H, Vanderschueren DM. Endocrinological aspects of aging in men: is hormone replacement
of benefit? Eur J Obstet Gynecol Reprod Biol. 2000 Sep;92(1):7-12.
29 Morley JE, Unterman TG. Hormonal fountains of youth. J Lab Clin Med. 2000 May;135(5):364-
6.
These findings in experimental models have generally been supported by observational studies in humans.2,4,5 Moreover, longevity in healthy humans6 and nonhuman primates is associated with relatively high levels of DHEA,[/u]7 a finding that has led to extensive promotion of DHEA as an antiaging agent by the lay media. However, the applicability of findings in rodents to humans is open to question, since rodents have very low levels of DHEA.8 Furthermore, a review of the literature indicated that most studies showing positive effects in humans have been short-term or have used pharmacologic doses of DHEA.8
But the threshold Shores used to define low testosterone is lower than what other researchers typically use, "so people with really low testosterone levels are at risk," he added.
[/u]I think people should monitor their blood testosterone levels as much as possible to keep the levels in the normal range. Certainly messing with these so called "natural levels" through drugs and such opens the door for some danger...HGH supplementation, steroid use, etc. can make serious changes in what makes a man an "man" and a woman a "woman." If you are a dude, growing breasts might not suit your appearance. Also, hypogonadism does not sound like fun to me. If one has low levels of natural hormones, I think it is rational to intervene...but self medicating with these compounds sounds sketchy to me.
Edited by nootropikamil, 19 October 2006 - 07:02 PM.
Posted 19 October 2006 - 08:27 PM
Studies in animals have shown beneficial effects of DHEA on many age-related changes in body composition and in conditions such as diabetes mellitus and cardiovascular disease.3 These findings in experimental models have generally been supported by observational studies in humans.2,4,5 Moreover, longevity in healthy humans6 and nonhuman primates is associated with relatively high levels of DHEA,7 a finding that has led to extensive promotion of DHEA as an antiaging agent by the lay media.
Posted 19 October 2006 - 08:55 PM
I think you're right! As you say essentially you are just staying younger longer so it makes sense your hormone levels (not just DHEA) will reflect this, good call. [thumb] [lol]Its important to note is that longevity is *associated* with higher levels of DHEA. That does not necessarily mean *caused* by DHEA. It seems likely that high levels of DHEA are serving as a biomarker of younger biological age -- this person happens to be aging in a favorable (slower than normal) manner. You see this with calorie restriction, where DHEA is conserved at higher levels in old animals and primates.
Basically, I think the causative relationship here is more like optimal health and slower aging result in high DHEA levels, with the activity of DHEA itself playing a relatively insignificant role. That's my hunch.
Posted 22 October 2006 - 07:22 PM
years) with age-related decrease in DHEA level.
Intervention Participants were randomly assigned to receive 50 mg/d of DHEA or matching placebo for 6 months.
Main Outcome Measures The primary outcome measures were 6-month change in visceral and subcutaneous abdominal fat measured by magnetic resonance imaging and glucose and insulin responses to an oral glucose tolerance test (OGTT).
Results Of the 56 men and women enrolled, 52 underwent follow-up evaluations. Compliance with the intervention was 97% in the DHEA group and 95% in the placebo group. Based on intention-to-treat analyses, DHEA therapy compared with placebo induced significant decreases in visceral fat area (–13 cm2 vs +3 cm2, respectively; P = .001) and subcutaneous fat (–13 cm2 vs +2 cm2, P = .003). The insulin area under the curve (AUC) during the OGTT was significantly reduced after 6 months of DHEA therapy compared with placebo (–1119 µU/mL per 2 hours vs +818 µU/mL per 2 hours, P = .007). Despite the lower insulin levels, the glucose AUC was unchanged, resulting in a significant increase in an insulin sensitivity index in response to DHEA compared with placebo (+1.4 vs –0.7, P = .005).
Conclusion DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.
Author Affiliations: Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St Louis, Mo.
RELATED ARTICLE
This Week in JAMA
JAMA. 2004;292:2189.
Posted 08 November 2006 - 06:57 PM
Posted 15 December 2006 - 08:56 PM
Posted 20 December 2006 - 06:19 PM
Posted 16 January 2007 - 01:38 AM
No longevity benefit with growth hormone
By ED SUSMAN
PHILADELPHIA, Jan. 15 (UPI) -- Doctors said Monday their analysis of 31 scientific papers found that human growth hormone -- oft-touted as an anti-aging wonder -- does nothing to help a person live longer.
However, the papers do show that use of the expensive therapy has the potential to create adverse side effects.
"There is certainly no data out there to suggest that giving growth hormone to an otherwise healthy person will make him or her live longer," said Dr. Hau Liu, a research fellow in the Division of Endocrinology and in the Center for Primary Care and Outcomes Research at Stanford University School of Medicine in Stanford, Calif.
Liu and colleagues' conclusions will be published in Tuesday's edition of the Annals of Internal Medicine, the journal of the Philadelphia-based American College of Physicians.
"We did find that there was substantial potential for adverse side effects," Liu said, including such problems as joint swelling and pain, carpal tunnel syndrome and a trend toward increased new diagnoses or pre-diabetes. "You're paying a lot of money for a therapy that may have minimal or no benefit and yet has a potential for some serious side effects," Liu said. "You've got to really think about what this drug is doing for you."
"Growth hormone has been touted by people practicing fringe medicine for decades," Dr. Barry Horowitz, co-director of the Metabolic Research Institute in West Palm Beach, Fla., told United Press International. "They say growth hormone is an anti-aging therapy, can make your skin look better and improve your sex drive.
"But there is no proof -- as Dr. Liu has demonstrated -- that growth hormone does anything to extend a person's life," Horowitz said. "Our great fear is that in patients with occult, asymptomatic cancer, the administration of growth hormone may cause that cancer to grow and spread."
He said that growth hormone has been approved for treating children who have growth hormone deficiencies and to treat some adults with growth hormone deficiencies due to injury or disease to the pituitary gland.
"In many anti-aging clinics, growth hormone is prescribed willy-nilly off-label, without any proof that patients are better off," he told UPI. He also noted that the drug is highly expensive, and is not reimbursed for its off-label (unapproved) use.
Growth hormone is widely promoted on the Internet, and its use as a purported anti-aging drug has caught the attention of the popular media, ranging from the "Today Show" to Business Week. Between 20,000 and 30,000 people in the United States used growth hormone as an anti-aging therapy in 2004, a ten-fold increase since the mid-1990s, according to the authors of an unrelated study published in the Journal of the American Medical Association in 2005.
Growth hormone is naturally produced by the pituitary gland, a pea-sized organ at the base of the brain. Growth hormone is critical to proper development in children, particularly their height, and injections of growth hormone are considered a legitimate treatment for short children and for adults whose pituitary glands don't produce enough growth hormone to maintain normal metabolism. But most promoters of growth hormone as an anti-aging therapy target the healthy elderly.
Liu's team undertook a systematic review and analysis of published studies, excluding any that looked at diseases for which growth hormone is an accepted therapy. They focused solely on studies using growth hormone to treat the elderly, specifically those whose main maladies were nothing worse than age and being mildly to moderately overweight. They also included only studies that evaluated the use of the hormone in randomized, controlled clinical trials.
Of all the papers contained in two of the largest databases of medical literature in the world, only 31 met the team's criteria. The 31 studies had a combined total of slightly more than 500 participants, and the average duration of therapy was about six months, said Liu, adding that he was surprised at the limited amount of data in the literature.
"These studies were designed to look at what happens when you give growth hormone to a healthy elderly person," said Liu. "For example, what happens to their bone density, to their exercise levels and to their exercise capacity."
The researchers found that growth hormone had a modest effect on body composition, increasing lean body mass, or muscle, by slightly more than 2 kilograms and decreasing body fat by roughly the same amount.
But, Liu said, "It did not change other clinically important outcomes, such as bone density measurements, cholesterol and lipid measurements, and maximal oxygen consumption." In short, the studies provided no real evidence that the therapy resulted in increased fitness.
"From our review, there's no data to suggest that growth hormone prolongs life, and none of the studies makes that claim," said Liu.
Copyright 2007 by United Press International. All Rights Reserved.
Posted 10 April 2007 - 09:02 AM
As someone who takes both DHEA and testosterone, I can easily say there's a substantial benefit.
I highly recommend anyone over the age of 40 to read Suzanne Somers' latest book on bio-identical hormones. She interviews a dozen top doctors/practitioners in this field:
http://www.amazon.co...ie=UTF8&s=books
What the hell does Somers know about HRT, you stupidly ask. One hellavu lot more than you. Really. And she is absolutely reaping the benefits, too.
It's really this simple: After the age of 40-ish, your hormones purposely decline. You lose energy, libido, and a substantial layer of protection against age-related illnesses. Therefore -- hang with me on this! -- doesn't in make sense to restore your hormones to more youthful levels?
Oddly enough, many people don't get this. Then again, oddly enough, many people think death is okay. It takes all types...
The Herald: News Source
HRT ‘reduces the risk of heart disease’
JAMES MORGAN
April 10 2007
Hormone replacement therapy, the treatment used by millions of post-menopausal women, may not be harmful after all.
HRT may actually reduce, rather than increase, the risk of heart disease in women who use it to prevent osteoporosis, say US researchers.
The therapy was at the centre of a health scare five years ago when an American study linked it to an increased risk of heart attacks, strokes and breast cancer.
At the time health chiefs advised HRT should be taken for as short a time as possible and in Britain it was no longer recommended as a drug to prevent bone loss in women with a family history of osteoporosis.
However, a study published yesterday in the Journal of the American Medical Association found no increased risk of heart attack for women in their 50s taking HRT.
The Women's Health Initiative Study discovered that any additional risks may apply only to older women.
Women in their 60s and 70s still experiencing the symptoms of the menopause such as hot flushes and night sweats were at an increased risk of heart attacks and strokes even if they were not taking HRT.
The study concludes: "Women who initiated hormone therapy closer to menopause tended to have reduced coronary heart disease risk compared with the increase in coronary heart disease risk among women more distant from menopause."
However, it said the trend "did not meet our criterion for statistical significance".
Dr John Stevenson, an HRT expert from London's Royal Brompton Hospital, speaking to the British Menopause Society, said the findings were a "U-turn of dramatic proportions".
He said: "We are astonished that a study which made such a claim for the dangers of HRT is now showing just the opposite. It is an affront to science, adding insult to injury to the thousands of women who abandoned HRT as a result."
Women had been advised for many years that HRT after menopause might reduce their risk of heart disease and various aspects of aging.
However, in 2002 the Women's Health Initiative study found that women undergoing HRT had a slightly increased risk of breast cancer, heart disease, stroke, and Alzheimer's disease sufficient to justify stopping the study.
After these results were reported, the number of prescriptions written for two brands of oestrogen - Premarin and PremPro - dropped almost in half in the US as many women discontinued HRT altogether.
This drop in prescriptions was followed by large and successively greater fals in new breast cancer diagnoses at six months, one year, and 18 months after that announcement, for a cumulative 15% drop by the end of 2003.
Surprisingly, no similar drop in Canada's breast cancer rates was observed during the same period, though prescriptions of PremPro and Premarin were reduced in Canada as well. Studies are now under way to determine if the drop is related to the reduced use of HRT.
In December last year research by experts from the University of Texas said a sharp drop in breast cancer cases could have been caused by women abandoning HRT.
© All rights reserved. Reproduction in whole or in part without permission is prohibited.
Posted 19 April 2007 - 08:31 AM
Science Daily: News Source
Source: University of Texas M. D. Anderson Cancer Center
Date: April 19, 2007
Strong Link Between Breast Cancer And Hormone Replacement Therapy Found
Science Daily — An extended analysis of cancer rates reinforces a strong association between use of hormone replacement therapy (HRT) and increased breast cancer incidence, according to research led by scientists at The University of Texas M. D. Anderson Cancer Center and published in the New England Journal of Medicine.
In the published study, the investigators say that plummeting use of HRT in mid-2002, after results of the Women's Health Initiative study were announced, correlated with a steep decline in new breast cancer diagnoses that started shortly thereafter and continued through 2003. Incidence in 2004 leveled maintained the same low level of incidence, the lowest rate seen since about 1987, the researchers say.
The decline occurred primarily in women age 50-69, the researchers find, and was predominantly seen in estrogen-receptor(ER)-positive cancer - the type of tumors is fueled by estrogen, a hormone that is supplemented in HRT. Such cancers declined 14.7 percent in this time period, compared to a non-significant decline of 1.7 percent in ER-negative tumors.
"For our new data set, 2004, the drop in breast cancer incidence leveled off and remained low in that year, "showing that the decreased rates seen in 2003 were also present in 2004, meaning that the decline was not a one-year wonder, a short-lived anomaly," says Ravdin, the study's lead investigator.
"This kind of study can't prove causality, but the data present a very compelling link between hormone replacement therapy and breast cancer," says Berry, the study's senior investigator.
Using data derived from National Cancer Institute (NCI) cancer registries that report on 9 percent of the U.S. population, they found that the total decrease in breast cancer incidence was 6.7 percent between 2002 and 2003. They also calculated that by the end of 2002, about 20 million fewer prescriptions for HRT were written in the United States- a decrease of 38 percent. Interest in HRT use dropped after the 16,608-participant federal Women's Health Initiative study results were announced in July 2002 and showed that the risks of taking these agents outweighed the benefits for many post-menopausal women.
Ravdin and Berry strongly stress, however, that their study is not suggesting that all women stop their use of HRT. "This study is not saying that an individual woman will reduce her absolute risk of developing breast cancer by 15 percent by immediately discontinuing use of HRT," Berry says.
While it may be true that stopping use of HRT may have prevented as many as 14,000 breast cancers in 2003 compared with 2002, the percentage of decline is based on an entire population, he explains. "At best, based on this analysis, an individual woman could reduce her individual risk of developing breast cancer by one in 60, or about 1.7 percent, if she stopped using hormones," Berry says.
As a physician, Ravdin tells his patients to follow currently accepted guidelines for HRT use: to use the drug at the lowest dose and for the shortest time period to control hot flashes and other debilitating symptoms caused by the onset of menopause.
"The risk of developing breast cancer from use of these hormones is relatively small and for some women with postmenopausal symptoms, the benefits of HRT are well worth that risk," he says. "This is just another small piece of the puzzle to help women gauge the risks and benefits of using HRT."
The researchers also say that their study cannot answer three key questions: whether stopping the use of HRT leads to a permanent or a temporary decline in breast cancer incidence; if this effect is seen for stopping all types of HRT; and how much of a contributing role other factors may have played in the decline.
"There are several possibilities as to what effect stopping HRT has. Possibly, it slows the growth of tumors that are there but aren't big enough yet to be detected on a mammogram. Or it could be removing the hormone fuel stops the growth completely or even causes tumor regression," Berry says. "We don't know which is correct."
While Berry, an expert in statistics, adds that he was initially surprised that stopping HRT use could have such an immediate impact on breast cancer growth, Ravdin, the clinician, says he was not.
"We know that if you treat ER-positive breast cancer with anti-hormone treatment, you can see shrinkage within weeks, so why wouldn't withdrawing hormones have the same kind of effect on smaller cancers that have not yet been detected?" says Ravdin. "My thought is that these tumors don't completely disappear, but they have stopped growing - hopefully, for many of them, forever."
As to the impact of other factors on breast cancer decline, the researchers say that one contributing factor could be declining use of mammography by women who have stopped using HRT. NCI data has reported a 3.2 percent decline in screening mammography in 2003 for women 50-65 years old, compared to 2000, Berry says, but adds, "such a change would seem insufficient to explain the decline in breast cancer incidence." A large drop in screening would have been seen in breast tumors that are both ER-positive and ER-negative, and that wasn't the case.
Finally, the researchers say that this study may lead to new insights into both the etiology of breast cancer and its prevention. "We will continue modeling incidence rates to try to understand whether what we are seeing is a slowing or a regressing of tumors, or a mix between these two things," Berry says.
The study was funded by grants from the National Cancer Institute and from M. D. Anderson. Co-authors also include Kathy Cronin, Ph.D., Nadia Howlander, M.S., Christine Berg, M.D., Eric Feuer, Ph.D., and Brenda Edwards, Ph.D., from the National Cancer Institute, and Rowan Chlebowski, M.D., Ph.D., from Harbor UCLA Medical Center.
M. D. Anderson's Peter Ravdin M.D., Ph.D., professor in the Department of Biostatistics, and Donald Berry, Ph.D., head of the Division of Quantitative Sciences, presented the first analysis of the 2002-2003 falling breast cancer rates at the December 2006 meeting of the San Antonio Breast Cancer Symposium. They have since examined breast cancer incidence in 2004.
Note: This story has been adapted from a news release issued by University of Texas M. D. Anderson Cancer Center.
Full text available free here.
Volume 356:1670-1674 April 19, 2007 Number 16
The Decrease in Breast-Cancer Incidence in 2003 in the United States
Peter M. Ravdin, Ph.D., M.D., Kathleen A. Cronin, Ph.D., Nadia Howlader, M.S., Christine D. Berg, M.D., Rowan T. Chlebowski, M.D., Ph.D., Eric J. Feuer, Ph.D., Brenda K. Edwards, Ph.D., and Donald A. Berry, Ph.D.
ABSTRACT
An initial analysis of data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries shows that the age-adjusted incidence rate of breast cancer in women in the United States fell sharply (by 6.7%) in 2003, as compared with the rate in 2002. Data from 2004 showed a leveling off relative to the 2003 rate, with little additional decrease. Regression analysis showed that the decrease began in mid-2002 and had begun to level off by mid-2003. A comparison of incidence rates in 2001 with those in 2004 (omitting the years in which the incidence was changing) showed that the decrease in annual age-adjusted incidence was 8.6% (95% confidence interval [CI], 6.8 to 10.4). The decrease was evident only in women who were 50 years of age or older and was more evident in cancers that were estrogen-receptor–positive than in those that were estrogen-receptor–negative. The decrease in breast-cancer incidence seems to be temporally related to the first report of the Women's Health Initiative and the ensuing drop in the use of hormone-replacement therapy among postmenopausal women in the United States. The contributions of other causes to the change in incidence seem less likely to have played a major role but have not been excluded.
Source Information
From the Department of Biostatistics, M.D. Anderson Cancer Center, Houston (P.M.R., D.A.B.); the Division of Cancer Control and Population Sciences (K.A.C., N.H., E.J.F., B.K.E.) and the Division of Cancer Prevention (C.D.B.), National Cancer Institute, Bethesda, MD; and the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center, Torrance, CA (R.T.C.).
Posted 20 April 2007 - 08:46 AM
The New York Times: News Source
April 19, 2007
Sharp Drop in Rates of Breast Cancer Holds
By GINA KOLATA
Breast cancer rates fell sharply in 2003, and the lower rate remained in 2004, researchers are reporting today.
The finding, they say, fits with a hypothesis they advanced last December when they had data only from 2003. At that time, national data showed that breast cancer rates fell by nearly 15 percent in the 18 months from July 2002 through December 2003.
The most likely reason for the fall in rates, the investigators, led by Donald A. Berry of M. D. Anderson Cancer Center in Houston, said, was that large numbers of women stopped taking hormone therapy for menopause. And that therapy, a combination of estrogen and progestins, can increase the incidence of breast cancer.
Now, with the 2004 data, the researchers say the effect is less likely to be an anomaly. If rates had gone up again, they explain, it would have meant that their hypothesis was incorrect.
The analysis relied on “statistical sleuthing,” said Dr. Berry, head of the division of quantitative sciences at M.D. Anderson and senior author of the paper published today in The New England Journal of Medicine.
Over all, in 2003 and 2004, there were nearly 10 percent fewer breast cancer cases than expected. It is the first substantial drop in breast cancer incidence in more than a quarter century. And it involved women age 50 and older, not younger women, and nearly all the decline was in the common type of breast cancer, fed by estrogen, the so-called estrogen-receptor-positive tumors.
The hormone connection came because the Women’s Health Initiative, a large federal study examining the health effects of Prempro, the most popular drug prescribed for menopause, was halted in July 2002. The study found that women taking Prempro had an increased risk of heart disease, rather than protection from it. And the presumed benefit of taking the drug was to prevent heart disease. In addition, there was more breast cancer among women taking Prempro than those taking a placebo for comparison. Immediately, sales of Prempro, made by Wyeth, plummeted, falling by 50 percent, and they continued to fall slightly in 2004.
The drop in breast cancer followed immediately.
“Those are the facts,” said Dr. Peter Ravdin, an oncologist and Dr. Berry’s colleague. “We think there is a likely connection between them.”
Even so, Dr. Ravdin said, hormone therapy does not cause most of breast cancer in the United States. Some cancers do not need estrogen to grow. Others that depend on estrogen grow whether or not a woman is taking Prempro or a similar drug; they are fueled by the estrogen in a woman’s body.
Dr. Ravdin added that he thought the current guidelines, advising women to use hormone therapy for as short a time as possible for the relief of menopause symptoms, were appropriate.
Dr. Joseph Camardo, senior vice president for global medical affairs for Wyeth Pharmaceuticals, urged caution in interpreting the data. Just because one event follows another does not mean one event caused the other, he pointed out.
“I don’t think anyone involved can say they have a specific alternative explanation,” Dr. Camardo said, “but I think other factors should be explored.” For example, he said, mammogram use or changes in diet or other drug use might be contributing.
But any alternative explanation must also take into account the fact that the drop in breast cancer rates was almost entirely estrogen-fed tumors, Dr. Ravdin said.
Dr. Berry said the researchers were well aware of the limitations of their analysis and never said they proved that declining hormone use led to 10 percent less breast cancer.
“Of course, we’re not sure. We never are,” Dr. Berry said. “But it fits. It’s a smoking gun.”
Edited by nootropikamil, 20 April 2007 - 09:14 AM.
Posted 03 May 2007 - 08:01 AM
News Source: International Herald Tribune
Study suggests hormones may ward off dementia, if women take them soon after menopause
The Associated Press
Wednesday, May 2, 2007
BOSTON: New research suggests that hormone therapy taken soon after menopause may help protect against the mental decline of dementia, even though it raises that risk in elderly women.
The study adds yet another frustrating twist to the back-and-forth findings about whether hormone-replacement therapy protects against diseases of aging. Though the accepted answer has been "no" in recent years, the latest evidence suggests that timing of treatments may be key, at least for heart attacks and now for dementia.
"When you give it may be very important," said Dr. Sam Gandy, an Alzheimer's disease expert at Thomas Jefferson University in Philadelphia.
The new findings were released Wednesday in Boston at a meeting of the American Academy of Neurology. Experts cautioned that they are preliminary.
Lead researcher Dr. Victor Henderson, of Stanford University, agreed that it is too soon to consider putting younger women back on hormones to forestall dementia.
For decades, women routinely took hormones to treat the hot flashes of menopause and to ward off ailments of aging. Then, in 2002, a milestone study showed higher risks of heart attack, stroke, and breast cancer with estrogen-progestin treatments. Estrogen-only pills were later also linked to stroke.
As a result, millions of women gave up the pills, and government experts advised women to use them only for severe menopause symptoms and to take the lowest dose for the shortest time possible.
But in recent weeks, mounting evidence has emerged that women who take such drugs closer to menopause may get more benefit or confront less risk than women who start taking them later. An analysis this month indicated the drugs do not raise the risk of heart attack for women ages 50-to-59, and they seem to survive longer with the drug.
The latest findings focused on 7,153 women in an offshoot study of the huge Women's Health Initiative that tracked breast cancer and heart disease. The cognitive study was funded by the National Institutes of Health and by Wyeth, which sells hormone treatments.
Previous research showed that women who take hormones after age 65 experience a 75 percent increased risk of dementia over other women.
But this study found the opposite for women who took hormones before age 65: Dementia risk was reduced by nearly half.
Dementia developed in 22 of 2,228 women — or only 1 percent — who took hormones at the earlier time, but in 84 of 4,925 who did not — or 1.7 percent. The apparent protective effect was especially strong for Alzheimer's disease, a common form of dementia.
"It's an intriguing and biologically plausible finding ... but it needs to be confirmed," said Dr. JoAnn Manson, of Brigham and Women's Hospital in Boston, who helped research the Women's Health Initiative.
She said replacement hormones may preserve blood circulation in the brain.
Posted 14 May 2007 - 09:34 PM
Health Day: News Source
Testosterone May Benefit Men With Multiple Sclerosis
But this preliminary study was tiny and needs confirmation
By Randy Dotinga
HealthDay Reporter
MONDAY, May 14 (HealthDay News) -- Testosterone gel may slow the progression of multiple sclerosis in men with the disease, a new study suggests.
Only 10 men took part in the research, all had milder forms of MS, and more studies will be needed before doctors determine whether the treatment really works. Still, the researchers were impressed that the men's mental decline ceased, and the shrinking of their brains returned to the normal levels expected due to aging.
"We saw an improvement which was exciting," said study co-author Dr. Rhonda Voskuhl, professor of neurology at the University of California, Los Angeles. "This looks like it would be neuroprotective, which would be great."
But another expert, Dr. Moses Rodriguez, professor of neurology and immunology at the Mayo Clinic, said he was skeptical that the treatment would become common and noted that MS research has had a history of promising therapies that ultimately failed.
A treatment that protects the central nervous system against multiple sclerosis would be a major breakthrough for the 400,000 Americans with the disease. MS is thought to be caused when the immune system attacks the myelin sheath, a fatty substance that insulates nerves in the brain and spinal cord. It can cause a wide range of symptoms, from cognitive decline and pain to severe fatigue and difficulty walking. Most people with the disease have normal or near-normal life spans.
Women are two to three times more likely to get the disease, and there has been speculation that testosterone -- the male hormone -- could protect men against MS.
While injection drugs can slow the progress of the disease, researchers have been trying to find a way to boost their effectiveness.
In the new study, the researchers followed 10 men with mild MS who, for a variety of reasons, chose not to take injection treatments. The average age of the participants was 46. After the researchers monitored the men's conditions for six months, each man applied 10 grams of a gel containing 100 milligrams of testosterone to his upper arms once daily for 12 months.
"The cognition improved instead of declining," Voskuhl said. "We were pretty surprised by seeing an improvement." The study authors also found that the rate of brain atrophy declined by two-thirds, to the rate expected during normal aging. In another promising sign, the men ended up with more muscle mass after undergoing the treatment.
Unfortunately, testosterone treatment would not be feasible in women because of its side effects, Voskuhl said. But researchers are looking into other possible treatments for women.
Voskuhl also thinks that testosterone treatment -- if it turns out to work in other studies -- could lead to better therapies for diseases such as Alzheimer's and Parkinson's.
The findings are published in the May issue of the Archives of Neurology.
But the Mayo Clinic's Rodriguez, who's familiar with the study findings, said he doubts that testosterone therapy will become standard, because it has side effects and has been connected to an increased risk of prostate cancer. Also, much promising but preliminary MS research fails to bear fruit, he said.
Voskuhl said further research will take three to five years, largely because it takes time to get funding. Doctors could legally give testosterone to MS patients now, but she said it's not approved for that purpose.
"You really should wait until the larger trials are finished and we go for FDA (U.S. Food and Drug Administration) approval," Voskuhl said.
However, Rodriguez believes MS patients would be taking a "great risk" if they underwent testosterone treatment before it was federally approved for that purpose.
More information
Learn more about MS from the National Multiple Sclerosis Society.
http://www.nationalm..._ABOUT_homepage
SOURCES: Rhonda Voskuhl, M.D., professor of neurology, University of California, Los Angeles; Moses Rodriguez, M.D., professor of neurology and immunology, Mayo Clinic, Rochester, Minn.; May 2007, Archives of Neurology
Copyright © 2007 ScoutNews, LLC. All rights reserved.
Posted 06 June 2007 - 12:13 AM
News Source: UCSD Medical Center
Date: June 05, 2007
Older Men May Not Live As Long If They Have Low Testosterone
Low levels of testosterone may increase the long-term risk of death in men over 50 years old, according to researchers with the Department of Family and Preventive Medicine at the University of California, San Diego School of Medicine.
“The new study is only the second report linking deficiency of this sex hormone with increased death from all causes, over time, and the first to do so in relatively healthy men who are living in the community,” said Gail Laughlin, Ph.D., assistant professor and study author.
http://health.ucsd.e...hlinGAil213.jpg
Gail Laughlin, Ph.D.
Laughlin will present the findings to The Endocrine Society Tuesday June 5th, 2007. The findings will be among selected articles published in the distinguished The Endocrine Society's ENDO 07 Research Summaries Book.
“We have followed these men for an average of 18 years and our study strongly suggests that the association between testosterone levels and death is not simply due to some acute illness,” said Laughlin.
In the study, Laughlin and co-workers looked at death, no matter the cause, in nearly 800 men, ages 50 to 91 years, who were living in Rancho Bernardo, California. The participants have been members of the Rancho Bernardo Heart and Chronic Disease Study since the 1970s. At the beginning of the 1980s, almost one-third of these men had suboptimal blood testosterone levels for men their age.
The group with low testosterone levels had a 33 percent greater risk of death during the next 18 years than the men with higher testosterone. This difference was not explained by smoking, drinking, physical activity level or pre-existing diseases (such as diabetes or heart disease).
In this study, "low testosterone" levels were set at the lower limit of the normal range for young adult men. Testosterone declines slowly with aging in men and levels vary widely, with many older men still having testosterone levels in the range of young men. Twenty-nine percent of Rancho Bernardo men had low testosterone.
Distinguishing Factors
Men with low testosterone were more likely to have elevated markers of inflammation, called inflammatory cytokines, which contribute to many diseases. Another characteristic that distinguished the men with low testosterone was a larger waist girth along with a cluster of cardiovascular and diabetes risk factors related to this type of fat accumulation. Men with low testosterone are three times more likely to have the metabolic syndrome than men with higher testosterone levels; metabolic syndrome is the name for the presence of three or more of these risk factors:
o waist measurement more than 40 inches in men (more than 35 inches in women),
o low HDL (good) cholesterol,
o high triglycerides (levels of fat in the blood),
o high blood pressure
o high blood glucose (blood sugar)
While the study lends support to the belief that supplemental hormone therapy may help older men with low testosterone levels, those who practice weight control and increase their physical activity may also live longer.
“It’s very possible that lifestyle determines what level of testosterone a patient has,” commented principal investigator, Elizabeth Barrett-Connor, M.D., UCSD Distinguished Professor of Family and Preventive Medicine and chief of the Division of Epidemiology. “It may be possible to alter the testosterone level by lowering obesity.”
http://health.ucsd.e...rcolorphoto.JPG
Elizabeth Barrett-Connor, M.D.
Barrett-Connor and Laughlin were also careful to clarify what the study did not show.
“The study did show there may be an association between low testosterone levels and higher mortality. It did not show that higher levels of testosterone are associated with decreased mortality," explained Laughlin. Researchers agree only randomized placebo-controlled clinical trials can determine whether testosterone supplements can safely promote longer life. Such a trial is in the planning stages at UCSD.
Barrett-Connor cautioned, “We are very excited about these findings, which have important implications, but we are not ready to say that men should go out and get testosterone to prolong their lives. We’re not ready to take this to the prescribing pharmacist.”
“Conventional wisdom is that women live longer because estrogen is good and testosterone is bad,” said Barrett-Connor. “We don’t know. Maybe the decline in testosterone is healthy and comes with older age. Maybe the decline is bad and is associated with chronic diseases of aging.”
The National Institute on Aging and the American Heart Association funded the study.
The Rancho Bernardo Study
Dr. Elizabeth Barrett-Connor is founder and director of the Rancho Bernardo Heart and Chronic Disease Study, now in its 35th year. Since 1972, the RB study has greatly increased knowledge of cardiovascular disease, diabetes, cancer, osteoporosis, exogenous and endogenous hormones, and the connections between lifestyle, behavior and health.
Six thousand residents, 82 percent of the original population of adults in Rancho Bernardo, agreed to participate in this history-making study and significant collection of data. Barrett-Connor and a team of UCSD researchers have conducted clinical research visits with the participants every four years for more than three decades.
The clinical research visits last three to four hours, thoroughly examining the participant’s physical condition by gathering information through bone and heart scans, blood samples, heart disease risk factor measurements such as lipid levels and cognitive function assessment.
The rate of follow-up with those who have moved or died (through cooperation of family and friends), has been exceptionally high.
A Living Legacy
The RB study has just been re-funded for what Barrett-Connor predicts will be the final clinic visit. Another newly funded grant from the National Institutes of Health (NIH) will allow analysis of information gathered over the course of the study to provide new insights on the link between heart disease risk and cognitive function.
“Although more than 400 scientific papers based on RB data have already been published, it’s a wonderful legacy for participants to realize that the knowledge gathered has not come close to being exhausted. It’s an enormous bank of data,” said Laughlin. “Though we are beginning the final visits with the RB group, analyzing the data from the RB study, including the new data being acquired at this final visit, will continue to contribute to our knowledge about healthy aging for years to come.”
Barrett-Connor added, “We must note that this would not be possible without the remarkable contributions of our loyal participants. They are really very special people.”
# # #
Media Contact: Kimberly Edwards, 619-543-6163, kedwards@ucsd.edu
Posted 16 June 2007 - 06:18 AM
Heatlh Day: News Source
Hormone Therapy Extends Lives of Ovarian Cancer Patients
The use of letrozole may also delay need for chemotherapy, study says
By Steven Reinberg
HealthDay Reporter
FRIDAY, June 15 (HealthDay News) -- Hormone therapy that has proved successful against breast cancer may also extend and improve the lives of women with estrogen-sensitive ovarian cancer, a British study suggests.
Letrozole hormone therapy may also be an alternative to chemotherapy for some women with the disease, according the report in the June 15 issue of Clinical Cancer Research.
"This study demonstrates that some ovarian cancers are responsive to anti-estrogen hormonal therapy, and these cancers, and therefore the patients who would benefit, can be identified," said lead researcher Simon Langdon, a Cancer Research UK scientist and a senior lecturer in cancer research at the University of Edinburgh.
Langdon noted that his team's research has shown that growth of certain ovarian cancers is stimulated by the female hormone estrogen. "These cancers could be identified as those possessing high levels of the estrogen receptor," he said.
For the study, which included 44 women, the researchers used letrozole, which works by limiting production of estrogen in the body. "This treatment then effectively starves the ovarian cancer of estrogen and inhibits growth," Langdon said.
During six months of treatment, 25 percent of the women had no tumor growth, and 33 percent of the women with the greatest estrogen values had a positive response that delayed the use of chemotherapy. "Within the trial, we were able to show that tumors with the highest levels of estrogen receptor were the most likely to respond to treatment," Langdon said.
"This approach provides an addition to chemotherapy for this disease," he added. "It is unlikely to replace chemotherapy but could be used to delay the need for chemotherapy."
The patients most likely to benefit from the therapy can be identified before treatment starts. So, this kind of approach means women can be better targeted and the drug not given to those unlikely to benefit who should receive some other type of treatment, Langdon said.
The American Cancer Society reports that ovarian cancer is the eighth most common cancer in women, not including skin cancer. There will be about 22,430 new cases of ovarian cancer in the United States this year, and an estimated 15,280 women will die from the disease.
A large majority -- about two-thirds -- of women with ovarian cancer are 55 or older. A woman's risk of getting ovarian cancer is about one in 67, according to the cancer society.
Dr. Len Lichtenfeld, the deputy chief medical officer at the American Cancer Society, said, "Letrozole is already approved for treating ovarian cancer in women who have failed other treatment. This study refines these researchers' previous work by identifying those women with estrogen-receptor-sensitive ovarian cancer who are the most likely to respond to this drug.
"Whether the drug should be started earlier in the course of ovarian cancer and whether we should be evaluating whether or not a woman has estrogen-receptor-sensitive ovarian cancer are questions that need to be answered," he said.
More information
For more information on ovarian cancer, visit the American Cancer Society:
http://www.cancer.or...sitearea=&dt=33
SOURCES: Simon Langdon, Ph.D., Cancer Research UK scientist, senior lecturer, Edinburgh Cancer Research Centre, University of Edinburgh, United Kingdom; Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; June 15, 2007, Clinical Cancer Research
Copyright © 2007 ScoutNews, LLC. http://www.healthday.com/
All rights reserved.
Posted 21 June 2007 - 06:17 AM
NPR: News Source
All Things Considered, June 20, 2007 ·
Five years ago, the mammoth Women's Health Initiative startled millions of women and their doctors with the finding that women who take menopausal hormone supplements have a higher risk of heart disease.
Now, researchers from the same study say hormone therapy actually lowers the risk of heart disease for some women, at least while they're taking the drugs. Women in their 50s taking estrogen pills had 40 percent to 60 percent fewer calcium deposits in their coronary arteries — a reliable marker of heart disease.
Study leader JoAnn Manson says the absence of a heart disease risk changes the equation for hormone replacement therapy among women just entering the menopause years.
"The findings are reassuring to younger women close to the onset of menopause who are considering hormone therapy for the treatment of moderate to severe hot flashes or night sweats," Manson says.
She says the risk of breast cancer and blood clots is not elevated among women who take hormones for fewer than five years.
Women in the study took estrogen alone because they'd had hysterectomies. Women who still have a uterus need to add a second hormone, progestin, to protect against uterine cancer. But Manson says the message is now the same for both groups.
"Whether they would need estrogen alone or estrogen together with progestin, there's really no substantial evidence that younger women would have an increased risk of heart disease."
The news is the kind of thing that exasperates many people about medical research.
"The pendulum has swung from one extreme to the other," Manson says. "Originally, hormone therapy was considered good for all women — and that was clearly not the case. Many more women were taking hormone therapy than actually needed it or should have been taking it."
In 2002, the Women's Health Initiative gave the pendulum a big push in the opposite direction with its conclusion that hormone therapy increases heart disease. As a result, the number of menopausal women taking hormones plummeted from 15 million to around 5 million.
Manson says the new findings don't justify a return to the old days.
Fewer than one in five women would be considered appropriate candidates for hormone therapy, Manson says. These are women in their 50s who have persistent, moderate-to-severe hot flashes and night sweats that interfere with sleep.
Perhaps 1 million to 2 million additional women might fit that definition and might safely take hormones. But only early in menopause, and only for a few years, to avoid the risk of breast cancer and blood clots.
The new findings, published in the New England Journal of Medicine, raise a question: How could research results be so contradictory?
Dr. Michael Mendelsohn of New England Medical Center says it's because estrogen has a dual effect. It works in opposite ways in the coronary blood vessels of younger and older women.
"We believe that the response to (the) hormone in a younger vessel leads to differences in which genes are turned on and off, compared to genes that are turned on and turned off in an older blood vessel," Mendelsohn says.
In a younger woman, estrogen delays blood vessel disease. But in a woman with established coronary disease, estrogen can cause the built-up deposits in arteries to rupture and cause clots to form.
That new insight explains the previously contradictory research, experts say. The protective effect had been observed years ago in studies that observed the rates of heart attacks and heart disease in younger women on hormone therapy.
But the Women's Health Initiative, which enrolled more than 27,000 women randomly assigned to hormone therapy or placebo, largely enrolled older women who continued taking hormones into their 60s. That led to a higher rate of heart problems and the premature termination of the hormone replacement trial.
Experts considered the Women's Health Initiative more believable because it was a so-called randomized placebo-controlled trial – the gold standard of medical research.
Only recently, when researchers looked specifically at hormone therapy in younger versus older women and those who had been on hormone therapy for shorter or longer periods of time, did they discover estrogen's dual effect.
In retrospect, Manson says, the lesson is that researchers should pay attention to "the totality of the evidence," including both randomized trials and so-called observational studies.
But, she adds, if the Women's Health Initiative had not enrolled and randomized many older women, the link between hormone therapy and increased risk of heart disease in that group would have been missed.
Manson says it will take awhile before many women suffering from menopause symptoms choose hormone therapy.
"There was a lot of alarm five years ago, and many women who would otherwise be considered good candidates tossed their hormone pills and decided that the risk very likely outweighed the benefits," Manson says.
She says she hopes younger women with troublesome menopausal symptoms will consider the new evidence carefully — and try to understand why it took years of research to resolve the frustrating contradictions.
Click here to See the March 2007 position statement on hormone replacement by the North American Menopause Society.(Requires Adobe Acrobat)
The New England Journal of Medicine (N Engl J Med or NEJM) is a peer-reviewed medical journal published by the Massachusetts Medical Society. It is one of the most popular and widely-read peer-reviewed general medical journals in the world. It is also the oldest continuously published medical journal in the world.
It was founded by Dr. John Collins Warren in 1812 as a quarterly called The New England Journal of Medicine and Surgery. In 1828, it became a weekly, and was renamed The Boston Medical and Surgical Journal; one hundred years later, it took on its present name.
It publishes editorials, papers on original research, widely-cited review articles, correspondences, case reports, and has a special section called "Images in Clinical Medicine".
Authors have included Oliver Wendell Holmes, Sr., Hans Zinsser, and Lewis Thomas. One of its early editors, Jerome V. C. Smith, resigned in 1857 to assume his duties as mayor of the City of Boston.
The website for the George Polk Awards noted that its 1977 award to the New England Journal of Medicine "provided the first significant mainstream visibility for a publication that would achieve enormous attention and prestige in the ensuing decades"[1]
The journal usually has the highest impact factor of the journals of clinical medicine (including the Journal of the American Medical Association, and The Lancet); in 2005, the impact factor was 44.016, according to Journal Citation Reports.
Estrogen Therapy and Coronary-Artery Calcification
JoAnn E. Manson, M.D., Dr.P.H., Matthew A. Allison, M.D., M.P.H., Jacques E. Rossouw, M.D., J. Jeffrey Carr, M.D., Robert D. Langer, M.D., M.P.H., Judith Hsia, M.D., Lewis H. Kuller, M.D., Dr.P.H., Barbara B. Cochrane, Ph.D., Julie R. Hunt, Ph.D., Shari E. Ludlam, M.P.H., Mary B. Pettinger, M.S., Margery Gass, M.D., Karen L. Margolis, M.D., M.P.H., Lauren Nathan, M.D., Judith K. Ockene, Ph.D., Ross L. Prentice, Ph.D., John Robbins, M.D., Marcia L. Stefanick, Ph.D., for the WHI and WHI-CACS Investigators
Editorial
by Mendelsohn, M. E.
ABSTRACT
Background Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial.
Methods In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status.
Results The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence.
Conclusions Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways. (ClinicalTrials.gov number, NCT00000611 [ClinicalTrials.gov] .)
Source Information
From Brigham and Women's Hospital, Harvard Medical School, Boston (J.E.M.); the University of California, San Diego, San Diego (M.A.A.); the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (J.E.R., S.E.L.); Wake Forest University School of Medicine, Winston-Salem, NC (J.J.C.); Geisinger Health System, Danville, PA (R.D.L.); George Washington University, Washington, DC (J.H.); the University of Pittsburgh, Pittsburgh (L.H.K.); the University of Washington (B.B.C.) and Fred Hutchinson Cancer Research Center (J.R.H., M.B.P., R.L.P.) — both in Seattle; the University of Cincinnati, Cincinnati (M.G.); HealthPartners Research Foundation and the University of Minnesota — both in Minneapolis (K.L.M.); the University of California at Los Angeles, Los Angeles (L.N.); the University of Massachusetts Medical School, Worcester (J.K.O.); the University of California at Davis, Sacramento (J.R.); and Stanford University, Palo Alto, CA (M.L.S.).
Address reprint requests to Dr. Manson at the Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Ave. E., 3rd Fl., Boston, MA 02215, or at jmanson@rics.bwh.harvard.edu.
Posted 21 June 2007 - 02:44 PM
http://news.yahoo.co...DltBHNlYwM3MTY-
I really hate that news is more about entertainment than fact.
When you actually read the article, the study only say's DHEA and testosterone patches don't work. It says NOTHING about other anti-aging supplements. sigh.
Posted 12 July 2007 - 06:47 AM
British Medical Journal
From Wikipedia, the free encyclopedia
BMJ is one of the most popular and widely-read peer-reviewed general medical journals in the world [1]. It is published by the BMJ Publishing Group Ltd (owned by the British Medical Association), whose other publications include popular sub-speciality journals like The Journal of Neurology, Neurosurgery and Psychiatry, Heart, Thorax, among others, and Student BMJ for medical students globally. Originally called the British Medical Journal, the title was shortened to BMJ in 1988 [2].
The current editor of BMJ is Fiona Godlee, who replaced the former editor-in-chief, Richard Smith after he resigned in July 2004. She was appointed in February 2005, and Kamran Abbasi served as acting editor in the interim.
Journal content
BMJ is an emphatic advocate of evidence-based medicine, and publishes original research, clinical reviews, news, editorial perspectives, personal views and career focus articles, to mention a few. Recently its readership has witnessed a surge in the number of articles focusing on medical ethics and health in developing nations.
The journal also releases a number of 'theme issues' every year, when it publishes research and review articles pertaining to the theme addressed. Some of the popular theme issues in recent years include 'Health in Africa', 'Management of Chronic Diseases' and 'Global Voices on the AIDS Catastrophe'. A special 'Christmas Issue' is published annually, on the Friday before Christmas.
^ According to PubMed Central: http://en.wikipedia..../PubMed_Central
BMJ, doi:10.1136/bmj.39266.425069.AD (published 11 July 2007)
Research
Main morbidities recorded in the women's international study of long duration oestrogen after menopause
(WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women
Madge R Vickers, former head, MRC general practice research framework1, Alastair H MacLennan, professor, department of obstetrics and gynaecology2, Beverley Lawton, director women's health research centre3, Deborah Ford, senior statistician4, Jeannett Martin, former senior nurse manager1, Sarah K Meredith, senior clinical epidemiologist4, Bianca L DeStavola, reader in biostatistics5, Sally Rose, research fellow3, Anthony Dowell, professor3, Helen C Wilkes, senior statistician4, Janet H Darbyshire, director4, Tom W Meade, emeritus professor5
1 MRC General Practice Research Framework, Stephenson House, London NW1 2ND, 2 University of Adelaide, Women's and Children's Hospital, Adelaide SA 5006, Australia, 3 Department of Primary Health Care and General Practice, Wellington School of Medicine and Health Sciences, New Zealand, 4 MRC Clinical Trials Unit, London NW1 2DA, 5 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT
Correspondence to: A H MacLennan alastair.maclennan@adelaide.edu.au
Objective To assess the long term risks and benefits of hormone replacement therapy (combined hormone therapy versus placebo, and oestrogen alone versus combined hormone therapy).
Design Multicentre, randomised, placebo controlled, double blind trial.
Setting General practices in UK (384), Australia (91), and New Zealand (24).
Participants Postmenopausal women aged 50-69 years at randomisation. At early closure of the trial, 56 583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22 300) started treatment.
Interventions Oestrogen only therapy (conjugated equine oestrogens 0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of treatment planned.
Main outcome measures Primary outcomes: major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life.
Results The trial was prematurely closed during recruitment, after a median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women years) in those enrolled, after the publication of early results from the women's health initiative study. The mean age of randomised women was 62.8 (SD 4.8) years. When combined hormone therapy (n=2196) was compared with placebo (n=2189), there was a significant increase in the number of major cardiovascular events (7 v 0, P=0.016) and venous thromboembolisms (22 v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were no statistically significant differences in numbers of breast or other cancers (22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40 v 58, 0.69 (0.46 to 1.03)), and overall deaths (8 v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no significant differences.
Conclusions Hormone replacement therapy increases cardiovascular and thromboembolic risk when started many years after the menopause. The results are consistent with the findings of the women's health initiative study and secondary prevention studies. Research is needed to assess the long term risks and benefits of starting hormone replacement therapy near the menopause, when the effect may be different.
Trial registration Current Controlled Trials ISRCTN 63718836
BMJ, doi:10.1136/bmj.39272.445428.80 (published 11 July 2007)
Editorials
Hormone replacement therapy comes full circle
Further evidence on the early benefits and late risks does not change advice to menopausal women
The publication of the combined treatment arm of the women's health initiative study in July 2002 led to a dramatic fall in the use of hormone replacement therapy and a revision of the package insert for all hormone therapy preparations. This clinical trial randomised 16 608 women, aged 50-79 years, to 0.625 mg conjugated equine oestrogen and 2.5 mg medroxyprogesterone acetate or placebo.1 The study was stopped early, at an average follow-up of 5.2 years, because analysis did not find the expected benefit in preventing coronary heart disease. In addition, the global index score—which measures the balance between benefit and harm—showed that the benefits in preventing hip fracture and colorectal cancer were outweighed by the increased risk of breast cancer, stroke, and deep vein thrombosis.
...
Long term use of hormone replacement therapy to prevent chronic disease is no longer recommended, because available randomised evidence shows that the negative outcomes outweigh the positive benefits. Menopausal genitourinary symptoms, however, usually last a long time and require ongoing treatment. Current low dose vaginal oestrogen preparations have minimal systemic absorption, and recent position statements support long term use of these preparations as long as distressing symptoms remain.10
Helen Roberts, senior lecturer in women's health
Department of Obstetrics and Gynaecology, University of Auckland, Private Bag 92019, Auckland, New Zealand 1142
h.roberts@auckland.ac.nz
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Competing interests: None. Provenance and peer review: Commissioned; not externally peer reviewed.
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