Showing posts with label post WHI. Show all posts
Showing posts with label post WHI. Show all posts
Sunday, July 08, 2012
10 years after hormone therapy study: What doctors know now – USATODAY.com
10 years after hormone therapy study: What doctors know now – USATODAY.com
"It's been 10 years since researchers of the Women's Health Initiative, a large randomized, controlled trial on hormone therapy sponsored by the National Institutes of Health, announced their first findings: that the health risks outweighed the benefits of estrogen plus progestin hormone therapy (HT) in postmenopausal women. Since then, additional research has advanced the understanding of the benefits and risks. JoAnn Manson, one of the study's lead investigators and a professor of medicine at Harvard Medical School, is the president of the North American Menopause Society. She spoke with USA TODAY's Janice Lloyd about what women need to know to get through the challenging time and to protect their health......
Tuesday, May 22, 2012
The Women's Health Initiative study and hormone therapy -- what have we learned 10 years on? (note blogger's opinion)
Blogger's Note/Opinion: at the time of the initial publication this blogger attended numerous meetings which critically analyzed the WHI study; fear, poor communication and media hype led to many poor choices without any indepth analysis even at the time; most often the WHI/media were quoted to refer patients to their physicians; those physicians were in the same dilemma as the patients - a mess, in fact; to this day patients/consumers, led by fear, choose to ignore/not believe (?) post-WHI findings and analyses - more on these issues in this article as below
~~~~~~~~~~~~~~~~~~~~~~~~~~~~
The Women's Health Initiative study and hormone therapy -- what have we learned 10 years on?
Public release date: 21-May-2012
International Menopause Society
The Women's Health Initiative study and hormone therapy -- what have we learned 10 years on?
In July 2002 the publication of the first Women's Health Initiative (WHI) report caused a dramatic drop in Menopausal Hormone Therapy (HT ) use throughout the world. Now a major reappraisal by international experts, published as a series of articles in the peer-reviewed journal Climacteric (the official journal of the International Menopause Society), shows how the evidence has changed over the last 10 years, and supports a return to a "rational use of HT, initiated near the menopause".The reappraisal has been carried out by some of the world's leading experts in the field, including clinicians who worked on the original WHI study. Summarising the findings of the special issue, authors Robert Langer, JoAnn Manson, and Matthew Allison conclude that "classical use of HT" – MHT initiated near the menopause – will benefit most women who have indications including significant menopausal symptoms or osteoporosis.
Dr. Robert Langer, Principal Scientist at the Jackson Hole Center for Preventive Medicine, Jackson Wyoming, was the Principal Investigator of the WHI Clinical Center at the University of California, San Diego. He said
"With 10 years hindsight we can put the lessons learned from the WHI HT trials into perspective. In some ways we've come full circle – studies in recently menopausal women that suggested protection against major diseases led to testing whether that would carry over to older women who have even greater risks of heart attacks and fractures. That hope proved false. Unfortunately the results were wrongly generalized back to women like those who inspired the study. Information that has emerged over the last decade, shows that for most women starting treatment near the menopause, the benefits outweigh the risks, not just for relief of hot flashes, night sweats and vaginal dryness, but also for reducing the risks of heart disease and fractures".
Langer continued:
"Overgeneralizing the results from the women who were -- on average -- 12 years past menopause to all postmenopausal women has led to needless suffering and lost opportunities for many. Sadly, one of the lessons from the WHI is that starting HT 10 years or more after menopause may not be a good idea, so the women who were scared away by the WHI over this past decade may have lost the opportunity to obtain the potential benefits."
Professor JoAnn Manson (Harvard Medical School and Brigham and Women's Hospital, Boston, MA), who has been one of the WHI Principal Investigators since the study started, said:
"An important contribution of the WHI was to clarify that, for older women at high risk of cardiovascular disease, the risks of HT far outweighed the benefits. This halted the increasingly common clinical practice of prescribing HT to women who were far from the onset of menopause. Unfortunately, these findings were extrapolated to newly menopausal and healthy women who actually had a favourable benefit: risk ratio with HT. The WHI results point the way towards treating each woman as an individual. There is no doubt that HT is not appropriate for every woman, but it may be appropriate for many women, and each individual woman needs to talk this over with her clinician".
The authors note that the initial press reaction, following the lead
of the WHI press release, over-emphasised a relatively small increase
in breast cancer, so distorting the overall view of the report.
WHI researcher Professor Matthew Allison (University of California, San Diego), said:
"It is important to put the results of the WHI trials into context. That is, being obese, not exercising or excess alcohol consumption confer higher absolute risks for breast cancer than HT use."
###
Note that a brief summary of the papers in this special issue of Climacteric appears below.This special issue, "The Women's Health Initiative – a decade of progress" will appear in the June 2012 issue of Climacteric (vol 15, issue 3). This goes on line on 22nd May, at this URL: http://informahealthcare.com/cmt. Climacteric is the official journal of the International Menopause Society (IMS).
ABSTRACT:
Have we come full circle-or moved forward? The Women's Health Initiative 10 years on", by R.D Langer, J.E Manson, and M.A. Allison, Climacteric Vol15 no 3 pp206-213
In mid-summer 2002, the announcement that the Women ' s Health Initiative (WHI) trial of combination hormone therapy (HRT) had stopped jolted the field of women's health. It set off a cascade that first stunned, then meaningfully changed the future for millions of women, their partners, and tens of thousands of clinicians and scientists. With 10 years' hindsight, we can begin to put the lessons learned from the WHI HRT trials into perspective. These trials were primarily designed to test whether women initiating HRT considerably past menopause, and mostly asymptomatic, experienced treatment benefits from HRT expected from studies of generally symptomatic women who started near menopause. The definitive answer was ' no ' . Unfortunately, the findings were generalized to all postmenopausal women regardless of age. Data accumulated from the WHI and other studies over the past decade have shown that, in women with symptoms or other indications, initiating HRT near menopause – the classic pattern of use – will probably provide a favourable benefit : risk ratio. Spurred by the WHI, many hypotheses and some insights about potential mechanisms for HRT effects on diverse organ systems have emerged, along with new perspectives on regimens, compounds, and routes of administration. This overview provides an historical perspective on the WHI design and the evolution of its message; summarizes current perspectives and insights contributed by eminent colleagues; reviews the state of the art; and looks to the future. We have come full circle in some ways, with mounting evidence supporting benefit for HRT started near menopause and with hard lessons learned about pathophysiology, publicity and interpreting data. Now we move on.
Summary of papers This special issue of Climacteric contains a series of articles reviewing the position of HRT, 10 years after the WHI. There is a wealth of information here, which is impossible to communicate in a single press statement. Here are simplified summaries of each article, please refer to each individual article for more details.
Quality of Life The WHI study suggested that HRT use led to minimal improvement in quality of life (QoL). As the WHI study wasn't designed to look at women going through the menopause, it underestimated the real extent of effect of HRT on QoL. This has caused suffering to many women (Pines et al).
HRT for Urogynecological and sexual health Around 50% of postmenopausal women will suffer urogenital atrophy. Studies indicate that locally applied hormone therapy is generally more effective than systemic HRT for urogenital symptoms, including dyspareunia, which can be a critical determinant of a woman's interest in sex.(Nappi & Davis)
Timing of HRT initiation, and cost effectiveness The weight of evidence now supports a ' window-of-opportunity ' for women taking HRT before the age of 60 and/or within 10 years of the menopause. This reduces the risk of coronary heart disease and overall mortality. HRT is more effective for this than other medicines such as statins and aspirin, and is cost-effective. Starting HRT later than this increases risks to women (Hodis et al).
Stroke There is a modest increase in stroke risk with HRT use if stated near the menopause. This risk rises considerably in women who start at older ages. There is some evidence that use of HRT patches (as opposed to pills) may not increase stroke risk, but this needs to be confirmed (Henderson and Lobo).
Venous Thromboembolism There is an increased risk of venous thromboembolism with oral HRT. This may be increased with age and obesity, and may vary by the progestogen used. Observational studies suggest that it may not be associated with transdermal HRTs (patches), but this needs confirmation (Archer and Ogar).
Breast cancer There is an increase in breast cancer with E+P HRT, but this is small. It has also been exaggerated by press reports, causing fear in many women. They conclude that large numbers of women with substantial menopausal symptoms and low breast cancer risk will benefit from HRT use (Gompel and Santen).
Colorectal Cancer This is the second most common cancer in women (after breast cancer). Evidence from the WHI and other trials suggests that current HRT users have a 40% reduction in colorectal cancers. The authors say that it is too early to consider HRT use in the prevention of colon cancer (Barnes and Long) Dementia Initial WHI results showed an increase in dementia for both E+P and E alone users. This review including recent publications from other studies suggests that this may be influenced by the timing of the HRT initiation, with benefits for those starting nearer the menopause, but increased risks for women starting at older ages (Maki and Henderson).
Fractures The WHI "Global Index", which looked at the balance of risks and benefits, inappropriately downgraded the importance of fractures. The authors argue for a more rounded view. They say that that HRT gives more bone benefits than many other drugs (e.g. bisphosphonates), and so restrictions on HRT use as a first-line therapy are not appropriate (de Villiers and Stevenson)
Overall effects of the drop in HRT use This is difficult to gauge, because data varies from country to country. In one large study HRT discontinuation led to a 55% increase in fractures after 6.5 years. There was also a small drop in breast cancers after the drop in use in HRT, most notably in the US, but not seen in all countries, that was consistent with an effect on existing tumours. HRT discontinuation may lead to an increase in cardiovascular disease, but given the long lag time for cardiovascular events this would take substantial time to become apparent (Burger et al)
The WHI and media The author suggests that the WHI's dramatic presentation of the initial findings set the subsequent tone for the way that the media came to view the HRT issue (Simon Brown).
Wednesday, March 07, 2012
Tuesday, March 06, 2012
Medpage: LaCroix A, et al "Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial" JAMA 2011; 305: 1305-1314.
Blogger's Note: also see website for video
~~~~~~~~~~~~~~~
New WHI Estrogen Analysis Shows Lower Breast Ca Risk
In contrast to other studies of unopposed postmenopausal estrogen therapy, long-term follow-up of Women's Health Initiative (WHI) Estrogen-Alone Trial participants showed a persistent reduction in breast cancer risk, researchers said.
But other benefits and risks associated with use of conjugated equine estrogens (CEE) quickly dissipated after the therapy was stopped, according to Andrea Z. LaCroix, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues.
"Considering the entire follow-up period, rates of total mortality and the global index of chronic diseases were essentially the same in the conjugated equine estrogen and placebo groups," LaCroix and co-authors wrote in the April 6 issue of the Journal of the American Medical Association.
"Statistically significant age interactions for conjugated equine estrogen use, suggesting greater safety and possible benefit among women in their 50s and potential harm among older women, were observed for coronary heart disease, total MI, colorectal cancer, total mortality, and the global index of chronic diseases," they added.
An editorial in the same issue suggested more caution in interpreting the breast cancer results.
Sunday, May 29, 2011
EvidenceUpdates + professional commentaries (numerous): Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women`s Health Initiative limited access dataset and meta-analysis
OBJECTIVES: To investigate the effects of personal calcium supplement use on cardiovascular risk in the Women`s Health Initiative Calcium/Vitamin D Supplementation Study (WHI CaD Study), using the WHI dataset, and to update the recent meta-analysis of calcium supplements and cardiovascular risk.
DESIGN: Reanalysis of WHI CaD Study limited access dataset and incorporation in meta-analysis with eight other studies.........
Conclusions: Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.
Sunday, April 24, 2011
abstract: Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy — JAMA
Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy
A Randomized Controlled Trial
Abstract
Context
The Women's
Health Initiative Estrogen-Alone Trial was stopped early after a mean of
7.1 years of follow-up because of an
increased risk of stroke and little likelihood of
altering the balance of risk to benefit by the planned trial termination
date. Postintervention health outcomes have not
been reported.
Objective
To examine health outcomes associated with randomization to treatment with conjugated equine estrogens (CEE) among women
with prior hysterectomy after a mean of 10.7 years of follow-up through August 2009.
Design, Setting, and Participants
The intervention phase was a double-blind, placebo-controlled,
randomized clinical trial of 0.625 mg/d of CEE compared with
placebo in 10 739 US postmenopausal women aged 50
to 79 years with prior hysterectomy. Follow-up continued after the
planned
trial completion date among 7645 surviving
participants (78%) who provided written consent.
Main Outcome Measures
The
primary outcomes were coronary heart disease (CHD) and invasive breast
cancer. A global index of risks and benefits included
these primary outcomes plus stroke, pulmonary
embolism, colorectal cancer, hip fracture, and death.
Results
The
postintervention risk (annualized rate) for CHD among women assigned to
CEE was 0.64% compared with 0.67% in the placebo
group (hazard ratio [HR], 0.97; 95% confidence
interval [CI], 0.75-1.25), 0.26% vs 0.34%, respectively, for breast
cancer
(HR, 0.75; 95% CI, 0.51-1.09), and 1.47% vs 1.48%,
respectively, for total mortality (HR, 1.00; 95% CI, 0.84-1.18). The
risk
of stroke was no longer elevated during the
postintervention follow-up period and was 0.36% among women receiving
CEE compared
with 0.41% in the placebo group (HR, 0.89; 95% CI,
0.64-1.24), the risk of deep vein thrombosis was lower at 0.17% vs
0.27%,
respectively (HR, 0.63; 95% CI, 0.41-0.98), and the
risk of hip fracture did not differ significantly and was 0.36% vs
0.28%,
respectively (HR, 1.27; 95% CI, 0.88-1.82). Over
the entire follow-up, lower breast cancer incidence in the CEE group
persisted
and was 0.27% compared with 0.35% in the placebo
group (HR, 0.77; 95% CI, 0.62-0.95). Health outcomes were more favorable
for younger compared with older women for CHD (P = .05 for interaction), total myocardial infarction (P = .007 for interaction), colorectal cancer (P = .04 for interaction), total mortality (P = .04 for interaction), and global index of chronic diseases (P = .009 for interaction).
Conclusions
Among
postmenopausal women with prior hysterectomy followed up for 10.7 years,
CEE use for a median of 5.9 years was not
associated with an increased or decreased risk of
CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer, or
total
mortality.
A decreased risk of breast cancer
persisted.
free full access: Calcium supplements with/without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative - bmj.com (including responses)
Abstract/Conclusions:
Calcium supplements with or without vitamin D modestly increase the risk of cardiovascular events, especially myocardial infarction, a finding obscured in the WHI CaD Study by the widespread use of personal calcium supplements. A reassessment of the role of calcium supplements in osteoporosis management is warranted.
excerpt (from full text):
"...An important question that arises is whether co-administered
calcium and vitamin D affects cardiovascular risk. The Women’s Health
Initiative reported no adverse effect of calcium and vitamin D (1 g
calcium/400 IU vitamin D daily) on any cardiovascular end point in their
large (n=36 282), seven year, randomised, placebo controlled trial.3 4
However, 54% of the participants were taking personal (non-protocol)
calcium supplements at randomisation and 47% were taking
personal vitamin D supplements,
effectively rendering this trial a comparison of higher dose and lower
dose calcium and vitamin
D for most of the participants.
Allowing clinical trial
participants free access to the intervention being studied is unusual
and has the potential to obscure both adverse and beneficial effects..."Wednesday, April 20, 2011
Revisiting the Women’s Health Initiative Estrogen-Alone Trial - hcp.obgyn.net
Note: scroll to bottom for addition references
Sunday, April 10, 2011
(timeline) Landmarks From Two Decades of Study - NYTimes.com
By THE NEW YORK TIMES
Published: April 9, 2011
1991 National Institutes of Health embarks on a study of menopause hormones after observational data suggest that women who use hormones have lower rates of heart disease.
Related
-
The Women’s Health Initiative and the Body Politic (April 10, 2011)
2003 Women taking E+P are not protected from mild memory loss; they are found to be at increased risk for developing dementia.
2004 The second W.H.I. hormone study is stopped one year early because women taking estrogen only show a small increased risk of stroke.
2006 An updated analysis of the estrogen-only trial shows hormone therapy does not increase the risk of breast cancer in postmenopausal women.
2007 Combined data from both hormone trials suggest that timing of therapy may affect risk; hormones may reduce heart disease in women who start therapy closer to menopause.
2009 Women using E+P for more than about five years double their annual risk of breast cancer. That risk is higher than previously thought.
2011 Follow-up of women in the estrogen-only study shows those who took just estrogen had 23 percent fewer breast cancers; younger estrogen users had 46 percent fewer heart attacks.
Sources: Women’s Health Initiative; New York Times reports
Wednesday, April 06, 2011
Wednesday, December 29, 2010
Friday, August 20, 2010
Editorial: Note from the editors: change is afoot -- Menopause International
Note: in the absence of available full paper/s (pay per view/subscription) of the several related articles blogged, there is no reference to those with genetic predispositions/risks/advantages with hormone replacement therapy. The one abstract (Review - Hinds/Price) discusses risks related to sarcoma/granulosa but no mention of genetics eg. BRCA's/familial colorectal cancers and/or prior research regarding ERT/colorectal cancers.
"Our understanding of the menopause and the management of its issues is in a continual state of flux. Since the publication of the original Women's Health Initiative study and the immediate conclusions and position statements from various specialist societies and regulatory authorities, clinicians have had little choice other than to significantly change their clinical management. So, is this a change for good? Whether you were a supporter or detractor of hormone replacement therapy (HRT), or even sat on the academic fence you will be aware that many clinicians have withdrawn from even discussing the place of HRT in the management of menopausal issues with their patients. This cannot be a good thing...."cont'd
Friday, August 13, 2010
Caveats and Concerns With New Study on Hormone Therapy and Breast Cancer
Note: references studies - WHI (Women's Health Initiative) and California Teachers Study
Clinicians vary in their approaches to HT, said Dr. Ursin. "Certain gynecologists are very careful with finding the right dose for each woman, and some even prescribe [estrogen] alone for women who have a uterus, but then monitor the uterus carefully. Please keep in mind that the risk of breast cancer associated with EPT is relatively moderate. The risk of endometrial cancer with [estrogen] alone is much higher — a more than 4-fold increase in risk in this same population of California teachers," she said.
Tuesday, June 22, 2010
Postmenopausal Hormone Therapy: An Endocrine Society Scientific Statement -- Concensus Statement/Review
Conclusions:
The major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women's Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause.
At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.
Thursday, June 17, 2010
The breast cancer “plunge” after initial publication of the WHI results: An alternative explanation
Abstract
From
2002 to 2003, the breast cancer incidence in the United States, as
reported by the National Cancer Institute's Surveillance Epidemiology
and End Results (SEER 9) database, appeared to decrease by 6.7%. This
phenomenon has been attributed to a reduction in the use of menopausal
hormone therapies after the initial publication of the Women's Health
Initiative (WHI) study results in July of 2002.
However, attempts to
draw a causal association between the use of menopausal hormone
therapies and the incidence of breast cancer have not accounted for the
facts that prescriptions of estrogen-plus-progestin menopausal
therapies, which are associated with increased rates of breast cancer,
fell by 53% from 2002 to 2003, while prescriptions of estrogen-only
therapies fell by only 27%. To address this issue,...
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