Postmenopausal women should still steer clear of HRT: task force

Yet again, the nation's leading authority on preventive medicine says postmenopausal women should avoid hormone replacement therapy (HRT).
The U.S. Preventive Services Task Force is standing by its original recommendation that women who have already gone through menopause should avoid using female hormones to guard against osteoporosis or diabetes, said task force chairman Dr. David Grossman, a senior investigator at the Kaiser Permanente Washington Health Research Institute in Seattle.

15 dec 2017--"Basically, the task force concluded there was no overall benefit from taking hormones to prevent chronic conditions," Grossman said. "There are some benefits, but we believe those potential benefits are outweighed by the harms, making this essentially no net benefit overall."
The advisory covers all formulations of hormone replacement therapy, the task force said. The therapy can consist of pills or patches containing either estrogen or an estrogen/progesterone mix.
However, women undergoing menopause can use hormone replacement therapy short-term to treat symptoms such as hot flashes and vaginal dryness, said Dr. Suzanne Fenske, an assistant professor of obstetrics, gynecology and reproductive science with the Icahn School of Medicine at Mount Sinai in New York City.
"Hormone replacement therapy does still have a benefit to women with menopause whose symptoms do not respond to other treatment options," Fenske said. "It really should be used to manage menopausal symptoms, rather than being used for any sort of preventative medicine."
The task force first recommended against hormone replacement therapy for postmenopausal women in 2012. It updates its recommendations every four years to make sure they reflect the latest medical evidence.
In its evidence review, the task force considered results from 18 clinical trials including more than 40,000 women.
All of the evidence suggests that combined estrogen and progesterone increase older women's risk of breast cancer and heart disease, while estrogen alone increases risk of stroke, blood clots and gallbladder disease, the task force said.
Those risks outweigh hormone therapy's benefits in preventing brittle bones and diabetes, the task force concluded.
"When hormone replacement therapy first was brought out on the market in the 1960s, it was touted as a way to keep feminine forever," Fenske said. "Then in the 1980s they began to see there were some potential benefits otherwise, like [preventing] osteoporosis.
"Then the infamous and famous Women's Health Initiative [WHI] study came out, which kind of put the kibosh on hormone replacement therapy," Fenske added.
Results from the WHI trials were published in the early 2000s; the trials were halted early after linking hormone therapy with increased risk of breast cancer, heart disease and stroke.
The updated task force recommendation contains the latest long-term follow-up data from the WHI trials, Grossman said.
"It didn't change our conclusion, but there is new information available that we incorporated into our evidence review," Grossman said.
Dr. Stephanie Faubion, director of the Mayo Clinic Office of Women's Health in Rochester, Minn., took issue with the task force's recommendation.
"I think this report is going to scare women," Faubion said. "Even those who are having symptoms and not excluded from hormone therapy according to this guideline are going to avoid it because they're afraid of it."
For example, the guideline does not apply to women who go through menopause early or prematurely, at age 45 or younger, Faubion said.
"Those women actually have adverse health consequences if they don't use hormone therapy at least until the natural age of menopause," Faubion said.
She said she also takes issue with a blanket recommendation covering all age groups.
"This is a key issue," Faubion said. "If you do break it down by age, there are more clear benefits for women in their 50s than women in their 60s and 70s.
"The task force is trying to make this more black-and-white than it can ever be," Faubion concluded.
Fenske said women in menopause suffering from hot flashes, vaginal dryness and other related symptoms can still safely turn to hormone therapy to ease their discomfort.
There are no clear guidelines for how long a menopausal woman can remain on hormone replacement therapy, or what dose is best for treating menopause symptoms, Fenske said. In large part, doctors are urged to be cautious because of the long-term health risks.
"It should be the smallest dose possible for the shortest period of time necessary," Fenske said.
Women interested in using hormone therapy to treat their menopause symptoms should talk with their doctor, because there is a lot of false and misleading information out there, Fenske said.
The task force recommendation was published online Dec. 12 in the Journal of the American Medical Association.

More information: David Grossman, M.D., M.P.H., pediatrician and senior investigator, Kaiser Permanente Washington Health Research Institute, Seattle; Suzanne Fenske, M.D., assistant professor, obstetrics, gynecology and reproductive science, Icahn School of Medicine at Mount Sinai, New York City; Stephanie Faubion, M.D., director, Mayo Clinic Office of Women's Health, Rochester, Minn.; Dec. 12, 2017, Journal of the American Medical Association

Recommendation Statement
Evidence Report
Editorial 1
Editorial 2
Editorial 3

For more on hormone replacement therapy, visit the American Congress of Obstetricians and Gynecologists.

Latest evidence on using hormone replacement therapy for treating menopausal symptoms

Hormone replacement therapy (HRT) is the most effective treatment for menopausal symptoms, in particular for younger women at the onset of the menopause, suggests a new review published today in The Obstetrician & Gynaecologist (TOG).

20 dec 2014--The review highlights that menopausal symptoms, including hot flushes and night sweats are common, affecting around 70% of women for an average of 5 years but may continue for many years in about 10% of women.

Every woman experiences the menopause differently; some experience one or two symptoms mildly while others have more severe symptoms. Menopausal symptoms can be debilitating and can adversely affect a woman's quality of life.

HRT is a medical treatment for the menopause. It provides low doses of the hormone estrogen, with or without progestogen, which a woman no longer produces.

The review notes that the risk-benefit ratio of HRT has always been debated and discusses previous studies examining the effects of HRT.

The Women's Health Initiative Study in 2003 examined the effect of HRT on healthy postmenopausal women with a particular interest in cardiovascular outcomes. The study reported an increase in breast cancer, stroke and venous thromboembolism. Consequently, an 80% reduction in HRT use was reported. However, the re-analysis in 2007 demonstrated that giving HRT to women within 10 years of the menopause was associated with fewer risks and a reduction in cardiovascular problems.

The Million Women Study in 2001 suggested that HRT use increased the risk of breast cancer significantly and the Cochrane Collaboration systematic review identified an increased risk of similar conditions.

However, the authors of the TOG review highlight that such studies failed to address the effect of HRT in symptomatic younger postmenopausal women and have not addressed the benefits of HRT given at the window of opportunity, for example, administrating HRT for symptom relief during the early phase of the menopausal transition.

Additionally, the review advises that any woman with relative contraindications should be offered the option of discussing this further with a menopause specialist. Women with premature ovarian sufficiency should be strongly advised to consider taking HRT until the average menopausal age of 51.4 years, state the authors.

The authors conclude that doctors should not be concerned about discussing the risks and benefits of HRT with women who have menopausal symptoms, or be hesitant to offer a trial of appropriate treatment. They also emphasise that HRT is a patient choice.

Shagaf Bakour, Honorary Senior Lecturer and Consultant Obstetrician and Gynaecologist at City Hospital, Birmingham, and co-author of the review said:

"Women are sometimes concerned about the increased risk of breast cancer related to HRT. However, this risk is much lower than that associated with other factors such as obesity, alcohol consumption and later maternal age.

"HRT is the most effective treatment for symptoms of the menopause and when HRT is individually tailored, women gain maximum advantages and the risks are minimised.

"There are various types and regimens of HRT and healthcare professionals will be able to advise on the suitability of HRT to any woman."

Jason Waugh, TOG Editor-in-chief added: "The use of HRT is an individual decision, which a woman can only make once she has been given correct information and advice from healthcare professionals.

"If women have any concerns about menopausal symptoms or HRT, they should talk to their doctor who will be happy to discuss treatment options further."

More information: S H Bakour, J Williamson. Latest evidence on using hormone replacement therapy in the menopause. The Obstetrician & Gynaecologist 2014; onlinelibrary.wiley.com/doi/10.1111/tog.12155/

Provided by Wiley

Hormone replacement therapy—clarity at last

The British Menopause Society and Women's Health Concern have today released updated guidelines on Hormone Replacement Therapy (HRT) to provide clarity around the role of HRT, the benefits and the risks. The new guidelines appear in the society's flagship title,Menopause International.

26 may 2013--Over the last 11 years, HRT has changed from being branded the "elixir of youth" to being considered extremely risky and only to be used in certain circumstances. Since the publication of the Women's Health Initiative (WHI) trial in 2002, and the Million Women study (MWS) in 2003, confusion and controversy has surrounded the use of HRT and the known benefits have often been forgotten.

A panel of experts have carefully considered, researched and reanalyzed the WHI and MWS studies alongside conducting further trials and studies, to offer practioners a detailed review of the evidence to help them optimize their clinical decisions, and provide women with more balanced and accurate advice on HRT treatment for menopause.

The new HRT recommendations are designed to complement the BMS Observations and Recommendations on menopause. The updated guidelines detail key recommendations targeting access to advice on how women can optimize their menopause transition and beyond, focusing in particular on lifestyle and diet and an opportunity to discuss the pros and cons of complementary therapies and HRT.

"Our aim is to provide helpful and pragmatic guidelines for health professionals involved in prescribing HRT and for women considering or currently using HRT" says Nick Panay, Chair of The British Menopause Society and lead author of the recommendations. "With these updated recommendations, it is hoped that HRT will once again be used appropriately and provide benefits for many women in their menopause."

More information: "The 2013 British Menopause Society & Women's Health Concern recommendations on hormone replacement therapy" by Nick Panay, Haitham Hamoda, Roopen Arya and Michael Sarvas on behalf of the British Menopause Society and Women's Health Concern, published by SAGE in Menopause International, June 2013.

Provided by SAGE Publications

Study identifies potential 'safe period' for hormone replacement use

03 feb 2009--A new study makes important new findings on the role of hormone use on the risk of breast cancer, confirming that the use of estrogen plus progesterone increases the risk of both ductal and lobular breast cancer far more than estrogen-only; suggesting a two-year "safe" period for the use of estrogen and progesterone; and finding that the increased risk for ductal cancers observed in long-term past users of hormone replacement therapy drops off substantially two years after hormone use is stopped. The study appears in CANCER, a peer-reviewed journal of the American Cancer Society.

Previous studies have shown that hormone replacement therapy after menopause increases the risk of breast cancer and that use of a regimen that includes both estrogen and progesterone is more detrimental for the breast than the use of estrogen alone. But more data from large prospective studies are needed to fully characterize the impact of exogenous hormones on breast cancer incidence by type of hormone preparation and histology of the cancer.

To investigate the association in more detail, American Cancer Society epidemiologists led by Eugenia E. Calle, PhD, did a prospective study of 68,369 postmenopausal women who were cancer-free at baseline in 1992. They examined the use of estrogen-only and estrogen and progesterone in current and former users of varying duration, and the subsequent risk of developing invasive ductal and lobular carcinoma of the breast. They also looked at whether the risk for each type of breast cancer and each type of hormone regimen varied by body mass index (BMI), stage of disease at diagnosis, and estrogen receptor (ER) and progesterone receptor (PR) status. For the present study, the follow-up period ended on June 30, 2005.

They confirmed the findings from previous work that estrogen and progesterone increases the risk of both ductal and lobular breast cancer far more estrogen alone. They also found the risk associated with use of estrogen and progesterone increases significantly and substantially within three years of beginning hormone use. The data showed no increased risk for women who used estrogen and progesterone for less than two years, potentially identifying a "safe" period for estrogen and progesterone use.

The study also found no increased risk of breast cancer in women who had stopped using estrogen and progesterone two or more years ago, suggesting a window of two to three years for the risks of estrogen and progesterone both to become apparent after initial use and to diminish after cessation. Few estimates of risk within two to three years of initiation and cessation are available, so these findings need replication in other large studies.

The study found the use of estrogen and progesterone was associated with a doubling of risk of lobular cancer after three years of use, and a doubling of risk of ductal cancer with 10 years of use. Estrogen-only use was not associated with increased risk of ductal cancer, even after 20 years of use, but was associated with a 50 percent increase in risk of lobular cancer after 10 years of use.

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Article: “Postmenopausal hormone use and breast cancer associations differ by hormone regimen and histologic subtype.” Eugenia E. Calle, PhD, Heather Spencer Feigelson, PhD, Janet S. Hildebrand, MPH, Lauren R. Teras, MPH, Michael J. Thun, MD, Carmen Rodriguez, MD, MPH CANCER; Published Online: January 20, 2008 (DOI: 10.1002/cncr.24101); Print Issue Date: March 1, 2009

New study firmly ties hormone use to breast cancer

By MARILYNN MARCHIONE

SAN ANTONIO, 13 dec 2008– Taking menopause hormones for five years doubles the risk for breast cancer, according to a new analysis of a big federal study that reveals the most dramatic evidence yet of the dangers of these still-popular pills.

Even women who took estrogen and progestin pills for as little as a couple of years had a greater chance of getting cancer. And when they stopped taking them, their odds quickly improved, returning to a normal risk level roughly two years after quitting.

Collectively, these new findings are likely to end any doubt that the risks outweigh the benefits for most women.

It is clear that breast cancer rates plunged in recent years mainly because millions of women quit hormone therapy and fewer newly menopausal women started on it, said the study's leader, Dr. Rowan Chlebowski of Harbor-UCLA Medical Center in Los Angeles.

"It's an excellent message for women: You can still diminish risk (by quitting), even if you've been on hormones for a long time," said Dr. Claudine Isaacs of Georgetown University's Lombardi Comprehensive Cancer Center. "It's not like smoking where you have to wait 10 or 15 years for the risk to come down."

Study results were given Saturday at the San Antonio Breast Cancer Symposium.

They are from the Women's Health Initiative, which tested estrogen and progestin pills that doctors long believed would prevent heart disease, bone loss and many other problems in women after menopause. The main part of the study was stopped in 2002 when researchers saw surprisingly higher risks of heart problems and breast cancer in hormone users.

Since then, experts have debated whether these risks apply to women who start on hormones when they enter menopause, usually in their 50s, and take them for shorter periods of time. Most of the women in the federal study were in their 60s and well past menopause.

So the advice has been to use hormones only if symptoms like hot flashes are severe, and at the lowest dose and shortest time possible. The new study sharpens that message, Chlebowski said.

"It does change the balance" on whether to start on treatment at all, he said.

Even so, most women will not get breast cancer by taking the pills short-term. The increased cancer risk from a couple of years of hormone use translates to a few extra cases of breast cancer a year for every 1,000 women on hormones. This risk accumulates with each year of use, though.

The Women's Health Initiative study had two parts. In one, 16,608 women closely matched for age, weight and other health factors were randomly assigned to take either Wyeth Pharmaceuticals' Prempro — estrogen and progestin — or dummy pills.

This part was halted when researchers saw a 26 percent higher risk of breast cancer in those on Prempro.

But that was an average over the 5 1/2 years women were on the pills. For the new study, researchers tracked 15,387 of these women through July 2005, and plotted breast cancer cases as they occurred over time.

They saw a clear trend: Risk rose with the start of use, peaked when the study ended and fell as nearly all hormone users stopped taking their pills. At the peak, the breast cancer risk for pill takers was twice that of the others.

Think of it as President Bush's public approval rating, said another study leader, Dr. Peter Ravdin of the University of Texas M.D. Anderson Cancer Center in Houston.

"Bush's popularity may be 50 percent on average, but it might have been descending the whole time he was president," Ravdin said.

In the second part of the federal study, researchers observed just 16,121 women who had already been on hormones for an average of seven years and another group of 25,328 women who had never used them. No results on breast cancer risk in these women have been given until now.

Plotting cases over time, researchers saw in retrospect that hormone users had started out with twice the risk of breast cancer as the others, and it fell as use declined. Among those taking hormones at the start of the study, use dropped to 41 percent in 2003, the year after the main results made news.

In the general population, use of hormone products has dropped 70 percent since the study, said another of its leaders, Dr. JoAnn Manson, preventive medicine chief at Harvard's Brigham and Women's Hospital in Boston.

That corresponds with big drops in breast cancer cases, but some scientists have said this could be due to a fall-off in mammograms, which would mean fewer cancers were being detected, not necessarily that fewer were occurring.

The new study puts that theory to rest. Mammography rates were virtually the same among those taking hormones and those not.

"It is clear that changing mammography patterns cannot explain the dramatic reductions in breast cancer risk," Manson said.

"The data are getting stronger," said Dr. C. Kent Osborne, a breast cancer specialist at Baylor College of Medicine in Houston.

Women who do need the pills should not panic, though the doubling of risk — a 100 percent increase — for long-term users is quite worrisome, cancer specialists say. Although the new study does not calculate risks in terms of actual cases, previous research showed that the average increased risk of 26 percent meant a difference of a few extra cases a year for every 1,000 women on hormone pills, compared with nonusers.

"Hormone therapy remains a good health care choice to relieve moderate to severe menopausal symptoms," says a statement from Wyeth, which made the pills used in the study.

"Most women should be able to discontinue hormones in three to four years," or at least reduce their dose, Manson said.

A future analysis will look at other women in the study who took only estrogen, generally women who have had hysterectomies.

____

On the Net:

Cancer conference: http://www.sabcs.org

Hormone study: http://www.nhlbi.nih.gov/whi/estro_pro.htm

Estrogen reduces risk of fracture after menopause

20 sept 2008--From the end of the 1970s to the late 1990s there was a significant reduction in the incidence of hip and distal forearm fractures among Oslo women in the early phase after menopause. Part of this decline can be explained by the large increase in the use of hormone replacement therapy after menopause in the same period, a new study shows.
The study is a collaboration between the University of Oslo, Aker University Hospital and the Norwegian Institute of Public Health.
Half of reduction in fractures may be due to hormone replacement therapy
From the end of the 1970s to the late 1990s the hip fracture rate dropped by 39 percent, while the distal forearm fracture rate fell by 33 percent among women aged 50-64 years. A similar decline was not registered among older women or among men.
- Interestingly, use of post-menopausal hormone replacement therapy increased greatly in the same period. It is shown that treatment with oestrogen reduces the risk of osteoporosis and fracture. Based on data from the Oslo Health Studies, we have estimated that almost half of the decline in fracture rates among women in the early phase after menopause in Oslo can be caused by hormone replacement therapy, says Professor Haakon Meyer, at the Norwegian Institute of Public Health and University of Oslo.
Could cause increased risk of serious illness
In recent years, however, the use of post-menopausal hormone replacement therapy has been significantly reduced. This is the result of new studies that have shown that such treatment leads to increased risk of breast cancer and may increase the risk of cardiovascular disease.
- Future monitoring of fracture frequency in the population is therefore important to examine whether this has resulted in a new increase in fracture frequency, says Meyer.
Collaborative study
Data on bone mass was taken from the Oslo Health Study 2000-01, while data on the use of drugs that contain oestrogen was taken from the Norwegian Prescription Database.
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The study is a collaboration between the University of Oslo, Aker University Hospital and the Norwegian Institute of Public Health.
Reference:
Haakon E. Meyer, Cathrine M. Lofthus, Anne Johanne Søgaard, Jan A. Falch. Change in the use of hormone replacement therapy and the incidence of fracture in Oslo. Osteoporos International 2008 June 19. [Epub ahead of print]. DOI 10.1007/s00198-008-0679-y

Study shows improved quality of life for older women on HRT

22 aug 2008--New evidence published on BMJ.com today shows that hormone replacement therapy (HRT) can improve the health related quality of life of older women.
HRT guidelines should be reviewed in light of this evidence, say the authors.
Previous research has suggested that HRT can improve general quality of life (the way patients feel or function) and reduce the number and severity of symptoms associated with the menopause, but these studies have used general rather than more sensitive condition specific measures.
Professor Alastair MacLennan and colleagues present the findings on health related quality of life from the WISDOM trial*. The WISDOM trial began in 1999 and aimed to evaluate the long term benefits and risks of HRT in postmenopausal women over 10 years. It randomised 5 692 healthy women aged 50󈞱 from general practices in the UK, Australia and New Zealand to receive either combined HRT (oestrogen and progestogen) or placebo.
All women were monitored for an average of 12 months, and in addition to the main clinical outcomes of cardiovascular disease, fractures and breast cancer, a detailed assessment of the impact of HRT on quality of life was recorded.
Quality of life was measured using a modified version of the women's health questionnaire designed to assess physical and emotional components of health such as depressed mood, memory and concentration, sleep problems and sexual functioning, and a symptoms questionnaire.
After one year, the researchers found significant improvements in sexual functioning, sleep problems and vasomotor symptoms (hot flushes and sweats) in the combined HRT group compared to the placebo group.
Significantly fewer women in the HRT group reported hot flushes (9% v 25%), night sweats (14% v 23%), aching joints and muscles (57% v 63%), insomnia (35% v 41%), and vaginal dryness (14% v 19%) than in the placebo group, but more reported breast tenderness (16% v 7%) and vaginal discharge (14% v 5%).
Other menopausal symptoms, depression, and overall quality of life were not significantly different in the two groups.
These results are consistent with the findings of the Women's Health Initiative and support the conclusion that after one year, women who started taking combined HRT many years after the menopause, experienced reduced hot flushes and night sweats, improved sleep, and less bodily pain, say the authors.
These findings may have important benefits for many symptomatic women, claim the authors, but they caution that the health related quality of life benefits must be weighed against the risk of increased cardiac events, venous thromboembolism and breast cancer.
###
Notes to Editors:
*The WISDOM trial was halted early when another trial, the Women's Health Initiative (WHI), which also initiated HRT on average 13 years after menopause, found that elderly women taking HRT had more heart attacks than non-HRT users. This was not seen when HRT was initiated near menopause, which is the common time of use.

Hormone Therapy's Heart Risks May Hang on Cholesterol

By Crystal Phend
PHILADELPHIA, 23 may 2008-- Lipid levels may be enough to help women decide whether hormone replacement therapy is worth the heart risk, researchers said.
Women with an LDL-to-HDL cholesterol ratio less than 2.5 were not at elevated risk of coronary heart disease while using hormone therapy, said Paul F. Bray, M.D., of Thomas Jefferson University here, and colleagues.
Those who had higher ratios were more likely to develop heart disease when they took hormone therapy, the researchers reported in the June 1 issue of the American Journal of Cardiology.
Their analysis of the larger Women's Heath Initiative (WHI) trials may provide a simple tool for clinicians and patients to determine individual risk, they said.
The WHI studies showed no benefit in the primary endpoint of reduction in coronary events with estrogen in women who had a hysterectomy or with estrogen plus progesterone in postmenopausal women. In other studies, hormone therapy actually increased heart attack and stroke risk.
"Despite increasing information and understanding of clinical benefits and risks of hormone therapy, practitioners are still challenged in making management choices for individual postmenopausal women," they said, noting that the Framingham risk prediction model excludes hormone therapy as a factor.
However, lipids aren't the whole story, Dr. Bray's group cautioned. "The decision to use postmenopausal hormones must consider the totality of health risks and benefits, including stroke, thrombosis, and gall bladder disease."
The researchers analyzed biomarker findings from the trials in a nested case-control study of 271 patients with incident coronary heart disease and 707 healthy controls.
Among the findings in the combined trial results, the researchers reported that hormone therapy increased risks of coronary heart disease in association with:
LDL cholesterol levels of 130 mg/dl and above (odds ratio 1.46, 95% confidence interval 1.02 to 2.10) but not lower levels (OR 0.66, 95% CI 0.34 to 1.27, P=0.03 for interaction).
Non-HDL cholesterol at or above 169 mg/dl (OR 1.64, 95% CI 1.11 to 2.42) but not lower levels (OR 0.88, 95% CI 0.53 to 1.47, P=0.04 for interaction).
Total-to-HDL cholesterol ratios at or above 4.182 (OR 1.69, 95% CI 1.15 to 2.49) but not lower ratios (OR 0.76, 95% CI 0.44 to 1.29, P=0.01 for interaction).
LDL-to-HDL cholesterol ratios at or above 2.5 (OR 1.73, 95% CI 1.18 to 2.53) but not lower ratios (OR 0.60, 95% CI 0.34 to 1.06, P=0.002 for interaction).
The results remained the same when women who used lipid-lowering drugs were excluded.
High sensitivity C-reactive protein at or above 2.0 mg/dl was also associated with elevated heart disease risk (OR 1.58, 95% CI 1.05 to 2.39). However, the interaction with hormone therapy use was not significant (P=0.16).
Low C-reactive protein added little to the value of the best predictor, LDL-to-HDL ratio, the researchers said. Women with low baseline LDL-to-HDL cholesterol ratios were not at elevated risk of coronary heart disease events on hormone therapy regardless of C-reactive protein, they added.
"Importantly, we found no clear evidence that either form of hormone therapy posed a risk of coronary heart disease events" for women with favorable baseline cholesterol levels and ratios, Dr. Bray and colleagues said.
Based on animal studies, the link between hormone therapy and lipids may be that the cholesterol metabolite 27-hydroxycholesterol competes with estrogen to block the vascular benefits of estrogen for nitric oxide production and endothelial cell migration, they said.
The researchers cautioned that the subgroup analysis of the WHI study had relatively small numbers of patients without sufficient sample size to stratify by age.
"Women considering the use of postmenopausal hormone therapy should determine their overall cardiac risk and specifically their lipid profile," the investigators concluded.
The Women's Health Initiative program was supported by the National Heart, Lung, and Blood Institute. The researchers provided no information on conflicts of interest.
Primary source: American Journal of CardiologySource reference:Bray PF, et al "Usefulness of baseline lipids and c-reactive protein in women receiving menopausal hormone therapy as predictors of treatment-related coronary events" Am J Cardiol 2008; 101: 1599-1605.

Postmenopausal Hormone Therapy Does Not Enhance Cognition

WEST CHESTER, Pa., Sept. 24 -- Hormone therapy had no significant effects on the cognitive performance of women shortly after menopause, according to investigators here.
Among 180 recently postmenopausal women with memory or concentration complaints, those randomized to hormone therapy for four months had significantly increased sexual desire and thoughts, but no difference in cognition, reported Michael J. Gast, M.D., Ph.D., of Wyeth Pharmaceuticals, and colleagues, in the Sept. 25 issue of Neurology.
The pilot study, called the Cognitive Complaints in Early Menopause Trial (COGENT), was terminated before the final expected enrollment of 275 patients, following the release of findings from the Women's Health Initiative linking hormone replacement to breast cancer, Dr. Gast and colleagues noted.
Even during the short duration, the authors saw evidence of modest but non-significant negative effects on long- and short-term verbal memory among women on hormonal therapy.
On the plus side, women with vasomotors symptoms who took hormones reported a reduction in symptoms and subjective improvement in quality of life, but these measures, too, were not significantly different from placebo.
The decline in enrollment coinciding with the publication of the WHI study effectively sealed the fate of the COGENT study, the authors noted.
"Although this is the largest randomized trial to date of hormonal therapy and cognition in recently menopausal women, the lower than expected participation likely rendered this study underpowered to decisively distinguish between hormonal therapy effects versus placebo (effect size <0.45)," they wrote.
COGENT was a randomized, double-blind, placebo-controlled study of healthy women from the ages of 45 to 55. The women had intact uteruses and were one to three years past their last menstrual period.
All participants had reported one or more cognitive complaints on the Self-Reported Cognitive Function Questionnaire, a brief, subjective survey of memory and concentration. Women with neurologic, systemic, or psychiatric diseases that could influence cognition were excluded.
The women were randomly assigned to conjugated equine estrogen at 0.625 mg/medroxyprogesterone acetate 2.5 mg (Prempro), or placebo, for four months.
Study endpoints included memory, subjective cognition, quality of life, sexuality, and sleep. Change in cognition from baseline was measured using validated instruments, including the California Verbal Learning Test, Memory Function Questionnaire, and Brief Test of Attention.
Of the 180 women who were randomized, 158 completed the study. The authors found that there were no differences between the hormone and placebo groups on any cognitive function or quality-of-life measures, with the exception of a significant increase among women on hormones in sexual interest and thoughts, two of six subscales on the McCoy Female Sexuality Scale Questionnaire. Analysis was by intention to treat.
Women who received hormones had an increase from baseline scores on the level of interest in sex subscale (P<0.05), and this difference was significantly greater at four months compared with placebo (P<0.001).
Women in the hormone therapy group also had higher reported levels of sexual thoughts than those in the placebo group at both one and four months (P<0.05). There were no differences between the treatment groups in the remaining four subscales on the questionnaire, however.
Women in the hormone therapy group also had modest but non-significant decline in short-delay free verbal recall subscores (P=0.054) and long-delay free recall (P=0.066).
"Women with baseline vasomotor symptoms showed a decrease in vasomotor symptoms and an improvement in general quality-of-life, but no cognitive benefit versus placebo," the authors wrote.
They noted that two larger studies looking at the effects of the daily conjugated equine estrogen/medroxyprogesterone acetate therapy on cognitive test performance in older women showed trends toward negative effects on verbal memory (P=0.06, in the Heart and Estrogen/progestin Replacement Study, or HERS) and modest decreases in in three measures of verbal learning and memory on an abbreviated version of the California Verbal Learning Test in the Women's Health Initiative Study of Cognitive Aging.
"Our finding of near-significant, modest negative effects of combined estrogen and progestin therapy on verbal memory contrasts with previous clinical trials using estrogen alone," they wrote, "which reported improvements in verbal memory in small samples of recently menopausal women, and neutral effects in large samples of older postmenopausal women. This raises the possibility that progestins might modulate the effects of estrogen on verbal memory."
The study was funded Wyeth, maker of Prempro. Dr. Gast and two of his four co-authors are current or former employees of the company, and the remaining two co-authors have received grants in excess of $10,000 and honoraria from the company. Primary source: NeurologySource reference: Maki PM et al. "Hormone therapy in menopausal women with cognitive complaints: A randomized, double-blind trial." Neurology 2007; 69: 1322-1330.

For a Low-Dose Hormone, Take Your Pick

By RONI CARYN RABIN
Patches, pumps, pills, low-dose pills and super-low-dose creams and gels: Ever since the landmark Women’s Health Initiative study found that hormone therapy could be harmful, a dizzying array of new low-dose treatment options have been offered to counter the symptoms of menopause.
Some deliver hormones the old-fashion way, by mouth. Others do it through the skin, by patch, cream or gel, or through vaginal rings or suppository tablets. On Aug. 3, the Food and Drug Administration approved yet another treatment, a spray that delivers low-dose estrogen to the skin.
For doctors and patients, the wealth of options can be overwhelming. “There are a trillion products out there,” said Dr. Mary Jane Minkin, professor of obstetrics and gynecology at Yale. “You can take that low dose many different ways, and ultimately it boils down to personal preferences.”
Dr. Minkin said she was not surprised that patients were confused, adding, “So am I.”
The variety reflects the industry’s efforts to win back women with symptoms like hot flashes, night sweats and vaginal dryness who are reluctant to use traditional products because of the Women’s Health Initiative findings, released five years ago.
The large clinical trials found that hormones increased the risk of strokes and potentially life-threatening blood clots, and that combined estrogen and progestin also increased the risk of breast cancer and heart attacks. (Women who have not had hysterectomies must use the combined hormones.)
The current recommendation for troubling menopausal symptoms is to take the lowest hormone dose needed for relief for the shortest possible time. But doctors acknowledge the lack of proof that lower doses are safer. “We assume the lower doses are going to be safer, but we don’t really have any data that has examined that,” said Dr. Michelle P. Warren, founder and medical director of the Center for Menopause, Hormonal Disorders and Women’s Health at Columbia University Medical Center and a consultant for Bradley Pharmaceuticals, the maker of Elestrin.
Many women seeking natural remedies have turned to compounding pharmacies, druggists who promise so-called bioidentical hormones that are chemically synthesized but have the same molecular structure as hormones produced by a woman’s body.
Medical experts and professional organizations point out that just like other hormones, bioidentical hormones are not really found in nature, and that they are available in many commercial hormone products, where they are more likely to be covered by health insurance.
Proponents of bioidenticals suggest that they are safer than other hormones because they mimic a woman’s hormones. Many mainstream medical scientists say there is no conclusive evidence for that. Even a spokesman for the pharmacists’ trade group, the International Academy of Compounding Pharmacists, said it was not clear. “We need more research to see if the risks are different,” said the spokesman, Joshua Wenderoff. “For the time being, we have to assume they’re not.”
Dozens of products on the market offer different dosages and delivery methods. A complete list compiled by the North American Menopause Society is at www.menopause.org/edumaterials/hormoneprimer.htm.
Low doses can be quite effective for symptoms like sweating and hot flashes, though some doctors caution that low doses may take longer than standard ones. A new study of Elestrin, a gel that delivers 0.0125 milligrams a day of the hormone 17-beta-estradiol through the skin, found that it significantly reduced the number and severity of hot flashes compared with a placebo.
Hormone patches have not proved very popular in the United States, but experts suggest that because they bypass the liver they may be safer for women concerned about high triglycerides, heart disease and clots.
Women whose chief complaints are vaginal dryness and irritation may want to consider a vaginal cream or tablet or a vaginal ring, a rubberlike device that releases a steady amount of hormone for several months. Most of these products deliver local relief but not enough hormone to be absorbed in the system.
For women who have had hysterectomies that lead to sudden and severe menopausal symptoms, recent studies showing less heart risk from estrogen to women still in their 50s should be reassuring, said Dr. Jacques Rossouw, chief of the women’s health branch of the National Heart, Lung and Blood Institute. These women can take estrogen alone, which is associated with fewer risks than combination therapy.
Dr. Warren, at Columbia, said anyone taking hormones should be closely monitored by a physician, should have regular breast examinations and mammograms, should be screened regularly for high blood pressure and should be alert for warning signs of a clot.
Even women who plan to stop taking hormones after a few years may be in a quandary. The symptoms often resume when medication stops, said Dr. Wulf Utian, executive director of the North American Menopause Society. “That’s the Catch-22,” he said. “And that’s when the so-called short term therapy becomes long-term therapy.”

Another Caution on Cardiovascular Risks From HRT

ADELAIDE, Australia, July 12 -- Once again, hormone replacement therapy started a decade or more past menopause has been found to increase the risk for cardiovascular and thromboembolic events, with no significant benefits in return.
The 12-month follow-up results of the Women's International Study of Long Duration [O]estrogen After Menopause (WISDOM) trial, reported online in the BMJ, came on the fifth anniversary of the report from the Women's Health Initiative, the clinical trial with similar findings that dashed hopes that HRT could be cardioprotective in postmenopausal women.
"Data from WISDOM suggest that women starting or restarting combined estrogen and progestogen therapy an average of 14 years after menopause are at increased risk of cardiovascular disease and venous thromboembolism, at least in the early years of treatment," wrote Alastair H. MacLennan, M.D., of the University of Adelaide, and colleagues in Britain and New Zealand.
Enrollment in the WISDOM study, originally planned to include 23,000 women, was stopped after fewer than 5,700 had started treatment, following publication of the initial WHI results. Similarly, the two studies in WHI trial were also halted early because of an excess number of thromboembolic events, and no evidence of a protective cardiovascular benefit.
Although the investigators found that compared with placebo, combined HRT significantly increased the risk of major cardiovascular events or venous thromboembolism, the trial did not answer the question of whether use of HRT for control of severe hot flashes and night sweats in early menopause has any long term benefits or detriments.
In an accompanying BMJ editorial, Helen Roberts, M.D., M.P.H., of the University of Auckland, in New Zealand, pointed out that "postmenopausal hormone therapy has come full circle." Originally used to treat menopausal symptoms, then becoming an agent to a prevent late coronary risks, HRT has gone back to its original purposes of hot flashes, night sweats, and vaginal dryness. "It is the best treatment we have at present for these symptoms."
Dr. Roberts noted that hot flashes and night sweats are mostly self limiting, and cited current recommendations that women use the lowest dose needed for relief for the shortest possible time.
"Healthy women in early menopause are at a low absolute risk whether they take hormones or not, and they are unlikely to face substantially increased risks when using hormones for a few years," she wrote.
That sentiment was echoed by JoAnn Manson, M.D., Dr.P.H., of Boston's Brigham and Women's Hospital and Harvard, who was on the steering committee of the WHI, at a briefing to mark the WHI anniversary.
"When you combine the findings from the estrogen-plus-progestin trial and the estrogen-alone trial, there's a suggestion of a lower risk of heart disease in the women who were less than 10 years since onset of menopause," she said, "whereas there's an increased risk of heart disease for women who were more than 20 years past menopause, and a suggestion of a trend across time since menopause."
Dr. Manson and colleagues reported in the June 21 issue of the New England Journal of Medicine that estrogen reduced coronary calcium in women younger than 60 who took the hormone following a hysterectomy. (See Estrogen May Reduce Coronary Calcium in Women Younger than 60)
But they also said that the findings should not be construed as evidence that estrogen should be routinely used to reduce the risk of heart disease in older women.
At the WHI-anniversary briefing, Nieca Goldberg, M.D., of New York University's Women's Heart Program, agreed that "hormone therapy should never be given to a woman who has cardiovascular disease." Yet she noted that this represents a clinical problem for young women who have had heart attacks who are going through menopause because "there is nothing that we can prescribe that's as effective as hormone therapy" for their symptoms."
Before trial enrollment was halted, the WISDOM investigators enrolled 5,692 healthy women in the United Kingdom, Australia, and New Zealand. The mean t age was 63, and the mean time from menopause was 15 years.
Women with intact uteruses were randomly assigned to placebo or combined HRT with conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg orally daily (Prempro). Women who had had hysterctomies were assigned to estrogen alone, combined therapy, or placebo. The mean follow-up was 11.9 months.
The primary endpoints were major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes were other cancers, death from all causes, venous thromboembolism, cerebrovascular disease, dementia, and quality of life.
The authors found in a comparison of combined HRT (2,196 patients) and placebo (2,189 patients) that there was a significant increase in major cardiovascular events among patients on the active drugs. There were seven events among patients on combined HRT, compared with none for patients on placebo (P=0.016). In addition, there were 22 cases of venous thromboembolism among patients on the combined therapies, compared with three among patients on placebo (hazard ratio 7.36, 95% confidence interval. 2.20 to 24.60).
There were no statistically significant differences in either numbers of breast or other cancers (22 for HRT versus 25 for placebo, hazard ratio 0.88, 95% CI, 0.49 to 1.56), cerebrovascular events (14 versus 19 respectively, HR 0.73, 95% CI, 0.37 to 1.46), fractures (40 versus 58, HR 0.69, 95% CI. 0.46 to 1.03), or overall deaths (eight versus five, HR, 1.60 (0.52 to 4.89).
There were also no significant differences in outcomes among patients on combined HRT compared with estrogen alone.
The WISDOM study was supported by multiple government and non-profit agencies in the United Kingdom, Australia, and New Zealand. All of the co-authors declared that they have no direct conflicts of interest.Additional source: BMJSource reference: Vickers MR et al. "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." BMJ 2007; DOI:10.1136/bmj.39266.425069.AD. Additional source: BMJSource reference: Roberts H. "Hormone replacement therapy comes full circle." BMJ 2007; DOI: 10.1136/bmj.39266.425069.AD

Breast Cancer Incidence Stayed Low After HRT Decline

HOUSTON, April 18 -- Evidence linking a decrease in the annual incidence of breast cancer to a decline in hormone replacement therapy is as robust as first reported, investigators here said. As Peter Ravdin, M.D., Ph.D., of the University of Texas M.D. Anderson Cancer Center, and colleagues reported at the San Antonio Breast Cancer Symposium last December, the incidence fell 7% from 2002 to 2003, reversing a 20-year trend.
That reversal followed closely on the heels of publication of the Women's Health Initiative results, which showed that five years of hormone replacement therapy (HRT) in postmenopausal women increased breast cancer risk by 24%, and a subsequent plunge in HRT prescriptions.
And now, in an extended analysis of their previous study, Dr. Ravdin, and colleagues, showed that the breast cancer incidence was unchanged from 2003 to 2004, indicating that the decline they had previously seen was not a statistical fluke, they reported in the April 19 issue of the New England Journal of Medicine.
"This kind of study can't prove causality, but the data present a very compelling link between hormone replacement therapy and breast cancer," said co-author Donald Berry, Ph.D., also of M.D. Anderson.
In their earlier report, Dr. Ravdin and colleagues used data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, which collects information on 9% of the U.S. population, to study breast cancer rates.
Using the SEER data, they found that the total decrease from 2002