HRT and the Heart
One of the benefits of HRT in the menopause is the reduction in strokes and heart attacks. Over 1/2 of all women over 50 will die from a heart attack, so this benefit of HRT is very significant, and often overlooked when discussing whether to take HRT or not.
New evidence for cardiac benefit of postmenopausal hormone therapy.
Author information
- 1
- a Obstetrics and Gynecology , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.
Abstract
Coronary artery disease (CAD) is still the most common killer of western women. Coronary arteries, expressing estrogen receptors, are a target for estrogen action. Prior to the Women’s Health Initiative (WHI) study, postmenopausal hormone therapy (HT) was widely advocated for primary prevention of CAD, but such use was criticized after the WHI publication. However, new data accumulated in the USA and in Europe indicate that the use of estradiol-based HT regimens does not endanger the heart, but rather, it significantly reduces the incidence of CAD events and mortality. This effect may be related to the presence of hot flushes before HT initiation, because they may indicate a greater responsiveness of the cardiovascular system to HT. To get maximal cardioprotective efficacy of HT, a woman should initiate HT as soon as symptoms occur, and preferably within the first 10 postmenopausal years. Recent guidelines for optimal use of HT recommend pauses of HT at 1-2-year intervals to see whether hot flushes and other symptoms still persist. However, new data question the safety of this policy, because acute withdrawals of estradiol from the circulation may predispose to potentially fatal CAD events. All these data support modernized guidelines for optimal HT use.
Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality.
Author information
- 11Department of Obstetrics and Gynecology, Helsinki University, Helsinki University Hospital, Helsinki, Finland 2Folkhälsan Research Center, Helsinki, Finland 3EPID Research Oy, Espoo, Finland 4National Institute for Health and Welfare, Helsinki, Finland 5Nordic School of Public Health, Gothenburg, Sweden.
Abstract
OBJECTIVE:
Data on the health benefits and risks of postmenopausal hormone therapy (HT) are derived mainly from the use of conjugated equine estrogens. Estradiol-based regimens may have a different risk-benefit profile. We evaluated the risk of death caused by coronary heart disease (CHD), stroke, or any disease among users of estradiol-based HT regimens in a nationwide study in Finland.
METHODS:
A total of 489,105 women who used HT from 1994 to 2009 (3.3 million HT exposure years), as indicated in the nationwide reimbursement register and the national Cause of Death Register, were followed. A total of 28,734 HT users died during follow-up; among the deaths, 3,843 were caused by CHD and 2,464 were caused by stroke. Mortality risk in HT users with varying duration of exposure (≤1 y, >1 to 3 y, >3 to 5 y, >5 to 10 y, or >10 y) was compared with that in an age-matched background population.
RESULTS:
Risk of CHD death was significantly reduced by 18% to 54% in HT users and was positively related to HT exposure time. Risk of stroke death was also reduced by 18% to 39%, but this reduction was not clearly related to HT exposure time. Risk of all-cause mortality was reduced in HT users by 12% to 38%, almost in linear relationship with duration of exposure. All these risk reductions were comparable in women initiating HT before age 60 years and women initiating HT at age 60 years or older.
CONCLUSIONS:
In absolute terms, the risk reductions mean 19 fewer CHD deaths and 7 fewer stroke deaths per 1,000 women using any HT for at least 10 years.
Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality.
Author information
- 11Department of Obstetrics and Gynecology, Helsinki University, Helsinki University Hospital, Helsinki, Finland 2Folkhälsan Research Center, Helsinki, Finland 3EPID Research Oy, Espoo, Finland 4National Institute for Health and Welfare, Helsinki, Finland 5Nordic School of Public Health, Gothenburg, Sweden.
Abstract
OBJECTIVE:
Data on the health benefits and risks of postmenopausal hormone therapy (HT) are derived mainly from the use of conjugated equine estrogens. Estradiol-based regimens may have a different risk-benefit profile. We evaluated the risk of death caused by coronary heart disease (CHD), stroke, or any disease among users of estradiol-based HT regimens in a nationwide study in Finland.
METHODS:
A total of 489,105 women who used HT from 1994 to 2009 (3.3 million HT exposure years), as indicated in the nationwide reimbursement register and the national Cause of Death Register, were followed. A total of 28,734 HT users died during follow-up; among the deaths, 3,843 were caused by CHD and 2,464 were caused by stroke. Mortality risk in HT users with varying duration of exposure (≤1 y, >1 to 3 y, >3 to 5 y, >5 to 10 y, or >10 y) was compared with that in an age-matched background population.
RESULTS:
Risk of CHD death was significantly reduced by 18% to 54% in HT users and was positively related to HT exposure time. Risk of stroke death was also reduced by 18% to 39%, but this reduction was not clearly related to HT exposure time. Risk of all-cause mortality was reduced in HT users by 12% to 38%, almost in linear relationship with duration of exposure. All these risk reductions were comparable in women initiating HT before age 60 years and women initiating HT at age 60 years or older.
CONCLUSIONS:
In absolute terms, the risk reductions mean 19 fewer CHD deaths and 7 fewer stroke deaths per 1,000 women using any HT for at least 10 years.
HRT does reduce the number of heart attacks
There are about 30 years of evidence from many observational trials that estrogens reduce the incidence of coronary heart disease. This has subsequently been questioned by the 2002 WHI Study, which showed an increase in heart attacks. However, this study looked at patients of the wrong age and who were using the wrong dose of estrogen and progestogen. Subsequent reports from the same investigators have shown a very much reduced incidence of heart attacks in women who start HRT below the age of 60. This is particularly apparent in women who have had a hysterectomy and can have estrogens without progestogen. The view now is that HRT, particularly estrogen alone, is very safe and is associated with a reduced number of heart attacks if started below the age of 60. Thus there is primary prevention of coronary heart disease, but there is no evidence of protection in women with established coronary damage.
It would appear that the factor that is associated with the apparent increase in severe side-effects such as breast cancer and heart attacks and possibly stroke is the progestogen component of HRT. As progestogen also produces unwanted PMS-type side-effects of depression, anxiety, bloating and loss of libido in patients who are progestogen intolerant, it is sensible to keep the dose of oral gestogen to a minimum. The alternative is to insert a Mirena intrauterine system, which produces amenorrhoea and avoids the use of oral progestogen with its side-effects for five years or more.
– Prof John Studd.
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Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial
BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e6409(Published 9 October 2012)
- Louise Lind Schierbeck, registrar1,
- Lars Rejnmark, associate professor, consultant2,
- Charlotte Landbo Tofteng, staff specialist 11,
- Lis Stilgren, consultant3,
- Pia Eiken, consultant, senior endocrinologist4,
- Leif Mosekilde, professor, senior consultant2,
- Lars Køber, professor, consultant5,
- Jens-Erik Beck Jensen, associate professor, consultant1
Abstract
Objective To investigate the long term effect of hormone replacement therapy on cardiovascular outcomes in recently postmenopausal women.
Design Open label, randomised controlled trial.
Setting Denmark, 1990-93.
Participants 1006 healthy women aged 45-58 who were recently postmenopausal or had perimenopausal symptoms in combination with recorded postmenopausal serum follicle stimulating hormone values. 502 women were randomly allocated to receive hormone replacement therapy and 504 to receive no treatment (control). Women who had undergone hysterectomy were included if they were aged 45-52 and had recorded values for postmenopausal serum follicle stimulating hormone.
Interventions In the treatment group, women with an intact uterus were treated with triphasic estradiol and norethisterone acetate and women who had undergone hysterectomy received 2 mg estradiol a day. Intervention was stopped after about 11 years owing to adverse reports from other trials, but participants were followed for death, cardiovascular disease, and cancer for up to 16 years. Sensitivity analyses were carried out on women who took more than 80% of the prescribed treatment for five years.
Main outcome measure The primary endpoint was a composite of death, admission to hospital for heart failure, and myocardial infarction.
Results At inclusion the women on average were aged 50 and had been postmenopausal for seven months. After 10 years of intervention, 16 women in the treatment group experienced the primary composite endpoint compared with 33 in the control group (hazard ratio 0.48, 95% confidence interval 0.26 to 0.87; P=0.015) and 15 died compared with 26 (0.57, 0.30 to 1.08; P=0.084). The reduction in cardiovascular events was not associated with an increase in any cancer (36 in treated group v 39 in control group, 0.92, 0.58 to 1.45; P=0.71) or in breast cancer (10 in treated group v 17 in control group, 0.58, 0.27 to 1.27; P=0.17). The hazard ratio for deep vein thrombosis (2 in treated group v 1 in control group) was 2.01 (0.18 to 22.16) and for stroke (11 in treated group v 14 in control group) was 0.77 (0.35 to 1.70). After 16 years the reduction in the primary composite outcome was still present and not associated with an increase in any cancer.
Conclusions After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke.
What’s new in hormone replacement therapy: focus on transdermal estradiol and micronized progesterone.
Source
Department of Obstetrics and Gynecology, George Washington University, Washington, DC 20036, USA.
Abstract
The original conclusions of the Women’s Health Initiative study have been questioned as a result of the availability of age-stratified data. Initial concerns regarding the risk of coronary heart disease (CHD) in association with the use of hormone replacement therapy (HRT) have been replaced with concerns regarding thromboembolic disease, encompassing venous thromboembolism (VTE), particularly in younger postmenopausal women, and stroke, particularly in older women. The original publication of the study results led to a dramatic decrease in the use of oral HRT; however, the use of transdermal HRT has increased over recent years. Guidelines from the North American Menopause Society, the Endocrine Society, the International Menopause Society, and specific guidelines from the European Menopause and Andropause Society for the management of menopausal women with a personal or family history of VTE all contain positive statements regarding both transdermal estradiol and micronized progesterone. Unlike oral estrogens, transdermal estradiol has been shown not to increase the risk of VTE, or stroke (doses ≤ 50 μg), and to confer a significantly lower risk for gallbladder disease. Unlike some progestogens, progesterone is also not associated with an increased risk of VTE, or with an increased risk of breast cancer. Based on these data, which are now included in the guidelines, the use of transdermal estradiol and micronized progesterone could reduce or possibly even negate the excess risk of VTE, stroke, cholecystitis, and possibly even breast cancer associated with oral HRT use.
- PMID:
- 22432810
- [PubMed – in process]
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Climacteric. 2012 Apr;15 Suppl 1:11-7.
Postmenopausal hormone replacement therapy and cardiovascular disease: the value of transdermal estradiol and micronized progesterone.
Source
Department of Endocrinology and Menopause, Center of Women’s Health, University Women’s Hospital, Tuebingen, Germany.
Abstract
Most available postmenopausal hormone replacement therapies (HRT) offer similar efficacy, but differ with respect to the cardiovascular risks associated with their use. There is a wealth of evidence to suggest that, unlike oral estrogens, transdermal estradiol does not increase the risk of venous thromboembolism, probably due to its lack of effect on the coagulation cascade, including thrombin generation and resistance to activated protein C, and does not increase the risk of stroke. It is cardioprotective, significantly reducing the incidence of myocardial infarction compared with non-users; it significantly reduces the incidence of new-onset diabetes, a risk factor for myocardial infarction. Micronized progesterone has also been shown not to increase the risk of venous thromboembolism and further reduced the incidence of new-onset diabetes when combined with transdermal estrogen. Micronized progesterone has a neutral effect on the vasculature, including a neutral or beneficial effect on blood pressure. Therefore, experimental and clinical data indicate that transdermal estradiol and micronized progesterone could represent the optimal HRT, particularly in women at risk of adverse events.
- PMID:
- 22432811
- [PubMed – in process]
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Estrogen May Prevent Younger Menopausal Women from Strokes, Study Suggests
ScienceDaily (Oct. 12, 2011) — Estrogen may prevent strokes in premature or early menopausal women, Mayo Clinic researchers say. Their findings challenge the conventional wisdom that estrogen is a risk factor for stroke at all ages.The study was published in the journal Menopause.
Researchers combined the results from a recent Mayo Clinic study with six other studies from across the world and found that estrogen is protective for stroke before age 50. That is roughly the average age when women go through menopause.
“We were very surprised because these results were unexpected,” says study author Walter Rocca, M.D., an epidemiologist and neurologist at Mayo Clinic. “The old idea that estrogen is always a problem in the brain has to be corrected.” Estrogen can be a problem in older women, he explains, but in younger women, estrogen may be important to protect the brain from strokes.
The study has implications for women who experience premature (before age 40) or early menopause (before age 45) from natural causes or from ovary removal. Women in these groups should consider taking estrogen up to approximately age 50 to prevent stroke, Dr. Rocca says.
Ischemic stroke occurs as a result of an obstruction within a blood vessel supplying blood to the brain. According to the American Stroke Association, these types of strokes account for 87 percent of all stroke cases.
Co-authors of the study include: Brandon Grossardt, M.S.; Virginia Miller, Ph.D.; Lynne Shuster, M.D.; Robert Brown, Jr., M.D.
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From the International Menopause Society Update:
Cardiovascular disease
Cardiovascular disease is the principal cause of morbidity and mortality in postmenopausal women. Major primary prevention measures (besides smoking cessation and diet control) are weight loss, blood pressure reduction, regular exercise and diabetes and lipid control. HRT has the potential for improving the cardiovascular risk profile through its beneficial effects on vascular function, cholesterol levels, glucose metabolism and blood pressure.
There is evidence that estrogen therapy may be cardioprotective if started around the time of menopause and continued long term (often referred to as the ‘window of opportunity’ concept). HRT reduces the risk of diabetes and, through improving insulin action in women with insulin resistance, it has positive effects on other related risk factors for cardiovascular disease such as the lipid profile and metabolic syndrome.
In women less than 60 years old, recently menopausal and without evidence of cardiovascular disease, the initiation of HRT does not cause early harm and may reduce morbidity and mortality from coronary heart disease. Continuation of HRT beyond the age of 60 years should be decided as a part of the overall risk–benefit analysis.
CLIMACTERIC 2011;14:302–320. Updated IMS recommendations on postmenopausal hormone therapy
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Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration
Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration
Menopause, 05/24/2016
The point of the study was to evaluate the risk of venous thromboembolism (VTE) associated with systemic hormone therapy as indicated by sort and route of administration and the risk of VTE associated with locally administered estrogen. The risk of VTE risk is higher in users of systemic combined estrogen–progestogen treatment than in users of estrogen only. Besides, the risk of VTE was lower for women who utilized local estrogen than among those using oral estrogen only. Transdermal estrogen just treatment and estrogen for local impact appear not to be identified with an increased risk of VTE.
Methods
- In this case-control study, conducted in Sweden between 2003 and 2009, they included 838 cases of VTE and 891 controls with a mean age of 55 years.
- Controls were matched by age to the cases and randomly selected from the population.
- The authors used logistic regression to calculate odds ratios (ORs) with 95% CIs and adjusted for smoking, body mass index, and immobilization.
Results
- Current use of any hormone therapy was associated with an increased risk of VTE (OR 1.72, 95% CI 1.34-2.20).
- For estrogen in combination with progestogen the OR was 2.85 (95% CI 2.08-3.90), and for estrogen only the OR was 1.31 (95% CI 0.78-2.21).
- In orally administered estrogen combined with progestogen, the OR was slightly, but not significantly, higher among users of medroxyprogesterone acetate (OR 2.94, 95% CI 1.67-5.36) than among norethisterone acetate users (OR 2.55, 95% CI 1.50-3.40).
- Transdermal estrogen combined with progestogen was not associated with VTE risk (crude and imprecise ORs ranging from 0.87 to 1.16).
- For local effect of estrogen, there was no association with VTE risk (OR 0.69, 95% CI 0.43-1.10
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Dr Colin Holloway 
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