The History of Hormone Replacement Therapy
In 1942, the first drug containing estrogen was marketed and sold as Premarin (pregnant mare's urine). It was not until 1975 that the first study linking Premarin use and a 4.5 times increased incidence of endometrial carcinoma was published. In 1983, a study revealed that this risk was negated by adding progestin to the regimen. The first study linking a doubling of breast cancer and Premarin was published in the New England Journal of Medicine (NEJM) in 1976. More bad news loomed on the horizon for Premarin in the 1980's with the publication of the Framingham Heart Study, which showed a 50% increased risk of cardiac morbidity and a more than two fold risk for cardiovascular disease.
This news was countered by the Nurses' Health Study which cited lower rates of heart disease in 121,964 post-menopausal women than those not using Bio-HRT. By 1989, NEJM reported a 4.4 times increase in relative risk for women taking estrogen-progestin and development of breast cancer. The risk appeared further increased by the addition of progestin. The National Institutes of Health (NIH) launched the first double blind randomized controlled study on Premarin in 1991. One arm of the study looked at the effects of Premarin and Provera on women with intact uteruses and the other arm looked at the effects of only Premarin on women that did not have a uterus. Both studies were terminated early due to their increased associated risks of heart disease (additional 7 in 10,000 women) and stroke (additional 8 in 10,000 women). Due to study design issues, the fact that symptomatic women were excluded and the relative older age of patients (average 62.3 years), a lot of doubt has been shed on their conclusions.
The Premarin-Provera study revealed that patients had an increased relative risk (1.26 times) of breast cancer (additional 8 in 10,000 women) and the Premarin only group revealed a decreased relative risk (.55 times). These findings suggest that the previously recognized relationship to progestin and breast cancer may be more of a problem than estrogen alone. The reduced risks of colon cancer and osteoporosis associated with hormone use are well established in multiple studies. The Premarin- only arm showed a decrease in coronary heart disease in the younger age group women (50-59 times), the hazard ratio (HR) being .59. The media has been relatively silent on these findings.
Years of observational studies that found a beneficial effect on women using HRT now appear supported. However, this is if HRT is used in women before the onset of Coronary Artery Disease (CAD), thus in early, not late, menopause. Researchers are now concluding that once CAD has been established, HRT has no beneficial effect and may be harmful. The arm of the Women's Health Initiative study that looked at dementia was comprised on women of average age of 71 years; an age after vascular damage has already started. As recently published in Family Practice News, Feb. 1, 2004; 69, the crux of observational data confirms that HRT during a critical period (early menopause) is protective against dementia.
Additional data is now being published in support of the use of HRT in women in early menopause (typically age 50-55). The Journal of the American Medical Association (JAMA), 2004; 291:3005-07 made these claims and indicated that the neuroprotective effects may protect against illness that could develop twenty years later. In 1995, the Nurses' Health Study reported a 32% increase of breast cancer with the use of estrogen and a 41% increase with progestin. In 1998, the first large multi-centered, randomized and controlled study, the Heart and Estrogen/Progestin Replacement Study (HERS) found an increased risk of coronary heart disease incidents of 52% during the first year of therapy in women with known coronary heart disease. Studies on the patented 17-Beta estradiol, chemically more similar to women's natural hormones than Premarin (Premarin is native to a horse, not human), have not shown the deleterious effects of HRT found with the equine preparations such as Premarin.
It appears that the research currently does not support the use of HRT for the purpose of prevention of stroke or dementia if initiated in women over the age of 65, but probably has beneficial effects in the younger population. Women more at risk for colon cancer or osteoporosis, may elect to start HRT at any age if the risk benefit ratio appears best for them. The negative findings of HRT research have been based on the use of oral synthetic preparations and not Bio-HRT. It is very conceivable that the different metabolism involved with Bio-HRT does not stimulate the same coagulation complications as set in action with metabolizing the synthetic hormone preparations.
While science has not provided all of the answers, men and women must make informed choices about hormone replacement and know that there are uncertainties with the recommendations for or against HRT. Nova is not making any statements about the linking between current research on Premarin or 17- Beta Estradiol and the inferences of risk and benefit to patients utilizing Bio-HRT.
In 1942, the first drug containing estrogen was marketed and sold as Premarin (pregnant mare's urine). It was not until 1975 that the first study linking Premarin use and a 4.5 times increased incidence of endometrial carcinoma was published. In 1983, a study revealed that this risk was negated by adding progestin to the regimen. The first study linking a doubling of breast cancer and Premarin was published in the New England Journal of Medicine (NEJM) in 1976. More bad news loomed on the horizon for Premarin in the 1980's with the publication of the Framingham Heart Study, which showed a 50% increased risk of cardiac morbidity and a more than two fold risk for cardiovascular disease.
This news was countered by the Nurses' Health Study which cited lower rates of heart disease in 121,964 post-menopausal women than those not using Bio-HRT. By 1989, NEJM reported a 4.4 times increase in relative risk for women taking estrogen-progestin and development of breast cancer. The risk appeared further increased by the addition of progestin. The National Institutes of Health (NIH) launched the first double blind randomized controlled study on Premarin in 1991. One arm of the study looked at the effects of Premarin and Provera on women with intact uteruses and the other arm looked at the effects of only Premarin on women that did not have a uterus. Both studies were terminated early due to their increased associated risks of heart disease (additional 7 in 10,000 women) and stroke (additional 8 in 10,000 women). Due to study design issues, the fact that symptomatic women were excluded and the relative older age of patients (average 62.3 years), a lot of doubt has been shed on their conclusions.
The Premarin-Provera study revealed that patients had an increased relative risk (1.26 times) of breast cancer (additional 8 in 10,000 women) and the Premarin only group revealed a decreased relative risk (.55 times). These findings suggest that the previously recognized relationship to progestin and breast cancer may be more of a problem than estrogen alone. The reduced risks of colon cancer and osteoporosis associated with hormone use are well established in multiple studies. The Premarin- only arm showed a decrease in coronary heart disease in the younger age group women (50-59 times), the hazard ratio (HR) being .59. The media has been relatively silent on these findings.
Years of observational studies that found a beneficial effect on women using HRT now appear supported. However, this is if HRT is used in women before the onset of Coronary Artery Disease (CAD), thus in early, not late, menopause. Researchers are now concluding that once CAD has been established, HRT has no beneficial effect and may be harmful. The arm of the Women's Health Initiative study that looked at dementia was comprised on women of average age of 71 years; an age after vascular damage has already started. As recently published in Family Practice News, Feb. 1, 2004; 69, the crux of observational data confirms that HRT during a critical period (early menopause) is protective against dementia.
Additional data is now being published in support of the use of HRT in women in early menopause (typically age 50-55). The Journal of the American Medical Association (JAMA), 2004; 291:3005-07 made these claims and indicated that the neuroprotective effects may protect against illness that could develop twenty years later. In 1995, the Nurses' Health Study reported a 32% increase of breast cancer with the use of estrogen and a 41% increase with progestin. In 1998, the first large multi-centered, randomized and controlled study, the Heart and Estrogen/Progestin Replacement Study (HERS) found an increased risk of coronary heart disease incidents of 52% during the first year of therapy in women with known coronary heart disease. Studies on the patented 17-Beta estradiol, chemically more similar to women's natural hormones than Premarin (Premarin is native to a horse, not human), have not shown the deleterious effects of HRT found with the equine preparations such as Premarin.
It appears that the research currently does not support the use of HRT for the purpose of prevention of stroke or dementia if initiated in women over the age of 65, but probably has beneficial effects in the younger population. Women more at risk for colon cancer or osteoporosis, may elect to start HRT at any age if the risk benefit ratio appears best for them. The negative findings of HRT research have been based on the use of oral synthetic preparations and not Bio-HRT. It is very conceivable that the different metabolism involved with Bio-HRT does not stimulate the same coagulation complications as set in action with metabolizing the synthetic hormone preparations.
While science has not provided all of the answers, men and women must make informed choices about hormone replacement and know that there are uncertainties with the recommendations for or against HRT. Nova is not making any statements about the linking between current research on Premarin or 17- Beta Estradiol and the inferences of risk and benefit to patients utilizing Bio-HRT.
Links:
Women's Health Initiative
Journal of the American Medical Association
New England Journal of Medicine
Customized Programs and Services:
Women's Health Initiative
Journal of the American Medical Association
New England Journal of Medicine
Customized Programs and Services: