However, the findings are still preliminary and have yet to be submitted for peer review before publication in a journal.
The researchers presented the early results of their HRT study at the North American Menopause Society's Annual Meeting, which is taking place in Orlando, Florida from 3 to 6 October.
The study was designed and funded by the Kronos Longevity Research Institute to answer questions raised by the Women's Health Initiative (WHI), and is called KEEPS (short for Kronos Early Estrogen Prevention Study).
Landmark HRT Study of Ten Years Ago Coming Into QuestionTen years ago, the publication of the results of a large landmark study of HRT, the Women's Health Initiative (WHI) in the US, closely followed by the Million Women Study (MWS) in the UK a year later, led to doctors and women doubting the long term safety of HRT, and a dramatic fall in its use around the world.
The WHI results appeared to suggest that giving women HRT did not benefit the heart, and if anything, put them at higher risk for breast cancer, strokes, high blood pressure and blood clots.
But, the presentation and interpretation of the WHI results have since come under much criticism.
For example, there is a view that media and health professionals don't understand enough about "relative risk", "absolute risk" and "attributable risk". This leads to the perception for example, that a doubling of risk is a huge effect, when in fact it could be just doubling of what is a very tiny risk in the first place (for example from one in a million to two in a million).
Failure to Keep Women InformedOther points have also been raised. For instance, earlier this year, the International Menopause Society (IMS) suggested the NIH has been guilty of unbalanced reporting in failing to inform women about the latest information on the WHI findings. They say the NIH was very vocal when the results first came out apparently highlighting the harms of HRT, but has failed to tell women that the WHI has continued to re-evaluate results, and some of the interpretations have changed.
For example, in 2002, the initial WHI results failed to point out that women who started HRT before the age of 60 or right at the start of the menopause had very little risk compared to women who started HRT later in life. This is considered an important oversight because many women who start HRT do so before the age of 60.
Another criticism is that the WHI also failed to emphasize the later findings that estrogen-alone therapy, as given to women who have had a hysterectomy, actually decreases the risk of breast cancer.
KEEPS Early FindingsAgainst such a backdrop, there has been considerable anticipation to seeing early results from KEEPS. However, it is important to note, these are only initial findings, and they have yet to be published in a peer-reviewed journal.
The Orlando meeting heard about some overall results of KEEPS, which were presented by its overall director, S Mitchell Harman, and JoAnn Manson (NAMS President and principal investigator of the Boston center for KEEPS).
KEEPS is a four-year, randomized, double-blinded, placebo-controlled clinical trial that enrolled 727 women aged from 42 to 58, who were in the first three years since menopause onset.
The women were given either a low-dose daily estrogen pill (0.45 mg of Premarin, a horse estrogen: this is much lower than the 0.625 mg that the women in the WHI trial took), a skin patch (containing estradiol, which comes from plants but is closer to the estrogen made in the body), or a placebo.
The women on estrogen were also given a natual progesterone (the WHI participants were given a synthetic form).
As expected, both types of estrogen relieved symptoms of menopause, such as hot flashes and night sweats, and they also benefited bone mineral density, compared with placebo.
The results also showed that neither type of estrogen was linked to any changes in blood pressure, coronary calcium (specks of calcium on the walls of the heart artery), or atherosclerosis (thickening of the artery wall), all key measures of cardiovascular risk. The measures are taken from ultrasound readings of the carotid artery.
Contrasts with WHI ResultsThe WHI had found possible negative effects on cardiovascular events: but had also hinted that the timing of therapy could make a difference.
However, in general, the women in the WHI trial had started HRT much later (average age 63) than is usual in HRT trials. In KEEPS, the mean age was 52 and all the women started HRT much earlier, within three years of starting menopause symptoms. And they had no evidence of cardiovascular disease.
In KEEPS, using HRT did not appear to increase blood pressure: in WHI it did.
In KEEPS, oral estrogen also appeared to have favorable effects on HDL (the so-called "good" cholesterol), and LDL ("bad" cholesterol) levels, although it did appear to increase triglycerides and CRP (a marker of inflammation).
Skin-patch estrogen had no effect on bimarkers but did appear to improve glucose levels and insulin sensitivity.
The KEEPS results also showed HRT had no significant impact on rates of breast cancer, endometrial cancer, heart attacks, stroke, mini-strokes (TIAs, transient ischemic attacks), or blood clots (VTEs, venous thromboembolisms). However, the presenters pointed out the study was too small to make definite conclusions about these outcomes.
Smaller Estrogen Doses Appeared to Improve Mood Without Memory LossThe meeting members also heard about an ancillary study called KEEPS-Cog, short for the KEEPS Cognitive Function and Mood/Affective Outcomes Ancillary Study. These results were presented by the study's pricinpal investigator, Sanjay Asthana, who is a professor of geriatric medicine at the University of Wisconsin School of Medicine and Public Health.
KEEPS-Cog was a four-year study of 662 women (average age 52.7 years) from the 727 women in the overall KEEPS cohort who underwent memory and cognition tests and assessments of their emotional health.
Asthana says in a press statement:
"At the four-year point, the women using the oral estrogen or estrogen patch showed no evidence of adverse effects on memory compared to the placebo group."
"There were also reduced symptoms of depression, anxiety and tension among women taking the oral estrogen," he adds.
Asthana says these findings are important because their study is the first to look at a much youngr group of women.
"This will help physicians understand whether or not it is safe for women to begin treatment for managing their menopausal symptoms," he suggests.
ImplicationsIn a statement to the press, the North American Menopause Society (NAMS) says:
"These findings from KEEPS and the KEEPS Cognitive Study should reassure women who are recently menopausal about using hormone therapy for short-term treatment of menopausal symptoms."
They say the results also highlight the importance of making decisions about HRT on an individual basis, since "oral and transdermal estrogens have different effects and different women have different symptoms, risk factors, and goals for their therapy".
The Kronos Longevity Research Institute calls for more studies of newly menopausal women to better define specific differences in hormone treatment, such as routes of delivery, doses and formulation. They also think cardiovascular studies should also look at coronary soft plaque and even estimates of plaque quality in relation to HRT.
Written by Catharine Paddock PhD