A new US study suggests that the risk of heart disease for postmenopausal women taking hormone therapy could go up the longer she leaves it after starting menopause.
However, the researchers and other experts point out that this was not statistically significant and that all women considering hormone therapy should discuss the risks and benefits with their doctors in the light of their individual health status.
The study is published in the Journal of the American Medical Association (JAMA).
The researchers performed a secondary analysis on the data from two trials in the Women’s Health Initiative (WHI), a major 15-year programme to establish the most common causes of death, disability and poor quality of life in postmenopausal women: cardiovascular disease, cancer, and osteoporosis.
For this study, the researchers used WHI data from randomized controlled trials of hormone therapy on postmenopausal women aged 50 to 79 years recruited from 40 US clinical centers between September 1993 and October 1998.
The trials were designed to look at the effects of postmenopausal hormone therapy, diet changes, and calcium and vitamin D supplements on cardiovascular disease, fractures, and breast and colorectal cancer.
There were two trials: an estrogen-alone study of women without a uterus and an estrogen-plus-progestin study of women with a uterus. In the second trial, women with a uterus were given progestin with estrogen because this is what is normally done in practice to prevent endometrial cancer.
The first trial involved 10,739 postmenopausal women who had had a hysterectomy and were were randomized to receive estrogen-alone hormone therapy in the form of conjugated equine estrogens (CEE) or placebo.
The second trial involved 16,608 postmenopausal women who had not had a hysterectomy and were randomized to estrogen-plus-progestin (CEE plus medroxyprogesterone acetate: CEE + MPA) or placebo.
The objective of the secondary analysis was to “explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began”.
The researchers used statistical tests to examine how the relationship between hormone therapy and the risk of coronary heart disease (CHD) and stroke varied with age and the time delay between onset of menopause and start of hormone therapy.
The WHI website summarizes the findings as follows.
When compared with a placebo, estrogen plus progestin was linked to increased risk of heart attack, stroke, blood clots, and breast cancer. The combination was also linked to reduced risk of colorectal cancer and fewer bone fractures. There was no evidence of protection against mild cognitive impairment and increased dementia risk in the over 65 age group.
When compared with a placebo, estrogen alone showed no link with heart attack risk and colorectal cancer and uncertain correlation with breast cancer risk. It was however linked to elevated risk of stroke and blood clots. And it was linked to reduced risk of bone fracture. Results on memory and cognition in the older age group are not yet available.
The WHI website cautions readers not to compare these two trials directly because the women in the two trials had different characteristics when they were enrolled.
For example, the women in the estrogen-alone study had a higher risk of cardiovascular disease than the women in the estrogen-plus-progestin study. They tended to have higher blood pressure, higher blood cholesterol, more diabetes, and be more obese.
In addition to the above results the study found that:
— Between the two trials there were more CHD and stroke cases in the hormone therapy groups (396 CHD and 327 stroke cases) compared with the placebo groups (379 CHD and 239 stroke cases).
— The women who started hormone therapy closer to onset of menopause had a lower risk of CHD compared to women who started later, but this was not statistically significant.
— This pattern was the same for total mortality with a slight favourable tendency for younger women, but this was also not statistically significant.
— The risk of stroke, however, was higher regardless of age and when hormone therapy started after the menopause.
The women in the two trials are now taking part in a follow up phase that finishes in 2010.
The National Institutes of Health advice to women asking about the results of these studies is that they follow the FDA advice on hormone therapy (estrogen-alone or estrogen-plus-progestin).
The FDA advises that hormone therapy should not be used to protect against heart disease. Also dosage and duration of therapy should be the minimum required to achieve treatment goals.
Although hormone therapy reduces postmenopausal osteoporosis somewhat, doctors should only offer it to women who are at significant risk of the disease and who cannot take non-estrogen drugs.
Estrogen-alone or estrogen-plus-progestin are approved only for the relief of “moderate to severe hot flashes and symptoms of vulvar and vaginal atrophy“.
The overall advice is that women should discuss the risks and benefits with their doctor before embarking on hormone therapy treatment.
“Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause.”
Jacques E. Rossouw, Ross L. Prentice, JoAnn E. Manson, LieLing Wu, David Barad, Vanessa M. Barnabei, Marcia Ko, Andrea Z. LaCroix, Karen L. Margolis, Marcia L. Stefanick.
JAMA. 2007;297:1465-1477.
Vol. 297 No. 13, April 4, 2007
Written by: Catharine Paddock
Writer: Medical News Today