| Women's Health Initiative |
Article Index for Women's |
Website Links For Womens Health |
Information AboutWomen's Health Initiative |
|
An outline of the WHI interventions and study components: There are actually 4 different randomized interventions and a separate observational-only cohort in the WHI. All 4 of the randomized components overlap with each other to some extent (and a few even overlap with the observational study). The 4 interventions and their abbreviated terminology are: Estrogen plus progestin vs. placebo (the “WHI-E+P” trial), among healthy postmenopausal women. Interesting notes about this trial:
Conjugated equine estrogen vs. placebo (“WHI-CEE” trial), among women with prior hysterectomy:
Low fat dietary pattern (WHI-LowFat). This had 4 major papers that arose from it so far (all published in JAMA 2006):
Calcium + VitaminD combination vs. placebo (WHI-CalcVitD). This had 2 major papers arise from it in NEJM 2006, and one in May 2007 in the Archives Of Internal Medicine {Link without Title} :
The non-interventional observational cohort study (WHI-OS) of 93,000 women drawn from the same national clinical coordinating centers (many Epidemiology studies conducted within this observational component of the WHI). The WHI Postmenopausal Hormone Therapy Trials were part of the effort to address the high risk of Cardiovascular Disease in older women. By the early 1990s, many physicians had come to interpret results from previous clinical trials and studies using experimental animals as indicating that administration of an Estrogen supplement to postmenopausal women would lower the incidence of cardiovascular disease. Two hormone clinical trials were designed and conducted: The estrogen that was administered in the WHI studies was conjugated equine estrogen (CEE). This consists of a mixture of estrogens isolated from horse urine ( Premarin ). The CEE was administered orally. Both studies were randomized, placebo-controlled studies. Half the women were given an inactive placebo rather than hormone(s). Both studies were terminated early because a reduction in cardiovascular disease was not observed for most women and some women had dangerous side-effects. In particular, an increased risk of dangerous blood clotting is associated with oral administration of CEE. A review of the observational and WHI estrogen trial results describes potential explanations for the conflicting results. In addition, co-administration of MPA (medroxyprogesterone acetate, a type of progestin) with CEE was associated with a slightly increased risk of breast cancer. Some benefits of using an estrogen supplement such as reduced risk of bone fractures were confirmed by these studies. However, for the older postmenopausal women who were recruited for this study, the undesirable side-effects of treatment generally were greater than the health benefits. Based on the results of these studies, CEE and MPA are no longer given to women in order to try to prevent cardiovascular disease in older women. Younger postmenopausal women seeking relief from conditions such as hot flashes, sleep disturbance and urinary/vaginal atrophy are still candidates for hormone replacement therapy. Alternatives to orally administered CEE and MPA are being increasingly used by women since the termination of the WHI studies. For example, other forms of estrogen (such as esterified estrogens) or topical administration of Estradiol may reduce the risk of blood clotting compared to that for oral CEE. Finally, the low fat dietary pattern trial of the WHI yielded conflicting and controversial results. However, the WHI trial has been argued as unnecessary by many scientists, who already knew a full decade ago that total fat intake is not related to cardiovascular risk nor postmenopausal breast cancer risk. A review of the WHI low fat trial describes methodologic issues in more detail. REFERENCES |
|
|