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heart surgery including bypass, angioplasty or narrowing of the arteries. Half of the group took 0.635 mg of Premarin and 2.5 mg of Provera daily; the other half took a placebo. They were fol- lowed for a five-year period."* The findings from this study, which were released in August 1998, sent shock waves throughout the medical community worldwide. For the women taking hormones, the risk of myocar- dial infarction increased by about 50 per cent the first year and then decreased by the fourth and fifth years, leaving "no overall enefit". In addition, there was a threefold increase in venous thromboembolic events (blood clots in the legs and lungs) and a significant increase in gall bladder disease in the user group. Other surprising findings revealed that although the 'good' cho- esterol increased by 10 per cent and the 'bad' cholesterol decreased by 10 per cent, this change had virtually no protective effect. It brought to light that the great emphasis placed on cho- lesterol levels in preventing heart attacks may indeed be a red her- ring. More and more studies are emerging that support this belief. Professor Barrett-Connor commented on the study: "I wouldn't @ putting women with heart disease on HRT to prevent a heart attack because there is an increased risk in people with heart dis- ease. This excess of heart disease was really surprising."'® The results of this study stopped the use of HRT for secondary prevention of heart disease dead in its tracks. But what about its effectiveness for primary prevention? Does it really have any protective benefits against cardiovascular disease? While all the focus has been on oestrogen, what about the effect when it is combined with a progestin? (Oestrogen is not usually prescribed alone to a woman with an intact uterus because of its known car- cinogenic effect on the uterus.) regnant—the greater your risk of breast cancer and the lower your risk of osteoporosis...but there is no clear relationship tween heart disease and your body's own estrogen. The amount of estrogen your body makes over your lifetime doesn't appear to ave any effect on your risk of heart disease." However, it does seem that supplemental oestrogen has a bene- icial effect on cholesterol by increasing the 'good' HDL (high- density lipoproteins) and decreasing the ‘bad’ LDL (low-density lipoproteins). It is believed that this can have a marked effect on subsequent heart disease. But, there is more to heart disease than just cholesterol levels. Dr John Lee comments: "Yes, estrogen does lower total choles- terol and raise the good HDL, but at what cost? This is only one risk factor for heart disease, and a questionable one at that. Given the risks and side-effects of estrogen, wouldn't it be more sensible to improve cholesterol levels through well-proven and safer routes through a good diet, exercise and antioxidant supplements?""” Since it is well researched that "unopposed" oestrogen given to a woman with an intact uterus will put her at high risk of endome- trial cancer, hormone treatments now include a synthetic prog- estin, such as Provera, as well as oestrogen. What are the effects on the heart by including a progestin? The first randomised controlled study to investigate oestrogen, progestin and progesterone therapy and its effects on lipids in women was the three-year PEPI (postmenopausal estrogen/prog- estin interventions) trial, the results of which were published in 1995.'* It included 875 healthy, naturally or surgically post- menopausal women, aged 45 to 64 years old, who were randomly asked to take one of four hormone replacement programs for three years. They included a placebo group, an unopposed oestrogen (Premarin) group, a Premarin and a synthetic progestin (Provera) group, and a Premarin and a natural (oral micronised) proges- terone group. (A progestin is a drug that has some similar charac- teristics as the natural progesterone the body makes but is not the exact molecular match, thus causing many side-effects. Oral micronised natural progesterone is formulated in a laboratory to be the exact molecular match as the progesterone made by the body.) Since the study was only conducted over three years, the researchers couldn't study the effects of oestrogen/progesterone on heart attacks, so they focused on changes in HDL levels. The study found that the most positive results (the highest levels of HDL) occurred in the oestrogen-only group, with a 0.14 increase in HDL. The group that most closely followed was the oestro- gen plus natural progesterone group, with a 0.11 increase in HDL. It was found that adding Provera to Premarin counteracted some of the beneficial effects of Premarin on cholesterol (a 0.03 increase in HDL). This study clearly showed that natural progesterone was much more effective in maintaining HDL levels than the synthetic progestins which actually lowered the HDL quite significantly. It is interesting to note that the researchers buried their recommen- dation for natural progesterone in the very last sentence of their paper." tt In an interview published on the Internet by the American Medical Association, the PEPI trial's principal investigator Dr Elizabeth Barrett-Connor remarked: "If I PROGESTINS: A GUILTY PARTY The claims that oestrogen therapy can prevent heart disease are problematic. Moreover, women's natural oestrogen levels seem to have little or no effect on their rate of heart disease. Dr Susan Love states: "In osteoporosis, breast cancer and endometrial cancer, factors associated with the body's own estro- gens correlate with the risk of the disease. For example, the larger your lifetime supply of oestrogen—whether because your started menstruating early, took certain medications or never became Swen lhe. 22 - NEXUS FEBRUARY — MARCH 1999