Re: Menopause and HRT

Was I ever pleased to see [Dr Frinton’s] discussion and lead editorial in the October BCMJ on issues concerning hormone support for women with symptoms of menopause [ 2001;43(8):446]. Prevention of heart attack is a serious business. A 50-year-old North American woman has a 46% lifetime risk of heart attack, with a median age of occurrence of 74.[1] She is four times more likely to die of one than a male counterpart.[2] Like many busy practitioners, I had accepted the conclusions presented in the Nurses’ Health Study,[3] along with improved cholesterol profile data from the PEPI prospective study.[4] I presented this information for patients to consider, whether starting or maintaining what I believed to be hormone replacement therapy (HRT). I received ample support for this from consultants, upgrade courses, and pharmaceutical representatives. Voices that cited strong evidence that conjugated estrogens did not provide protection against MI were largely unheeded.[5] More recent information however, such as the latest review of the Nurses’ Health Study, the PEPI conclusions, and the HERS study, ably reviewed by Dr Hammell in your October issue [2001;43(8):447], led to questions about the earlier authors’ conclusions. Increased incidence of gallstones, breast cancer rates, and other morbidity led me back to the original data in that land-breaking observational study. What I found there, in Table 1 of the study, was the non-users of (mostly) Premarin and the C-21 progestin medroxyprogesterone were 29% more likely to have diabetes, 29% more likely to be smokers, and 53% more likely to meet standard criteria for obesity than users of these drugs.[3] Studies of diabetics have shown the lifetime risk of heart attack approaches 80%. Smoking increases the risk threefold. As a group, the non-user nurses were vastly more at risk to acute, fatal heart attack than those on these drugs. As well, the authors’ own data showed substantially more thrombotic strokes in the users’ group, despite the increased demonstrated risk factors in the non-users (47 versus 32).[3] My conclusion is the reduced portion of the 112 reported MIs was not due to nurses being on these drugs. Most of the nurses were below the median age of onset of this occurrence. The Women’s Health Initiative has already identified increased risk of MI from Premarin/Provera. The second conclusion I have drawn is that we have been engaged in drug therapy, not HRT. There is no human deficiency of equine estrogens and medroxyprogesterone acetate. These do not and cannot replace adrenal or ovarian human steroid hormones except as a partial measure. We are only now beginning to get a measure of the cost. The PEPI trial shows a better lipid profile outcome with progesterone versus Provera. The WEST trial shows an even better outcome for all causes mortality and stroke using estradiol.[6] These data recommend us back in the direction of hormone support, at least for the short term. My patients are now informed that long-term use of conjugated estrogen/progestin drugs have serious risk of MI. The Women’s Health Initiative randomized prospective study may afford us even better data on this by 2005. For our patients, it cannot come soon enough. —Robert D. Grist, MD Maple Ridge HRT: The guest editor replies Thank you for your well-considered letter. Dr Hammell presented the clinical dilemmas we face when discussing heart disease and HRT with our patients. Only two things are fairly clear: HRT is not to be started for the secondary prevention of heart disease; and, we are waiting for more information from the Women’s Health Initiative and other studies. At this time I do not feel it is correct to advise women that HRT is dangerous. I prefer to help them make informed, individualized decisions by educating them of the potential benefits as well as the potential harmful effects. We are all waiting for 2005! —Vera Frinton, MD Vancouver

References

1. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992;117:1016-1937. PubMed Abstract 
2. Love S, Lindsey K. Doctor Susan Love’s Hormone Book: Making Informed Choices about Menopause. New York: Random House, 1997:106. 
3. Stampfer MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses' health study. N Engl J Med 1991;325:756-762. PubMed Abstract 
4. Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: The postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1995;272:199-208. PubMed Abstract 
5. Prior JC. Postmenopausal estrogen therapy and cardiovascular disease [correspondence]. N Engl J Med 1992;326:705-706. PubMed Citation 
6. Brass L. Women’s Estrogen for Stroke Trial. Presented at the International Stroke Conference, Ft. Lauderdale, Florida, February 2001.