Hormone Replacement Therapy - The Risks
by Dr. Gary Farr on 4 June 2002
Introduction
Hormone Replacement Therapy
INTRODUCTION TO HORMONE REPLACEMENT THERAPY
Each year, doctors prescribe hormone replacement therapy (HRT) to millions of women entering menopause. They tell their patients how HRT offsets a woman's decreased ovarian hormone production and how it thereby relieves the distress of hot flashes, sweats, disturbed sleep and vaginal dryness, while preventing cardio-vascular disease and osteoporosis. According to a recent survey, health care providers have reached ¾ of the postmenopausal female population with their counseling on supplementation with exogenous hormones (1).
As physicians, the drug industry and the media continue to convince women that the benefits of ingesting hormones outweigh any potential risk, the use of HRT steadily rises. During the period from 1982 to 1992, the use of hormone therapy in the U.S. more than doubled (2) and today about a third of women aged 45 to 65 rely on it (3,4). Such widespread promotion of this treatment implies that credible science has proven it safe and effective, but unfortunately this is not so.As early as 1994, a study in the British Medical Journal revealed that 3 meta-analyses showing a reduced risk of cardiovascular diseases in HRT users were flawed because their results were due to the selection of healthy sample populations, rather than to a protective effect of HRT.(5) The authors concluded that routine prescription of HRT for the prevention of cardiovascular disease was not warranted. Unfortunately they were ignored, as were researchers who, 25 years earlier, had reported increased heart attacks and death in men given high doses of estrogens, compared to the control group.(6)
In 1997, the British Medical Journal again published a study that debunked the theory that HRT protects the cardiovascular system. This time, analysis of the results of 22 trials involving more than 4,000 post-menopausal women showed that women given exogenous hormones had a 40% greater incidence of cardiovascular events other than pulmonary embolism and deep venous thrombosis, and a 64% increased incidence of cardiovascular events including venous thrombembolism, compared to those not taking hormones.(7)
Current reports confirm that, not only does HRT not avert cardiovascular disease, but it may play a causative role in a wide range of adverse effects, including heart attacks. A study in the February 2000 issue of The Lancet, for instance, examined the results of trials submitted to the Finnish Drug Agency by drug companies seeking licensing approval of HRT drugs. They judged the quality of the trials and their reporting of adverse events to be inadequate, but analysis of the 6 that met the criteria to be included in the study, revealed that users of HRT had a two-fold increased incidence of cardiovascular and thromboembolic events, compared to nonusers.(8)
In 1998, the Journal of the American Medical Association published the results of the double-blind, placebo-controlled HERS trial which examined the effect of HRT on over 2700 post- menopausal women with coronary heart disease. Women on HRT had a 50% increased risk of coronary heart disease events in the first year of treatment, and fewer events in the 4th and 5th year, compared to women on placebo. In addition, women on HRT had an almost 3-fold increased incidence of deep venous thrombosis and pulmonary embolism, compared to those taking placebos, and a 40% increased rate of gallbladder disease. The two groups had similar rates of fractures (9)
Recently, the preliminary results of a trial by the NIH's National Heart, Lung, and Blood Institute showed that women on hormone therapy had experienced more heart attacks, strokes, deep venous thrombosis and pulmonary embolism, compared to those on a placebo.(10) This ongoing trial, which will last up to 11 years, is being conducted on 27,000 women aged 50-79, who had been randomly assigned to receive estrogen, estrogen plus a progestin, or a placebo.
Even in the face of extensive research documenting the downside of HRT, the scientific community is reluctant to change its practices. As of August 2000, the National Women's Health Information Center still stated that: "most scientists think that for most women, the benefits of hormone replacement therapy (for example, a reduction in the risk of osteoporosis and possibly of cardiovascular disease) clearly outweigh the possible cancer risks" (11) In fact, the AMA's "Complete Guide to Women's Health" (available online) recommends that to reduce their risk of heart disease women should "consider hormone replacement therapy (HRT)."(12) The American Academy of Family Physicians' brochure "Menopause: What to Expect When Your Body is Changing," reassures women that HRT "reduces the risk of osteoporosis (a problem with the bones) and heart disease (such as heart attacks)"(13) The US Food and Drug Administration also reports in its online document, "Help for Menopause," that "besides protecting against osteoporosis, researchers think that estrogen also lowers the risk of heart disease."(14)
We are struck by the number of so-called experts who choose to ignore the mounting evidence of heart attack risk associated with HRT. Why do they release statements to the media calling results "inconclusive" and warning women against making decisions about interrupting treatment? How can they ignore studies like the one in the May 2000 Annals of Internal Medicine that showed that women on HRT experienced a three-fold higher rate of deep venous thrombosis and pulmonary embolism compared to those on placebos (15), as well as numerous other studies (16-19) that reach similar conclusions? We wonder whether they are ignorant of these findings or is it that they are swept up by vested personal and industry interests?
As if the evidence of increased cardiovascular risk were not damning enough, there are also credible studies that link synthetic hormones with breast cancer, showing increased risk with duration and dosage. In 2000, J.A.M.A. published a study conducted on more than 46,000 women that showed that estrogen replacement therapy increased breast cancer risk by 20% and even more when a progestin was added. Women who took an estrogen-progestin combination in the previous 4 years were found to have a 40% increased risk of breast cancer, compared to nonusers. The authors concluded that each year of use of combination therapy increased the risk of breast cancer by 8%.(20)Another article, in the February 2000 issue of the Journal of the National Cancer Institute, confirmed that HRT with estrogen and progestin increases the risk of breast cancer more than HRT with estrogen alone. For every five years of treatment, the study demonstrated a 6% increased incidence of breast cancer in women using estrogen only, and a 24% increase in those using an estrogen-progestin combination, compared to nonusers.(21) In fact, 3 years earlier, researchers had reported that women using HRT for more than 10 years had a twofold increased incidence of breast cancer, compared to nonusers. The incidence was significantly higher in women who used an estrogen-progestin combination (2.4-fold increase) compared to unopposed estrogen (30% increase).(22)
It is noteworthy that the above studies conclude that the estrogen-progestin combination is more dangerous than estrogen alone. Ironically progestins had been introduced because unopposed estrogens had increased the incidence of uterine cancer. The solution, merely substituted problems, as HRT has been conservatively estimated to cause an excess of 2, 6, and 12 breast cancers for every 1,000 women who use it for 5, 10, and 15 years, respectively.(23) Considering that a third of U.S. women aged 45 to 65 years use some form of HRT, the implications of its breast cancer promoting effect on the population (some 16 million women) are enormous.
Unfortunately, the dangers of HRT reach beyond the cardiovascular system and the breast. Use of HRT has also been associated with a 30% to 2-fold increased risk of ovarian cancer(24-27) and, for users of unopposed estrogens, with a 3- to 5-fold increased risk of uterine cancer.(28-31) Additionally, women who use HRT have a two-fold increased risk of undergoing gallbladder removal(32-33) and of developing systemic lupus erythematosus.(34,35) In both instances, the risk increases with the duration of hormone intake.
In light of the above, we invite readers to carefully review the following studies which document the effects of HRT on multiple systems.
Hormone Replacement Therapy Study Fact Sheet & WHI HRT Update
From: www.mhlbi.nih.gov/whi/hrt.htm and www.mhlbi.nih.gov/whi/hrt-en.htm
This online document reports on the preliminary results of a trial conducted by the NIH' National Heart, Lung, and Blood Institute, indicating that hormone replacement therapy increases the risks of heart attack, stroke and venous thromboembolism in post-menopausal women. The trial, designed to last up to 11 years, is being conducted on 27,000 women aged 50-79, who had been randomly assigned to receive estrogen, estrogen plus a progestin, or placebo. Up to this point, women on hormone therapy experienced more heart attacks, strokes, deep venous thrombosis and pulmonary embolism, compared to those on placebo. These findings add to the results of several recent studies indicating that post-menopausal hormone replacement therapy, rather than exerting protective effects, may in fact be associated with an excess risk of fatal and nonfatal cardiovascular events.
Study throws doubt on protective effects of HRT for heart disease.
Gottlieb S.
BMJ 2000;320:826 ( 25 March).This article reports on the results of the Estrogen Replacement and Atherosclerosis (ERA) Trial, presented at the American College of Cardiology's 49th annual scientific meeting held in California, showing that hormone replacement therapy has no beneficial effects on the cardiovascular system. The study was conducted on 309 post-menopausal women with coronary heart disease who were randomly assigned to receive one of three treatments: estrogen, estrogen plus progestin, or placebo. Women were followed-up for 3.5 years and disease progression was assessed through coronary angiography, a test used to detect the blockages caused by hardening in the arteries. No differences in disease progression were observed between the three groups, suggesting that neither estrogen alone nor estrogen combined with a progestin, offer protection to women from heart disease.
Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials.
Elina Hemminki, et al.
BMJ 1997;315:149-153 (19 July).This study reviewed the results of 22 trials conducted on 4,124 post-menopausal women comparing the effects of hormone replacement therapy, placebo, no therapy, or vitamins on the incidence of cardiovascular diseases. The results of the analysis indicated that, overall, women who took hormones had a 40% increased risk of cardiovascular events other than pulmonary embolism and deep vein thrombosis, and a 64% increased risk of cardiovascular events including venous thrombembolism, compared to women who did not take hormones. These results are in contrast with the commonly held assumption that hormone replacement therapy prevents cardiovascular diseases.
Value of drug-licensing documents in studying the effect of postmenopausal hormone therapy on cardiovascular disease.
Hemminki R, McPherson K.
Lancet 2000 Feb 12;355(9203):566-9.The results of this study indicate that use of hormone replacement therapy (HRT) is associated with a 2-fold increased risk of cardiovascular and thromboembolic disease in postmenopausal women. These findings come from the analysis of the results of trials submitted to the Finnish Drug Agency by drug companies seeking licensing approval of HRT drugs. The quality of the trials and their reporting of adverse events experienced by participants were found to be mostly inadequate. In addition, analysis of the 6 trials that met the criteria to be entered in the study revealed that users of HRT had a 2-fold increased incidence of cardiovascular and thromboembolic events, compared to nonusers.
Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women
Heart and Estrogen/progestin Replacement Study (HERS) Research Group.
Hulley S, et al.
JAMA 1998 Aug 19;280(7):605-13.This double-blind placebo controlled trial investigated the effects of hormone replacement therapy (HRT) on the prevention of recurrent coronary heart disease. The study was conducted on 2763 postmenopausal women with a history of coronary artery disease who were randomly assigned to receive either an estrogen-progestin combination, or placebo. Rates of myocardial infarction, cardiac arrest, angina, congestive heart failure, stroke, transient ischemic attack, peripheral artery disease, cardiovascular mortality and overall mortality did not differ between patients taking HRT or placebo. Women on HRT had a 50% increased risk of coronary heart disease events in the first year of treatment, and fewer events in the 4th and 5th year, compared to women on placebo. In addition, women on HRT had an almost 3-fold increased incidence of deep venous thrombosis and pulmonary embolism than those taking placebo, and a 40% increased rate of gallbladder disease. Rates of fractures were similar in the two groups. These data indicate that hormone therapy in postmenopausal women is not protective towards coronary heart disease and is instead associated with an early increase in coronary death and nonfatal myocardial infarction.
Early risk of Hormone Therapy in Patients With Coronary Heart Disease.
Wenger NK, Knatterud GL, and Canner PL.
JAMA, Vol. 284 No. 1, July 5, 2000.This article emphasizes that the early increase in fatal and nonfatal coronary events documented in the HERS trial (described in the above article) in women with coronary heart disease (CHD) taking hormone replacement therapy, has been documented 30 years ago in a large study conducted on men with CHD randomized to receive different doses of estrogens or placebo. The trial arm that tested the effects of 5.0 mg/d of estrogen was interrupted after a median 1.5 years of follow-up, because of an increase in rates of mortality and nonfatal myocardial infarction in men taking estrogens, compared to those taking placebo. The trial harm that tested the effects of 2.5 mg/d of estrogen was discontinued after a median of almost 5 years of follow-up because of treatment-related adverse effects such as thromboembolic events and gallbladder disease in men taking estrogen, and no benefit on overall mortality. The authors conclude that postmenopausal hormone therapy for the prevention of coronary heart disease is not advisable, and is associated with an early increased risk of fatal and nonfatal coronary events. The finding that the same pattern of adverse effects and early excess in coronary death and nonfatal myocardial infarction found in women was also demonstrated 3 decades earlier in men is striking, and points to a precise biological effect of this class of hormones.
Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased?
Posthuma WF, Westendorp RG, Vandenbroucke JP.
BMJ 1994 May 14;308(6939):1268-9.The results of this study show that data gathered from 3 meta-analysis indicating that hormone replacement therapy (HRT) reduces the risk of cardiovascular disease in postmenopausal women, are due to bias originated from the selection of a relatively healthy sample population, rather than to a protective effect of HRT. The authors conclude that, based on the available data, routine prescription of HRT for the prevention of cardiovascular disease is not indicated.
Postmenopausal hormone therapy increases risk for venous thromboembolic disease
The Heart and Estrogen/progestin Replacement Study.
Grady D, et al.
Ann Intern Med 2000 May 2;132(9):689-96.The results of this study show that hormone replacement therapy significantly increases the risk of deep venous thrombosis and pulmonary embolism in post-menopausal women. The study was conducted on 2,763 women postmenopausal women who were randomly assigned to receive hormone replacement therapy (1380 women) or placebo (1383 women). During a 4-year follow-up period, 34 women in the hormone group experienced deep venous thrombosis or pulmonary embolism, compared to 13 in the placebo group. These data indicate that use of synthetic hormones almost triples the risk of venous thromboembolism in post-menopausal women. The authors conclude that the potential risks and benefits of hormone therapy must be weighted before considering initiation of therapy.
Hormone replacement therapy and risk of venous thromboembolism: population based case-control study.
Perez Gutthann S, Garcia Rodriguez LA, Castellsague J, Duque Oliart A.
BMJ 1997 Mar 15;314(7083):796-800.The results of this study, conducted on 347,253 women aged 50 and older, show that users of hormone replacement therapy have a 2- to 3-fold increased risk of developing pulmonary embolism or deep venous thrombosis, compared to nonusers. The risk is particularly elevated during the first year of use, as indicated by an over 4-fold increased incidence of venous thromboembolism documented during the first six months of treatment.
Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens.
Jick H; Derby LE; Myers MW; Vasilakis C; Newton KM.
Lancet, 348(9033):981-3 1996 Oct 12.The results of this study show that post-menopausal women on hormone replacement therapy have a 3.6-fold increased risk of idiopathic venous thromboembolism (IVT), compared to nonusers. The risk increases with increasing daily doses of estrogen intake, and women using 0.325 mg, 0.625 mg, and 1.25 mg or more estrogen per day, were shown to have a 2-, 3.3-, and 7-fold increased incidence of IVT, compared to nonusers.
HRT and the risk of deep vein thrombosis.
Barlow DH.
Int J Gynaecol Obstet, 59 Suppl 1():S29-33 1997 Oct.This article reports on 4 recent epidemiological studies demonstrating a three-fold increased incidence of pulmonary embolism and deep venous thrombosis in women using hormone replacement therapy, compared to nonusers.
Prospective study of exogenous hormones and risk of pulmonary embolism in women.
Grodstein F, et al.
Lancet, 348(9033):983-7 1996 Oct 12.The results of this study show that users of postmenopausal hormone replacement therapy have an over 2-fold increased risk of primary pulmonary embolism secondary to deep venous thrombosis, compared to nonusers
Thrombosis of the straight sinus complicating hormone replacement therapy.
Strachan R; Hughes D; Cowie R.
Br J Neurosurg, 9(6):805-8 1995.This article reports on the case of a woman who developed venous thrombosis of the dura mater (the outer of the 3 membranes or meninges that cover the brain and the spinal cord) while on hormone replacement therapy (HRT). The authors suggest that this life-threatening complication, already documented in women taking oral contraceptives, may also be rarely associated with HRT.
Cerebral venous thrombosis in association with hormonal supplement therapy.
Knox AM; Brophy BP; Sage MR.
Clin Radiol, 41(5):355-7 1990 May.This article reports on the case of a woman who developed cerebral venous thrombosis while on postmenopausal hormone replacement therapy.
Part 2
Hormone Replacement Therapy
Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk.
Schairer C, et al.
JAMA 2000;283:485-491.The results of this study, conducted on a sample population of 46,355 postmenopausal women, show that use of estrogen replacement therapy increases the risk of breast cancer by 20%. The addition of a progestin further increases the risk, and women who took an estrogen-progestin combination in the previous 4 years were found to have a 40% increased incidence of breast cancer, compared to nonusers. Each year of use of combination therapy increases the risk of breast cancer by 8%. The results of this study are important because they indicate that combination replacement therapy may be more dangerous than estrogens alone. Progestins have been added to estrogen replacement therapy because it was shown that unopposed estrogens increase the incidence of uterine cancer. Hormone replacement therapy (HRT), consisting of a combination of estrogen and progestin, is widely used to relieve symptoms of menopause and to prevent bone fractures and heart diseases, even though several studies have demonstrated no beneficial effects on heart diseases associated with HRT use, and some excess risk. Since, according to a survey performed by the North American Menopause Society, approximately one-third of U.S. women aged 45 to 65 years use some form of hormone replacement therapy, this increase in breast cancer risk can have enormous implications on the overall health of this population -some 16 million women. Women must be informed that there are no proven benefits associated with HRT while it is well established that treatment results in a significantly increased incidence of uterine cancer, breast cancer, stroke, gall bladder disease, deep venous thrombosis, pulmonary embolism, and possibly fatal and nonfatal myocardial infarction.
Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen
Versus Estrogen Plus Progestin.
Ross, RK et al.
J Natl Cancer Inst. 2000 Feb 16;92(4):328-332.The results of this study, conducted on over 3,500 postmenopausal women, confirm that hormone replacement therapy (HRT) with estrogen and progestin increases the risk of breast cancer more than HRT with estrogen alone. The risk increases with duration of treatment, and for every 5 years of treatment the study demonstrated a 6% increased incidence of breast cancer in women using estrogen only, and a 24% increase in those using an estrogen-progestin combination, compared to nonusers.
Hormone replacement therapy and the risk of breast cancer
Nested case-control study in a cohort of Swedish women attending mammography screening.
Persson I, Thurfjell E, Bergstrom R, Holmberg L.
Int J Cancer 1997 Sep 4;72(5):758-61.The results of this study show that women who use hormone replacement therapy for more than 10 years have a twofold increased risk of developing breast cancer, compared to nonusers. The risk is higher for women who use replacement therapy consisting of a combination of estrogen and progestin. In particular, use of unopposed estrogen for longer than 10 years after menopause is associated with a 30% increased breast cancer risk, while use of an estrogen-progestin combination is associated with a 2.4-fold increased risk.
The adverse effects of hormone replacement therapy.
Tavani A, La Vecchia C.
Drugs Aging 1999 May;14(5):347-57.This article reviewed 51 epidemiological studies investigating the effects of hormone replacement therapy (HRT) on the risk of breast cancer. The results of the analysis showed that the risk of breast cancer increases by 2.3% for every year of HRT use. These data translate in an excess of 2, 6, and 12 breast cancers for every 1,000 women using HRT for 5, 10, and 15 years, respectively.
Hormone replacement treatment and breast cancer risk
A cooperative Italian study.
La Vecchia C, et al.
Br J Cancer 1995 Jul;72(1):244-8.The results of this case-control study, conducted on 2569 women with breast cancer and 2588 controls, show that use of hormone replacement treatment (HRT) for 1 to 4 years is associated with a 20% increased risk of breast cancer, while use for 5 or more years is associated with a 50% increased risk of breast cancer. Women who had stopped HRT within the 10 previous years had a two-fold increased incidence of breast cancer, compared to nonusers.
Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis.
Garg PP, Kerlikowske K, Subak L, Grady D.
Obstet Gynecol 1998 Sep;92(3):472-9.In this study, the investigators analyzed the results of nine published study to determine whether there is an association between hormone replacement (HRT) therapy and invasive ovarian cancer. The results of the analysis revealed that the risk of ovarian cancer increases by 15% in women who had used at some point in their life HRT, and by 27% in those who used it for more than 10 years, compared to nonusers.
Hormonal therapy for menopause and ovarian cancer in a collaborative re-analysis of European studies.
Negri E, et al.
Int J Cancer 1999 Mar 15;80(6):848-51.This study analyzed 4 previous case-control studies conducted on 1,470 women with ovarian cancer and 3,271 controls, to determine the impact of hormone replacement therapy (HRT) on ovarian cancer. The results of the analysis revealed that users of HRT have a 70% increased risk of ovarian cancer, compared to nonusers.
Estrogen replacement therapy and risk of epithelial ovarian cancer.
Risch HA.
Gynecol Oncol 1996 Nov;63(2):254-7.The results of this study show that women who use estrogen replacement therapy for 5 or more years have a 2-fold increased risk of developing ovarian cancer of the serous type and a 2.8-fold increased risk of developing ovarian cancer of the endometroid type, compared to nonusers.
Hormone replacement therapy and risk of epithelial ovarian cancer.
Purdie DM, et al.
Br J Cancer 1999 Oct;81(3):559-63.The results of this study show that estrogen replacement therapy increases the risk of ovarian cancer of the endometrioid or clear cell type by 2.5 times. Women with an intact genital tract are particularly susceptible, their risk being 3 times higher than that of women with a history of hysterectomy or tubal ligation.
Risk of endometrial cancer following estrogen replacement with and without progestins.
Weiderpass E, et al.
J Natl Cancer Inst 1999 Jul 7;91(13):1131-7.The results of this study show that women using unopposed estrogen replacement therapy have an over 6-fold increased risk of uterine cancer, compared to nonusers. Women who use combination hormone replacement therapy (HRT) with a progestin added to the estrogen for fewer than 16 days of the cycle have a 3-fold increased risk of uterine cancer. Use of HRT with a progestin added continuously during the cycle is associated with an 80% reduction of risk of uterine cancer.
Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement.
Persson I, Weiderpass E, Bergkvist L, Bergstrom R, Schairer C.
Cancer Causes Control 1999 Aug;10(4):253-60.The results of this study, conducted on a sample population of 11,231 Swedish women employing hormone replacement therapy, show that use of estrogens alone for 6 years and longer is associated with an over 4-fold increase in uterine cancer, compared to nonuse. The risk of uterine cancer is significantly attenuated by use of estrogens combined with a progestin, with a 40% non-significant excess risk in users of combination therapy for longer than 6 years. In addition, the study found that use of estrogens combined with progestins for 1 to 6 years and 6 or more years is associated with a 40% and 70% increased risk of breast cancer, respectively, compared to nonuse.
Menopausal hormone use and endometrial cancer, by tumor grade and invasion.
Shapiro JA, Weiss NS, Beresford SA, Voigt LF.
Epidemiology 1998 Jan;9(1):99-101.The results of this study show that use of unopposed hormone replacement therapy (HRT) for 3 or more years is associated with a 5-fold increased risk of uterine endometrial cancer, while use of combination HRT with a progestin added cyclically or continuously is associated with a 30% increased risk of endometrial cancer.
Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy.
Hunt K, Vessey M, McPherson K, Coleman M.
Br J Obstet Gynaecol 1987 Jul;94(7):620-35.The results of this study, conducted on 4544 postmenopausal women who employed hormone replacement therapy (HRT) for a median of 5.5 years, show that users of HRT have an almost 3-fold increased incidence of uterine cancer and a 60% increased incidence of breast cancer, compared to nonusers. In 43% of women, HRT was of the "opposed" type, although the amount of progestin they received was generally inferior to that employed in more recent times.
Postmenopausal estrogen replacement therapy and the risk of developing systemic lupus erythematosus or discoid lupus.
Meier CR; Sturkenboom MC; Cohen AS; Jick H.
J Rheumatol, 25(8):1515-9 1998 Aug.The results of this study show that women who use either estrogen-only or combined hormone replacement therapy for 2 years or longer, have a 5-fold and 2-fold increased risk of developing systemic lupus erythematosus and discoid lupus, respectively, compared to nonusers.
Hormone replacement therapy in systemic lupus erythematosus.
Kreidstein S, Urowitz MB, Gladman DD, Gough J.
J Rheumatol 1997 Nov;24(11):2149-52.The results of this study show that while hormone replacement therapy (HRT) does not increase the number of lupus flares in patients with lupus, it significantly increases the duration of the disease. In particular lupus lasted an average of 18 years in patients taking HRT, and an average of 5.6 years in patients not on hormones.
Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus.
Sanchez-Guerrero J, Liang MH, Karlson EW, Hunter DJ, Colditz GA.
Ann Intern Med 1995 Mar 15;122(6):430-3.The results of this study, conducted on almost 70,000 women aged 30 to 55 years who were followed up for an average of 15 years, show that women who used postmenopausal hormone replacement therapy (HRT) had a twofold increased incidence of lupus, compared to nonusers. Current and past use of HRT was associated with a 2.5-fold and 80% increased risk of lupus, respectively. The risk of lupus increased with increasing duration of HRT use.
Urinary tract infections and estrogen use in older women.
Orlander JD; Jick SS; Dean AD; Jick H.
J Am Geriatr Soc, 40(8):817-20 1992 Aug.The results of this study show that older women taking exogenous estrogens have a two-fold increased risk of urinary tract infections, compared to nonusers. The risk of urinary tract infections is not increased in women who had their uterus removed.
Postmenopausal hormone use and cholecystectomy in a large prospective study.
Grodstein F, Colditz GA, Stampfer MJ.
Obstet Gynecol 1994 Jan;83(1):5-11.The results of this study, conducted on 54,845 postmenopausal women, show that users of hormone replacement therapy have a two-fold increased risk of undergoing gall bladder removal, compared to nonusers. The risk of gall bladder removal increases with the duration of hormone use, and is 2.6-folds higher in current users of postmenopausal hormones for longer than 10 years, compared to nonusers.
Increased risk of cholecystectomy in users of supplemental estrogen.
Petitti DB, Sidney S, Perlman JA.
Gastroenterology 1988 Jan;94(1):91-5.The results of this study show that users of estrogen replacement therapy have a two-fold increased risk of gall bladder removal, compared to nonusers. The risk is increased by 2.7-folds in current users of postmenopausal estrogens, and by 60% in past users.
References
HRT REFERENCES
Ref 1. The North American Menopause Society 1998 Menopause Survey: Part II. Counseling About Hormone Replacement Therapy: Association With Socioeconomic Status and Access to Medical Care. Ettinger B, Fugate Woods N, Barrett-Connor E, Pressman A. Menopause: The Journal of The North American Menopause Society. Vol. 7, No. 3, pp. 143 - 148.
Ref 2. Use of menopausal estrogens and medroxyprogesterone in the United States, 1982-1992. Wysowski DK, Golden L, Burke L. Obstet Gynecol 1995 Jan;85(1):6-10.
Ref 3. Use of hormone replacement therapy by postmenopausal women in the United States. Keating NL, Cleary PD, Rossi AS, Zaslavsky AM, Ayanian JZ.
Ann Intern Med 1999 Apr 6;130(7):545-53.Ref 4. Use of postmenopausal hormone replacement therapy: estimates from a nationally representative cohort study. Brett KM, Madans JH. Am J Epidemiol. 1997 Mar 15;145(6):536-45.
Ref 5. Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased? Posthuma WF, Westendorp RG, Vandenbroucke JP.
BMJ 1994 May 14;308(6939):1268-9.Ref 6. Early risk of Hormone Therapy in Patients With Coronary Heart Disease. Wenger NK, Knatterud GL, and Canner PL. JAMA, Vol. 284 No. 1, July 5, 2000.
Ref 7. Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials. Hemminki E, et al. BMJ 1997;315:149-153 (19 July).
Ref 8. Value of drug-licensing documents in studying the effect of postmenopausal hormone therapy on cardiovascular disease. Hemminki R, McPherson K. Lancet 2000 Feb 12;355(9203):566-9.
Ref 9. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Hulley S, et al. JAMA 1998 Aug 19;280(7):605-13.
Ref 10. Hormone Replacement Therapy Study Fact Sheet and WHI HRT Update.
www.mhlbi.nih.gov/whi/hrt.htm and www.mhlbi.nih.gov/whi/hrt-en.htmRef 11. http://www.4woman.gov/menopaus.htm
Ref 12. From the AMA Complete Guide to Women's Health.
http://www.ama-assn.org/insight/h_focus/wom_hlth/menopaus/menopaus.htmRef 13. Menopause: what to expect when your body is changing "AAFP Family Health Facts" series. http://www.nlm.nih.gov/cgi/medlineplus/leavemedplus.pl?theURL=http%3A%2F%2Ffamilydoctor%2Eorg%2Fhealthfacts%2F125%2Findex%2Ehtml
Ref 14. http://www.fda.gov/opacom/lowlit/menopause.html
Ref 15. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Grady D, et al. Ann Intern Med 2000 May 2;132(9):689-96.
Ref 16. Hormone replacement therapy and risk of venous thromboembolism: population based case-control study. Perez Gutthann S, Garcia Rodriguez LA, Castellsague J, Duque Oliart A.BMJ 1997 Mar 15;314(7083):796-800.
Ref 17. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Jick H; Derby LE; Myers MW; Vasilakis C; Newton KM. Lancet, 348(9033):981-3 1996 Oct 12.
Ref 18. HRT and the risk of deep vein thrombosis. Barlow DH. Int J Gynaecol Obstet, 59 Suppl 1():S29-33 1997 Oct.
Ref 19. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Grodstein F, et al. Lancet, 348(9033):983-7 1996 Oct 12.
Ref 20. Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk. Schairer C, et al. JAMA 2000;283:485-491.
Ref 21. Effect of Hormone Replacement Therapy on Breast Cancer Risk: Estrogen
Versus Estrogen Plus Progestin. Ross, RK et al. J Natl Cancer Inst. 2000 Feb 16;92(4):328-332.Ref 22. Hormone replacement therapy and the risk of breast cancer. Nested case-control study in a cohort of Swedish women attending mammography screening.
Persson I, Thurfjell E, Bergstrom R, Holmberg L. Int J Cancer 1997 Sep 4;72(5):758-61.Ref 23. The adverse effects of hormone replacement therapy. Tavani A, La Vecchia C. Drugs Aging 1999 May;14(5):347-57.
Ref 24. Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis. Garg PP, Kerlikowske K, Subak L, Grady D. Obstet Gynecol 1998 Sep;92(3):472-9.
Ref 25. Hormonal therapy for menopause and ovarian cancer in a collaborative re-analysis of European studies. Negri E, et al. Int J Cancer 1999 Mar 15;80(6):848-51.
Ref 26. Estrogen replacement therapy and risk of epithelial ovarian cancer.
Risch HA.Gynecol Oncol 1996 Nov;63(2):254-7.Ref 27. Hormone replacement therapy and risk of epithelial ovarian cancer.
Purdie DM, et al. Br J Cancer 1999 Oct;81(3):559-63.Ref 28. Risk of endometrial cancer following estrogen replacement with and without progestins.Weiderpass E, et al. J Natl Cancer Inst 1999 Jul 7;91(13):1131-7.
Ref 29. Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. Persson I, Weiderpass E, Bergkvist L, Bergstrom R, Schairer C. Cancer Causes Control 1999 Aug;10(4):253-60.
Ref 30. Menopausal hormone use and endometrial cancer, by tumor grade and invasion. Shapiro JA, Weiss NS, Beresford SA, Voigt LF. Epidemiology 1998 Jan;9 (1): 99 -101.
Ref 31. Long-term surveillance of mortality and cancer incidence in women receiving hormone replacement therapy. Hunt K, Vessey M, McPherson K, Coleman M. Br J Obstet Gynaecol 1987 Jul;94(7):620-35.
Ref 32. Postmenopausal hormone use and cholecystectomy in a large prospective study. Grodstein F, Colditz GA, Stampfer MJ. Obstet Gynecol 1994 Jan;83(1):5-11.
Ref 33. Increased risk of cholecystectomy in users of supplemental estrogen.
Petitti DB, Sidney S, Perlman JA. Gastroenterology 1988 Jan;94(1):91-5.Ref 34. Postmenopausal estrogen replacement therapy and the risk of developing systemic lupus erythematosus or discoid lupus. Meier CR; Sturkenboom MC; Cohen AS; Jick H. J Rheumatol, 25(8):1515-9 1998 Aug.
Ref 35. Postmenopausal estrogen therapy and the risk for developing systemic lupus erythematosus. Sanchez-Guerrero J, Liang MH, Karlson EW, Hunter DJ, Colditz GA. Ann Intern Med 1995 Mar 15;122(6):430-3.
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