Clip Art Michael Vick

Hormone Therapy in Menopause: True and False Alarms Concerns

Menopause Hormone Therapy: Concerns and Interests False Alarms
Wednesday July 29, 2009
Menopause Hormone Therapy: Concerns Real and False Alarms-First Party: Breast Cancer

Jaime Urdinola
MD Medical Association Andes CS AK 9116 20 326 Bogotá DC Colombia - Tel 571/215 23 00 Ext 13 80 e-mail: jaimeurdinolamd@gmail.com blogger: http://www.urdinola . blogspot.com http://www.urdinolamenopausia2.blogspot.com/

Symposium / Luncheon on Women's Health and Menopause Medical Association Andes

First Floor - Board Room - Wednesday, July 29 , 2 009

Summary from 2 002-2 008 reports of the WHI (Women's Health Initiative = Women's Health Initiative) stated that the Menopausal Hormone Therapy (HT) significantly increased risk for developing breast cancer, cardiac events, Alzheimer's disease and stroke. These statements have alarmed the public and to health professionals, immediately causing a sharp decrease in the number of women who are prescribed or taken HT.
However, current data published in the articles on the WHI show that the findings reported in the press releases and interviews with principal investigators, were often distorted, oversimplified or wrong.
This review examines the findings on breast cancer in this first part, most of which are weak or not statistically significant. On these complicated issues, physicians and the public should be very cautious in accepting the "findings of press releases" to determine on their part if they prescribe or take HT. (Cancer J. 2009, 15: 93-104) 1

Introduction
Most women in the U.S. or Colombia does not take any form of HT after menopause and those who do, not take more than 5 years 2 . Only a minority of women take HRT for the rest of his life.

As is known, the TH is very effective to relieve common menopausal symptoms like hot flashes, night sweats, emotional lability, palpitations, insomnia, increased urination frequency and discomfort and painful intercourse. Some women who are at high risk for osteoporosis also are prescribed HRT, and that estrogens reduce the incidence of osteoporotic hip fracture in 25 to 50%. As currently there are alternative drugs-bisphosphonates such as alendronate, risedronate and ibandronate, which offer a similar protective benefit, most Doctors are not recommending the use of hormones to prevent hip fracture, although the former may have adverse effects such as gastric and esophageal irritation and in rare cases, osteonecrosis of the jaw.

has been debated for decades about the risks and benefits of estrogen combined with or without progestin. Since the 50 and 60 of the last century, when at that time Ayerst Laboratories began to aggressively market its estrogen preparation, Premarin, hormone supplements or as they were called "replacement" was presented as a panacea, that seductive words New York gynecologist, Robert Wilson, remain women "feminine forever." Since the 80's many critics argued that this treatment was a serious and unnecessary risk to the health of women. The biggest concern of these critics was breast cancer, a disease dreaded by women and heart disease causes more deaths than breast cancer occurs.

In July 2002, the first publication of the WHI study findings announced with fanfare and bold headlines in the media, that the damage of HT included not only breast cancer but also heart disease and accident cerebrovascular 3 . The news was alarming, since this study was a prospective, randomized study in which women took hormones or placebo, the largest to date and with a considerable time tracking. The cost is now approaching one trillion dollars. As a result of initial claims, not surprising that attention generated worldwide has led to the rate of prescription for HRT has fallen more than 50%.

A previous study, prospective, randomized, double-masked found no risk for breast cancer in women even up after 22 years who took the TH 4 , but this research has never made headlines in the media.

data extraction, reporting risk and other problems in research
be denied HT short or long term to women with menopausal symptoms, because they are afraid of breast cancer, heart disease or stroke? Their concerns are justified by the data available?
If analyzed closely to findings published in the articles on the WHI and placed in the context of research on HT over the past decades, no big surprises for the huge discrepancies found between the belief that hormones are dangerous and lack of data to support these beliefs.

Science is a process and therefore, a simple, single study does not provide a definitive answer. Two statistical errors have contributed to research on TH is unclear, one has to do with the way it reports on the risks, the other with the "extraction" inappropriate data, ie, when researchers are looking for something or thing about their findings, which may come to be regarded as a significant risk factor.

There are differences between absolute risk and relative risk. Media and researchers tend to report the relative risks, which are expressed in percentages may seem more important than they are. Not the same 300%, the increase that occurs when switching between the incidence of 1 in 10 000 women to 3 in 10 000 women, mean 300% increase, but it is very likely to be a random artifact.
But if the risk is clear that 100 was passed to 300 cases in 10 000, can be reasonably worried. In large epidemiological studies, which generally include tens of thousands of people, you may find a small link that might be considered "significant" statistically, but in practical terms means little or nothing, according to the low absolute numbers. The recommendation of various projects of consensus on the way they should report the findings of clinical studies, is that it must provide not only absolute numbers and percentage changes.

Risk Factors Associated with Breast Cancer
Risk Factor Risk 95% Reference Interval
Relative Confidence (IC) *
-
Conjugated equine estrogens 0.77-0.59 - 1.01 5
- Consumption of fish 1.14-1.03 - 1.26 6
- Premarin / gestagen 1.24-1.01 - 1.54 3
- Premarin / gestagen 1.26-1.00 - 1.59
7 - Consumer-A
fries extra serving per week 1.27-1.12 - 1.44
8 - 1.3 Grapefruit Juice - 1.06 - 1.58 9
- Night work 1.51-1.36 - 1.68 10
- Hostess (Finland) 1.87-1.15 - 2.23 11
- Dutch Famine 2.01-0.92 - 4.41 12
- Use antibiotics 7.2-1.48 - 2.89
13 - Hostess (Iceland) 4.1- 1.70 - 8.50 14
- Using electric blanket 4.9-1.50 - 15.6
15 - smoking / lung Ca 7.26-6.58 - 103.3 16

As shown in the table above, many studies of HT and breast cancer risk have produced inconclusive results or statistically really modest, which has tried to give the appearance of imposing the report as relative risks. At first glance you can see the weakness of these associations when compared with the actual discovery of the association at the end of the table, cigarette to lung cancer. In any case the relative risks are low, with virtually the lowest TH, compared with consumption of fish or grapefruit juice, the use of antibiotics or the fact of being a flight attendant.

extraction research data, in turn, can lead to bias, that when there are significant associations that led to the hypothesis of the study to a possible risk factor and disease or problem, returns to the data, "probe", looking at other factors that can establish a statistical connection with the dependent variable in question. This effort may result in interesting questions or hypotheses for future research but the problem is that in the data set of thousands of people could find any relationship discovered in retrospect, which may become significant only by chance. The contrast is that despite numerous investigations, the relationship between HRT and breast cancer is not yet clear.

there a link between HRT and breast cancer?
In the press release from the National Institutes of Health U.S. 9 July 2002, it was reported that he had interrupted a very important clinical trial (of the WHI) by relative risk (RR) increased (1.26) for breast cancer in healthy women who had received a combination of estrogen plus progestin compared to women who they had been randomly assigned placebo. What few noticed was this sentence in the publication "26% increase in the incidence of breast cancer among HT group compared with the placebo group almost reached nominal statistical significance." But the word "almost" means that did not reach statistical significance. Neither showed a marked increase in cases of noninvasive breast cancer, which precedes the invasive type cancer. There was, however, the difference between the 2 groups in the incidence of this cancer early, nor in cases of death from breast cancer. In terms absolute, this would mean that HRT increased the risk of 5 women in 100 to 6 100.

2 003 In the WHI published a follow up to 2 002 17, confirming that the use of combined estrogen with progestin increased the risk of invasive breast cancer significantly during a period of 5 years. The reported RR was 1.24, lower than the finding of 1.26 in 2 002 and that "only" reached statistical significance.

2 006 In another update from the same cohort of patients 18, the WHI reported no increased risk for breast cancer in women randomized to combination therapy. Significant relative risk was gone. This news did not make the headlines.

Nor Nurses Study found increased risk for breast cancer among women taking HT 19 , researchers compared women who had used HT previously with women who had never taken. No increased risk was found for breast cancer, even among those who had taken HT for more than 10 years, compared with those who never users. Then they subestratificaron again shown in a) current users and b) women who had used TH in the past and had been suspended. In this way the researchers found an increased risk for breast cancer, but only those who were taking combined HRT or estrogen alone for at least 5 years. But what is the explanation for that risk is increased in the group of women who take HRT for 5 years but not for those who have taken over 10 years?

In contrast, if the TH represents a risk factor will be for women with BRCA1 and BRCA2 gene mutation, which predisposes them to develop the disease. If they do oophorectomy, the risk of developing cancer breast halves. But the surgery induced menopause and some women take HT to relieve menopausal symptoms, which evokes questions as they are in danger? Taking estrogen denied the benefits of surgery? The study 20 of 236 patients with breast cancer and 236 controls who were all carriers of BRCA1 (no women with BRCA2 that may be included), found no increased risk among women taking hormones, whether natural menopause had been presented by age or surgery. It seems a contradiction, because if the decrease of estrogen to practice oophorectomy is the reason for the decline risk for breast cancer in carriers of BRCA1, estrogen administration would be irrational sumplementarios for relief of symptoms.

Estrogen does cause cancer?
The hypothesis that hormones are related to breast cancer is derived from two well-documented facts: the incidence of breast cancer is 100 times greater in women than in men, and the earlier presentation of menarche and the latest of the menopause, the greater the risk of women for breast cancer.

reasonably
These observations suggested that estrogen may be the culprit, the circular for more years. In the scientific process, the first step is to establish a reliable association, which according to previous data has become very weak or nonexistent. The second step is to demonstrate a mechanism responsible for the phenomenon, which in the case of breast cancer is contradictory according to the following lines of evidence:

- Birth control pills contain more estrogen than those of TH. Therefore, should increase the risk for breast cancer. Although the controversy continues, most studies in this field are not at increased risk 21.

- Women who take estrogen only should have a greater risk for breast cancer, but do not. So I checked the WHI study, after an average of 6.8 years follow 22.

- The incidence of breast cancer increases as women get older. If you take estrogen were part of the reason, the rate of breast cancer in women not taking HT should decrease with age, consistent with the natural decline in estrogen levels, but this does not happen.

- Estrogens do not act directly as carcinogens on mammary cells. But estrogen can induce cell proliferation. WHI investigators have modified their hypothesis, stating that agents that induce mutations are around us and to the extent that the rate of cell proliferation is high, the greater the probability that a cell is exposed to the mutagen and malignice. Endometrial cells are very sensitive to estrogen because women account for only taking estrogen have a risk 5 to 6 times higher for endometrial cancer, but not at higher risk for breast cancer. Term stimulation by estrogen in the case of early menarche and menopause should predispose late endometrial cancer, which does not appreciate 23.

As can be inferred from the above, the relationship between HRT and breast cancer has not yet been clarified despite the vast amount of research has been done 24.





References 1 - Bluming AZ, Tavris C. Hormone Replacement Therapy: Real Concerns and False Alarms. J. Cancer 2009, 15: 93-104.
2 - Pilon D, Castilloux AM, Lelorier J. Estrogen replacement therapy: Determinants of persistence with steam treatment. Obstet Gynecol. 2001, 97:97-100.
3 - Rossouw JE, Anderson GL, Prentice RL, et al. Writing Group for the Women’s Health Initiative investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative Randomized Controlled Trial. JAMA.2002; 288: 321.333.
4- Nachtigall MJ, Smilen SW, Nachtigall RD, et al. Incidence of breast cancer in a 22-year study of women receiving estrogen-progestin replacement therapy. Obstet Gynecol. 1992;80: 827– 830.
5- The Women’s Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative Randomized Controlled Trial. JAMA. 2004; 291:1701–1712.
6- Stripp C, Overvad K, Christensen J, et al. Fish intake is positively associated with breast cancer incidence rate. J Nutr. 2003;133:3664 –3669.
7- Chlebowski RT, Hendrix SL, Langer RD, et al; for the WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA. 2003; 289:3243–3253.
8- Michels KB, Rosner BA, Chumlea WC, et al. Preschool diet and adult risk of breast cancer. Int J Cancer. 2006; 118:749 –754.
9- Monroe KR, Murphy SP, Kolonel LN, et al. Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study. Br J Cancer. 2007; 97:440–445.
10- Megdal SP, Kroenke CH, Laden F, et al. Night work and breast cancer risk:a systemic review and meta-analysis. Eur J Cancer. 2005; 41:2023–2032.
11- Pukkala F, Auvinen A, Wahlberg G. Incidence of cancer among Finnish airline cabin attendants, 1967–1992. BMJ. 1995; 311:649–652.
12- Elias SG, Peeters PH, Grobbee DE, et al. Breast cancer risk after caloric restriction during the 1944–1945 Dutch famine. J Natl Cancer Inst. 2004; 96:539 –546.
13- Velicer CM, Heckbert SR, Lampe JW, et al. Antibiotic use in relation to the risk of breast cancer. JAMA. 2004; 291:827– 835.
14- Rafnsson V, Tulinius H, Jo´nasson JG, et al. Risk of breast cancer in female flight attendants: a population-based study (Iceland). Cancer Causes Control. 2001;12:95–101.
15- Kangmin Z, Hunter S, Payne-Wiks K, et al. Use of electric bedding devices and risk of breast cancer in African-American women. Am J Epidemiol. 2003; 158:798–806.
16- Sasco AJ, Merrill RM, Dari I, et al. A case-control study of lung cancer in Casablanca, Morocco. Cancer Causes Control. 2002; 13:609–616.
17- Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A; WHI Investigators. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA. 2003. 25; 289:3243-53.
18- Anderson GL, Chlebowski RT, Rossouw JE, Rodabough RJ, McTiernan A, Margolis KL, Aggerwal A, David Curb J, Hendrix SL, Allan Hubbell F, Khandekar J, Lane DS, Lasser N, Lopez AM, Potter J, Ritenbaugh C. Prior hormone therapy and breast cancer risk in the Women's Health Initiative randomized trial of estrogen plus progestin. Maturitas. 2006. 20;55:103-15.
19- Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ, Hennekens C, Rosner B, Speizer FE. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med. 1995;332:1589-93.
20- Eisen A, Lubinski J, Gronwald J, Moller P, Lynch HT, Klijn J, Kim-Sing C, Neuhausen SL, Gilbert L, Ghadirian P, Manoukian S, Rennert G, Friedman E, Isaacs C, Rosen E, Rosen B, Daly M, Sun P, Narod SA; Hereditary Breast Cancer Clinical Study Group. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst. 2008; 100:1361-7.
21- Casey PM, Cerhan JR, Pruthi S. Oral contraceptive use and risk of breast cancer. Mayo Clin Proc. 2008;83: 86-90.
22- Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE, Schenken RS, Yasmeen S, Lessin L, Chlebowski RT; WHI Investigators Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA. 2006, 295:1647-57.
23 - Thomas DB. Do hormones cause breast cancer? Cancer.1984, 53: 595-604.
24 - spied M, Daura JP, Chevallier T, Mares P, Micheletti MC, De Reilhac P. Breast cancer incidence, and hormone replacement therapy: results from the MISSION study, prospective phase. Gynecol Endocrinol. 2007; 23:391-7.


If you have any comments, questions or concerns, you can "click" on comments and sending your message. Or if you prefer, you can send your comments, questions or concerns e-mail jaimeurdinolamd@gmail.com