The Doctor, the Patient and QoL. Manuel Neves-e-Castro Lisboa-Portugal

Transcription

1 The Doctor, the Patient and QoL by Manuel Neves-e-Castro Lisboa-Portugal

2 The Doctor, the Woman and QoL

3 There are controversies about the present management of the climacterium which are due to: a lack of culture that prevents a correct criticism of the published results a bad practice of medicine that ignores the woman in her totality (holism) political lobbies from the NIH a lack of scientific honesty manifested by many of the WHI writers lobbies from several pharmaceutical industries through the activities of many well known doctors that offer themselves to transmit their messages

4 HOW TO DO IT? The Objective The Target QoL the Woman The Agent (or Actor) the Doctor

5 Quality of Life (QoL)

6 How to promote it?

7 QoL = Health! A condition of physical, mental and social well-being and not only the absence of disease Therefore one must: - prevent diseases - promote health WHO

8 The midaged Woman How does she feel? Confused? Insecure? What is she afraid of? Hormones? What does she want from the Doctor? QoL!

9 Definition A Climacteric woman is a woman (gender based medicine) is an ageing person (geriartrics) is perimenopausal (hormone deficient)

10 Looking after a menopausal woman is a most fascinating, gratifying and complex vivid experience in the life of a physician. MNC/2005

11 man woman

12 The Doctor : a Gynecologist? If so What is in his/her mind? WHI? Million WS? What does he/she know about it? What is he/she afraid of? Cancer? TED? How does he/she practice Medicine? How should midaged women be taken care of?

13 What has experience thought me over the years about how to give QoL after the menopause:

14 Is there a Menopausal Medicine? There is only ONE Medicine (L. Speroff) There are only TWO Medicines (M.N.C.): a BAD Medicine and a GOOD Medicine

15 Therefore, what we must learn, is how to practice a GOOD MEDICINE! mnc/05

16 We are drowning in information, but starved for knowledge John Naisbilt

17 then... how is Medicine practiced today?

18 There are two types of medical practice: the Medicine for one individual, at a time (Clinical Medicine) the Medicine for many individuals, the population, at the same time, (Social Medicine,Public Health Medicine) MNC/05

19 Who are the actors? The practitioner Is a clinician Sees patients in the office Treats individuals Works in Hospitals The public health doctor Is not a clinician Does not see patients in an office Does not treat individuals Works in a Public Health department

20 Concerns of the Doctor of an individual (practitioner) Absolute risk reduction Absolute risk increase Benefit/risk analisys The Public Health Doctor Relative risk reduction Relative risk increase Cost/benefit analysis

21 But... today... many practitioners Act in their offices as if they were public health doctors... and many public health doctors Act in their departments as if they were clinicians... This is wrong!

22 WHI results calculated as: NNT/1 year NNH/1 year CHD 1428 Stroke 1250 VTE 588 Breast Cancer 1250 Colon Cancer 1667 Osteoporotic fractures 227 Neves-e-Castro M. Menopause in crisis post-women s health Initiative? A view based on personal clinical experience. Human Reproduction 2003;18:2512-8

23 Public Health doctors are guided by what epidemiologists suggest... but... most epidemiologists only establish associations of events and seldom determine cause/effect relationships MNC/05

24 Practioners are guided: by the best available information that can be extrapolated with validity to their patients, and by their acumulated experience MNC/05

25 thus... both,the practitioners who act as if they were public health doctors, and the public health doctors who act as if they were clinicians, should not overemphasize the epidemiological associations of events that are not necessarily cause/effect findings MNC/05

26 We must manage our Clinical Practice by objectives: - Critical Objectives (C.O.) - Specific Objectives (S.O.) - S.O. Targets (S.O.T.) - S.O. Projects (S.O.P.)

27 Critical Objectives a) The diagnosis of health b) The identification of risk factors c) The presence of symptoms gender related age related hormone related

28 Critical Objectives d) The treatment of symptoms e) The elimination of risk factors f) The diagnosis of diseases g) The treatment of diseases

29 Specific Objectives (S.O.) 1. CVD and metabolic diseases a) obesity b) dislipidemias c) hypertension d) insulin resistance (metabolic syndr.) etc

30 S.O. 2. CNS a) vasomotor symptoms b) mood, sleep c) sexual disfunctions, libido, etc

31 S.O. 3. Bone a) osteoarticular, etc

32 S.O. 4. Reproductive organs - vaginal discharges - atrophic vaginitis - fibroids - meno and metrorrhagia, etc

33 S.O. 5. Breast lumps and tenderness, etc

34 S.O. 6. Bladder incontinence chronic cystitis, etc

35 7.Contraception S.O.

36 S.O. Targets 1. exercise 2. nutrition 3. mental health 4. sexual conseling 5. pharmacotherapy a) hormonal b) non-hormonal

37 S.O. Projects (treatments) P, E+P, E Androgens Ca + vit D Bisfosfonates, Strontium Statins IACE Diuretics α and β Blockers Aspirin Serm s Tibolone Gabapantin Psychotherapy etc routes, schemes of administration

38 and now think about the interelation of CVD, Osteoporosis and Obesity... since they seem to share common risk factors...

39 The unified hypothesis of interactions among the bone, adipose and vascular systems: 'osteo-lipo-vascular interactions'. Epidemiological evidence has established a link among hyperlipidemia, visceral obesity, osteoporosis, and cardiovascular diseases (CVD). Koshiyama H et al. Med Hypotheses 2006;66:960-3

40 The unified hypothesis of interactions among the bone, adipose and vascular systems: 'osteo-lipo-vascular interactions'. The unified hypothesis of three organs, which we call 'osteo-lipo-vascular interactions', may be explained by the common origin of the cells in each organ. Koshiyama H et al. Med Hypotheses 2006;66:960-3

41 The unified hypothesis of interactions among the bone, adipose and vascular systems: 'osteo-lipo-vascular interactions'. The mesenchymal stem cells are capable of differentiating into osteoblasts, vascular smooth muscle cells, and adipocytes. Koshiyama H et al. Med Hypotheses 2006;66:960-3

42 The unified hypothesis of interactions among the bone, adipose and vascular systems: 'osteo-lipo-vascular interactions'. Alternatively, macrophages may evolve into osteoclasts or infiltrate both the vascular and adipose tissues, thereby leading to chronic inflammation. Koshiyama H et al. Med Hypotheses 2006;66:960-3

43 Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Elevated LDL and low HDL cholesterol are associated with LBMD; altered lipid metabolism is associated with both bone remodeling and the atherosclerotic process, which might explain, in part, the co-existence of osteoporosis and atherosclerosis in patients with dyslipidemia. Similarly, inflammation plays a pivotal role in both atherosclerosis and osteoporosis. McFarlane SI et al. Encdocrine 2004;23:1-10

44 Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Elevated plasma homocysteine levels are associated with both CVD and osteoporosis. McFarlane SI et al. Encdocrine 2004;23:1-10

45 Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Nitric oxide (NO), in addition to its known atheroprotective effects, appears to also play a role in osteoblast function and bone turnover. McFarlane SI et al. Encdocrine 2004;23:1-10

46 Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Statins, agents that reduce atherogenesis, also stimulate bone formation McFarlane SI et al. Encdocrine 2004;23:1-10

47 Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Bis- phosphonates, used in the treatment of osteoporosis, have been shown to inhibit atherogenesis. Intravenous bisphosphonate therapy significantly decreases serum LDL and increases HDL in postmenopausal women McFarlane SI et al. Encdocrine 2004;23:1-10

48 anyway,and in the light of the present evidence, doctors and women should be reassured that the suggested HT s for the relief of symptoms in the menopause are safe and very effective!

49 Many women taking hormones were urged by their physicians to stop taking these medications immediately or decided to stop taking them on their own. Petitti DB. JAMA. 2005;294:

50 Convictions are more dangerous enemies of thruth than lies Friedrich Wilhelm Nietzsche

51 Based on the WHI study group, implementation of the results into clinical practice has little, if any, scientific basis. Adam Ostrzenski and Katarzyna M Ostrzenska. Am J Obst Gynecol 2005;193:

52 The applicability of the WHI findings to women between age of 51.1 and 56.1 years and younger is unknown... Ostrzenski A and Ostrzenska KM. Am J Obst Gynecol 2005;193:

53 The WHI Estrogen only arm

54 Effects of conjugated Equine Estrogen in Postmenopausal Women with Hysterectomy.JAMA, 2004;291:

55

56

57 Stroke In women years not taking HT, ischemic stroke is expected to occur in 3 out of 1000 women during 5 years. Five years use of HT would yield 1 additional case of stroke/ 1000 women EMAS Statement; 2004.

58

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60 Biased opinions be they pro or con, dishonor the profession and harm our patients. Sacket DL. The arrogance of preventive medicine. Can Med Assoc J 2002;167:

61 Then, why all this noise?... Mainly because the conclusions of recent trials were severely misinterpreted by the medical professionals, the media and by the women, themselves MNC/05

62 Causes of Death Among Women* Other Cancers Breast Cancer 34% Diabetes Chronic Lower Respiratory Disease 4% 3% 6% 15% Heart Disease Other 28% 10% Cerebrovascular Disease *Percentage of total deaths in 1999 among women aged 65 years and older. Anderson RN. Natl Vital Stat Rep. 2001;49:1-13.

63 Hormones and the Heart 1 in 3 women will die from coronary heart disease (CHD) in the USA. 1 in 25 women will die from breast cancer Fitzpatrick LA. JCEM 2003;88(12):

64 HRT is associated with a 35% reduction in mortality for women who suffered myocardial infarction. Shlipack MG, Angeja B, Go AS, et al Circulation 2001;104:

65 Effect on the risk of CHD WHI Significant increased risk RR 1.29 (CI ); 29 % increased risk AR 0.37% vs 0.30% (ie, 37 vs 30 events annually per women) HERS Nonsignificant decreased risk RR 0,99 (CI ); 1% decreased risk AR 3.66% vs 3.68% (ie, 366 vs 368 events annually per women)

66 NNH / Year (Number Needed to Harm) (the reciprocal of the AR,or of the atributable AR) Coronary Heart Disease WHI (RR 1.29) 1428 HERS (RR 0.99) 5000 Breast Cancer WHI (RR 1.26) 1250 HERS (RR 1.27) 833 MNC

67 Not everything that can be counted counts; and not everything that counts can be counted Albert Einstein

68 Hormone replacement therapy: where to now? Recent studies suggest HRT may inhibit the process of atherosclerosis in healthy arteries soon after menopause, and observational studies (NHS, updated 2006) in younger women starting HRT strongly suggest a potential cardiovascular benefit Mikkola TS, Clarkson TB. Cardiovasc Res 2002;53:

69 Lessons from the WHI most articles and broadcast segments tended to focus exclusively on either the small absolute risks or the larger relative risks, neglecting the more even-handed picture that presented both. Since the sharply increased relative risks got the most play, news coverage about the trial s findings had an alarming cast. Denzer S. Editorial. Ann Intern Med.2003;138:

70 WHI: Now that the dust has settled To publish data that may or may not be entirely true or certainly premature is a disservice to the medical profession and, most important, to our patients. The majority of the data that were published is not statistically significant even at the nominal level. Creasman WT. et al. Am J Obst Gynecol 2003;189:

71 Recent reports did not find, for continuous combined treatments, any increased risk of either CHD or breast cancer. The difference from WHI being that women were younger, symptomatic and with lower body weights Heikkinen J. NAMS 2004, Abstract LB38 Lobo R. Arch Int Med 2004;164:

72 At the moment, I believe we can say with relative certainty that hormone therapy in younger postmenopausal women results in lower coronary heart disease events and total mortality. Salpeter S. Climacteric 2005;8:

73 An update of the WHI Study! WHI investigators reported (Feb 2006) a statistically significant (34%) lower risk for the combined endpoint of myocardial infarction (heart attack), coronary death, coronary revascularization and confirmed angina among women who were between the ages of 50 and 59 at the start of the study (RR 0.66; 95% CI ). Hsia J et al.arch Intern Med 2006;166:

74 Younger Women May Receive Heart Protection From Estrogen Therapy In women ages who had undergone a hysterectomy, a significant protective effect of estrogen treatment, when both primary (heart attacks and heart attack death) and secondary (coronary artery bypass surgery, angioplasty, confirmed angina pectoris) cardiac endpoints were considered. Dr. S. Mitchell Harman, director and president of Phoenix-based Kronos Longevity Research Institute (KLRI) in Archives of Internal Medicine 2006;106:

75 Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heart disease. Arch Int Med 2006;166:357-65

76 Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heart disease. Arch Int Med 2006;166:357-65

77 Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heart disease. Arch Int Med 2006;166:357-65

78 Press Statement IMS In a subgroup of women demographically similar to those in the WHI, there was no significant relation between HT and CHD among women who initiated therapy at least 10 years after the menopause (RR = 0.87, 95% CI for estrogen alone; RR = 0.90, 95% CI for estrogen with progestogen). Feb 2006

79 Press Statement IMS The estrogen plus progestogen arm of the WHI and the estrogen-alone arm actually showed that HT does not increase the risk of coronary heart disease in the peri- and early menopause, and may even carry beneficial effects. Feb 2006

80 Press Statement IMS The WHI study was not designed, and therefore was not powered, to investigate the consequences of hormone therapy (HT) in women below 60 years of age. Therefore, any attempt to present the results of the study as indicating that HT may inflict damage to the heart in general a message that was accepted by many medical societies and regulatory Authorities is simply wrong and must be amended.

81 Breast Cancer

82 Menopausal women and their doctors are scared about the side effects of HRT mainly about breast cancer MNC/05

83 It must be emphasized that we are talking about an increased incidence of the disease, which does not automatically translate into an increase in deaths from the disease. Baum M. The Breast 2005;14:178-80

84 Extended use of estrogen for 10 years increases risks by 0,5%, and by 15 years increases risks by 0,9% but.. upon cessation of HRT, the relative risk quickly returns to 1.0! Coombs N J, Taylor R, Wilcken N. and Boyages J. BMJ 2005;331:

85 Breast Cancer The diagnosis of a breast cancer after the initiation of a HRT (with a duration of less than 5 years) is only a proof of its growth stimulatory effect (not of its carcinogenic effect) Therefore, the reversal of the risk to 1 after the cessation of HRT confirms again only its growth promoting effect and denies a carcinogenic effect. Dietel M., Lewis MA. and Shapiro S. Human Reproduction 2005;20:

86 Breast Cancer The doubling time of an initial cancer cell, up to the diagnosis of a resultant 1cm tumor, is most likely greater than 10 years. This is why many dormant cancer cells may exist in a normal breast! MNC/05

87 Occult Breast Cancer Clinically occult in situ BC s are frequent in young and middle-aged women. Nielsen M et al-br J Cancer 1987;56:814-9

88 Occult Breast Cancer Breast malignancy was found in 22 women (20%) Nielsen M et al-br J Cancer 1987;56:814-9

89 Thus Mammographies give more false negative than false positive results! A normal mammography does not exclude the presence of cancer cells that may explode a few months later MNC/05

90 Estrogen replacement therapy in patients with early breast cancer The mortality rates from breast cancer for the ERT users was 4.28% compared with 22.3% in the nonusers. Natrajan PK and Gambrell RD. Am J Obstet Gynecol 2002;187:289-95

91 Recurrent breast cancer was found in 9% of HRT users and 15% of nonuser. O Meara ES et al.jnci 2001;93:

92 Mortality following development of breast cancer while using oestrogen or oestrogen plus progestin: W Chen, DB Petitti and AM Geiger. British Journal of Cancer 2005;93:

93 This study explored survival after exposure to oestrogen or oestrogen plus progestin at or in the year prior to breast cancer diagnosis oestrogen plus progestin users had lower all-cause mortality and breast cancer mortality Chen W, Petitti DB and Geiger AM. British Journal of Cancer 2005; 93:

94 Breast cancer survival after hormone exposure

95 Overall survival after hormone exposure

96 A menopausal woman expects from her attending physician to be receptive to all of her complains, to understand her psychic and physical concerns, to support her insecurity and to help overcome her crisis. MNC/05

97 Many Doctors fail to persuade them to go on with HRT, in despite of telling that the benefits are far greater than any potential risk MNC/05

98 One may easily conclude that without an adequate technique of communication, using the proper language, there is no possible help Thus, physicians must acquire expertise in the technique of communication MNC/05

99 then... let us talk about Risks...

100 Are there risks? It is crucial that information be given about the difference between relative risks and absolute risks, since the latter are the major cause of misinformation and alarmism, being the favorites of the media MNC/05

101 Example of Risks If you buy one lottery ticket you will have a one in 1 million chance of winning ( absolute risk ) 1x 10 6 If you buy five lottery tickets your chances are five fold higher or 5 in one million ( absolute risk ) 5x 10 6 Your chances of winning are increased by five fold ( relative risk ) 5.0

102 Relative Risk The risk of an event occuring under certain circumstances compared to the risk under other circumstances

103 Attributable or Excess Risk The difference between underlying risk and risk when receiving HT is called the attributable or excess risk

104 Do not confuse Relative Risk with Absolute Risk!

105 Conclusion Relative risk is a confusing word and is only important if the absolute chances of an event are high Attributable or excess risk is the thing that one should be most concerned about

106 Validity Internal: the study measured what is set out to measure External: the results can be extrapolated to one s patients Observational research (NHS) may have poorer internal validity better external validity Randomized controlled trial (WHI) better internal validity poorer external validity MNC/04

107 Confidence interval (C.I.) A 95% C.I. signifies that there is a 95% chance that the population true value lies between the two limits. If C.I. crosses the line of no difference the point at which a benefit becomes a harm (i.e.1) then one can conclude that the results are not statiscally significant MNC/04

108 Risks of women medicated with E+P (5.2 years) women

109 Risks of women medicated with E only (6.8 years) women

110 Risks of Breast Cancer according to different factors

111 It appears that half of the benefits in the prevention of cardiovascular diseases are not hormone related! Mosca L, Grundy SM, Judelson D, et al. Circulation 99;99:2480-4

112 Nurses s Health Study from 1980 to 1994 CHD 31% Smoking 13% Obesity 8% THS 9% Better nutrition 16% Hu FB, Grodstein F et al. Trends in the Incidence of Coronary Heart Disease and Changes in Diet and Lifestyle in Women. NEJM 2000;343:

113 Can side effects be minimized?

114 What about the best treatments during the climacterium and beyond? Little attention is paid to other pharmacological interventions (non hormonal) and strategies that have been shown to be important for the prevention of diseases and to maintain or improve health. MNC/05

115 Hippocrates promoted specific diets to prevent and cure diseases, such as illnesses of the heart. Lyons AS et al. In Medicine: an illustrated History. New York:Abradale Press,1990:20719

116 The Polymeal Franco O et al. BMJ 2004;329:

117 Doctors could retrain as Polymeal chefs or wine advisers The Polymeal an evidence based menu that includes, wine, fish, dark chocolate fruits, vegetables, garlic, and almonds promises to be an effective, safe, cheap, and tasty solution to reducing cardiovascular morbidity and increasing life expectancy. Polymeal could reduce cardiovascular disease by more than 75%. Franco O et al. BMJ 2004;329:

118 The Polypill Wald N and Law M. BMJ 2003;326:

119 Wald N and Law M. BMJ 2003;326:

120 One third of people taking this pill from age 55 would benefit, gaining on average about 11 years of life free from an IHD event or stroke. Wald N and Law M. BMJ 2003;326:

121 Moderate exercise cuts breast cancer biomarkers in postmenopausal women Increased physical activity significantly reduces serum estrogens in postmenopausal women and thus may reduce the risk of breast cancer. McTiernan A. Cancer Res 2004;364:2923-8

122 Aspirin could be used to prevent cancer Three recently published studies indicate that aspirin, already enjoying a second lease of life in the prevention of heart disease, may soon become a first line of defense against cancer. London O. BMJ 2003;326:565

123 In conclusion and to make a long story short

124 There are no really safe biological active drugs... There are only safe physicians! Kaminetzy HA 1993

125 Each time we learn something new, the astonishment comes from the recognition that we were wrong before In truth, whenever we discover a new fact, it involves the elimination of old ones... thus, as it turns out, WE ARE ALWAYS IN ERROR! Lewis Thomas English Biologist ( )

126 My Message is:.to prescribe postmenopausal hormonal treatments when clinically indicated, if not contraindicated. No answers from ongoing clinical trials are indispensable to practice today a good Medicine MNC/05

127 To know the disease that a woman has is as important as to know the woman who has the disease William Osler

128 What are the best recommendations of the climacteric woman s doctor? 1. Understand what is happening to the body during the climacteric and the postmenopause 2. Mental occupation 3. Physical exercise 4. Proper nutrition (moderate consumption of red wine, and abundant fish, vegetables, fruits, soy, milk, garlic, chocolate, etc) 5. Keep the body mass index (BMI) within normal limits 6. Keep a normal girdle/hip ratio, waist circumference 7. Refrain from smoking 8. Keep a normal blood pressure 9. Keep the blood lipids within normal values (statins?) 10. Examine the breasts (palpation, inspection, mammography)

129 What about the best treatments during the climacterium and beyond? There is a general tendency to consider that sex steroid hormones are the only instruments with which to treat women when they enter in the climacteric phase of their lives MNC/05

130

131 Which is the best treatment? In general terms, is the one that is wisely indicated, if not contraindicated, after balancing benefits and risks, of all strategies and interventions, hormonal or not. It must be aimed at specific objectives and targets that will be monitored at regular intervals in order to determine its efficacy and to estimate the occurrence of any side effects, a condition that will determine its duration. MNC/05

132 Which is the best treatment? Patient needs and preferences are decisive, based on the doctors advice. Let it not be forgotten that although many treatments are available, they are nevertheless not indispensable. Doctors have the duty to give their best unbiased information to their patients so that they may make the right choices and then be compliant. The woman is the decision maker, if the doctor sees no contraindication. thus, the best treatment is what a well informed woman has chosen. MNC/05

133 I personally believe that for the healthy early post menopausal woman the long term HT s, other than relieving vasomotor symptoms, may play an important role in improving QoL and in the prevention of CVD, osteoporosis and Alzheimer, under surveillance. Systemic (parenteral) estrogens, added when needed to vaginal progesterone or progestagen loaded IUD s, may be very beneficial, largely overpassing minimal risks. MNC/05

134 The conclusions of the WHI trial suggest that the safe woman (NNH between women) to initiate HT is - between years of age - with vasomotor symptoms - less than 10 years after the menopause - being treated with statins - with a good lipid profile and - with a Body Mass Index >25 Neves-e-Castro M. Human Reproduction 2003;18:

135 This is precisely the profile of the great majority of women who come for consultation after their menopause. Therefore it seems that what most gynecologists are doing to their predominant population of patients is not unsafe and contributes not only to a good quality of life but to prevention, as well. Neves-e-Castro M. Human Reproduction 2003;18:

136 Postmenopausal hormone therapy: critical reappraisal and unified hypothesis 83:558-66

137 Do others agree?

138 He who learns, but does not think is lost. He who thinks, but does not learn is dangerous. Confucius

139 If we both learn and think we will neither be lost nor dangerous to our postmenopausal women patients Wenger NK. Am J Geriatr Cardiol 2000;9:204-9

140 NAMS position statement on estrogen and progestagen use in peri-and postmenopausal women Revised breast cancer statements indicate that the risk of breast cancer probably increases with EPT use but not with ET use.

141 NAMS position statement on estrogen and progestagen use in peri-and postmenopausal women Place no limit on ET/EPT treatment duration, provided it is consistent with treatment goals; if monitored regularly, no stipulation is made regarding when to reduce or stop therapy

142 If there are no incoming contraindications we see no reason to establish a time limit to the duration of therapy, mainly if there is a recovery of symptoms after its discontinuation Cochrane B, NAMS 2004, P53 IMS NAMS

143 Evidence informed practice It is clearly time to change evidence based medicine to evidence informed practice. I suggest the era of evidence informed rather than evidence based medicine has arrived Glasziou P. Centre for Evidence-Based Medicine. University of Oxford OX3 7LF. BMJ 2005;330:92

144

145 What has been learned from the major observational studies and clinical trials? the first lesson systematically administered progestagens may in part suppress some of the beneficial effects of estrogens and may also slightly increase the risk of breast cancer after treatments with duration greater than five years.

146 What has been learned from the major observational studies and clinical trials? the second lesson estrogens, when given alone to histerectomized women, did not appear to minimally affect the risk for breast cancer when compared with controls MNC/05

147 What has been learned from the major observational studies and clinical trials? the third lesson Metabolic effects of estrogens and progestagens, as a whole, can differ depending on the route of administration, i.e. oral vs. parentheral, and on the combination of both, in a sequential regimen or in continuous combined administration. MNC/05

148 What has been learned from the major observational studies and clinical trials? the fourth lesson Hormonal treatments are the first choice for vasomotor symptom relief as long as they are needed (on and off assessment). They should not be used for the secondary prevention of CVD, when atheroma plaques are already present. MNC/05

149 What has been learned from the major observational studies and clinical trials? the fourth lesson (cont) Conversely, they may protect from CVD if started early during the transition into the post menopause. Hormonal treatments are preventive of osteopenia and osteoporosis at any stage in life MNC/05

150 What has been learned from the major observational studies and clinical trials? the fifth lesson Estrogens may prevent degenerative lesions of the CNS since, so far, they seem to be the only available drugs with nerve growth effects MNC/05

151 Preventing a woman from the benefits of a sound postmenopausal hormone therapy because of the fear of rare side effects does not seem to be satisfactory Medicine... M.Neves-e-Castro, 2000

152 Primum non nocere : neither by excess, nor by deffect M.Neves-e-Castro

153 and now... see the differences... in QoL :

154 like this one?...

155 Secret for longevity!

156 Secret for longevity A passerby noticed an old lady sitting on her front step: I couldn t help noticing how happy you look! What is your secret for such a long, happy life?

157 Secret for longevity A passerby noticed an old lady sitting on her front step: I couldn t help noticing how happy you look! What is your secret for such a long, happy life?! I smoke 4 packs of cigarettes a day, she said. Before I go to bed, I smoke a nice big joint. Apart from that, I drink a whole bottle of Jack Daniels every week, and eat only junk food. On weekends I pop a huge number of pills and do no exercise at all.

158 Secret for longevity A passerby noticed an old lady sitting on her front step: I couldn t help noticing how happy you look! What is your secret for such a long, happy life?! This is absolutely amazing at your age!!!!, says the passerby. How old are you?

159 I m 24 years old...

160 or like these?

161 MEDICINE! (hormones, life style, nutrition, exercise, etc) They are living after MATURE WOMEN S

162 A WOMAN in the autumn of her life deserves an indian summer rather than a winter of discontent... Robert B Greenblatt

163 and now... this is not the end... nor even the begining of the end. It is perhaps, the end of the begining! Winston Churchill

164 This is what I have learned thank you