Florençafinal corrigida


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  • In contrast with the previous slide of perceived health concerns, this slide shows actual rates for cause of death. What is apparent is that a generalized fear of cancer, and breast cancer specifically, skews postmenopausal women’s understanding of their health risks. Such misinformation often represents a barrier when women make decisions about ET/HT. Although the results of the WHI trial have provided and will continue to provide valuable information on the effects of various preventive strategies on chronic disease in menopausal women, they are unlikely to change this misperception. Anderson RN. Deaths: leading causes for 1999. Natl Vital Stat Rep . 2001;49:1-13.
  • Florençafinal corrigida

    1. 1. The Climacteric Woman treatment options in 2006 : what has experience taught me Manuel Neves-e-Castro, MD Lisbon, Portugal, 2006
    2. 2. I am - a normal human being - a medical doctor - a feminologist (gender medicine) - a gynecologist - an endocrinologist
    3. 3. But... certainly I am nota menopausologist ...
    4. 4. Is there a Menopausal Medicine?There is only ONE Medicine (L.Speroff)There are only TWO Medicines (MNC):a BAD Medicine anda GOOD Medicine
    5. 5. Therefore,what we must learn,is…how to practice a GOOD MEDICINE! mnc/05
    6. 6. Looking after a menopausal woman is amost fascinating, gratifying and complex vivid experience in the life of a physician. MNC/05
    7. 7. • It is fascinating – because one is dealing with the holistic dimension of a woman’s life where there is the interplay of her macro and micro social environments, of her self and her id , and of all her body functions. MNC/05
    8. 8. • It is gratifying – because the help of a physician who is well aware of that holistic dimension may lead to very positive results in terms of the quality of her life, that are the best reward for a health care giver. MNC/05
    9. 9. • It is complex – because the abundance of specific medical literature, and its often misinterpreted results, leads to a climate of scare of potential risks that overcomes the known benefits of treatments. MNC/05
    10. 10. DefinitionA Climacteric woman is a woman (gender based medicine) is an aging person (geriartrics) is perimenopausal (hormone deficient)
    11. 11. Managing byObjectives:
    12. 12. Critical Objectivesa) The diagnosis of healthb) The identification of risk factorsc) The presence of symptoms • gender related • age related • hormone related
    13. 13. Critical Objectivesd) The treatment of symptomse) The elimination of risk factorsf) The diagnosis of diseasesg) The treatment of diseases
    14. 14. Specific Objectives (S.O.)1. CV and metabolic a) obesity b) dislipidemias c) hypertension d) insulin resistance
    15. 15. S.O.2. CNS a) vasomotor symptoms b) mood, sleep c) sexual disfunctions, libido
    16. 16. S.O.3. Bone a) osteoarticular
    17. 17. S.O.4. Reproductive organs - vaginal discharges - atrophic vaginitis - fibroids - meno and metrorrhagia
    18. 18. S.O.5. Breast lumps and tenderness
    19. 19. S.O.6. Bladder incontinence chronic cystitis
    20. 20. S.O.7.Contraception
    21. 21. S.O. Targets1. exercise2. nutrition3. mental health4. sexual conseling5. pharmacotherapy a) hormonal b) non-hormonal
    22. 22. S.O. TreatmentsP, E+P, EAndrogensCa + vit Dbisfosfonates, strontiumStatins, IACE, diuretics, α and β blockersaspirinpsychotherapySerm’stibolonegabapantinroutes, schemes
    23. 23. Causes of Death Among Women* Other Cancers Heart Disease 15% Breast Cancer 34% 4% Diabetes 3%Chronic Lower 6% Respiratory Disease 28% 10% Other 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.
    24. 24. In the light of present evidence,doctors and women should bereassured that the suggested HT’s forthe relief of symptoms in themenopauseare safe and very effective
    25. 25. There are controversies about thepresent management of theclimacterium 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• 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”
    26. 26. Many women taking hormones wereurged by their physicians to stop takingthese medications immediately ordecided to stop taking them on their own. Petitti DB. JAMA. 2005;294:245-246.
    27. 27. Based on the WHI study group,implementation of the resultsinto clinical practice has little, ifany, scientific basis.Adam Ostrzenski and Katarzyna M Ostrzenska. Am J Obst Gynecol2005;193:1599-604
    28. 28. The applicability of the WHIfindings to women between age of51.1 and 56.1 years and younger isunknown. Ostrzenski A and Ostrzenska KM. Am J Obst Gynecol 2005;193:1599-604
    29. 29. “W I: Now that the dust has settled…” H • 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. Creasm W et al. Am JObst Gynecol 2003;189:621-626 an T.
    30. 30. “Lessons from the WHI”“…most articles and broadcast segmentstended to focus exclusively on either the sm allabsolute risks or the larger relative risks,neglecting the more even-handed picture thatpresented both.Since the sharply increased relative risks gotthe most play, news coverage about the trial’sfindings had an alarming cast.” De nz e r S. Editorial. A I rn M d . 2 0 0 3 ; 1 3 8 : 3 5 2 -3 5 3 nn nte e
    31. 31. Biased opinionsbe they pro or con,dishonor the professionandharm our patients.Sacket DL. The arrogance of preventive medicine. Can Med Assoc J2002;167:363-364
    32. 32. NNH / Year (Number Needed to Harm)Coronary Heart Disease W (RR 1.29) HI 1428 HERS (RR 0.99) 5000Breast Cancer W (RR 1.26) HI 1250 HERS (RR 1.27) 833 MNC
    33. 33. Effects of conjugated Equine Estrogen in Postmenopausal Womenwith Hysterectomy.JAMA, 2004;291:1701-1712
    34. 34. Stroke“In women 50-59 years not taking HT,ischemic stroke is expected to occur in3 out of 1000 women during 5 years.Five years use of HT would yield 1additional case of stroke/ 1000 women” EMAS Statement; 2004.
    35. 35. Then, why all this noise?...Mainly because the conclusions ofrecent trials were severely misinterpretedby the medical professionals, the mediaand by the women, themselves MNC/05
    36. 36. “We are drowing in information, but starved for knowledge” John Naisbilt
    37. 37. Practioners are guided:• by the best available information that can be extrapolated with validity to their patients,and• by their acumulated experience MNC/05
    38. 38. Public Health doctors are guided bywhat epidemiologists suggest ...but ...Most epidemiologists only establishassociations of events and seldomdetermine cause/effect relationships MNC/05
    39. 39. 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 theepidemiological associations of eventsthat are not necessarily cause/effectfindings
    40. 40. But ... today ...many • Act in their offices as if they were public health doctors...practitionersmanypublic health doctors • Act in their departments as if they were clinicians ... This is wrong!
    41. 41. Effect on the risk of CHDWHI Significant increased risk RR 1.29 (CI 1.02-1.63); 29 % increased risk AR 0.37% vs 0.30% (ie, 37 vs 30 events annually per 10.000 women)HERS Nonsignificant decreased risk RR 0,99 (CI 0.84-1.17); 1% decreased risk AR 3.66% vs 3.68% (ie, 366 vs 368 events annually per 10.000 women)
    42. 42. Hormones and the Heart1 in 3 women will die from coronary heartdisease (CHD) in the USA.1 in 25 women will die from breast cancer Fitzpatrick LA. JCEM 2003;88(12):5609-10
    43. 43. “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;104:2300-2304
    44. 44. Hormone replacement therapy: where to now?Recent studies suggest HRT may inhibitthe process of atherosclerosis inhealthy arteries soon after menopause,and observational studies in youngerwomen starting HRT suggest a potentialcardiovascular benefit Mikkola TS, Clarkson TB. Cardiovasc Res 2002;53:605-19.
    45. 45. Recent reports did not find, forcontinuous combined treatments, anyincreased risk of either CHD or breastcancer.The difference from WHI being thatwomen were younger, symptomaticand with lower body weightsHeikkinen J. NAMS 2004, Abstract LB38Lobo R. Arch Int Med 2004;164:482-484
    46. 46. • Manson et al reported a nonstatiscally significant decreased relative risk of cardiovascular events in hormone therapy users who were <10 years from the onset of menopause. Manson JE et al. JAMA 2002;288:321-33
    47. 47. Hormone therapy for youngerpostmenopausal women: how can we make sense out of the evidence? 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;8:307-310
    48. 48. Younger Women May Receive Heart Protection From Estrogen Therapy In women ages 50-59 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;106:357-363
    49. 49. WHI StudyWHI investigators reported a statisticallysignificant (34%) lower risk for the combinedendpoint of myocardial infarction (heart attack),coronary death, coronary revascularization andconfirmed angina among women who werebetween the ages of 50 and 59 at the start ofthe study (RR 0.66; 95% CI 0.45-0.96). Hsia J et al.Arch Intern Med 2006;166:357-363
    50. 50. Press Statement IMSThe estrogen plus progestogen arm of the WHIand the estrogen-alone arm actually showed thatHT does notincrease the risk of coronary heart disease inthe peri- and early menopause,and may even carry beneficial effects. Feb 2006
    51. 51. Press Statement IMSAlso, in a subgroup of women demographicallysimilar to those in the WHI, there was nosignificant relation between HT and CHD amongwomen who initiated therapy at least 10 yearsafter the menopause(RR = 0.87, 95% CI 0.69–1.10 for estrogen alone; RR = 0.90, 95% CI 0.62–1.29 for estrogen with progestogen). Feb 2006
    52. 52. Press Statement IMSThe WHI study was not designed, andtherefore was not powered, to investigate theconsequences of hormone therapy (HT) inwomen below 60 years of age. Therefore,any attempt to present the results of the studyas indicating that HT may inflict damage to theheart in general – a message that was acceptedby many medicalsocieties and regulatory Authoritiesis simply wrong and must be amended.
    53. 53. Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heartdisease. Arch Int Med 2006;166:357-65
    54. 54. Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heartdisease. Arch Int Med 2006;166:357-65
    55. 55. Hsia J, Langer RD, Manson J et al. Conjugated equine estrogens and coronary heartdisease. Arch Int Med 2006;166:357-65
    56. 56. Breast Cancer
    57. 57. Menopausal women and theirdoctors are scared about the side effects of HRT mainly about breast cancer MNC/05
    58. 58. Hormone replacement therapy and breast cancer: estimate of riskExtended use of estrogen for10 years increases risks by 0,5% ,and by15 years increases risks by 0,9%upon cessation of HRT, the relative riskquickly returns to 1.0 !Coombs N J, Taylor R, Wilcken N. Boyages J. BMJ 2005;331:347-349
    59. 59. Breast cancer and the use of HRT Considering 10.000 women on the combination HRT then for each year there would be: Seven additional cases of heart attacks Eight cases of stroke, Eight cases of pulmonary embolus, Eight cases of invasive breast cancer, Six fewer cases of hip fractures Baum M. The Breast 2005;14-178-80
    60. 60. Breast cancer survival and the use of HRT 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
    61. 61. 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
    62. 62. 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
    63. 63. 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;20:2052-60
    64. 64. Occult Breast CancerClinically occult in situBC’s are frequent inyoung and middle-agedwomen. Nielsen M et al-Br J Cancer 1987;56:814-9
    65. 65. Occult Breast CancerBreast malignancy wasfound in 22 women(20%) Nielsen M et al-Br J Cancer 1987;56:814-9
    66. 66. 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
    67. 67. Estrogen replacement therapy inpatients 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
    68. 68. “Recurrent breast cancer was found in 9% of HRT users and 15% of nonuser”. O’Meara ES et al
    69. 69. Mortality following development of breast cancer while usingoestrogen or oestrogen plus progestin: a computer record-linkage study W Chen, DB Petitti and AM Geiger. British Journal of Cancer (2005) 93, 392 – 398
    70. 70. This study explored survival afterexposure to oestrogen or oestrogenplus progestin at or in the year prior tobreast cancer diagnosisoestrogen plus progestin users had lowerall-cause mortality and breast cancermortalityChen W, Petitti DB and Geiger AM. British Journal of Cancer 2005 93, 392-398
    71. 71. Breast cancer survival after hormone exposure
    72. 72. Overall survival after hormone exposure
    73. 73. Breast cancer survival after hormone exposure
    74. 74. Overall survival after hormone exposure
    75. 75. A menopausal woman expects from her attending physicianto be receptive to all of her complains,to understand her psychic and physical concerns,to support her insecurity andto help overcome her crisis. MNC/05
    76. 76. One may easily conclude thatwithout an adequate technique ofcommunication, using the properlanguage,there is no possible helpThus,physicians must acquire expertise inthe technique of communication MNC/05
    77. 77. Talking about Risks...
    78. 78. Are there risks?It is crucial that information be givenabout the difference between relativerisks and absolute risks, since the latterare the major cause of misinformation andalarmism, being the favorites of themedia… MNC/05
    79. 79. Nurses’s Health Studyfrom 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 HeartDisease and Changes in Diet and Lifestyle in Women. NEJM2000;343:530-537.
    80. 80. “It appears that half of thebenefits in the prevention ofcardiovascular diseases arenot hormone related”! Mosca L, Grundy SM, Judelson D, et al. Circulation 99;99:2480-4
    81. 81. Can side effects be minimized ?
    82. 82. First of all, there are many differentpost-menopausal hormonetherapies: different estrogens,different progestins, differentroutes of administration, differentregimens, which have differentprofiles. Neves-e-Castro M. Maturitas 2001;38(3):235-237
    83. 83. Second, there are those who knowand those who do not know totailor-make it to a particular womanand to monitor its efficacy in thetargets that have justified itsselection. Neves-e-Castro M. Maturitas 2001;38(3):235-237
    84. 84. Third, there are those who thinkthat the menopause is a disease tobe treated solely with sexhormones, and there are thosewho believe that the menopause isan event in a mid-aged woman’slife. Neves-e-Castro M. Maturitas 2001;38(3):235-237
    85. 85. 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
    86. 86. The PolymealFranco O et al. BMJ 2004;329:1447-50
    87. 87. Doctors could retrain asPolymeal chefs or wine advisersThe Polymeal—an evidence based menu thatincludes wine, fish, dark chocolate, fruits,vegetables, garlic, and almonds—promises to be aneffective, safe, cheap, and tasty solution to reducingcardiovascular morbidity and increasing lifeexpectancy.Polymeal could reduce cardiovascular disease bymore than 75%. Franco O et al. BMJ 2004;329:1447-50
    88. 88. The PolypillWald N and Law M. BMJ 2003;326:1419-25
    89. 89. Wald N and Law M. BMJ 2003;326:1419-25
    90. 90. A strategy to reducecardiovascular disease by more than 80%One third of people taking this pill from age 55would benefit, gaining on average about 11years of life free from an IHD event orstroke. Wald N and Law M. BMJ 2003;326:1419-25
    91. 91. 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
    92. 92. Aspirin could be used to prevent cancerThree recently published studies indicatethat aspirin, already enjoying a secondlease of life in the prevention of heartdisease, may soon become a first line ofdefense against cancer. London O. BMJ 2003;326:565
    93. 93. “Not everything that can becounted counts;and not everything thatcounts can be counted” Albert Einstein
    94. 94. “There are no really “safe”biological active drugs. There are only “safe” physicians” K inetzy H 1 9 9 3 am A
    95. 95. ?
    96. 96. In conclusion …and to make a long story short…
    97. 97. 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)
    98. 98. 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
    99. 99. Let us not medicalize theMenopause..instead… Let us holistically approach the Climacteric and Aging Women. MNC /05
    100. 100. To know the disease a woman hasis as important asto know the woman who has thedisease William Osler
    101. 101. “Each time we learn something new,the astonishment comes from therecognition that we were wrongbefore.In truth, whenever we discover a new fact, itinvolves the elimination of old ones.WE ARE ALWAYS, as it turns out,fundamentally IN ERROR.” Lewis Thomas English Biologist (1913-1993)
    102. 102. What about the best treatments during the climacterium and beyond?There is a general tendency to considerthat sex steroid hormones are the onlyinstruments with which to treat womenwhen they enter in the climacteric phaseof their lives… MNC/05
    103. 103. What about the best treatments during the climacterium and beyond?However, little attention is paid to otherpharmacological interventions (nonhormonal) and strategies that have beenshown to be important for theprevention of such diseases and tomaintain or improve health. MNC/05
    104. 104. Which is the best treatment?In general terms, is the one that is wiselyindicated, if not contraindicated, afterbalancing benefits and risks, of all strategiesand interventions, hormonal or not.It must be aimed at specific objectives andtargets that will be monitored at regular intervalsin order to determine its efficacy and to estimatethe occurrence of any side effects, a conditionthat will determine its duration. MNC/05
    105. 105. Which is the best treatment?Patient needs and preferences are decisive, based onthe doctors’ advice. Let it not be forgotten that althoughmany treatments are available, they are neverthelessnot indispensable. Doctors have the duty to give theirbest unbiased information to their patients so that theymay make the right choices and then be compliant.The woman is the decision maker, if the doctor seesno contraindication.Thus,the best treatment is what she haschosen. MNC/05
    106. 106. The conclusions of these studies suggest thatthe “safe “ woman (NNH between 600-1000 women) to initiate HT is - between 50-59 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;18:2512-2518
    107. 107. 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;18:2512-2518
    108. 108. I personally believe that in the healthy earlypost menopausal woman the long term HT’s,other than relieving vasomotor symptoms,may play an important role in improving QoLand in the prevention of CVD, osteoporosisand Alzheimer, under surveillance.Systemic estrogens, added when needed tovaginal progesterone or progestagen loadedIUD’s, may be very beneficial, largelyoverpassing minimal risks.The well-informed woman will be the onlydecision- maker. MNC/05
    109. 109. Continuous combined parenteral estrogen substitution and intrauterine progestogen delivery:the ideal HST combination?Wildemeersch D, Janssens D and Weyers S. Maturitas 2005;51:207-214
    110. 110. Continuous intrauterine compared with cyclic oral progestinadministration in perimenopausal HRT This method of HRT with the Lng-IUD’s as progestin delivery system is efficient in protecting the endometrium against hyperplasia, and will make withdrawal bleedings unnecessary. Boon J et al. Maturitas 2003;46:69-77
    111. 111. Relationship between breast cancer and use of the levonorgestrel-IUD These results suggest that the use of the levonorgestrel-releaing intrauterine system is not associated with an increased risk of breast cancerBackman T et al. Obstet & Gynecol 2005;106:813-7
    112. 112. Tibolone improves myocardialperfusion in postmenopausal women with ischemic heart disease: an open-label exploratory pilot study.In postmenopausal women with ischemic heartdisease, six months of therapy with tibolonesignificantly improved stress myocardialperfusion and the "amount of ischemia."Campisi R et al. J Am College Cardiol 2006;47:559-564
    113. 113. Postmenopausal hormone therapy: critical reappraisal and unified hypothesis 83:558-66
    114. 114. NAMS position statement onestrogen and progestagen use inperi-and postmenopausal women Revised breast cancer statements indicate that the risk of breast cancer probably increases with EPT use but not with ET use.
    115. 115. NAMS position statement onestrogen and progestagen use inperi-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
    116. 116. If there are no incoming contraindicationswe see no reason to establish a time limitto the duration of therapy, mainly if there isa recovery of symptoms after itsdiscontinuationCochrane B, NAMS 2004, P53IMS www.imsociety.orgNAMS www.menopause.org
    117. 117. What has been learned from themajor 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. MNC/05
    118. 118. What has been learned from themajor observational studies and clinical trials?the second lessonestrogens, when given alone tohisterectomized women, did not appear tominimally affect the risk for breast cancerwhen compared with controls MNC/05
    119. 119. What has been learned from themajor observational studies and clinical trials?the third lessonMetabolic effects of estrogens andprogestagens, as a whole, can differdepending on the route of administration, i.e.oral vs. parentheral, and on the combination ofboth, in a sequential regimen or in continuouscombined administration. MNC/05
    120. 120. What has been learned from themajor observational studies and clinical trials?the fourth lessonHormonal treatments are the firstchoice for vasomotor symptom reliefas long as they are needed (on and offassessment). They should not be used forthe secondary prevention of CVD, whenatheroma plaques are already present. MNC/05
    121. 121. What has been learned from themajor observational studies and clinical trials?the fourth lesson (cont.)Conversely ,they may protect from CVDif started early during the transitioninto the post menopause.Hormonal treatments are preventive ofosteopenia and osteoporosis at anystage in life MNC/05
    122. 122. What has been learned from themajor observational studies and clinical trials?the fifth lessonEstrogens may prevent degenerativelesions of the CNS since, so far, theyseem to be the only available drugs withnerve growth effects MNC/05
    123. 123. Convictions are moredangerous enemies of thruththan lies Friedrich Wilhelm Nietzsche
    124. 124. A WOMAN in the autumn of her lifedeserves an indian summer rather than a winter of discontent ... Robert B Greenblatt
    125. 125. This is what I have learned