emas curso

The Doctor, the Patient and The Doctor, the Patient and QoLQoL

by

Manuel Neves-e-Castro

Lisboa-Portugal

The Doctor, theThe Doctor, the Woman Woman and and QoLQoL

There are controversiescontroversies about the present management of the climacterium which are due to:

• a lack of culturelack of culture that prevents a correct criticism of the published results

• a bad practice of medicinebad practice of medicine that ignores the woman in her totality (holism)

• political lobbiespolitical lobbies from the NIH• a lack of scientific honestylack of scientific honesty manifested by manifested by

many of the WHI writersmany of the WHI writers• lobbies from several pharmaceuticallobbies from several pharmaceutical

industriesindustries through the activities of many well known doctors that “offer” themselves to transmit their “messages”

HOW TO DO IT ?HOW TO DO IT ?

•The Target Target the WomanWoman

•The AgentAgent (or Actor) the DoctorDoctor

•TheThe ObjectiveObjective QoLQoL

Quality of LifeQuality of Life(QoL)(QoL)

How to promote it ?How to promote it ?

QoL = QoL = Health !Health !

““A condition of physical, mental and A condition of physical, mental and social well-being and not only the social well-being and not only the absence of disease” absence of disease”

WHO

Therefore one must:

- prevent diseases

- promote health

The midaged WomanThe midaged Woman

• How does she feel? Confused? Insecure?

• What is she afraid of ? Hormones?

• What does she want from the Doctor? QoL !QoL !

Definition

A Climacteric woman

is a womanwoman (gender based medicine)

is an ageing personageing person (geriartrics)

is perimenopausalperimenopausal (hormone deficient)

Looking after a menopausal woman is a most

fascinating,gratifying and

complex

vivid experience in the life of a physician.

MNC/2005

manman

womanwoman

The Doctor : a Gynecologist?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?

What has experience thought What has experience thought me over the years about how me over the years about how

to give QoL after the to give QoL after the menopause:menopause:

Is there a Is there a Menopausal Menopausal MedicineMedicine??

There is only ONEONE Medicine (L. Speroff)

There are only TWOTWO Medicines (M.N.C.):

a BADBAD Medicine and

a GOODGOOD Medicine

Therefore,what we must learn, is…

how to practice a how to practice a GOOD GOOD

MEDICINEMEDICINE!!

mnc/05

““We are drowning in We are drowning in information,information,

but starved for but starved for knowledgeknowledge” John Naisbilt

how is Medicine practiced how is Medicine practiced today?today?

then...

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)

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Who are the actors ?

The practitioner

The public health doctor

• Is a clinician• Sees patients in the office• Treats individuals• Works in Hospitals

• Is not a clinician• Does not see patients in an

office• Does not treat individuals• Works in a Public Health

department

Concerns of the

Doctor of an individual

(practitioner)

The Public Health Doctor •Relative risk reduction

•Relative risk increase

•Cost/benefit analysis

•Absolute risk reduction

•Absolute risk increase

•Benefit/risk analisys

But ... today ...

manypractitioners

and manypublic health doctors

• Act in their offices as if they were public health doctors...

• Act in their departments as if they were clinicians ...

This is wrong!

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

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

Practioners are guided:

• by the best available information that can be extrapolated with validity to their patients, and

• by their acumulated experience

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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 events that are not necessarily cause/effect findings

MNC/05

We must managemanage our Clinical Practice by objectivesby objectives:

- - Critical Objectives (C.O.)Critical Objectives (C.O.)- Specific Objectives (S.O.)- Specific Objectives (S.O.)- S.O. Targets (S.O.T.)- S.O. Targets (S.O.T.)- S.O. Projects (S.O.P.)- S.O. Projects (S.O.P.)

Critical ObjectivesCritical Objectives

a) The diagnosis of health

b) The identification of risk factors

c) The presence of symptoms

• gender related

• age related

• hormone related

Critical ObjectivesCritical Objectives

d) The treatment of symptoms

e) The elimination of risk factors

f) The diagnosis of diseases

g) The treatment of diseases

Specific Objectives Specific Objectives (S.O.)(S.O.)

1. CVD and metabolic diseasesa) obesity

b) dislipidemias

c) hypertension

d) insulin resistance (metabolic syndr.)

etc

S.O.S.O.

2. CNSa) vasomotor symptoms

b) mood, sleep

c) sexual disfunctions, libido,

etc

S.O.S.O.

3. Bone

a) osteoarticular,

etc

S.O.S.O.

4. Reproductive organs- vaginal discharges

- atrophic vaginitis

- fibroids

- meno and metrorrhagia,

etc

S.O.S.O.

5. Breast

lumps and tenderness,

etc

S.O.S.O.

6. Bladder

incontinence

chronic cystitis,

etc

S.O.S.O.

7.Contraception

S.O. TargetsS.O. Targets

1. exercise

2. nutrition

3. mental health

4. sexual conseling

5. pharmacotherapy

a) hormonala) hormonal

b) non-hormonalb) non-hormonal

S.O. ProjectsS.O. Projects(treatments)(treatments)

P, E+P, EAndrogensCa + vit D

Bisfosfonates, StrontiumStatinsIACE

Diureticsα and β Blockers

AspirinSerm’s

TiboloneGabapantin

Psychotherapyetc

routes, schemes of administrationroutes, schemes of administration

and now think about the interelation of

CVD, Osteoporosis and Obesity...

since they seem to share common risk factors...

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



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.




The mesenchymal stem cells are capable of differentiating into osteoblasts, vascular smooth muscle cells, and adipocytes.




Alternatively, macrophages may evolve into osteoclasts or infiltrate both the vascular and adipose tissues, thereby leading to chronic inflammation.


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


Elevated plasma homocysteine levels are associated with both CVD and osteoporosis.



Nitric oxide (NO), in addition to its known atheroprotective effects, appears to also play a role in osteoblast function and bone turnover.



Statins, agents that reduce atherogenesis, also stimulate bone formation



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


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 effectiveare safe and very effective !!

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;294:245-246.

ConvictionsConvictions are more are more dangerous enemies of thruth dangerous enemies of thruth than liesthan lies

Friedrich Wilhelm Nietzsche

Based on the WHIWHI study group, implementation of the resultsimplementation of the resultsinto clinical practice has little, if into clinical practice has little, if any, scientific basis.any, scientific basis.

Adam Ostrzenski and Katarzyna M Ostrzenska. Am J Obst Gynecol 2005;193:1599-604

The applicability of theThe applicability of the WHIWHI findingsfindings to women between age of to women between age of 51.1 and 56.1 years and younger is 51.1 and 56.1 years and younger is unknown...unknown...

Ostrzenski A and Ostrzenska KM.

Am J Obst Gynecol 2005;193:1599-604

The WHI Estrogen only armThe WHI Estrogen only arm

Effects of conjugated Equine Estrogen in Postmenopausal Women with Hysterectomy.JAMA, 2004;291:1701-1712

Stroke

“In women 50-59 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 yieldFive years use of HT would yield 11 additional case of stroke/additional case of stroke/ 1000 women1000 women”

EMAS Statement; 2004.

Biased opinionsBiased opinions

be they be they propro or or concon, ,

dishonor the professiondishonor the profession andand

harm our patientsharm our patients. .

Sacket DL. The arrogance of preventive medicine. Can Med Assoc J 2002;167:363-364

Then, why all this why all this noisenoise?...

Mainly because the the conclusions of recent trials conclusions of recent trials were severelywere severely misinterpreted misinterpreted by the by the medicalmedical professionalsprofessionals, the media and by the women, themselves

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Causes of Death Among Women*

*Percentage of total deaths in 1999Percentage of total deaths in 1999 among women aged 65 years and olderamong women aged 65 years and older.Anderson RN. Natl Vital Stat Rep. 2001;49:1-13.

Heart DiseaseHeart DiseaseOther Cancers

Other

Diabetes

Chronic LowerRespiratory

Disease

Cerebrovascular Disease

Breast CancerBreast Cancer 34%34%

10%10%

6%6%3%3%

15%15%

28%

4%4%

Hormones and the HeartHormones and the Heart

1 in 31 in 3 women will die from coronary heart disease (CHD) in the USA.

1 in 251 in 25 women will die from breast cancer

Fitzpatrick LA. JCEM 2003;88(12):5609-10

“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

Effect on the risk of CHDrisk of CHD

WHIWHI SignificantSignificant increasedincreased risk 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)

HERSHERS Nonsignificant decreasedNonsignificant decreased risk 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)

NNHNNH / Year/ Year((NNumber umber NNeeded to eeded to HHarm)arm)

(the reciprocal of the AR,or of the atributable AR)(the reciprocal of the AR,or of the atributable AR)

Coronary Heart DiseaseCoronary Heart DiseaseWHI WHI (RR 1.29) 1428HERS (RR 0.99) 5000

Breast CancerBreast CancerWHIWHI (RR 1.26) 1250HERS (RR 1.27) 833

MNC

““Not everything that can be Not everything that can be counted counted countscounts;;and not everything that and not everything that countscounts can be counted” can be counted”

Albert EinsteinAlbert Einstein

Hormone replacement therapy:where to now?where to now?

Recent studies suggest HRT may inhibit HRT may inhibit the process of atherosclerosis in the process of atherosclerosis in healthy arteries soon after menopause,healthy arteries soon after menopause, and observational studies observational studies ((NHS, updatedNHS, updated 2006)2006) in younger women starting HRT in younger women starting HRT strongly suggeststrongly suggest a potential a potential cardiovascular benefitcardiovascular benefit

Mikkola TS, Clarkson TB. Cardiovasc Res 2002;53:605-19.

Lessons from the WHILessons from the WHI

“…most articles and broadcast segments tended to focus exclusively on either the small absolute riskssmall absolute risks or the larger relativelarger relative risksrisks, neglecting the more even-handed picture that presented both.

Since the sharply increasedsharply increased relative risksrelative risks got the most playgot the most play, news coverage about the trial’s findings had an alarming cast.”

Denzer S. Editorial. Ann Intern Med.2003;138:352-353

“WHI: Now that the dust has settled…”

• To publish data that may or may not be To publish data that may or may not be entirely true or certainly premature entirely true or certainly premature is a is a disservice to thedisservice to the medical professionmedical profession andand, , most important,most important, to our patientsto our patients..

• The majority of the data that were published is not statisticallynot statistically significantsignificant even at the nominal level.

Creasman WT. et al. Am J Obst Gynecol 2003;189:621-626

Recent reports did not find, for did not find, for continuous combined treatments, any continuous combined treatments, any increased risk of either CHD or breastincreased risk of either CHD or breast cancercancer..

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;164:482-484

“At the moment, I believe we can say with relative certainty that hormone therapy in

younger postmenopausal women younger postmenopausal women resultsresults

in lower coronary heart disease events in lower coronary heart disease events and total mortality.and total mortality.””

Salpeter S. Climacteric 2005;8:307-310

An update of the WHI Study !

WHI investigatorsWHI 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 0.45-0.96).

Hsia J et al.Arch Intern Med 2006;166:357-363

Younger Women May Receive Heart Protection From Estrogen Therapy

In women ages 50-59 who had undergone a hysterectomy, a significant protective effect ofa significant protective effect of estrogen treatmentestrogen 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

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

Press Statement IMS

In a subgroup of women demographicallysimilar to those in the WHI, there was nothere was nosignificant relation between HT and CHD among significant relation between HT and CHD among women women who initiated therapy at least 10 years who initiated therapy at least 10 years after the menopauseafter 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

Press Statement IMS

The estrogen plus progestogen arm of the WHI

and the estrogen-alone arm actually showed that

HT does not HT does not

increase the risk of coronary heart disease in increase the risk of coronary heart disease in

the peri- and early menopause, the peri- and early menopause,

and may even carry beneficial effectsand may even carry beneficial effects.

Feb 2006

Press Statement IMS

The WHI study was not designedThe WHI study was not designed, and

therefore was not powered, to investigate theto investigate the

consequences of hormone therapy (HT) in consequences of hormone therapy (HT) in

women below 60 years of agewomen 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 amendedis simply wrong and must be amended.

Breast CancerBreast Cancer

Menopausal women and theirand their doctorsdoctors are scared about the side

effects of HRT

mainly about breast cancermainly about breast cancerMNC/05

It must be emphasized that we are talking about an increased incidence ofincreased incidence of the diseasethe disease, , which does not which does not automatically translate into an increase automatically translate into an increase in deaths from the disease. in deaths from the disease.

Baum M. The Breast 2005;14:178-80

Extended use of estrogen for

10 years increases risks by 0,5%, and by

15 years increases risks by 0,9%

but..

upon cessationupon cessation of HRT of HRT, , the the relative risk quickly returns to 1.0 !relative risk quickly returns to 1.0 !

Coombs N J, Taylor R, Wilcken N. and Boyages J. BMJ 2005;331:347-349

Breast Cancer

• The diagnosisdiagnosis of a breast cancer after the initiation of a HRT (with a duration of less than 5 years) is only a proof of its is only a proof of its growth stimulatorygrowth stimulatory effecteffect (not of its carcinogenic effect)

• Therefore, the Therefore, the reversal of the risk to 1 afterreversal of the risk to 1 after thethe cessation of HRTcessation of HRT confirms again only its growth confirms again only its growth promoting effect and promoting effect and denies a carcinogenic denies a carcinogenic effect. effect.

Dietel M., Lewis MA. and Shapiro S. Human Reproduction 2005;20:2052-60

Breast CancerBreast Cancer

• The doubling timedoubling time of an initial cancer of an initial cancer cellcell, up to the diagnosis of a resultant 1cm tumor, is most likely greater than greater than 10 years.10 years.

• This is why many many dormant cancer cellsdormant cancer cells may exist in a “normal” breast !may exist in a “normal” breast !

MNC/05

Occult Breast CancerOccult Breast Cancer

CClinically occultlinically occult in situ BC’s are frequentfrequent in young and middle-aged young and middle-aged women.women.

Nielsen M et al-Br J Cancer 1987;56:814-9

Occult Breast CancerOccult Breast Cancer

Breast Breast malignancy was malignancy was found infound in 22 women 22 women (20%)(20%)

Nielsen M et al-Br J Cancer 1987;56:814-9

Thus…

• Mammographies Mammographies give more falsegive more false negativenegative than false positive resultsthan false positive results !

• A “normal” mammography does not A “normal” mammography does not exclude the presence of cancer cellsexclude the presence of cancer cells that may “explode” a few months later…

MNC/05

Estrogen replacement therapy in Estrogen replacement therapy in patients with early breast cancerpatients with early breast cancer

The mortalitymortality rates from breast cancer for the ERT usersERT users was was 4.28%4.28% compared with compared with 22.3% in the nonusers22.3% in the nonusers.

Natrajan PK and Gambrell RD. Am J Obstet Gynecol 2002;187:289-95

“Recurrent breast cancer was Recurrent breast cancer was found in found in 9% of HRT9% of HRT usersusers and and 15% of nonuser15% of nonuser”.”.

O’Meara ES et al.JNCI 2001;93:754-761

Mortality following development ofMortality following development of breast cancerbreast cancer while usingwhile using

oestrogen or oestrogen plus progestin:

W Chen, DB Petitti and AM Geiger.British Journal of Cancer 2005;93:392–398

This study explored survival after exposure to oestrogen or oestrogen plus progestin at or in the year prior to at or in the year prior to breast cancer diagnosisbreast cancer diagnosis

oestrogen plus progestin users oestrogen plus progestin users had had lower all-cause mortality and lower all-cause mortality and breast cancer mortalitybreast cancer mortality

Chen W, Petitti DB and Geiger AM. British Journal of Cancer 2005; 93:392-398

Breast cancer survival after hormone exposure

Overall survival after hormone exposure

A menopausal woman expects from her attending physician

to be receptivereceptive to all of her complains,

to understandunderstand her psychic and physical concerns,

to supportsupport her insecurity and

to helphelp overcome her crisiscrisis.MNC/05

Many Doctors fail to persuadeMany Doctors fail to persuade themthem to go on with HRT, in despite of telling that the

benefits are far greater than any potential risk

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One may easily conclude thatOne may easily conclude that

without an adequate technique ofwithout an adequate technique of communication,communication, using the proper using the proper language,language,

there is no possible helpthere is no possible help

Thus, Thus,

physicians must acquire expertise in physicians must acquire expertise in the technique of communicationthe technique of communication

MNC/05

then...

let us talk about

RisksRisks...

Are there risks?Are there risks?

It is crucial that information be given information be given about the about the difference between difference between relativerelative risksrisks and and absolute risksabsolute risks, since the latter are the major cause of misinformation and alarmism, being the favorites of the media…

MNC/05

Example of Risks

• If you buy one lottery ticket you will have a one in 1 millionone in 1 million chance of winning (“absolute risk”) 1x 10 (“absolute risk”) 1x 10 66

• If you buy five lottery tickets your chances are five fold higher or 5 in one 5 in one millionmillion (“absolute risk”) 5x 10 (“absolute risk”) 5x 10 66

• Your chances of winning are increased increased by five foldby five fold (“relative risk”) 5.0 (“relative risk”) 5.0

Relative Risk

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

Attributable or Excess Risk

The difference between underlying risk and risk when receiving HT is called the attributable or excess risk

Do not confuse…

Relative Risk

with

Absolute Risk!

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

ValidityInternal: the study measured what is set out to

measureExternal: the results can be extrapolated to the results can be extrapolated to

one’s patientsone’s patients

Observational research (NHS) may have poorer internal validitybetter externalbetter external validity validityRandomized controlled trial (WHI)better internalbetter internal validity validitypoorer external validity

MNC/04

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

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

women

Risks of women medicated with E only (6.8 years)

women

Risks of Breast Cancer according to different factors

“It appears that half of thehalf of thebenefitsbenefits in the prevention of cardiovascular diseases are are notnot hormone related”! hormone related”!

Mosca L, Grundy SM, Judelson D, et al. Circulation 99;99:2480-4

Nurses’s Health Study

from 1980 to 1994 CHD CHD 31% 31%

Smoking 13% Obesity 8% THSTHS 9% 9% Better nutritionBetter nutrition 16% 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;343:530-537.

Can side effects be minimizedCan side effects be minimized ?

What about the What about the best treatments best treatments during the climacterium and during the climacterium and

beyond?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

HippocratesHippocrates 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

The PolymealPolymeal Franco O et al. BMJ 2004;329:1447-50

Doctors could retrain as Polymeal chefs or wine advisers

The Polymeal—an evidence based menu that includes, wine, fish, dark chocolate fruits,wine, fish, dark chocolate fruits, vegetables, garlicvegetables, garlic, and, and almondsalmonds—promises to be an effective, safe, cheap, and tasty solution to reducing cardiovascular morbidity and increasing life expectancy.

PolymealPolymeal could reduce cardiovascular disease by could reduce cardiovascular disease by more than 75%.more than 75%.

Franco O et al. BMJ 2004;329:1447-50

The PolypillPolypill

Wald N and Law M. BMJ 2003;326:1419-25

One third of people taking this pill from age 55 would benefit, gaining on gaining on average about 11 years of lifeaverage about 11 years of life free from free from an IHD event or strokean IHD event or stroke..


Moderate exercise cuts breastModerate exercise cuts breast cancer biomarkerscancer biomarkers in

postmenopausal women

Increased physical activity significantly reduces serum estrogens in postmenopausal women and thus may may reduce the risk of breast cancer.reduce the risk of breast cancer.

McTiernan A. Cancer Res 2004;364:2923-8

Aspirin could be used to prevent Aspirin could be used to prevent cancercancer

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

In conclusionconclusion …

and to make a long story short…

There are no really “safe” There are no really “safe” biological active drugs...biological active drugs...

There are only “safe” physicians !There are only “safe” physicians ! Kaminetzy HA 1993

““Each time we Each time we learn something newlearn something new, , the astonishment comes from the the astonishment comes from the recognition that recognition that we were wrong we were wrong beforebefore……

In truth, whenever we discover a new fact, it involves the elimination of old ones...

thus, as it turns out,

WE ARE ALWAYSWE ARE ALWAYS IN ERROR ! IN ERROR ! ” Lewis Thomas English Biologist (1913-1993)

My MessageMessage is:

.To prescribe postmenopausal hormonal treatments when when clinically indicatedclinically indicated, , if not if not contraindicatedcontraindicated

. No answers from ongoing No answers from ongoing clinical trials are clinical trials are indispensableindispensable to practice to practice today a good Medicinetoday a good Medicine

MNC/05

To knowTo know

the disease that a woman hasthe disease that a woman has

is as important asis as important as

to knowto know

the woman who has the diseasethe woman who has the disease

William Osler

What are the best recommendations of What are the best recommendations of the climacteric woman’s doctorthe climacteric woman’s doctor??

1. Understand what is happening to the body during the climacteric and the postmenopause

2. Mental occupation3. Physical exercise4. 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 circumference7. Refrain from smoking8. Keep a normal blood pressure9. Keep the blood lipids within normal values

(statins?)10. Examine the breasts (palpation, inspection,

mammography)

What about the What about the best treatmentsbest treatments during the climacterium and during the climacterium and

beyond?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

Which is the best treatment?Which is the best treatment?

In general terms, is the one that is is the one that is wiselywisely indicatedindicated,, if not contraindicatedif not contraindicated, after , after balancing benefits and risksbalancing benefits and risks, , of all strategiesof all strategies andand interventions, interventions, hormonal or nothormonal 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

Which is the best treatment?Which is the best treatment?

Patient needs and preferences are decisivePatient needs and preferences are decisive, based on the doctors’ advice. Let it not be forgotten that although many treatments are available, they are neverthelessthey are nevertheless notnot indispensableindispensable. Doctors have the duty to give their Doctors have the duty to give their best unbiased information to their patients so that they best unbiased information to their patients so that they may make the right choices and then be compliantmay make the right choices and then be compliant.

The woman is the decision makerThe woman is the decision maker, if the doctor sees no contraindication.

thus,

the best treatment is what a well the best treatment is what a well informed woman has choseninformed woman has chosen. .

MNC/05

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) estrogensSystemic (parenteral) estrogens, added when needed to vaginal progesterone or vaginal progesterone or progestagen loadedprogestagen loaded IUD’sIUD’s, may be very beneficial, largely overpassing minimal risks.

MNC/05

The conclusions of the WHI trial suggestThe conclusions of the WHI trial suggest that the “safe “ woman (NNH between 600-1000 women)

to initiate HT is

- between between 50-59 years50-59 years of age of age- with vasomotor symptomswith vasomotor symptoms- less than 10 years after the menopauseless than 10 years after the menopause- being treated with statinsbeing treated with statins- with a with a good lipidgood lipid profile and profile and- with a with a Body Mass IndexBody Mass Index >25 >25

Neves-e-Castro M. Human Reproduction 2003;18:2512-2518

This is precisely the profile of the great majority of women who come for consultation after their menopause.

Therefore it seems that what most it seems that what most gynecologists are doing to their gynecologists are doing to their predominant population of patients is not predominant population of patients is not unsafe unsafe and contributes not only to a and contributes not only to a good quality of life but to prevention, as good quality of life but to prevention, as wellwell..

Neves-e-Castro M. Human Reproduction 2003;18:2512-2518

Postmenopausal hormone therapy: critical reappraisal and unified hypothesis

83:558-66

Do othersothers agree ?

““He who He who learnslearns,, but does not but does not thinkthink

is is lost.lost.

He who He who thinksthinks, but , but does not does not learnlearn is is

dangerousdangerous”.

Confucius

If we bothIf we both learnlearn andand thinkthink we willwe will

neither be neither be lostlostnor nor dangerousdangerous

to our postmenopausal women to our postmenopausal women patients”patients”

Wenger NK. Am J Geriatr Cardiol 2000;9:204-9

NAMS positionNAMS position statementstatement on estrogen and progestagen use in peri-and postmenopausal women

Revised breast cancer statements indicate that the risk of breast cancerrisk of breast cancer probably increases with EPT use but not with ET but not with ET use.use.

NAMS position statementNAMS position statement on estrogen and progestagen use in peri-and postmenopausal women

Place no limitPlace no limit on ET/EPT treatment on ET/EPT treatment durationduration, provided it is consistent with treatment goals; if monitored regularly, no no stipulation is made regarding when to stipulation is made regarding when to reduce or stop therapyreduce or stop therapy

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 www.imsociety.org

NAMSNAMS www.menopause.org

http://www.imsociety.org/

http://www.menopause.org/

Evidence informed practiceEvidence informed practice

• It is clearly time to changechange “evidence based“evidence based medicine”medicine” to to ““evidence informed practiceevidence informed practice”.

• I suggest I suggest the era of evidence informedthe era of evidence informed rather rather than evidence based medicine than evidence based medicine has arrivedhas arrived

Glasziou P. Centre for Evidence-Based MedicineCentre for Evidence-Based Medicine. University of Oxford OX3 7LF. BMJ 2005;330:92

What has been learned from the What has been learned from the major observational studies and major observational studies and

clinical trials?clinical trials?

the first lessonthe 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.



the second lessonthe 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



the third lessonthe third lessonMetabolic 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



the fourth lessonthe fourth lesson

Hormonal treatments are the first choice forHormonal treatments are the first choice for vasomotor symptom reliefvasomotor symptom relief as long as they are needed (on and off assessment). They They should not be used forshould not be used for the secondarythe secondary prevention of CVDprevention of CVD, when atheroma plaques are already present.

MNC/05



the fourth lessonthe fourth lesson (cont) (cont)Conversely, they may protect from CVD they may protect from CVD if started early during the transition if started early during the transition into theinto the post menopausepost menopause.

Hormonal treatments are preventive of osteopenia and osteoporosis at any stage in life

MNC/05



the fifth lessonthe fifth lesson

Estrogens may prevent degenerativemay prevent degenerative lesions of the CNSlesions of the CNS since, so far, they seem to be the only available drugs with nerve growth effects

MNC/05

Preventing a woman from the Preventing a woman from the benefits of abenefits of a

sound postmenopausal sound postmenopausal hormone therapyhormone therapy

because of the fear of rare because of the fear of rare side effects side effects

does not seem to be does not seem to be satisfactory Medicine...satisfactory Medicine...

M.Neves-e-Castro, 2000

Primum non nocere :

neither by excess, nor by deffect …

M.Neves-e-Castro

and now...

see the

differences...in QoL :

like this one ?...

Secret for longevity !

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?”


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.”


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?”

I’m 24 years old...




or like these?…

They are living after“MATURE WOMEN’S

MEDICINE”!(hormones, life style, nutrition, exercise, etc)

A A WOMANWOMAN

in the in the autumnautumn of her life of her life

deserves andeserves an indian summerindian summer

rather thanrather than aa winterwinter of discontentof discontent ...

Robert B Greenblatt

and now...and now...

this is not the end...this is not the end...

nor even the begining of the end.nor even the begining of the end.

It is perhaps,It is perhaps,

the end of the begining !the end of the begining !

Winston Churchill

This is what I have learned

thank you

emas curso

Health & Medicine