Is HRT a Replacement       medication?                 byManuel Neves-e-Castro, MD          (Lisbon, Portugal)10 th World ...
HormoneHRT = Replacement      Therapy
Physiology of the ovaryendocrine functionexocrine   function
Endocrine FunctionBirth           (+)Infancy         ++Adolescence     +++Adulthood       ++++Menopause       ++Postmenopa...
Exocrine FunctionBirth            0Infancy          0Adolescence     (+)Adulthood         +Menopause        (+)Postmenopau...
Symptoms of the pre and       postmenopause- hormone related- age related
Risk factors after menopauseRelated to:      -   hormones      -   age      -   life style      -   nutrition      -   exe...
Diseases with higher incidence       after menopause- CV   (dyslipidemias)- Bone (osteopenia, osteoporosis)- CNS (brain dy...
Objectives    Good quality of life:a) maintain and improve Healthb) prevent diseases
Health“Is a condition of physical, mental and social wellbeing and not only the absence of disease”                       ...
Strategies- change life style- proper nutrition- exercise- pharmacologic interventions       . hormonal       . non hormonal
Nurses’s Health Study          (NEJM, 2000)    from 1980 to 1994 CHD ↓ 31%↓   Smoking            ↓   13%↑   Obesity       ...
Pharmacologic interventions           (hormonal)-   estrogens-   SERM’s-   androgens (?)-   thyroid (?)
Menopausal hormonal treatments arevery good.  butTreatments without hormones may alsobe very good for a woman’s health
“When hormone replacementtherapy is not possible”Neves-e-Castro M in “The Management of the Menopause;The Millennium Revie...
Pharmacologic interventions            (non hormonal)-   Statins-   ß blockers-   Calcium – channel blockers-   Diuretics-...
“Recently revised NCEP guidelines indicate that for women aged 45 to 75, the favorable effects of therapy with “statins” i...
Lipid-lowering therapy promotes             clinically stable plaque- Prolonged intensive lipid-lowering therapy is  assoc...
“Lovastin together with continuous combined HRT seems to be more effective in the secondary prevention of coronary heart d...
Hormone Replacement        Therapy         concept   To add hormones that shouldphysiologically be present at anytime in l...
Examples:-   insulin (type I diabetes)-   cortisone (Addison’s disease)-   thyroid (hypothyrodism)-   growth hormone (dwar...
HRT must be changed to  Postmenopause Hormone    Treatments (PMHT)If Hormone Replacement Therapy isaccepted that would mea...
If Hormone Replacement Therapy was a correct designation then this was no therapy at all but simply a replacement. It woul...
PostMenopause Hormonal     Treatments (PMHT)         They are not          substituiveThey are important for:    - symptom...
It must be made clear thatHRT does not mean that allwomen must be underhormonal treatments.
- The important issue, after all, is not  HRT- What is important is the best possible approach to preventive medicine in a...
What is physiologic in thepostmenopause is a decline in theendocrine function of the ovary(hypoestrogenism). Therefore, th...
Thus, it is not physiologic to giveestrogens to all women, althoughestrogens    are    very     importantpharmacologic age...
“Pharmaceutical companies are actively involved in sponsoring the definition of diseases and promoting them to both prescr...
“The social construction of illness is being replaced by the corporate construction of disease”               Moynihan R e...
“Extending therapy to un-diseased population may also have important ethical implications, as treatment with statins may l...
“IHD deaths are much more frequent in the USA than in Italy, whereas CeVD deaths are more common in Italy”           Ricci...
“In the light of these differences, long-term  HRT should yield larger benefits in  North American women – with higher  IH...
“Our analysis of age group mortality indicates that in the 40-49 age group for each woman dying of IHD, 5 will die of BC i...
“Women who are to receive long-term HRT, should be selected much more carefully than in countries where IHD mortality is a...
Postmenopause (PMHT)Hormone Treatment        is aconcept that means thatestrogens (and androgens) areto be used when indic...
The gynecologists, or theendocrinologists are, above all, theinternists of the middle-aged womenthey accept to help.Either...
HRTis a misnomer !
This discussion is important becausethere is a tendency to consider thatthere is nothing but estrogens tooffer to a postme...
Neves-e-Castro M-Tthe Queen is naked-Maturitas 2001;38:235-7
Is hrt a replacement medication
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Is hrt a replacement medication

  1. 1. Is HRT a Replacement medication? byManuel Neves-e-Castro, MD (Lisbon, Portugal)10 th World Congress on the Menopause June 2002 Berlin
  2. 2. HormoneHRT = Replacement Therapy
  3. 3. Physiology of the ovaryendocrine functionexocrine function
  4. 4. Endocrine FunctionBirth (+)Infancy ++Adolescence +++Adulthood ++++Menopause ++Postmenopause +
  5. 5. Exocrine FunctionBirth 0Infancy 0Adolescence (+)Adulthood +Menopause (+)Postmenopause 0
  6. 6. Symptoms of the pre and postmenopause- hormone related- age related
  7. 7. Risk factors after menopauseRelated to: - hormones - age - life style - nutrition - exercise
  8. 8. Diseases with higher incidence after menopause- CV (dyslipidemias)- Bone (osteopenia, osteoporosis)- CNS (brain dysfunctions and degenerations )
  9. 9. Objectives Good quality of life:a) maintain and improve Healthb) prevent diseases
  10. 10. Health“Is a condition of physical, mental and social wellbeing and not only the absence of disease” WHO
  11. 11. Strategies- change life style- proper nutrition- exercise- pharmacologic interventions . hormonal . non hormonal
  12. 12. Nurses’s Health Study (NEJM, 2000) from 1980 to 1994 CHD ↓ 31%↓ Smoking ↓ 13%↑ Obesity ↑ 8%↑ THS ↓ 9%↑ Better nutrition ↓ 16%
  13. 13. Pharmacologic interventions (hormonal)- estrogens- SERM’s- androgens (?)- thyroid (?)
  14. 14. Menopausal hormonal treatments arevery good. butTreatments without hormones may alsobe very good for a woman’s health
  15. 15. “When hormone replacementtherapy is not possible”Neves-e-Castro M in “The Management of the Menopause;The Millennium Review 2000” Ed.John Studd; Parthenon,NY 2000
  16. 16. Pharmacologic interventions (non hormonal)- Statins- ß blockers- Calcium – channel blockers- Diuretics- Angiotensin C.E. inhibitors- Bisphosphonates/calcium- Tranquilizers- Serotonin and noradrenalin reuptake inhibitors- Metformin- etc
  17. 17. “Recently revised NCEP guidelines indicate that for women aged 45 to 75, the favorable effects of therapy with “statins” in clinical trials make a cholesterol-lowering drug preferable to HRT for CAD risk reduction”. Cleeman J. JAMA 2001;285(19):2486-97
  18. 18. Lipid-lowering therapy promotes clinically stable plaque- Prolonged intensive lipid-lowering therapy is associated with a markedly decreased lipid content in carotid atherosclerotic plaques- The clinical implication of this is that the low plaque lipid composition would predict greater plaque stability, and would thus reduce clinical ischemic events such as myocardial infarction or stroke. Zhao X-Q et al. Arterioscler Thromb Vasc Biol 2001;21:1623-1629,1563- 1564
  19. 19. “Lovastin together with continuous combined HRT seems to be more effective in the secondary prevention of coronary heart disease not only due to lipid lowering properties but also related to several other additive effects such as modification of endothelial function and inflammatory responses” El-Swefy SE et al. Pharmacological Research, 2002;45:167-173
  20. 20. Hormone Replacement Therapy concept To add hormones that shouldphysiologically be present at anytime in life
  21. 21. Examples:- insulin (type I diabetes)- cortisone (Addison’s disease)- thyroid (hypothyrodism)- growth hormone (dwarfism)- androgens (orchidectomy)- estrogens (surgical or premature menopause, gonadal agenesis)
  22. 22. HRT must be changed to Postmenopause Hormone Treatments (PMHT)If Hormone Replacement Therapy isaccepted that would mean that allpostmenopausal women must begiven hormones.
  23. 23. If Hormone Replacement Therapy was a correct designation then this was no therapy at all but simply a replacement. It would not be a treatment for a disease but a restoration of what would be physiologic, which is not the case in the natural postmenopause.
  24. 24. PostMenopause Hormonal Treatments (PMHT) They are not substituiveThey are important for: - symptom relief - disease prevention (primary and secondary)
  25. 25. It must be made clear thatHRT does not mean that allwomen must be underhormonal treatments.
  26. 26. - The important issue, after all, is not HRT- What is important is the best possible approach to preventive medicine in a middle-aged woman
  27. 27. What is physiologic in thepostmenopause is a decline in theendocrine function of the ovary(hypoestrogenism). Therefore, there is nothing toreplace !
  28. 28. Thus, it is not physiologic to giveestrogens to all women, althoughestrogens are very importantpharmacologic agents to specificallytreat symptoms and to prevent diseasesthat are associated with/or caused bythe decrease of estrogens in thepostmenopause
  29. 29. “Pharmaceutical companies are actively involved in sponsoring the definition of diseases and promoting them to both prescribers and consumers” Moynihan R et al.BMJ 2002;324:886-90
  30. 30. “The social construction of illness is being replaced by the corporate construction of disease” Moynihan R et al.BMJ 2002;324:886-90
  31. 31. “Extending therapy to un-diseased population may also have important ethical implications, as treatment with statins may lead to perceptions of illness” Freemand X et al.BMJ 1998;316:1241
  32. 32. “IHD deaths are much more frequent in the USA than in Italy, whereas CeVD deaths are more common in Italy” Ricci S et al.J Clin Basic Cardiol 2002;5:105-108
  33. 33. “In the light of these differences, long-term HRT should yield larger benefits in North American women – with higher IHD mortality and lower incidence of fatal CeVD – and probably less beneficial effects in Italian women, who exhibit a lower IHD mortality and a higher CeVD mortality”. Ricci S et al.J Clin Basic Cardiol 2002;5:105-108
  34. 34. “Our analysis of age group mortality indicates that in the 40-49 age group for each woman dying of IHD, 5 will die of BC in Italy but only 2 in the USA” Ricci S et al.J Clin Basic Cardiol 2002;5:105-108
  35. 35. “Women who are to receive long-term HRT, should be selected much more carefully than in countries where IHD mortality is altogether higher and more frequent in younger women” Ricci S et al.J Clin Basic Cardiol 2002;5:105-108
  36. 36. Postmenopause (PMHT)Hormone Treatment is aconcept that means thatestrogens (and androgens) areto be used when indicated, inconjunction with other nonhormonal treatments and nonpharmacological strategies.
  37. 37. The gynecologists, or theendocrinologists are, above all, theinternists of the middle-aged womenthey accept to help.Either they know how to select andmanipulate several treatments, in aditionto hormones, or they must cooperateclosely with internists.
  38. 38. HRTis a misnomer !
  39. 39. This discussion is important becausethere is a tendency to consider thatthere is nothing but estrogens tooffer to a postmenopausal woman,and that such treatments areobligatory for every woman and forvery long time. This is wrong !
  40. 40. Neves-e-Castro M-Tthe Queen is naked-Maturitas 2001;38:235-7
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