1) Hormone replacement therapy (HRT) is a misnomer and should be called postmenopause hormone treatment (PMHT) as it is not replacing anything physiological. 2) PMHT refers to the use of estrogens and other hormones when indicated along with non-hormonal treatments and lifestyle changes to maintain health and prevent diseases associated with menopause. 3) It is important not to view HRT/PMHT as obligatory or the only option for postmenopausal women. Treatments must be individualized based on risk factors and health needs.

1. Is HRT a Replacement
medication?
by
Manuel Neves-e-Castro, MD
(Lisbon, Portugal)
10 th World Congress on the Menopause
June 2002
Berlin

2. Hormone
HRT = Replacement
Therapy

3. Physiology of the ovary
endocrine function
exocrine function

4. Endocrine Function
Birth (+)
Infancy ++
Adolescence +++
Adulthood ++++
Menopause ++
Postmenopause +

5. Exocrine Function
Birth 0
Infancy 0
Adolescence (+)
Adulthood +
Menopause (+)
Postmenopause 0

6. Symptoms of the pre and
postmenopause
- hormone related
- age related

7. Risk factors after menopause
Related to:
- hormones
- age
- life style
- nutrition
- exercise

8. Diseases with higher incidence
after menopause
- CV (dyslipidemias)
- Bone (osteopenia, osteoporosis)
- CNS (brain dysfunctions and
degenerations )

9. Objectives
Good quality of life:
a) maintain and improve Health
b) prevent diseases

10. Health
“Is a condition of physical, mental
and social wellbeing and not only
the absence of disease”
WHO

11. Strategies
- change life style
- proper nutrition
- exercise
- pharmacologic interventions
. hormonal
. non hormonal

12. Nurses’s Health Study
(NEJM, 2000)
from 1980 to 1994 CHD ↓ 31%
↓ Smoking ↓ 13%
↑ Obesity ↑ 8%
↑ THS ↓ 9%
↑ Better nutrition ↓ 16%

13. Pharmacologic interventions
(hormonal)
- estrogens
- SERM’s
- androgens (?)
- thyroid (?)

14. Menopausal hormonal treatments are
very good.
but
Treatments without hormones may also
be very good for a woman’s health

15. “When hormone replacement
therapy is not possible”
Neves-e-Castro M in “The Management of the Menopause;
The Millennium Review 2000” Ed.John Studd; Parthenon,
NY 2000

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. “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. 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. “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. Hormone Replacement
Therapy
concept
To add hormones that should
physiologically be present at any
time in life

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. HRT must be changed to
Postmenopause Hormone
Treatments (PMHT)
If Hormone Replacement Therapy is
accepted that would mean that all
postmenopausal women must be
given hormones.

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. PostMenopause Hormonal
Treatments (PMHT)
They are not
substituive
They are important for:
- symptom relief
- disease prevention (primary
and secondary)

25. It must be made clear that
HRT does not mean that all
women must be under
hormonal treatments.

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

28. What is physiologic in the
postmenopause is a decline in the
endocrine function of the ovary
(hypoestrogenism).
Therefore, there is nothing to
replace !

29. Thus, it is not physiologic to give
estrogens to all women, although
estrogens are very important
pharmacologic agents to specifically
treat symptoms and to prevent diseases
that are associated with/or caused by
the decrease of estrogens in the
postmenopause

30. “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

31. “The social construction of illness is
being replaced by the corporate
construction of disease”
Moynihan R et al.BMJ 2002;324:886-90

32. “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

33. “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

34. “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

35. “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

36. “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

37. Postmenopause (PMHT)
Hormone Treatment is a
concept that means that
estrogens (and androgens) are
to be used when indicated, in
conjunction with other non
hormonal treatments and non
pharmacological strategies.

38. The gynecologists, or the
endocrinologists are, above all, the
internists of the middle-aged women
they accept to help.
Either they know how to select and
manipulate several treatments, in adition
to hormones, or they must cooperate
closely with internists.

39. HRT
is a misnomer !

40. This discussion is important because
there is a tendency to consider that
there is nothing but estrogens to
offer to a postmenopausal woman,
and that such treatments are
obligatory for every woman and for
very long time.
This is wrong !

41. Neves-e-Castro M-Tthe Queen is naked-Maturitas 2001;38:235-7