Hormonetherapy
in the Elderly
Endocrine aspects
of the aging
The many alterations
associated with aging are orchestrated by hormonal influences.
The endocrine
modulators of the maturation and senescência
are several and complex.
In part they act
of common agreement with the progress of the cycle of the life in the
evolution of the biological plan.
It can act inducing
pathologically to diseases associated with the aging process.
The recognition
of the hormonal effects in the aging has been waking up considerable
research in the possibility of the "Hormonal Replacement"
to prevent degenerative alterations.
The potential
armazened for therapeutic applications has been expanding quickly of
the traditional therapy of hormonal replacement (HRT) with estrogen
and progesterone for uses already considered of testosterone, androgens
adrenais (DHEA) hormone of the growth and
melatonin.
The replacement
of whole and any hormone should be made when there is deficiency of
the same.
The menopause in
the woman is an evident fact, that indicates the intervention time.
In the
man the "andropause" is less demarcated, masking a lot of
times to clinical absence of the testosterone.
Both sexes
suffer a deficiency of the adrenais - better
adrenopause exemplified by the deficiency in the production of DHEA.
Hormones
no steroids such as insulin, tiroxina,
tireocalcitonina, exhibit less previsible
chronological variation. Their effects in the metabolism begin or delay
physiologic processes that has deep impact in the aging process.
Insulin,
tiroxina, tireocalcitonina,
share the characteristic that their pathological roles can be moderated,
not for the deficiency, but for the excess, or resistance outlying tissular.
Less well
understood are the endocrine factors GH and the melatonin whose production
decreases strongly with the age. The practice of therapeutic application
of the same ones began in recent past.
Estrogen and Progesterone
The paper of HRT with estrogen and progesterone in the prevention of
the osteoporosis and cardiovascular disease has been considered accomplished
fact.Recent study suggests that the use of natural progesterone doesn't
commit the cardiovascular benefit of the estrogen. (The Writing Group
for the PEPI Trial. Effects of estrogen / progesterone regimens on heart
disease risk factors in postmenopause women. JAMA 1995).
The benefit of HRT is made through the decrease of the hepatic lipase,
increasing in the production of HLC-C, and increase in the conversion
of VLDL in LDL, and in the catabolism of LDL (Skouby-1994). Some researchers
also consider the effect direct antioxidant of the estrogen. (Sack,
Rader, Oestrogen and inhibition of oxidation of low-desity lipoproteins
in postmenopausal women. Lancet 1994).
The benefits
of the estrogens relieving the complaints climatericas,
improving humor, libido, senemonia and
delaying the Disease of Alzheimer is facts demonstrated already by Brenner
in the publication of Am. J. Epidoemial-1994.
The natural
progesterone, also (but not the synthetic progestacionais)
promote cardiovascular benefits.
The natural
progesterone besides inducing the lipolise
and fibinolise, the impediment against-acts
in the cardiovascular metabolism that is a fundamental element in the
risk of cardiovascular disease. Besides for their intrinsic properties
of reducing the symptoms climatéricos,
reduces the risk of cancer, reverts the " bone turnover",
and it allows a better emotional balance and libido (Lee J. R. The Multiple
Rolls of Remarkable Hormone-1993).
Testosterone
A lot has
been said in relation to the effects of the testosterone in perpetuating
the youth.
It is the
fundamental mantenedor of the libido in
both sexes, and the libido is popularly identified for juvenile energy,
and it can exercise a spectrum of wide plenty effect to against-act
the aging.
Several
studies, as of Armellini (Metabolism-1994), reveal that the testosterone
levels have inverse relationship with the fat intrabdominal,
a marked for the cardiovascular disease.
Exists
controversy if the testosterone promotes or resistance counter attack
to the insulin. The first impression originating from researches (Nestler
- The Effects of Hyperinsulinemia on serum
testosterone, progesterone dehydioepiandrosterone sulfate and cortissol
levels in normal women and in the woman with hiperandrogenism, insulin
resistance, acanthosis nicrans. J. CL. Endocrinol. Metab-1987), that
the women with excessive production of androgens with obesity would
have intolerance to carbohydrates.
The opposite idea comes from data that originating from
the therapy of hormonal replacement in diabetics no insulin dependent
(Moller J, Testosterone Treatment of of cardiovascular diseases. Berlin,
1984).
Surprisingly,
even with the predominance of cardiovascular disease in the men, several
facts demonstrate a protecting effect of the testosterone, as the activation
of the lipase lipoprotein, increase in the fibrogenolise,
retard in the microvasculars alterations , gets better in the "
heart performance", favorecimento
of the oxidative metabolism in the fabric isquêmico
through the promotion in the activity of ATP - as demonstrated by Moller
- Testosternone treatment of cardiovascular diseases, Berlin, 1984.
The testosterone
increases other parameters of human aging for delaying the loss of the
bone mass related to the advanced age; it reverts the insomnia, depression
and fatigue. It checks protection for the diseases solemnity immune
such as rheumatoid arthritis (found in very larger frequency in the
women) is the basic hormone to prevent osteoporosis. Snyder in Clinical
Use Androgens - Annu Reviewed Doctor, 1994.
Hormones Adrenais
The adrenal glandule is a complex endocrine organ whose
activity the aging in several ways.
Proposed
by some as Rebufk-Srive (Obesity in Europe), 1991, that the chronic
elevations induced by the stress of the cortisol and catecolaminas
would be the responsible for the obesity, dislipidemia
and intolerance to the carbohydrates.
At the same time, sanguine levels found in the ripe
individual, best exemplified by DHEA, begin its decline, arriving up
to 5% of the value found to 20 years.
The effects of the DHEA are mainly moderated - by decreasing
in the anaerobic glycolysis, proven fact by Bürkenhager-Gillesse
in the article Dehydroepiandrosterone Sulfate DHEA-S in the oldest old
aged 85 and over NYAS-1994.
Some researchers have been proposing that the DHEA prolongs
the life. The beneficial effects of the administration of DHEA are being
explored in relation to the immune solemnity disease, such as LES (GL
701 DHEA) Phase II/III clinical study patient information, 1994).
Prevention of the cardiovascular disease (Nestler -
DHEA: The missing link between hyperinsulinemia and atherosclerosis
FASEG 1992). the obesity to Against-act (Of Pergola - metabolism, 1991),
the diabetes, (Therapeutic effect of DHEA in diabetic mice) Diabetes
1992.
Their androgenic and autoimmune effects have been taking
ahead in the treatment of AIDS (Dyner, An open-labeldose-escalation
trial oral of DHEA tolerance and pharmacokinetics in patients with HIV
disease. J. AIDS 1993), and for opteciação(conferir) of
the immunological system in the senior (Loria, Regelson, Immune response
facilitation and resistance to virus and bacterial infeccions with DHEA)
(The Biological Rolls of DHEA).
The DHEA besides somebody, protects against the breast
cancer Regelson W. (DHEA - The "mother-steroid" 1: immunologic
action - The aging clock Ann NY Acad Sci., 1994).
Pacients with " Syndrome of Cronic Fatigue "
also benefits with DHEA-(Hoffman, Tired All the Team: how to regain
your lost energy, New york, Poseidon Press, 1993).
Insulin
In the
last years the insulin appeared, don't just as a middle regulator of
the metabolism of carbohydrate, but also as a mediator for a constellation
of pathological processes that can be central in the aging: " Syndrome
X". A term created by Reaven(22), Syndrome X refers to a triad
of consequences of the resistance to the insulin and of the hiperinsulinismo:dislipidemia,
hypertension and intolerance to the carbohydrate.
The outstanding
characteristic of the Syndrome X is the central adiposity, wich accentuates
the super insulin production. More related to an eventual cardiovascular
risk, is the promotion for the insulin of the production of muscles
in the flat vascular endotélio,
the decrease of the activity of the receiver LDL and the deterioration
of the " lipid profiles" (particularly the elevation of the
triglicerídios and of VDL(22)).
A supposed paper of the insulin in the initiation of the pathology of
the free radicals was already even considered(23).
Besides
that, the paper of the excess of insulin accentuating the "imunosupressão"
and osteoartrite, were explores(25). High
insulin levels can begin or perpetuate the glaucoma(26),
a frequent consequence of the hypertension and diabetes.
Therapeutics interventions aimed at the control of the
insulin overproduction and the resistance to the insulin is based strongly,
in the lifestyle modification with aerobic exercise and diet with low
level of carbohydrate in essence.
The proposed
therapeutic agents include the chrome, vanadium, magnesium, vitamin
E, and Omega 3. The administration of DHEA in mice, genetically obese,
and of the prone type the diabetes-Zucker control the weight increase
and it reduces the resistance to the insulin(27). The experimental introduction
of an approach resistance famacológica
to the insulin using the agent troglitazone
marks the recognition of Síndrome X(28'S patogenicidade thoroughly).
Insulin 2
The insulintherapy in the elderly is very similar to the diabetic young.
Patients
that don't get to maintain fast glycemia equals or inferior to 140 mg/dL
in spite of the diet and oral hipoglicemiantes
and exercises, have indication of doing insulintherapy as well as in
situations sharp emergencials-infections, surgery, or cases of sharp
stress.
Staying at a appropriate diet the initial dose of an
insulin of intermediate action should be from 10 to 20 U a day, for
subcutaneous road.
It increases
the dose gradually until the glycemia falls at inferior levels of 200
mg/dL in the posprandial-hemoglobin glicosilada
and normal frutosamina.
The ideal is to divide the dose - 2/3 in the morning
and 1/3 before dinner, and when necessary, to join a small dose of simple
insulin in the morning, that if the fast glycemia maintains high.
Several precautions should be taken with the insulin
use in the elderly, problems of visual sharpness or cognitive dysfunction,
can be responsible for the disarray of the diabetes, as well as for
a severe hypoglycemia.
The insulin dose is not mutable. It can vary in the
dependence of several factors, then the importance of the monitoration
of the glycemia at home through ribbons and apparels of home-made use.
The complications
of insulin used in the elderly are identical to the one of the juvenile
diabetics, in other words, lipodistrofia,
lipohipertrofia, allergic reactions and
the hypoglycemia.
In the
elderly, the contraregulatórios
mechanisms of the hypoglycemia can be altered, could create pictures
atypical or hypoglycemic sharp, frequently more serious than observed
in younger patients with neurological sequels, some of them irreversible.
Hormone of the growth
The consideration
of the pituitary hormone of the growth as an agent " anti-aging"
is emphasized by your decline related with the aging (illustration 6).
The research has already been demonstrating the paper of the substituition
of the hormone of growth in human beings in the deterioration of the
precocious senescência of the mass
and of the muscular force. Expressive improvements were documented in
the reason between the fat and the thin fabric and muscular force.
The hormone
of growth also plays a part in the cicatrization of wounds and control
of the imunity(30). Your use was proposed to prevent or to revert the
caquexia related with AIDS(31).
The reputation
of rejuvenate and reinvigorate imputed to the hormones of the growth
took to its abuse, particularly, among athletes. But we should remember
the global symptomatology of the acromegalia
to recognize the dangers of the imprudent self administration of the
hormone of growth. Facial deformity, swell of the feet and hands, arthritis,
irsutismo, characterize the acromegalia.
The osteoporosis and the diabetes harm plenty the longevity and they
are consequences of the excess of hormone of growth(30). The excess
of hormone of growth has been related with the emergence of the cancer(32).
Ironically,
those that try rejuvenate with the use of high doses of GH, can succumb
to symptoms, frequently, told by people that suffer of acromegalia:
weakness and fatigue(30).
The GH has been used in elderly with serious diseases
and when these are submitted to great interventions, because it reduces
the time of hospitalization.
Melatonin
If the estrogen and the testosterone can be symbolized, respectively,
as the planets Venus and Mars in the Solar system of the hormones of
the longevity, the melatonin is Pluto. Mysterious and wrapped up in
darkness, the melatonin is an own product of the gland pineal.
It seems to operate, independently, of the complex orchestration that
it relates to the activity of other hormones of the endocrine system.
Your action course is the variation of the day of light.
While previous researches almost focused that, exclusively, the paper
of the melatonin in the cronobiology, new discoveries suggest that it
can exercise powerful effects " anti-aging"(33).
The melatonin production decreases gradually, with the
age, weakening sleep patterns in the elderly(41). As the rest promoted
by the sleep seems to give support to processes of regeneration of the
organism, the melatonin of this sorts things out, acts indirectly, delaying
the aging.
Direct
effects " anti-aging" of the melatonin has also been considered.
The melatonin works as a primordial antioxidant, specifically, for the
free radical OH (Hydroxyl), delaying the adduced proliferation of DNA,
exposed to agents cancerígenos(34).
It can act as impediment to the changes neurodegenerativas,
to revert certain depression forms or schizophrenia and to delay the
pathological aging as what happens in the Syndrome of Down (a model
of the disease of Alzheimer(33)).
Researches
have been demonstrating the paper of the melatonin, exploring your safety
(lethal dose doesn't exist) and defining strategies for its clinical use.
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