Promoting Health and
Longevity Interventions:
Hormone Replacement Therapy
Spring 2007
PST
Hormone Replacement Therapy
1. Loss of a body constituent
•
Metabolite, hormone, enzyme, vitamin, etc.
2. Constituent is necessary for the organisms
survival and normal function
3. Involves the attempt to replace, or substitute, the
lost constituent with a similar exogenous
substance with comparable properties and
actions
•
Dose, duration, metabolism, target cells, and side
effects
Historical Aspects
•
Organotherapy
–
•
Charles Edouard Brown-Sequard
• Suggested that “internal secretions” were produced by
organs such as the testis, and that disease and aging
resulted from their deficiency
Hormones
–
Greek “I arouse to activity / I excite”
•
Term introduced by E. H. Starling in 1905 following
the discovery of Secretin with W. M. Bayliss
Dr. Brown Sequard (Physiologist,
Univ. Sorbonne, Paris) introduced
the idea that some glands secrete
internally (in the blood) potent
substances that affect the whole
organism.
In 1905, these substances were
called “hormones” by the British
physiologist E.H. Starling.
Replacement Therapy Problems
in Aging
• Complexity of endocrine system
• Loss or insufficiency of endogenous
hormones
• Target cells for hormones are themselves
aging and this may effect their
responsiveness
• Changes in hormones and their targets due
to disease and degenerative processes
Hormone Replacement Strategies
•
•
•
•
Adrenal Sex Steroids and DHEA
Growth Hormone
Insulin (as in Lecture on 4/13)
Reproductive Hormones
Dihydroepiandrosterone (DHEA)
• DHEA is the principal adrenal androgen
*Note-Does not bind androgen receptor
• DHEA(S) concentrations change throughout the human life
• DHEA(S) levels are lower in women than men
• Increased mortality is associated in men with a lower DHEA(S) baseline, but
not in women
DHEA and Aging
Epidemiological
Evidence (DHEA low
levels)
• cardiovascular mortality
• Found in:
– Autoimmune diseases
– Dementia
– Breast cancer
• DHEA(S) levels may be
indicative of a severe
disease or predictive of
a future disease
DHEA Replacement
beneficial in:
• Adrenal Insufficiency
• Healthy Elderly?
– No increase in well
being, cognition, nor
sexuality
• Elderly with
impaired mood,
cognition and
sexual
function?
DHEA
• Want to live to 100 or longer?
• Want to glow with energy every day,
well into your 80s and 90s?
• Want to overcome depression and
disease, and live a happier and
healthier life, starting now?
• Want to lose flab, erase (or
prevent) wrinkles, firm your skin
and harden your muscles?
• Want to look and feel sexy--so much
so that other people begin to
notice?
• A substance called DHEA could be
the key to achieving one or all of
these antiaging benefits--perhaps
even life extension itself.
Growth Hormone and Aging
• Study in 1990 demonstrated in small group
of elderly men that GH and IGF I levels
were reduced:
– 12 out of 21 men injected with hGH over a 6
month period showed small increases in muscle
mass and bone density (10-14%)
– Suggests that GH might be responsible in part
for decreased muscle and bone in elderly
Female GH dwarf
GH gigantism:
12-year old boy
Acromegaly
Role of GH in Aging
• GH and IGF-I serum levels decrease in
some elderly and nocturnal peak is lower or
absent
– Possibly due to:
• Decreased GHRH
• Increased GHIH (somatostatin)
• Stress
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Effects of GH Treatment
• 1998 study of ICU patients found:
– Mortality increased from 19% to 44% in patients
having GH therapy for 7-14 days
– Length of hospital stay was prolonged by GH therapy
• Attributed to:
– Decreased immune function
– Increased insulin resistance
– Multi-Organ Failure
HGH Enhancers (Human Growth
Hormone)
• Non-injectable HGH
• Herbal equivalents designed to release the body’s
own GH
– May elevate GH equivalent to that achieved by eating a
steak
• Oral HGH is broken down by the digestive
process
• “At best a waste of money, at worst an unknown
health risk”
Types of Hormones Used in PostMenopause
• Estrogens
– Alone or with progestin
– Types and route of
administration
– Optimal dose is the
lowest dose to treat
symptoms over the
shortest duration
• Progestins
– With Estrogen to reduce
risk of endometrial cancer
– Cardiovascular risks
outweigh benefits
– Other products for
osteoporosis treatment
Risks of HT
• Estrogen + Progestin
– Increases Risk of:
•
•
•
•
•
Breast Cancer
Heart Disease
Stroke
Blood Clots
Dementia
– Decreased Risk of:
• Hip Fractures (Osteoporosis)
• Colon Cancer
Benefits of HRT
• Relieves Short-Term
Symptoms of
Menopause:
– Hot Flashes
– Sweats
– Disturbed Sleep
• May also help prevent
colon cancer and agerelated vision loss
Alternatives to Hormone
Therapy?
(Recommendations from the Mayo Clinic)
• Maintain a Healthy Heart:
–
–
–
–
–
–
–
–
Don't smoke.
Be physically active.
Eat a low-fat, high-fiber diet, plentiful in fresh fruits and vegetables.
Maintain a healthy weight.
Manage high blood pressure.
Keep cholesterol and triglyceride levels in check.
Control diabetes.
Avoid excess alcohol.
• Healthy Bones
– Calcium and vitamin D. Make sure you're getting enough of
these nutrients in your diet to keep your bones strong.
– Exercise. Regular physical activity — especially weightbearing exercises such as walking or dancing — can help keep
your bones strong and healthy.
Resources
• National Heart, Lung, and Blood Institute Information Center
Internet Address: http://www.nhlbi.nih.gov/health/women/index.htm
• National Institute on Aging
Internet Address: http://www.nih.gov/nia/
• National Cancer Institute
Internet Address: http://www.nci.nih.gov/
• National Center for Complementary and Alternative Medicine
Internet Address: http://nccam.nih.gov/
• Endocrinology of Aging- Adrenal Androgens
Internet Address: http://www.endotext.org/aging/aging12/aging12.htm
• American College of Obstetricians and Gynecologists
Internet Address: http://www.acog.org/
• The Hormone Foundation
Internet Address: http://www.hormone.org/
• Women's Health Initiative (1-800-54-WOMEN)
Internet Address: http://www.nhlbi.nih.gov/whi/index.html