pmgamer18
Well-known member
- Awards
- 1
C O R T I S O L A B N O R M A L I T Y, E L E VAT E D E S T R O G E N, A N D IMMUNE D E S TA B I L I Z AT I O N
changes associated with a pre-cancerous process in
the uterus. Treatment with cortisone (dexamethasone)
in ovariectomized rats given estradiol reverses
these abnormalities.33
I routinely find the combination of abnormal cortisol
and elevated estrogen in animals with histories of
infertility and miscarriage, suggesting that reproductive
failures may be caused by inflamed and immune-deregulated
reproductive tract tissue. Such failures are routinely
corrected by proper hormone therapy, enabling
animals to conceive and produce healthy offspring.
Over decades of clinical experience, William Jefferies,
an emeritus clinical professor at the University of
Virginia, has reported that patients with cortisol insufficiency
and histories of ovarian dysfunction, infertility,
and failed pregnancies achieve significantly improved
conception and birth rates on low-dosage cortisone
therapy.34
Common variable immunodeficiency (CVID)
appears to be a grossly underdiagnosed enabling mechanism
for a multiplicity of disorders in humans just as it
is in animals, giving rise to chronic infections, autoimmune
conditions, an increased risk of cancer, and poor
response to immunization. In both humans and animals,
CVID is characterized by low IgA, IgG, and IgM
levels and abnormal T cell counts. In humans, the precise
trigger for such immune dysfunction is unknown.
Researchers have not linked CVID or other so-called
immunodeficiency mechanisms to hormones. I suggest
that exploring this connection, and looking specifically
at cortisol activity, may generate major clues for diagnosis
and treatment.
My clinical success and the growing clinical applications
of low-dosage cortisone therapy for humans
strongly argue for sustained research into the nature,
magnitude, and impact of cortisol defects, including an
associated estrogen-immune problem, in the etiology of
disease. While it is now recognized that the hypothalamic-
pituitary-adrenal axis, as part of the neuroendocrine
system, has central importance to immune
homeostasis,35 we still don’t understand the countless
details and interactions.
Estrogen measurements are generally assumed to
be expressions of ovarian function. This seems an
invalid assumption, since a deficit of active cortisol—
from genetics, stress, toxicity, or phytoestrogens—can
initiate a significant estrogen buildup—estrogen
dominance—independent of the ovaries. Estrogen
dominance not only causes inflammation of many of
the arteries, but it also binds active cortisol and active
thyroid, and deregulates the immune system. It can
also contribute to such ailments as cancer, autoimmunity,
and hypersensitivity diseases. It will contribute
to loss of homeostasis, deregulated immune
function, and increased risk of disease among females
with or without ovaries as well as neutered or intact
males. In other words, none are exempt.
In humans, routine testing for a cortisol deficit and
consequential hormonal-immune abnormalities, followed
by an appropriate low-dosage, remedial steroid
therapy program, may provide breakthrough strategies
in the perpetual battle against disease.
21
E N D O C R I N E - IMMUNE ME C H A N I S M S A N D HU M A N HE A LT H I M P L I CAT I O N S
22
1. Munck A., Naray-Fejes-Toth. A. Glucocorticoid action. In:
Endocrinology, Third edition, (Ed: DeGroot L). Philadelphia: W. B.
Saunders Co, 1995: 1642-1654.
2. Ibid.
3. Parker, L. N. Adrenal androgens. In: Endocrinology, Third edition, (Ed:
DeGroot L). Philadelphia: W. B. Saunders Co, 1995: 1836-47.
4. Adams, J. B. Control of secretion and the function of C19-delta 5-
steroids of the human adrenal gland. Molecular and Cellular Endocrinology,
1985; 41: 1-17.
5. Alesci S., Koch C. A., Bornstein S. R., Pacak K. Adrenal androgens regulation
and adrenopause. Endocrine Regulations, 2001; 35: 95-100.
6. Lemonick M. D. A Terrible Beauty: An obsessive focus on show-ring
looks is crippling, sometimes fatally, America’s purebred dogs. Time,
December 12, 1994; 65.
7. Plechner A. J., Shannon M. Canine immune complex diseases. Modern
Veterinary Practice, 1976: 917.
8. Harvey P.W. The Adrenal in Toxicology: Target Organ and Modulator of
Toxicity, Bristol, PA: Taylor & Francis, 1996: 7.
9. Symington T. Functional Pathology of the Human Adrenal Gland,
Edinburgh: E & S. Livingstone, 1969: 63-68.
10. Roberts E. The importance of being dehydroepiandosterone sulfate (in
the blood of primates): A longer and healthier life? Biochemical
Pharmacology, 1999; 57: 329-346.
11. Cutolo M., Seriolo B., Villaggio B., Pizzorni C., Craviotto C., Sulli A.
Androgens and estrogens modulate the immune and inflammatory
responses in rheumatoid arthritis. Annals of the New York Academy of
Sciences, June 2002; 966: 131-142.
12. Cid, M., Schnaper H. W., Kleinman H. Estrogens and the vascular
endothelium. Annals of the New York Academy of Sciences, June 2002; 966:
143-157.
13. Gell J.S., Oh J., Rainey W.E., Carr B.R. Effect of estradiol on DHEAS
production in the human adrenocortical cell line, H295R. Journal of the
Society for the Gynecologic Investigation, 1998; 5:144-148.
14. Arafah B.M. Increased need for thyroxine in women with hypothyroidism
during estrogen therapy. New England Journal of Medicine, 2001;
344 (23): 1743-1749.
15. Gross H.A., Appleman M.D., Nicoloff J.T. Effect of biologically active
steroids on thyroid function in man. The Journal of Clinical Endocrinology
and Metabolism, 1971; 33: 242-248.
16. Jefferies W.McK. Safe Uses of Cortisol, Springfield: Charles C. Thomas
Publisher, 1996: 160, 181.
17. Ibid, 106.
18. Orth D.N., Kovacs W.J. The adrenal cortex. In: Williams Textbook of
Endocrinology, Ninth edition, (Eds: Wilson J.D., Foster D.W., Kronenberg
H.M., Larsen P.R). Philadelphia: W. B. Saunders Co, 1998: 545.
19. Gruber C. J., Tschugguel W., Schneeberger C., Huber J.C. Production
and actions of estrogens. New England Journal of Medicine, 2002; 346 (5):
340-352.
20. Lahita R.G. The connective tissue diseases and the overall influence of
gender. International Journal of Fertility and Menopausal Studies (now
International Journal of Fertility and Women’s Medicine), 1996; 41 (2):
156-165.
21. Finkelstein J., Susman E.J., Chinchilli V.M., et al. Estrogen or testosterone
increases self-reported aggressive behaviors in hypogonadal adolescents.
The Journal of Clinical Endocrinology and Metabolism, 1997; 82 (8):
2433-2438.
22. Jefferies, op. cit., 91-113, 163-166.
23. Hickling P, Jacoby R.K, Kirwan J.R. Joint destruction after glucocorticoids
are withdrawn in early rheumatoid arthritis. British Journal of
Rheumatology, 1998; 37: 930-936.
24. Cutolo M., Sulli A., Pizzorni C., et al. Cortisol, dehydroepiandrosterone
sulfate, and androstenedione levels in patients with polymyalgia
rheumatica during twelve months of glucocorticoid therapy. Annals of the
New York Academy of Sciences, June 2002; 966: 91-96.
25. Klaitman V., Almog Y. Corticosteroids in sepsis: A new concept for an
old drug. The Israel Medical Association Journal, 2003; 5 (1): 51-54.
26. Gruber, op. cit., 340-352.
27. Spratt D. I., Longcope C., Cox P.M., Bigos S.T., Wilbur-Welling C.
Differential changes in serum concentrations of androgens and estrogens
(in relation with cortisol) in postmenopausal women with acute illness.
The Journal of Clinical Endocrinology and Metabolism, 1993; 76 (6):
1542-1547.
28. Personal communication with David Brownstein, M.D.,
West Bloomfield, Michigan.
29. Gruber, op cit., 340-352.
30. Wright J.V., Schliesman B., Robinson L. Comparative measurements
of serum estriol, estradiol, and estrone in non-pregnant, premenopausal
women: A preliminary investigation. Alternative Medicine Review, 1999;
4 (4): 266-270.
31. Ahmed S.A. The immune system as a potential target for environmental
estrogens: a new emerging field. Toxicology, 2000; 7 (150): 191-206.
32. Mesiano S., Katz S. L., Lee J. Y., Jaffe R. B. Phytoestrogens alter
adrenocortical function: genistein and daidzein suppress glucocorticoid and
stimulate androgen production by cultured adrenal cortical cells. The
Journal of Clinical Endocrinology and Metabolism, 1999; 84 (7): 2443-2448.
33. Gunin A.G., Sharov A.A. Proliferation, mitosis orientation, and morphogenetic
changes in the uterus of mice following chronic treatment with
both estrogen and glucocorticoid hormones. The Journal of Endocrinology,
2001; 169: 23-31.
34. Jefferies, op. cit., 67-90.
35. Cutolo M., Bulsma W. J., Lahita R.G., Masi A.T., Straub R. H.,
Bradlow H.L. Altered neuroendocrine immune (NEI) networks in
rheumatology. Annals of the New York Academy of Sciences, June 2002; 966:
xvii.
REFERENCES
Phil
changes associated with a pre-cancerous process in
the uterus. Treatment with cortisone (dexamethasone)
in ovariectomized rats given estradiol reverses
these abnormalities.33
I routinely find the combination of abnormal cortisol
and elevated estrogen in animals with histories of
infertility and miscarriage, suggesting that reproductive
failures may be caused by inflamed and immune-deregulated
reproductive tract tissue. Such failures are routinely
corrected by proper hormone therapy, enabling
animals to conceive and produce healthy offspring.
Over decades of clinical experience, William Jefferies,
an emeritus clinical professor at the University of
Virginia, has reported that patients with cortisol insufficiency
and histories of ovarian dysfunction, infertility,
and failed pregnancies achieve significantly improved
conception and birth rates on low-dosage cortisone
therapy.34
Common variable immunodeficiency (CVID)
appears to be a grossly underdiagnosed enabling mechanism
for a multiplicity of disorders in humans just as it
is in animals, giving rise to chronic infections, autoimmune
conditions, an increased risk of cancer, and poor
response to immunization. In both humans and animals,
CVID is characterized by low IgA, IgG, and IgM
levels and abnormal T cell counts. In humans, the precise
trigger for such immune dysfunction is unknown.
Researchers have not linked CVID or other so-called
immunodeficiency mechanisms to hormones. I suggest
that exploring this connection, and looking specifically
at cortisol activity, may generate major clues for diagnosis
and treatment.
My clinical success and the growing clinical applications
of low-dosage cortisone therapy for humans
strongly argue for sustained research into the nature,
magnitude, and impact of cortisol defects, including an
associated estrogen-immune problem, in the etiology of
disease. While it is now recognized that the hypothalamic-
pituitary-adrenal axis, as part of the neuroendocrine
system, has central importance to immune
homeostasis,35 we still don’t understand the countless
details and interactions.
Estrogen measurements are generally assumed to
be expressions of ovarian function. This seems an
invalid assumption, since a deficit of active cortisol—
from genetics, stress, toxicity, or phytoestrogens—can
initiate a significant estrogen buildup—estrogen
dominance—independent of the ovaries. Estrogen
dominance not only causes inflammation of many of
the arteries, but it also binds active cortisol and active
thyroid, and deregulates the immune system. It can
also contribute to such ailments as cancer, autoimmunity,
and hypersensitivity diseases. It will contribute
to loss of homeostasis, deregulated immune
function, and increased risk of disease among females
with or without ovaries as well as neutered or intact
males. In other words, none are exempt.
In humans, routine testing for a cortisol deficit and
consequential hormonal-immune abnormalities, followed
by an appropriate low-dosage, remedial steroid
therapy program, may provide breakthrough strategies
in the perpetual battle against disease.
21
E N D O C R I N E - IMMUNE ME C H A N I S M S A N D HU M A N HE A LT H I M P L I CAT I O N S
22
1. Munck A., Naray-Fejes-Toth. A. Glucocorticoid action. In:
Endocrinology, Third edition, (Ed: DeGroot L). Philadelphia: W. B.
Saunders Co, 1995: 1642-1654.
2. Ibid.
3. Parker, L. N. Adrenal androgens. In: Endocrinology, Third edition, (Ed:
DeGroot L). Philadelphia: W. B. Saunders Co, 1995: 1836-47.
4. Adams, J. B. Control of secretion and the function of C19-delta 5-
steroids of the human adrenal gland. Molecular and Cellular Endocrinology,
1985; 41: 1-17.
5. Alesci S., Koch C. A., Bornstein S. R., Pacak K. Adrenal androgens regulation
and adrenopause. Endocrine Regulations, 2001; 35: 95-100.
6. Lemonick M. D. A Terrible Beauty: An obsessive focus on show-ring
looks is crippling, sometimes fatally, America’s purebred dogs. Time,
December 12, 1994; 65.
7. Plechner A. J., Shannon M. Canine immune complex diseases. Modern
Veterinary Practice, 1976: 917.
8. Harvey P.W. The Adrenal in Toxicology: Target Organ and Modulator of
Toxicity, Bristol, PA: Taylor & Francis, 1996: 7.
9. Symington T. Functional Pathology of the Human Adrenal Gland,
Edinburgh: E & S. Livingstone, 1969: 63-68.
10. Roberts E. The importance of being dehydroepiandosterone sulfate (in
the blood of primates): A longer and healthier life? Biochemical
Pharmacology, 1999; 57: 329-346.
11. Cutolo M., Seriolo B., Villaggio B., Pizzorni C., Craviotto C., Sulli A.
Androgens and estrogens modulate the immune and inflammatory
responses in rheumatoid arthritis. Annals of the New York Academy of
Sciences, June 2002; 966: 131-142.
12. Cid, M., Schnaper H. W., Kleinman H. Estrogens and the vascular
endothelium. Annals of the New York Academy of Sciences, June 2002; 966:
143-157.
13. Gell J.S., Oh J., Rainey W.E., Carr B.R. Effect of estradiol on DHEAS
production in the human adrenocortical cell line, H295R. Journal of the
Society for the Gynecologic Investigation, 1998; 5:144-148.
14. Arafah B.M. Increased need for thyroxine in women with hypothyroidism
during estrogen therapy. New England Journal of Medicine, 2001;
344 (23): 1743-1749.
15. Gross H.A., Appleman M.D., Nicoloff J.T. Effect of biologically active
steroids on thyroid function in man. The Journal of Clinical Endocrinology
and Metabolism, 1971; 33: 242-248.
16. Jefferies W.McK. Safe Uses of Cortisol, Springfield: Charles C. Thomas
Publisher, 1996: 160, 181.
17. Ibid, 106.
18. Orth D.N., Kovacs W.J. The adrenal cortex. In: Williams Textbook of
Endocrinology, Ninth edition, (Eds: Wilson J.D., Foster D.W., Kronenberg
H.M., Larsen P.R). Philadelphia: W. B. Saunders Co, 1998: 545.
19. Gruber C. J., Tschugguel W., Schneeberger C., Huber J.C. Production
and actions of estrogens. New England Journal of Medicine, 2002; 346 (5):
340-352.
20. Lahita R.G. The connective tissue diseases and the overall influence of
gender. International Journal of Fertility and Menopausal Studies (now
International Journal of Fertility and Women’s Medicine), 1996; 41 (2):
156-165.
21. Finkelstein J., Susman E.J., Chinchilli V.M., et al. Estrogen or testosterone
increases self-reported aggressive behaviors in hypogonadal adolescents.
The Journal of Clinical Endocrinology and Metabolism, 1997; 82 (8):
2433-2438.
22. Jefferies, op. cit., 91-113, 163-166.
23. Hickling P, Jacoby R.K, Kirwan J.R. Joint destruction after glucocorticoids
are withdrawn in early rheumatoid arthritis. British Journal of
Rheumatology, 1998; 37: 930-936.
24. Cutolo M., Sulli A., Pizzorni C., et al. Cortisol, dehydroepiandrosterone
sulfate, and androstenedione levels in patients with polymyalgia
rheumatica during twelve months of glucocorticoid therapy. Annals of the
New York Academy of Sciences, June 2002; 966: 91-96.
25. Klaitman V., Almog Y. Corticosteroids in sepsis: A new concept for an
old drug. The Israel Medical Association Journal, 2003; 5 (1): 51-54.
26. Gruber, op. cit., 340-352.
27. Spratt D. I., Longcope C., Cox P.M., Bigos S.T., Wilbur-Welling C.
Differential changes in serum concentrations of androgens and estrogens
(in relation with cortisol) in postmenopausal women with acute illness.
The Journal of Clinical Endocrinology and Metabolism, 1993; 76 (6):
1542-1547.
28. Personal communication with David Brownstein, M.D.,
West Bloomfield, Michigan.
29. Gruber, op cit., 340-352.
30. Wright J.V., Schliesman B., Robinson L. Comparative measurements
of serum estriol, estradiol, and estrone in non-pregnant, premenopausal
women: A preliminary investigation. Alternative Medicine Review, 1999;
4 (4): 266-270.
31. Ahmed S.A. The immune system as a potential target for environmental
estrogens: a new emerging field. Toxicology, 2000; 7 (150): 191-206.
32. Mesiano S., Katz S. L., Lee J. Y., Jaffe R. B. Phytoestrogens alter
adrenocortical function: genistein and daidzein suppress glucocorticoid and
stimulate androgen production by cultured adrenal cortical cells. The
Journal of Clinical Endocrinology and Metabolism, 1999; 84 (7): 2443-2448.
33. Gunin A.G., Sharov A.A. Proliferation, mitosis orientation, and morphogenetic
changes in the uterus of mice following chronic treatment with
both estrogen and glucocorticoid hormones. The Journal of Endocrinology,
2001; 169: 23-31.
34. Jefferies, op. cit., 67-90.
35. Cutolo M., Bulsma W. J., Lahita R.G., Masi A.T., Straub R. H.,
Bradlow H.L. Altered neuroendocrine immune (NEI) networks in
rheumatology. Annals of the New York Academy of Sciences, June 2002; 966:
xvii.
REFERENCES
Phil
