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Effect of Oral Contraceptives on Experimental Demyelinating Disease

Barry G. Arnason, MD; David P. Richman, MD
[+] Author Affiliations

Submitted for publication March 4, 1969; accepted March 17.

Reprint requests to the Department of Neurology, Massachusetts General Hospital, Boston 02114 (Dr. Arnason).


Arch Neurol. 1969;21(1):103-108. doi:10.1001/archneur.1969.00480130117012
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AS THE USE of oral contraceptives has spread, certain hazards associated with their use have come to light.1,2 In the case of the human demyelinating disease, multiple sclerosis, no data have come forth as to whether oral contraceptives influence its course favorably, unfavorably, or at all. The point is of some moment to women with the disease, many of whom are terrified by the prospect of pregnancy and of the consequences which may be in store for them because of pregnancy.

Experimental allergic encephalomyelitis (EAE), an acute demyelinating disease of auto-allergic etiology, is produced readily in experimental animals, and mimics multiple sclerosis in many of its clinical and pathologic features. Whether or not it provides a reasonable model for multiple sclerosis is a matter of dispute, but on the basis that it may do so, a study of EAE in rats fed various oral contraceptive preparations, as well

REFERENCES

Inman, W.H., and Vessey, M.P.:  Investigation of Deaths From Pulmonary, Coronary and Cerebral Thrombosis and Embolism in Women of Child-Bearing Age , Brit Med J 11:193-199 ( (April-June) ) 1968;.
Vessey, M.P., and Doll, R.:  Investigation of Relation Between Use of Oral Contraceptives and Thromboembolic Disease , Brit Med J 11:199-205 ( (April-June) ) 1968;.
Lurie, M.B., et al:  Constitutional Factors in Resistance to Infection: II. The Effect of Estrogen on Tuberculin Skin Sensitivity and on the Allergy of the Tissues , Amer Rev Tuberc 59:186-218 ( (Feb) ) 1949;.
Kappas, A.; Jones, H.E.H.; and Roitt, I.M.:  Effect of Steroid Sex Hormones on Immunological Phenomena , Nature 198:902 ( (June) ) 1963;.
Lajos, L., and Gores, J.:  Pathological Proliferation of the Trophoblast Homograft in Women , Nature 196:178-179 ( (Oct) ) 1962;.
Simmons, R.L.:  Price, A.L.; and Ozerkis, A.J.: The Immunologic Problem of Pregnancy: V. The Effect of Estrogen and Progesterone on Allograft Survival , Amer J Obstet Gynec 100:908-911 ( (April) ) 1968;.
Zipper, J., et al:  Intrauterine Grafting in Rats of Autologous Adult Rat Skin , Amer J Obstet Gynec 94:1056-1061 ( (April) ) 1966;.
Krohn, P.L.:  The Effect of Steroid Hormones on the Survival of Skin Homografts in the Rabbit , J Endocr 11:78-82 ( (July) ) 1954;.
Medawar, P.B., and Sparrow, M.:  The Effects of Adrenocortical Hormones, Adrenocorticotrophic Hormone and Pregnancy on Skin Transplantation Immunity in Mice , J Endocr 14:240-256 ( (Nov) ) 1956;.
Hulka, J.F.; Mohr, K.; and Lieberman, M.W.:  Effect of Synthetic Progestational Agents on Allograft Rejection and Circulating Antibody Production , Endocrinology 77:897-901 ( (Nov) ) 1965;.
Mueller, M.N., and Kappas, A.:  Estrogen Pharmacology: II. Suppression of Experimental Immune Polyarthritis , Proc Soc Exp Biol Med 117:845-847 ( (Oct-Dec) ) 1964;.
Waksman, B.H.:  Experimental Allergic Encephalomyelitis and the Autoallergic Diseases , Int Arch Allerg 14( (suppl) ):1-87, 1959;.
Patterson, P.Y.: " Experimental Allergic Encephalomyelitis and Autoimmune Disease ," in Dixon, F.J., and Kunkel, H.G. (eds.): Advances in Immunology , New York: Academic Press, Inc., 1966;, vol 5, pp 131-208.
Money, W.L.; Fager, J.; and Rawson, R.W.:  The Comparative Effects of Various Steroids on Lymphoid Tissue of the Rat , Cancer Res 12:206-210 ( (March) ) 1952;.
Stern, K., and Davidsohn, I.:  Effect of Estrogen and Cortisone on Immune Hemoantibodies in Mice of Inbred Strains , J Immun 74:479-484 ( (June) ) 1955;.
Healy, J.W., and Leeman, S.:  Hemolysin Response of Rats Treated Neonatally With Steroids , Endocrinology 80:762-764 ( (April) ) 1967;.
VonHaam, E., and Rosenfeld, I.:  Influence of Estrone Upon Formation of Heterophil Antibodies , Proc Soc Exp Biol Med 49:710-711 ( (April) ) 1942;.
Caniggia, A., and Bolognine, M.:  Azione Degli Ormoni Sintetici Sulla Produzione di Anticorpi , Atti Accad Fisiocr Siena 17:132 ( (March) ) 1949;.
Beurey, J., and deLavergne, E.:  Oestrogenes et Production d' Agglutinines Typhiques Chez le Lapin , C R Soc Biol 146:1967-1969 ( (July) ) 1952;.
VonHaam, E., and Rosenfeld, I.:  The Effect of Estrone on Antibody Production , J Immun 43:109-119 ( (Jan) ) 1942;.
Dingle, J.H.; Meyer, R.K.; and Gustus, E.L.:  Effect of Gonadotropic and Oestrogenic Hormones on Agglutinin Response to B. Pertussis in Immature Animals , J Immun 30:139-147 ( (Feb) ) 1936;.
Oettgen, H.F.; Binaghi, R.A.: and Benacerraf, B.:  The Effect of Various Hormones on the Serum Level of Anaphylactic Antibody in the Rat , Int Arch Allerg 29:131-139 ( (Feb) ) 1966;.
Paterson, P.Y., and Harwin, S.M.:  Suppression of Allergic Encephalomyelitis in Rats by Means of Antibrain Serum , J Exp Med 117:755-774 ( (May) ) 1963;.
Heller, J.H., et al:  The Effect of Natural and Synthetic Estrogens on Reticuloendothelial System Function , Endocrinology 61:235-241 ( (Sept) ) 1957;.
Nicol, T.; Vernon-Roberts, B.; and Quantock, D.C.:  The Influence of Various Hormones on the Reticulo-endothelial System: Endocrine Control of Body Defence , J Endocr 33:365-383 ( (Nov) ) 1965;.
Nicol, T., et al:  Oestrogen: The Natural Stimulant of Body Defence , J Endocr 30:277-290 ( (Oct) ) 1964;.
Caren, L.D., and Rosenberg, L.T.:  Steroids and Serum Complement in Mice: Influence of Hydrocortisone, Diethylstilbestrol, and Testosterone , Science 152:782-783 ( (May) ) 1966;.
Weintraub, R.M., et al:  Mouse Complement: Influence of Sex Hormones on Its Activity , Science 152:783-785 ( (May) ) 1966;.
Lurie, M.B.; Abramson, S.; and Allison, M.J.:  Constitutional Factors in Resistance to Infection: I. The Effect of Estrogen and Chorionic Gonadotropin on the Course of Tuberculosis in Highly Inbred Rabbits , Amer Rev Tuberc 59:168-186 ( (Feb) ) 1949;.
Broome, A.W.J., and Lamming, G.E.:  Studies on the Relationship Between Ovarian Hormones and Uterine Infection: III. The Role of the Antibody System in Uterine Defence , J Endocr 18:229-236 ( (May) ) 1959;.
Slenn, E.M.; Richardson, S.L.; and Bowman, B.J.:  Biologic Activity of 6-Alpha-Methyl Compounds Corresponding to Progesterone, 17-Alpha-Hydroxy-Progesterone Acetate and Compound S , Metabolism 8:265-285 ( (May) ) 1959;.
Levine, S., et al:  Enhancement of Experimental Allergic Encephalomyelitis by Adrenalectomy , Proc Soc Exp Biol Med 111:383-385 ( (Oct-Dec) ) 1962;.
Brown, J.B.:  Urinary Excretion of Oestrogens, During Pregnancy, Lactation and the Re-establishment of Menstruation , Lancet 1:704-707 ( (May) ) 1956;.
Miller, H.G., and Schapira, K.:  Aetiological Aspects of Multiple Sclerosis , Brit Med J 1:737-739 ( (March 21) ) 1959;.
Millar, J.H.D.:  The Influence of Pregnancy on Disseminated Sclerosis , Proc Roy Soc Med 54:4-7 ( (Oct) ) 1961;.

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Inman, W.H., and Vessey, M.P.:  Investigation of Deaths From Pulmonary, Coronary and Cerebral Thrombosis and Embolism in Women of Child-Bearing Age , Brit Med J 11:193-199 ( (April-June) ) 1968;.
Vessey, M.P., and Doll, R.:  Investigation of Relation Between Use of Oral Contraceptives and Thromboembolic Disease , Brit Med J 11:199-205 ( (April-June) ) 1968;.
Lurie, M.B., et al:  Constitutional Factors in Resistance to Infection: II. The Effect of Estrogen on Tuberculin Skin Sensitivity and on the Allergy of the Tissues , Amer Rev Tuberc 59:186-218 ( (Feb) ) 1949;.
Kappas, A.; Jones, H.E.H.; and Roitt, I.M.:  Effect of Steroid Sex Hormones on Immunological Phenomena , Nature 198:902 ( (June) ) 1963;.
Lajos, L., and Gores, J.:  Pathological Proliferation of the Trophoblast Homograft in Women , Nature 196:178-179 ( (Oct) ) 1962;.
Simmons, R.L.:  Price, A.L.; and Ozerkis, A.J.: The Immunologic Problem of Pregnancy: V. The Effect of Estrogen and Progesterone on Allograft Survival , Amer J Obstet Gynec 100:908-911 ( (April) ) 1968;.
Zipper, J., et al:  Intrauterine Grafting in Rats of Autologous Adult Rat Skin , Amer J Obstet Gynec 94:1056-1061 ( (April) ) 1966;.
Krohn, P.L.:  The Effect of Steroid Hormones on the Survival of Skin Homografts in the Rabbit , J Endocr 11:78-82 ( (July) ) 1954;.
Medawar, P.B., and Sparrow, M.:  The Effects of Adrenocortical Hormones, Adrenocorticotrophic Hormone and Pregnancy on Skin Transplantation Immunity in Mice , J Endocr 14:240-256 ( (Nov) ) 1956;.
Hulka, J.F.; Mohr, K.; and Lieberman, M.W.:  Effect of Synthetic Progestational Agents on Allograft Rejection and Circulating Antibody Production , Endocrinology 77:897-901 ( (Nov) ) 1965;.
Mueller, M.N., and Kappas, A.:  Estrogen Pharmacology: II. Suppression of Experimental Immune Polyarthritis , Proc Soc Exp Biol Med 117:845-847 ( (Oct-Dec) ) 1964;.
Waksman, B.H.:  Experimental Allergic Encephalomyelitis and the Autoallergic Diseases , Int Arch Allerg 14( (suppl) ):1-87, 1959;.
Patterson, P.Y.: " Experimental Allergic Encephalomyelitis and Autoimmune Disease ," in Dixon, F.J., and Kunkel, H.G. (eds.): Advances in Immunology , New York: Academic Press, Inc., 1966;, vol 5, pp 131-208.
Money, W.L.; Fager, J.; and Rawson, R.W.:  The Comparative Effects of Various Steroids on Lymphoid Tissue of the Rat , Cancer Res 12:206-210 ( (March) ) 1952;.
Stern, K., and Davidsohn, I.:  Effect of Estrogen and Cortisone on Immune Hemoantibodies in Mice of Inbred Strains , J Immun 74:479-484 ( (June) ) 1955;.
Healy, J.W., and Leeman, S.:  Hemolysin Response of Rats Treated Neonatally With Steroids , Endocrinology 80:762-764 ( (April) ) 1967;.
VonHaam, E., and Rosenfeld, I.:  Influence of Estrone Upon Formation of Heterophil Antibodies , Proc Soc Exp Biol Med 49:710-711 ( (April) ) 1942;.
Caniggia, A., and Bolognine, M.:  Azione Degli Ormoni Sintetici Sulla Produzione di Anticorpi , Atti Accad Fisiocr Siena 17:132 ( (March) ) 1949;.
Beurey, J., and deLavergne, E.:  Oestrogenes et Production d' Agglutinines Typhiques Chez le Lapin , C R Soc Biol 146:1967-1969 ( (July) ) 1952;.
VonHaam, E., and Rosenfeld, I.:  The Effect of Estrone on Antibody Production , J Immun 43:109-119 ( (Jan) ) 1942;.
Dingle, J.H.; Meyer, R.K.; and Gustus, E.L.:  Effect of Gonadotropic and Oestrogenic Hormones on Agglutinin Response to B. Pertussis in Immature Animals , J Immun 30:139-147 ( (Feb) ) 1936;.
Oettgen, H.F.; Binaghi, R.A.: and Benacerraf, B.:  The Effect of Various Hormones on the Serum Level of Anaphylactic Antibody in the Rat , Int Arch Allerg 29:131-139 ( (Feb) ) 1966;.
Paterson, P.Y., and Harwin, S.M.:  Suppression of Allergic Encephalomyelitis in Rats by Means of Antibrain Serum , J Exp Med 117:755-774 ( (May) ) 1963;.
Heller, J.H., et al:  The Effect of Natural and Synthetic Estrogens on Reticuloendothelial System Function , Endocrinology 61:235-241 ( (Sept) ) 1957;.
Nicol, T.; Vernon-Roberts, B.; and Quantock, D.C.:  The Influence of Various Hormones on the Reticulo-endothelial System: Endocrine Control of Body Defence , J Endocr 33:365-383 ( (Nov) ) 1965;.
Nicol, T., et al:  Oestrogen: The Natural Stimulant of Body Defence , J Endocr 30:277-290 ( (Oct) ) 1964;.
Caren, L.D., and Rosenberg, L.T.:  Steroids and Serum Complement in Mice: Influence of Hydrocortisone, Diethylstilbestrol, and Testosterone , Science 152:782-783 ( (May) ) 1966;.
Weintraub, R.M., et al:  Mouse Complement: Influence of Sex Hormones on Its Activity , Science 152:783-785 ( (May) ) 1966;.
Lurie, M.B.; Abramson, S.; and Allison, M.J.:  Constitutional Factors in Resistance to Infection: I. The Effect of Estrogen and Chorionic Gonadotropin on the Course of Tuberculosis in Highly Inbred Rabbits , Amer Rev Tuberc 59:168-186 ( (Feb) ) 1949;.
Broome, A.W.J., and Lamming, G.E.:  Studies on the Relationship Between Ovarian Hormones and Uterine Infection: III. The Role of the Antibody System in Uterine Defence , J Endocr 18:229-236 ( (May) ) 1959;.
Slenn, E.M.; Richardson, S.L.; and Bowman, B.J.:  Biologic Activity of 6-Alpha-Methyl Compounds Corresponding to Progesterone, 17-Alpha-Hydroxy-Progesterone Acetate and Compound S , Metabolism 8:265-285 ( (May) ) 1959;.
Levine, S., et al:  Enhancement of Experimental Allergic Encephalomyelitis by Adrenalectomy , Proc Soc Exp Biol Med 111:383-385 ( (Oct-Dec) ) 1962;.
Brown, J.B.:  Urinary Excretion of Oestrogens, During Pregnancy, Lactation and the Re-establishment of Menstruation , Lancet 1:704-707 ( (May) ) 1956;.
Miller, H.G., and Schapira, K.:  Aetiological Aspects of Multiple Sclerosis , Brit Med J 1:737-739 ( (March 21) ) 1959;.
Millar, J.H.D.:  The Influence of Pregnancy on Disseminated Sclerosis , Proc Roy Soc Med 54:4-7 ( (Oct) ) 1961;.

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