Research Article| Volume 14, ISSUE 3, P201-210, March 1992

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Effect of 17β-oestradiol on lymphocyte subpopulations, delayed cutaneous hypersensitivity responses and mixed lymphocyte reactions in post-menopausal women

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      High-dose steroids are known to be potent modulators of the immune response. We accordingly investigated the effect of therapeutic doses of 17β-oestradiol (E2) on cellular immune responses in postmenopausal women. Fifteen (15) healthy women who had undergone a natural menopause were treated with E2 in the form of 100 mg estraderm patches applied twice weekly for 3 out of every 4 weeks over a 3-month period, followed by combined oestrogen and progestogen formulations as long-term therapy. Blood samples were taken on two occasions prior to treatment and at weeks 1, 3, 4, 7, 9, 12 and 24 after commencing therapy. Lymphocyte subsets (CD2, CD4, CD8, CD19, HLA-DR and NK) were studied in each blood sample using a monoclonal antibody kit and a two-colour fluorescence flow-cytometer. One-way mixed lymphocyte reactions (MLRs) were performed using the same stimulator throughout. Delayed hypersensitivity skin tests (DHTs) were carried out twice before treatment and at weeks 3, 4, 12 and 24 using Multitest 7-antigen kits (Institut Mérieux). Lymphocyte subsets did not change significantly with treatment, but both the MLRs and the DHTs were significantly depressed, maximally so by the third week of treatment. We conclude that therapeutic doses of E2 modulate certain immune responses. The significance of this is discussed in the light of the increasing use of long-term oestrogen replacement therapy.


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        • Brincat M
        • Magos AL
        • Studd JWW
        • et al.
        Subcutaneous hormone implants for the control of climacteric symptoms: a pro-spective study.
        Lancet. 1984; i: 16-18
        • Montgomery JC
        • Appleby L
        • Brincat M
        • Versi E
        • Tapp A
        • Fenwick PBC
        • Studd JWW
        Effect of oestrogen and testosterone implants on psychological disorders of the climacteric.
        Lancet. 1987; i: 297-299
        • Lindsay R
        • Aitken JM
        • Anderson JB
        • Hart DM
        • MacDonald EB
        • Clark AC
        Long-term prevention of postmenopausal osteoporosis by oestrogen.
        Lancet. 1976; i: 1038-1041
        • Lindsay R
        • Hart DH
        • Purdie D
        • Ferguson M
        • Clark AS
        Comparative effects of oestrogen and a progestogen on bone loss in postmenopausal women.
        Clin Sci Mol Med. 1978; 54: 193-198
        • Christiansen C
        • Christiansen MS
        • McNain P
        • Hagen C
        • Stockland K
        • Transbøl I
        Prevention of early menopausal bone loss: Controlled 2-year study in 315 normal females.
        Eur J Clin Invest. 1980; 10: 273-279
        • Savvas M
        • Studd JWW
        • Fogleman I
        • Dooley M
        • Montgomery J
        • Murby B
        Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women.
        Br Med J. 1988; 297: 331-333
        • Brincat M
        • Versi E
        • Studd JWW
        • et al.
        Skin collagen changes in postmenopausal women receiving different regimens of oestrogen therapy.
        Obstet Gynaecol. 1987; 70: 123-127
        • Ross RK
        • Paganini-Hill A
        • Mack TM
        • Henderson BE
        Oestrogen use and cardiovascular disease.
        in: Mishell DR Menopause: physiology and pharmacology. Year Book Medical Publishers, Chicago1986: 209-223
        • Bush TL
        • Barnett-Connor E
        • Cowan LD
        • et al.
        Cardiovascular mortality and non-contraceptive use of oestrogen in women: Results from the Lipid Research Clinic's Programme follow-up study.
        Circulation. 1987; 75: 1102
        • Studd JWW
        • Thom MH
        Oestrogens and endometrial cancer.
        in: Progress in obstetrics and gynaecology. Vol 1. Churchill-Livingstone, Edinburgh1981: 189-198
        • Gambrell Jr, RD
        Role of progestogens in the prevention of endometrial cancer.
        Maturitas. 1986; 8: 169-176
        • Gambrell Jr, RD
        Hormonal replacement therapy and breast cancer.
        in: The menopause. 22. Blackwell Scientific Publishers, Oxford, London, Edinburgh1988: 247-261
        • Rhodes K
        • Markam RL
        • Maxwell PM
        • Monk-Jones ME
        Immuno-globulins and the X chromosome.
        Br Med J. 1969; 3: 439-441
        • Terres G
        • Morrison SL
        • Habicht GS
        A quantitative difference in the immune response between male and female mice.
        in: Proc Soc Exp Biol Med. 127. 1968: 664-667
        • Michaels RH
        • Rogers KD
        A sex difference in immunologic responsiveness.
        Paediatrics. 1971; 47: 120-123
        • Raveche ES
        • Tjio JH
        • Boegel W
        • Steinberg AD
        Sex differences in formation of anti-T antibodies.
        Nature. 1976; 263: 415
        • Jungers P
        • Dougados M
        • Pelissier C
        • et al.
        Influence of oral contraceptive therapy on the activity of systemic lupus erythematosus.
        Arthritis Rheum. 1982; 25: 618-623
        • Vandenbroucke JP
        • Valkenburg HA
        • Boersma JW
        • et al.
        Oral contraceptives and rheumatoid arthritis: further evidence for a preventive effect.
        Lancet. 1982; ii: 839-842
        • Holmdahl R
        • Carlsten H
        • Jansson L
        • et al.
        Oestrogen is a potent immunomodulator of murine experimental rheumatoid disease.
        Br J Rheum. 1989; 28: 54-58
        • Ceuppens JL
        • Goodwin JS
        Regulation of immunoglobulin production in pokeweed mitogen-stimulated cultures of lymphocytes from young and old adults.
        J Immunol. 1982; 128: 2429-2434
        • Nagel JE
        • Chopra RK
        • Powers DC
        • Adler WH
        Effect of age on the human high affinity interleukin 2 receptor of phyto-haemagglutinin stimulated peripheral blood lymphocytes.
        Clin Exp Immunol. 1989; 75: 286-291
        • Roubinian JR
        • Talal N
        • Siiteri P
        • Sadakian J
        Sex hormone modulation of autoimmunity in NZB/NZW mice.
        Arthritis Rheum. 1979; 22: 1162-1169
        • Michalski JP
        • McCombs CC
        • Roubinian JR
        • Talal N
        Effect of androgen therapy on survival and suppressor cell activity in aged NZB/NZW F1 hybrid mice.
        Clin Exp Immunol. 1983; 52: 229-233
        • Steinberg AD
        • Melez KA
        • Raveche ES
        • Patton Reeves J
        • Boegel WA
        • Smathers PA
        • Taurog JD
        • Weinlein L
        • Duvic M
        Approach to the study of the role of sex hormones in auto-immunity.
        Arthritis Rheum. 1979; 22: 1170-1176
        • Grossman CJ
        Interactions between the gonadal steroids and the immune system.
        Science. 1985; 227: 257-261
        • Ahmed SA
        • Penhale WJ
        • Talal N
        Sex hormones, immune response and autoimmune disease: mechanisms of sex hormone action.
        Am J Pathol. 1985; 121: 531-551
        • Schuurs AHWM
        • Verheul HAM
        Effects of gender and sex steroids on the immune response.
        J Steroid Biochem. 1990; 35: 157-172
        • Chetkowski RJ
        • Meldrum DR
        • Steingold KA
        • et al.
        Biologic effects of transdermal oestradiol.
        N Engl J Med. 1986; 314: 1615-1620
        • Powers MS
        • Schenkel L
        • Darley PE
        • Good WR
        • Balestra JC
        • Place VA
        Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17β-oestradiol: Comparison with conventional oral oestrogens used for hormone replacement.
        Am J Obstet Gynecol. 1985; 152: 1099-1106
        • Fauci AS
        • Dale DDC
        The effect of in vivo hydrocortisone on subpopulations of human lymphocytes.
        J Clin Invest. 1974; 53: 240-246
        • Yu DTY
        • Clements PJ
        • Paulus HE
        • Peter JB
        • Levy J
        • Barnett EV
        Human lymphocyte subpopulations: Effect of cortico-steroids.
        J Clin Invest. 1974; 53: 565-571
        • Lesourd B
        • Winters WD
        Specific immune responses to skin test antigens following repeated multiple antigen skin tests in normal individuals.
        Clin Exp Immunol. 1982; 50: 635-643
        • Adami GF
        • Vitale B
        • Bachi V
        Delayed hypersensitivity serial evaluation by means of a multitest system.
        IRCS Med Science. 1981; 9: 1132
        • Kniker WT
        • Anderson CT
        • Roumiantzeff M
        The multi-test system: a standardized approach to evaluation of delayed hypersensitivity and cell-mediated immunity.
        Ann Allergy. 1979; 43: 73-79
        • Lesourd BM
        • Roumiantzeff M
        • Moulias R
        • Biron G
        • Kniker WT
        Reproducibility of delayed cutaneous hypersensitivity (DCH) measured by multi-test.
        in: Proceedings of the 11th Congress of the European Academy of Allergology and Clinical Immunology, Vienna, October 1980Allergol Clin Immunol. 8. 1980: 268
        • Carlsten H
        • Tarkowski A
        • Holmdahl R
        • Nilsson LA
        Oestrogen is a potent disease accelerator in SLE-prone MRL 1pr/lpr mice.
        Clin Exp Immunol. 1990; 80: 467-473