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OBJECTIVE: Our purpose was to investigate the effect of hormone replacement therapy on the postmenopausal changes in serum cytokine levels. STUDY DESIGN: Fifteen cytokines were measured by an enzyme-linked immunosorbent assay in 97 untreated and hormone replacement-treated women. Thirteen women were examined before and during hormone replacement therapy. RESULTS: Serum concentrations of macrophage colony-stimulating factor were significantly (P < .05) lower during the early postmenopausal period (< or = 10 years) than the values in premenopause and the elevated levels in the late postmenopausal period (< or = 30 years). A significant increase in tumor necrosis factor alpha and a decline in transforming growth factor beta1 were found in late postmenopausal women. Serum levels of macrophage colony-stimulating factor in women receiving hormone replacement therapy were significantly higher than those in untreated postmenopausal women. Furthermore, hormone replacement therapy induced a significant (P < .01) increase in serum levels of macrophage colony-stimulating factor, whereas serum levels of other cytokines were not affected. CONCLUSION: It is well documented that macrophage colony-stimulating factor lowers serum cholesterol concentrations and prevents atherosclerosis. Inducing the production of macrophage colony-stimulating factor is a possible additional mechanism of hormone replacement therapy in mediating the antiatherogenic effect.

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The influence of medroxyprogesterone acetate (MPA) on lymphoid tissue of rabbit appendix was investigated. The agent caused a uniform depletion of lymphoid cells, which confirmed the immunodepressive properties of the drug. Other findings suggested a corticoid action of the agent and a possible anticellular activity, interfering with nucleic acid synthesis of proliferating cells.

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To investigate the influence of sex-steroids on the in vitro correlate of cell-mediated immunity (CMI), blood samples from 49 women on hormonal contraceptives were tested on the lymphocyte response to the mitogens phytohemagglutinin (PHA) and concanavalin A (Con-A). Sixteen women were taking oral contraceptives of combined oestrogen/progestogen of the same brand (low oestrogenic and middle range progestogenic activity); 15 had received intramuscular injections of medroxyprogesterone acetate and 18 women were using a sequential pill. The results were compared with those of 18 women not taking contraceptive steroids and matched for age. No significant changes were observed between the different groups. Considering the previously found alterations in dinitrochlorobenzene (DNCB) skin test reactivity by sex steroids, it is hypothesized that sex-steroids have little or no influence on the central proliferative phase of the immune response, but have a profound effect on the efferent phase.

PIP: The influence of sex steroids on in vitro correlates of cell-mediated immunity (CMI) was studied by testing 49 blood samples of women on hormonal contraception for the lymphocyte response to 2 mitogens, phytohemagglutinin (PHA) and concanavalin A (ConA). Of the 49 women studied, 16 used combined oestrogen-progestogen pills of the same tradename (low-dose estrogen and midrange progestogen), 15 used injectable methods containing medroxyprogesterone, and 18 used sequential preparations. Age-matched controls, not using oral contraception, were studied for comparison. The results, presented tabularly, show no significant difference among any of the groups studied and controls by Student t test. These in vitro assessments differed from previously reported in vivo assessments by the same experimental group; therefore, the authors hypothesize that contraceptive steroids have little or no influence on the central proliferative phase of the immune response, but that they do have a profound effect on the efferent phase of immunity.

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A radioimmunoassay (RIA) method for measuring medroxyprogesterone acetate (MPA, Provera) in serum has been developed utilizing benzene:iso-octane extraction, 3H-MPA to assess procedural losses, goat anti-MPA-3-(0-carboxymethyl) oxime-bovine serum albumin serum and dextran-coated charcoal separation. Control serum blanks were undetectable, 200 pg/ml of MPA was measurable with a high reliability, and intra- and interassay coefficients of variation were 6 and 13 percent, respectively. MPA added to control serum was quantitatively recovered. Serum MPA levels measured in 2 women after ingestion of 10 mg MPA rose to 3.4 to 4.4 ng/ml within 1 to 4 hours after oral intake and fell rapidly thereafter to 0.3 to 0.6 ng/ml within 24 hours. Insertion of Silastic intra-vaginal rings (IVRs), containing 100 or 200 mg of MPA, into 4 women for periods of 3 weeks resulted in a rapid rise of serum MPA after insertion, rather stable MPA levels of 0.9 to 1.6 ng/ml while the IVRs were in place, and a rapid decline of serum MPA following IVR removal. Serum estradiol-17beta and progesterone concentrations, measured about 3 times a week in these patients, indicated that ovulation was consistently inhibited. The serum MPA levels observed in this study were approximately 5 times lower than those reported by other investigators using a double-antibody RIA of MPA in unextracted serum.

PIP: Radioimmunoassay of serum medroxyprogesterone (MPA, Provera) in 7 wo men following oral and intravaginal administration is presented. The assay utilizes benzene: isooctane extraction, tritiated-MPA to assess procedural losses, goat-MPA-(O-carboxymethyl) oxime-bovine serum albumin serum, and dextran coated charcoal separation. Buffer and control serum blanks were indistinguishable from 0. 200 pg/ml of MPA was measurable with high reliability, and intra- and interassy coefficients of variation were 6 and 13%, respectively. Various amounts of MPA added to control serum were measured with accuracy. MPA levels in the 3 women who injested 10 mg of MPA rose to 3.4-4.4 ng/ml within 1-4 hours after oral intake and fell rapidly thereafter to .3-.6 ng/ml within 24 hours. MPA levels in the 4 women with Silastic intravaginal rings (IVRs) containing 100 or 200 mg of MPA rose rapidly after insertion, were rather stable (.9-1.6 ng/ml) while the IVRs were in place, and declined rapidly following IVR removal. Estradiol-17 beta and progesterone levels indicated that ovulation was consistently inhibited. The MPA levels in this study were approximately 5 times lower than those reported by others using a double-antibody radioimmunoassay of MPA in unextracted serum.

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