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Influence of Hormonal Contraceptives on the Immune Cells and Thickness of Human Vaginal Epithelium

From the Departments of Clinical Microbiology, Immunology, and Clinical Science, Obstetrics and Gynecology, Umeå University, S-901 85 Umeå, Sweden.

Address reprint requests to: Marie-Louise Hammarström, PhD, Umeå University, Department of Immunology, SE-901 85 Umeå, Sweden; E-mail: marie-louise.hammarstrom{at}climi.umu.se.

OBJECTIVE: To determine whether use of steroid hormone contraceptives modifies immune defense parameters of the vaginal epithelium in humans.

METHODS: Vaginal biopsies were collected during the follicular and luteal phases in regularly menstruating women (controls) and in women using combined oral contraceptives, depot-medroxyprogesterone acetate injections, or levonorgestrel implants. Fifteen healthy women (aged 20–34 years) were enrolled in each group. Biopsies were analyzed in a blinded manner. Epithelial thickness was estimated by morphometry. Immune cells were analyzed by immunomorphometry with cell-type-specific monoclonal antibodies.

RESULTS: The epithelium of controls harbored 241 ± 35 leukocytes (CD45⁺ cells) per mm² (mean ± 1 standard error of the mean), and the thickness was 261 ± 16 µm. T lymphocytes (CD3⁺) dominated, and cytotoxic or suppressor T cells (CD8⁺) were more frequent than T helper cells (CD4:CD8 ratio: 0.7 ± 0.1). Macrophages (CD68⁺) constituted the second-largest population, followed by Langerhans cells (CD1a⁺). B cells, natural killer cells, monocytes, and granulocytes were generally absent. There were no significant differences between the follicular and luteal phases. The epithelium was significantly thicker in all three groups that used hormonal contraceptive (333 ± 9 µm) compared with controls, and it exhibited superficial hyperplasia. The frequency of intraepithelial leukocytes (CD45⁺) was increased in depot-medroxyprogesterone acetate (P < .001) and levonorgestrel implant users (P < .04). In depot-medroxyprogesterone acetate users, this was explained by an increased frequency of the CD8⁺ T lymphocyte subset.

CONCLUSION: Hormonal contraceptives induce hyperplasia of the vaginal epithelium. The significant changes in the intraepithelial leukocyte population in depot-medroxyprogesterone acetate and levonorgestrel implant users most probably reflect altered local immune capacity.

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