Abstract Objective: To investigate the effects of hormone therapy, estrogen therapy and tibolone on markers of apoptosis including bcl-2, and bax and cyclin D 1 expression in postmenopausal vaginal epithelium. Study design: Thirty postmenopausal women were randomized to the treatment protocols (0.625 mg conjugated equine estrogen (CEE) + 2.5 mg medroxyprogesterone acetate (MPA); 2 mg estradiol valerate; 2.5 mg tibolone). After baseline vaginal biopsy, control biopsies were performed after 70 days following the initiation of the therapy. Bcl-2, bax, Bcl-2/bax ratio, cyclin D 1 measurements were performed immunohistochemically. Data were analyzed by Kruskal–Wallis, Mann–Whitney U and Wilcoxon tests. Results: After the treatment period the above-mentioned parameters were not different among the groups except for cyclin D 1 levels. Cyclin D 1 expression was found to be strong in patients with treated estradiol valerate. Conclusions: The effects of estrogen on cyclin D 1 expression were not detected with tibolone or with the addition of progesterone to estrogen in the vaginal epithelium. Cyclin D 1 appeared to have stronger effects on the estrogen related proliferation compared to apoptotic markers in vaginal epithelial cells.