Histological and immunohistochemical evaluation of postmenopausal endometrium after 3 weeks of treatment with tibolone, estrogen only, or estrogen plus progestagen.

Objective: To evaluate histological and immunohistochemical parameters of short-term (21 days) tibolone, estrogen-only, and estrogen+progestagen treatment in the human postmenopausal endometrium.

Design: An observational, open, nonrandomized, controlled study.

Setting: Three collaborating centers: Amphia Hospital in Breda, Albert Schweitzer Hospital in Dordrecht, Erasmus Medical Center in Rotterdam, the Netherlands.

Patient(s): Thirty healthy, postmenopausal women.

Intervention(s): Control group (n = 9), no hormonal treatment; tibolone group (n = 8), patients were treated with 2.5 mg of tibolone (administered orally) every day, starting 21 days before surgery; estrogen group (n = 7), patients were treated with 2 mg of E(2) (Zumenon, administered orally; Zambon, Amerfoort; The Netherlands) every day, starting 21 days before surgery; estrogen+progestagen group (n = 6), patients were treated with 2 mg of E(2) (Zumenon, administered orally) and 5 mg of medroxyprogesterone acetate (administered orally) every day, starting 21 days before surgery.

Main Outcome Measure(s): Uterine tissues were collected, and two pathologists independently assessed histology. Immunohistochemical parameters measured were estrogen receptor alpha, progesterone receptor A/B, Hoxa10, Ki67, and Bcl-2.

Result(s): On the basis of a number of histological and immunohistochemical parameters measured after 21 days of treatment, it was observed that tibolone displays clearly less stimulation (proliferation) of the human postmenopausal endometrium than estrogen at the beginning of a treatment, but the stimulation is higher than with estrogen+progestagen.

Conclusion(s): Short-term (21 days) tibolone treatment results in a small stimulation of proliferation of the endometrium, and because long-term treatment with tibolone has been demonstrated to lead to an atrophic endometrium, it may be concluded that the stimulatory effect, as observed in this study, is transient in nature. It is hypothesized that tibolone first displays a more estrogenic mode of action, which over time, is counterbalanced by the induction of its progestagenic properties.