Histological Analysis And Gene Expression Profiling Of Endometrial Tissues Reflecting The Response To 3-Week-Treatment With Tibolone, E2 And E2 + Mpa

Tibolone is a tissue-specific compound used for treatment of climacteric complaints and prevention of osteoporosis. The aim of the current study was to gain more insight in the short-term progestagenic, estrogenic and tibolone-specific effects on the human endometrium. 30 healthy, postmenopausal women were included into this observational, open, non-randomized, and controlled study; 21 days of treatment were conducted: Control-group (n = 9); Tibolone-group (n = 8), 2,5 mg/day; Estrogen-group (n = 7), 2 mg/ day of estradiol; Estrogen+progestagen-group (n = 6), 2 mg/day of estradiol and 5 mg/day of MPA. Discussed results are on the histological and molecular analysis of the endometrial tissues reflecting the response to 3-week-treatment with tibolone, E2 and E2+MPA. Pathological revision of tissues and the assessment of proliferation (Ki67) showed that 21-day tibolone treatment results in clearly less proliferation of the postmenopausal endometrium than E2 treatment, but proliferation is higher than with E21MPA treatment. Expression profiles after tibolone treatment show weak similarity to the profiles after E2 treatment (overlap 72 genes) and even less similarity to profiles after E21MPA treatment (overlap 17 genes). Interestingly, 96 tibolone specific genes were identified. Furthermore, the impact of E2 treatment on the endometrium (800 regulated genes) was much higher than the effect of the tibolone (174 genes) or E2+MPA treatments (175 genes). 21-day tibolone treatment results in a small stimulation of proliferation of the endometrium, however, since longterm treatment with tibolone has been shown to lead to an atrophic endometrium it may be concluded that this stimulatory effect is transient in nature.