Sequential addition of low dose of medrogestone or medroxyprogesterone acetate to transdermal estradiol: a pilot study on their influence on the endometrium

We evaluated bleeding pattern and endometrium following the administration of two of the most common types of progestogens used in hormone replacement therapy, medroxyprogesterone acetate (MPA) and medrogestone acetate. Twenty eight patients in spontaneous menopause were randomly allocated to two groups. Group 1 ( n = 14) received 5 mg/day of MPA and group 2 ( n = 14) received 5 mg/day of medrogestone: both the progestogens were sequentially added for the last 12 days of a 21-day period of transdermal estradiol administration (50 μg per day). A 7-day treatment-free period completed the cycle. The study treatments were administered for 6 cycles. The endomtria were checked for their thickness by transvaginal ultrasound before starting treatment and at 6th treatment cycle (days 6–10 of the estrogen-only phase and during the period between days 8 and 12 of the progestogen addition). Endometrial biopsies were performed before starting treatment only in the patients with a positive progesterone challenge test and in all the patients at the end of the study during the addition of the progestogen. The bleeding pattern was closely monitored. MPA is accompanied by a thick endometrium with full secretory transformation in all cases. On the contrary, the same dose of medrogestone induced a consistent decrease of estrogen primed endometrium with only 4 cases of full secretory transformation. Four medrogestone-treated patients dropped out due to unscheduled bleeding. A low dose of medrogestone added to transdermal estradiol induced incomplete transformation of endometrium and oligo-amenorrhea more frequently than MPA, but it increased the chances of irregular bleeding. MPA fully transformed the endometrium: periods were thus heavier but regular. None of the patients in either group had endometrial hyperplasia.