Comparative endometrial histology in postmenopausal women with sequential hormone replacement therapy of estradiol and, either chlormadinone acetate or micronized progesterone
Introduction
During life, the endometrium is a very sensitive target for estradiol which induces a proliferation phase and for progesterone which induces a transformation of estradiol-primed endometria in secretory phase. Steroid receptors are located in glands, stroma and vessels. After menopause, hormonal receptors are still present but the vascularization is altered. This allows different interindividual and intraindividual behavior; the same endometrium can respond differently and show diverse histological aspects allowing some difficulty for interpretation [1]. The hormonal histological status is related as proliferative or secretory with a precise dating for the luteal phase of physiological cycles. This situation can be reproduced on a menopausal endometrium, but, in most hormone replacement therapies (HRTs), estradiol stimulation is generally weak and, in contrast, progestin action strong, to prevent hyperplasia and carcinoma.
The different progestins have some specific impact on the different structures of the endometrium. Among these, chlormadinone acetate (CA)—a non-androgenic pregnane progestin—has been used, with success, for luteal insufficiency during the last 25 years. The present study has been developed to compare the histological effects of CA and MP on endometrium, in sequential HRT in menopausal women.
Section snippets
Patients
A multicentric, double-blind, randomized trial was conducted for 18 months in healthy postmenopausal patients selected in the out-patient department. A first endometrial biopsy was performed at inclusion, and another one was done at the end of the trial 18 months later; this last biopsy was performed between day 18 and day 24 of the cycle, in the progestative phase.
Administration regimen
After randomization, patients received during the 18 months percutaneous E2 (Oestrogel®) 1.5 mg/day from day 1 to day 24 of the
Results
The study took place in France between November 1991 and December 1994. A total of 336 postmenopausal women were included: 167 were randomized to receive E2/CA (CA group), and 169 to receive E2/P (P group). The mean age was 51.3±3.8 years in the two groups and duration of menopause was 14.1±15.9 months in CA group and 17.9±22.3 months in MP group. Mean plasmatic basal levels were, for CA and MP groups, respectively, 68.0±63.6 and 66.1±44.1 pmol/l for estradiol, and 88.1±41.2 and 78.0±34.0 IU/l
Discussion
Most tissues are now usually fixed by a neutral formaldehyde, which represents an universal fixative suitable for routine histological analysis as well as new techniques such as in situ hybridization. But, when the tissues are not supported by a fibrosis stroma, formaldehyde appears as a poor morphologic fixative. This is the case for testicular biopsies, which are nearly not interpretable for the study of spermatogenesis and for endometrial biopsies to a lesser extent. We choose the Bouin
Acknowledgements
This work was supported by Aventis Laboratories, France.
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