The ovulation inhibiting effect of progestins has been suspected even longer for Beard in 1897, inferred that the corpus luteum suppressed ovulation during pregnancy.
Progesterone was first isolated in 1934 by Allen and in the next years it became know that progesterone, testosterone, and estrogen could each inhibit ovulation.
However, until 1954, these steroids were not of practical value as antifertility agents in human beings, either because of undesirable side effects, or because of lack of therapeutic effectiveness on continued therapy.
In addition to the 19-nor steroids as orally effefctive progestogens, there - has emerged a new groups, 17-icetoxyprogesterone and its various derivatives.
Several of these compounds in the from of sequential or combined with estrogen have also proved to be successful oral contraceptives.
An enormous amount of study has gone into the experiemtnal animal trials and oral contraceptives prevent pregnancy by action on other sites in the uterine body; the endometrium,cervix, or fallopian tubes.
Here, it appeared prudent to study one of the target organs of these agents, -the uterus or more specifically the endometrium.
Thus, this study concerns itself with endometrial .morphological changes and histochemical changes and carcinogenic effects of rabbit´s endometrium following administration of long term use of combined and sequential oral contraceptive and endometrial changes after cessation of oral contraceptive.
The methods of study was as follows.
Out of 20 non-pregnant normal rabbits weighing from 1. 6kg to 2. 2kg, four rabbits were enrolled in the control group and eight rabbits in the study of combined theraphy group and eight in the sequential theraphy group."´
In the study group, oral adult daily" does of the Eugynon (Ethinyl Estradiol 0. 1mg-Norgestrel 0. 5,:sng) and Serial (Ethinly Estradiol 0. img-Megestrol acetate 1.0mg) were given to each rabbit for 6 menstrual cycles and 9 menstrual cycles and sacrified on each designated menstrual day of proliferative phase and secretory phase.
The obtained materials of endometrial tissues were fixed immediately in neutral buffered for.rmalin .and stained with haematoxylin and eosin for general endometrial morphology, with Gomori´s method for alkaline phosphatase and P.A.S. and diastase-PA.S. for mucosubstances in the endom-etrium without buffering.
The results of the study was as follows:
1. Out of the 20 non-pregnant normal rabbits, the endometrial morphological changes and histochemical changes of endometrium were reviewed following administration of Eugynon and Serial -for 6 and 9 menstrual cycles and the endometrial changes after cessation of oral contraceptives for 1 or 2 months.
2.. In endometrium under the influence of combined therapy with Eugynon for 9 months, there was a marked stromal edema and moderate degree of stromal fibrosis, showing atrophic, inactive :secretory endometrium compared to Serial groups.
3. The endometrial changes after cessation of long term use of oral contraceptive were returned to normal functioning endometrium progressively in both combined, and sequential groups.
4. The alkaline phosphatase activity in the glands was increased during the proliferative phase, reached a peak during the early secretory phase and there was no remarkable difference between the control and sequential groups except the slight decreasing activity in combined groups.
5. The combined .or sequential therapy produced little changes in the stained mucosubstances during the various phases of the induced´ menstrual cycles as compared to the control groups.
6. There was no evidence of anaplagtic endometrial changes following long term use of oral contraceptives.
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