Classification of Endometrial Response to Synthetic Progestogen-Estrogen Compounds

Abstract

The endometrial responses of 206 infertility patients who were investigated for 371 menstrual cycles (124 regularly ovulating patients in 236 cycles and 82 anovulatory patients in 135 cycles) to 11 synthetic progestogens norethynodrel and medroxyprogesterone acetate with ethinyl estradiol were evaluated by endometrial biopsies taken at 5-day intervals. Most synthetic progestogen-estrogen compounds produced transient subnuclear vacuolation in ovulating patients after 5 days of treatment during the early part of the cycle. Continued administration resulted in progressive suppression of glandular secretion with the concurrent inhibition of glandular and stromal mitoses. The principal alteration in the vascular pattern of the endometrium was dilation of many sinusoidal channels with occasional abnormal development of spiral arterioles. In ovulating patients distorted patterns of glandular secretion were noted when the drug was administered shortly after ovulation occurred. There was more rapid secretory regression and the glands were very dilated by the end of 10 days of treatment. In nonovulating patients the effect of exogenous synthetic progestogens was unpredictable. This was probably due to the non-uniformity of the pathogenesis of the anovulation. With most of the compounds there were no significant changes when posttreatment biopsies were compared with pretreatment biopsies. A detectable decidualike stromal reaction was observed after 20 days of steroid therapy in only a few patients. The endometrial alterations were maximal with Provera Enovid Norlutate and Compound 11800. Allylestrenol and Compound 5071A produced minimal alterations. Chlormadinone Duphaston and Compounds 21240 11843 and 12688 produced endometrial changes between the 2 extremes.