Synthetic progestagen-oestrogen preparations and endometrial morphology

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Abstract
19-nor steroids in high and medium dosage in continuous or cyclic combined regimens with oestrogen produce an endometrium characterized by hyperinvoluted glands, a prominent predecidual reaction, suppressed arterioles, and dilated venules. When daily dosage is decreased to 2·0 mg. or less, the endometrium is composed of hyperinvoluted glands in an inert stroma; predecidual reactions are weak and infrequent; venules are rarely dilated, but spiral arterioles are suppressed. 17-α-Acetoxyprogesterone derivatives in high and medium dosage given in a cyclic combined regimen with oestrogen produce similar but less intense effects to the 19-nor steroids. When given in cyclic sequential regimen, they produce an early secretory endometrium closely resembling normal patterns, chronologically retarded by about five days; in some instances a regressing, undatable secretory pattern is found, but predecidual response is minimal, and dilated venules are not seen. 19-nor steroids in medium dosage given for 20 days without added oestrogen produce a late secretory endometrium with unpredictable variation from patient to patient and even from site to site within the same endometrium. Inhibition of the development of spiral arterioles is a common denominator in all progestagenoestrogen regimens. Modification of this element within the target tissue may be decisive for the morphogenesis of later vascular and stromal changes. Using synthetic progestagen-oestrogen regimens, endometrial gland secretion appears only after progestagen, whether given ab initio concomitantly with oestrogen or begun after a phase of oestrogen priming. Secretory vacuoles become evident about four to five days after progestagen is administered. The role of progestagen in secretion is interpreted as an indirect effect whereas its role in the development of decidual-like changes is construed as direct.