ABSTRACT
In an attempt to simulate some parts of the progesterone and oestradiol patterns found in the normal menstrual cycle by intramuscular injections of microcrystalline progesterone and oestradiol benzoate, two distinct effects of progesterone and oestradiol on the hypothalamic cyclic centre were observed. Both progesterone and oestradiol can produce a positive feedback on the cyclic centre as measured by a plasma LH surge when administered to women with primary amenorrhoea, to castrated women, to women in the postmenopause and to eugonadal women receiving oral therapy of 60 μg of ethinyloestradiol per day. Subsequent LH peaks could be induced with progesterone or oestradiol benzoate after an oestradiol induced LH peak, but no further LH peak could be induced by either progesterone or oestradiol following a first progesterone induced LH peak. The progesterone induced LH discharge differed from that induced by oestradiol: It always occurred immediately after progesterone injection regardless of the dose given and was terminated very abruptly. The duration of the release of LH seems to decrease with an increase in the progesterone dose. In contrast, the first significant rise in the plasma LH concentration after oestradiol benzoate injection occurred after a latent phase of at least 24 hours. A significant FSH increase in the plasma was only seen following progesterone injection.
The results of these feedback studies are interpreted in conjunction with the steroid pattern of the human female menstrual cycle. 17β-oestradiol was suggested as the initial triggering stimulus in the cycle leading to an LH surge. This first LH surge may cause the pre-ovulatory luteinization of the theca interna, thus, resulting in an increase of plasma progesterone. The biphasic stimulatory and inhibitory feedback effect of progesterone provides the final dosage regulation of the total LH discharge by regulating the amount of LH released in the second part of the biphasic midcycle peak. Progesterone also blocks the cyclic centre to further stimulation during the luteal phase of the cycle. The biphasic feedback effect of progesterone is interpreted as a possible periovulatory mechanism for mono-ovulation in the human female.