Effects of 17alpha-ethinyl-19-nortestosterone (ENT) on corpus luteum function.

PIP: The effect of ENT, a synthetic gestagen, on corpus luteum function in 62 normal and 31 insufficient cycles was studied by radioimmunassay o f plasma levels of progesteorne, immunoreactive estrogens, and gonadotro pins. Doses as high as 100 mg/day immediately after ovulation blocked synthesis of progesterone in normal cycles totally within 4-5 days. Estrogens seemed to be elevated. Smaller daily doses had the same effect, but less pronounced. The effect became weaker with every day after ovulation that therapy was begun. However, a start of therapy on Day 5 after ovulation showed some suppression. 3 tablets daily of a commercial preparation designed for corpus luteum phase defects (100 mcg EE2 and 2 mg ENT per tablet) showed slight suppression of progesterone levels if therapy began close to ovulation but administration during an insufficient luteal phase produced nothing but the expected menstrual delay. This indicates ENT suppresses corpus luteum function by blocking progesterone synthesis exclusively. Plasma levels of estrogens and gonadotropins remained unaltered. The blocking effect depends upon daily dose and age of corpus luteum at start of therapy. Substitution therapy of corpus luteum phase defects in patients with infertility problems should not be used any longer and should never begin earlier than 3 days after ovulation if used at all. Stimulation therapy during follicular phase with clomifene or gonadotropins gives better results.^ieng

Effect of post-ovulatory administered oestrogens on corpus luteum function.

The effect of orally given diethystilboestroldiphophate (DES) and 17alpha-ethinyl-oestradiol-3-methylether (EEM) on plasma progesterone levels was studied. Both compounds were administered for 5 days to 5 women in daily doses of 60 mg (DES) and 30 mg (EEM). The fully informed volunteers were found to have a normal menstrual cycle before the study. The mean corpus luteum phase (corpus luteum phase = days between LH surge and onset of menstruation) of all control cycles lasted 12.8 days. Daily plasma samples were collected for radioimmunoassay (RIA) of progesterone, immunoreactive oestrogens and LH. After a control cycle the first treatment was carried out with DES. The third and the fifth cycle were control cycles again. The EEM-treatment was done in the fourth cycle. Although the effect of the two compounds was different, a dependence of the age of the corpus luteum (CL) could be demonstrated for both. DES-treatment lowered plasma progesterone levels during administration. This effect was only demonstrable if the treatment was begun on the day of the LH-peak. The length of the CL-phase remained unaltered. EEM-treatment if started on the day of the LH surge, suppressed corpus luteum function in the late luteal phase. If the treatment was started later, the effect was less pronounced. The administration of both compounds did not shorten the time between ovulation and the next bleeding. After DES-treatment this interval was not altered. After EEM-treatment the subsequent bleeding was even delayed depending on slowly decreasing levels of plasma oestrogens.

[The acute feedback action of exogenously administered oestrogens on the serum-gonadotropin-levels in pre- and postmenopausal women (author's transl)]. / Der akute Rückkoppelungseffekt exogen zugeführter Oestrogene auf die Serum-Gonadotropinspiegel in der Prä- und Postmenopause.

PIP: The effects of estradiol benzoate (EB), ethinyl estradiol (EE), and mestranol in different dosages on serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were measured by dioxane-radioimmunoassay at intervals of hours and days. All postmenopausal women studied here reacted with a pronounced suppression of both FSH and LH. The LH decline starts 4-10 hours earlier than FSH and returns - after the minumum on Days 2-3 - to the controls on Days 5-6, while the FSH levels show a longer suppression. Neither in the type of estrogen nor in the administered dose a marked qualitative difference could be observed. Only after 3 mg EE and 15 mg mestranol a prolonged inhibitory effect on FSH and LH became evident. Results in premenopausal women were quite different. In 7 women with a history of amenorrhea or anovulatory cycles 5 mg EB was given. A small decline after 24 hours was followed by a sharp rise of LH 1 day later which is comparable to the preovulatory LH peak. In the subsequent days values returned to control levels. The FSH curve did not show a similar peak. Only 1 woman ovulated and became pregnant. In another group of 11 women with normal menstrual cycles, 5 mg EB was injected at different times of the follicular, periovulatory, and luteal phases. The patterns of serum LH and FSH were comparable to the results in amenorrheic patients. In all cases an LH peak appeared on Days 2-3, which seemed to be higher in the preovulatory than in the postovulatory phase. The FSH curves remained uncharacteristic with small oscillations. The role of the physiological follicular estrogen peak for triggering the LH surge is discussed as well as the possibility of checking the response of the hypothalamic-hypophyseal system by exogenous estrogen application.^ieng