[Postcoital contraception (without prostaglandins)].
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The natural sex steroids (E2, T, P) may be used in therapeutics. Estradiol and testosterone esters (decanoate and undecanoate) may be administered orally. A local effect always follows the percutaneous application of sex steroids, and this is usually accompanied by a systemic effect. But because of the very important metabolism of progesterone by the skin, it is necessary to administer it by other routes (intravaginal, intrarectal) in order to obtain a systemic effect.
In man both basal gonadotrophin levels and the pituitary responses to LHRH remained relatively constant throughout life. In women the pituitary sensitivity varied in the menstrual cycle due to the typical cyclic variation of oestradiol and progesterone. The max delta LH increase to 100 mug LHRH was observed in the periovulatory period (183 +/- 41 mU/ml); it was also significantly higher in the luteal (49 +/- 7 mu/ml) than in the early follicular phase (18 +/- 3 mU/ml). The effect of exogenous sex steroid hormones taken as contraceptive drugs was then studied in 15 women. Significantly lower LH and FSH basal values as well as responses to LHRH were observed in 8 normal women under oral combined contraceptives. Conversely, in 7 women under oral sequential contraceptives, basal LH and FSH remained in the normal range. The LH-FSH responses were increased and delayed when these tests were performed during the period of estrogen treatment. Thus, with combined oral contraceptives, constant and high levels of estrogens and progesterone not only inhibit the LH peak, but also decrease the basal LH-FSH levels and responses to releasing hormone. Conversely, with sequential oral contraceptives, the low level of estradiol does not inhibit these responses and even enhances them. In menopausal women both basal and gonadotrophin responses to LHRH were increased indicating an important pituitary reserve. In menstruating women a significant estradiol increase is observed 2 and 4 hours after a 100 mug LHRH injection, both during the follicular and the luteal phases whereas progesterone increases only in the luteal phase. In men, testosterone was found to increase 4 hours after a 100 mug LHRH injection. These studies show that in normal subjects, sex steroid hormones are important regulators of the sensitivity of the pituitary responsiveness to releasing hormone.
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Six sexual steroidal hormones (progesterone, pregnenolone, testosterone, ethinyl-oestradiol, oestriol and oestrone) inhibit acetylcholine- and histamine-induced contractions of the isolated guinea-pig ileum. Different degrees of inhibitory capacity were found. High concentrations of PGE1 and F2alpha reverse some of these inhibitions. This reversal seems to be non-specific and probably related to sensitization of the ileal smooth muscle by prostaglandins. The inhibitory action of sexual steroids might be non-specific as well. But a "corticoid-like" effect cannot be excluded.
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Administration of progesterone eugonadal women during the midfollicular phase of the menstrual cycle failed to induce a positive feedback effect on the serum concentrations of LH and FSH. The levels of estradiol in serum decreased following the injection of progesterone without a parallel change in LH and FSH concentrations indicating a direct ovarian effect of the exogenous progesterone. In the late follicular phase of the cycle, when preovulatory levels of estradiol were present in serum, or under a ethinyl estradiol treatment progesterone was able to induce an LH discharge indicating the requirement of an estradiol priming of the positive feedback of progesterone in eugonadal women. In order to establish the time required for a sufficient estrogen priming with preovulatory levels of estradiol in serum 3 mg of estradiol-benzoate were administered i.m. 1, 12 and 24 h prior to the administration of 30 mg of microcristalline progesterone in the midfollicular phase of the menstrual cycle, when progesterone alone did not cause an LH surge. Only when estradiol-benzoate was injected 24 h prior to the progesterone administration an LH surge reproducible in time course and magnitude occurred. Administration of estradiol-benzoate alone under these conditions did not cause an LH surge within the elapse of time after the injection when the progesterone induced LH surge occurred. Thus, these experiments demonstrate that a defined estrogen priming is required for the positive feedback effect of progesterone on the gonadotropin release in eugonadal women. Furthermore, progesterone levels in serum of about only 1--2 ng/ml were required for the induction of an LH surge indicating that under physiological conditions progesterone may have an supplementory effect on the primarily estradiol induced LH midcycle peak. 17-hydroxyprogesterone administered during the mid follicular phase of the menstrual cycle and under pretreatment with ethinyl estradiol failed to induce a positive feedback effect on the serum concentrations of LH and FSH, indicating that this steroid does not play a regulatory role on the midcycle LH release in women. 20alpha-dihydroprogesterone administered under the same experimental conditions as 17-hydroxyprogesterone seems to be able to induce an LH surge in serum provided there is an adequate estrogen priming.
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Daily measurements of human chorionic gonadotropin (HCG) beta subunit, luteinizing hormone (LH), and progesterone were carried out in 24 subjects wearing intrauterine contraceptive devices. Detectable HCG was not found in any subject, but in four subjects delayed LH pulses resulted in apparent low levels of HCG because of cross-reactivity in the HCG beta subunit radioimmunoassay.
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Prior studies have produced conflicting results about whether a change in electric potential occurs at the time of ovulation. This study was undertaken to determine whether the Ovutron, a digital voltmeter which displays the sign and magnitude of voltage measured when the index fingers are applied to the electrodes, would produce a mix in polarity, some positive and some negative voltages, with 5 consecutive measurements preceding ovulation. This device was used daily in 10 normally ovulating women to determine whether such a mix in polarity occurred during the menstrual cycle and its relationship to the corresponding daily measurements of luteinizing hormone, total immunoreactive estrogen (IRE) and progesterone heralding and confirming ovulation. In addition, the Ovutron readings were compared to the basal body temperature (BBT) measurements. In 8 of 10 women studied with the Ovutron device, a mix in polarity was observed in 2 of 3 consecutive days preceding ovulation and was associated in all but 2 subjects with a 50 pg/ml/day incremental increase in IRE. By comparison, only 4 of the 10 subjects had a "classic" biphasic BBT curve. This novel device should be evaluated in a large group of women employing these and other additional parameters (e.g., ultrasonography) in order to determine its efficacy and whether it has a role in the treatment of infertility as well as contraception.
The changes in plasma hormone levels were evaluated in matched healthy female volunteers investigated before and after 6 months' use of three new oral contraceptives (OCs): TrigynonR (n = 13), a triphasic OC containing low doses of ethinylestradiol (EE) + levonorgestrel (LNg); MarvelonR (n = 14), a monophasic OC containing low doses of EE + desogestrel (DOG, a new progestogen derived from LNg); and OvidolR (n = 10), a sequential OC containing higher doses (50 micrograms) of EE + DOG. Serum levels of FSH, LH, estradiol and progesterone were decreased in all cases to levels incompatible with ovulation. Prolactin concentrations were unchanged. Sex hormone binding globulin (SHBG) and Transcortin (CBG) levels were significantly increased by all three OCs (Ovidol greater than Marvelon greater than Trigynon); free testosterone levels decreased significantly while free cortisol concentrations remained unchanged. Collectively, these data indicate that (a) all three OCs are effective ovulation inhibitors, (b) Ovidol and Marvelon have greater estrogenic effects than Trigynon, (c) LNg is more effective than DOG in reducing the EE-induced increase in SHBG levels, and (d) free testosterone levels are equally well suppressed by all three Ocs.
Some conflicting reports have appeared in the literature as to the effect of progestogens on the endometrium and on the endo- and exocervix in animals and humans. Hyperplasia of the endometrial and endocervical epithelium has been reported in some non-human primates following the administration of progestogens. In other studies no evidence has been found for such changes. In women using combined oral contraceptives, it has been claimed that the progestogen component causes adenomatous hyperplasia of the endocervix and that this hyperplastic transformation could be a precursor to adenocarcinoma of the cervix. So far, there is, however, no evidence in the literature to confirm this hypothesis. In view of the development of new delivery systems with a constant release of small amounts of progestogens, previous reports in the literature on hyperplasia and potential malignant transformation of the endometrium and the endocervix have been a matter of concern. The aim of the present study is therefore to review results from studies in animals and humans in particular with reference to the effect of a local release of various progestogens on the endometrium and the endo- and exocervix.