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Estrogen and female fertility: I. failure of human chorionic gonadotropin or reserpine in the reversal of pregnancy wastage by estradiol cyclopentylpropionate.
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Luteolysis induced by a luteinizing hormone-releasing hormone agonist is prevented by human chorionic gonadotropin.
The superactive stimulatory luteinizing hormone-releasing hormone (LRH) analogue D-Ser(TBU)6-EA10-LRh was administered intranasally to five healthy women in a daily dose of 600 microgram during two successive days of the mid-luteal phase. Both the basal serum progesterone levels and the length of the luteal phase were reduced, i.e. luteolysis occurred. Three women who were given additional treatment with human chorionic gonadotropin (HCG) in a daily intramuscular dose of 1500 IU for 10 days, had increased basal progesterone levels and a prolongation of the luteal phase. Thus, HCG prevented the luteolytic effect caused by the LRH agonist.
Hormonal effects of the 300 microgram norethisterone (NET) minipill. 3. Comparison of the short-term (2nd month) and medium-term (6th month) effects in 21 subjects.
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Blood prolactin levels: influence of age, menstrual cycle and oral contraceptives.
The relationships between the serum levels of estradiol, progesterone and prolactin have been analysed in normal women in relation to age, to menstrual cycle, and in oral contraceptives users. We have been able to detect significant differences between the prolactinemia values during the cycle in different age groups as well as following oral contraceptives. A word of caution is presented for the evaluation of the prolactin blood level which should always be related to the physiological phase of the cycle and to the age of the subjects.
Evaluation of endocrine parameters in clinical trials with beta-hCG vaccine.
This report presents data on various endocrine parameters with respect to pituitary-ovarian axis in-depth in control vs 18 subjects immunized with three beta-hCG based vaccine formulations. Hormonal parameters such as TSH, PRL, ACTH, progesterone, cortisol, T3 and T4 were measured by RIA in sera in control pre-vaccine cycles as well as at 3, 6, and 12 months after primary vaccine immunization. In 6 women urinary E1G, PdG, LH and FSH were measured by ELISA/RIA tests on early morning urine (EMU) samples collected throughout the menstrual cycle in control vs post-booster vaccine cycles. The results indicated that none of the beta-hCG vaccine formulations altered the pituitary peptide or steroid hormone levels in blood at any time during the period of study. Serum P concentration was adequate and indicative of ovulatory cycle in almost all the cycles during the study. The in-depth study on urinary excretion pattern and levels of gonadotropins and E1G and PdG throughout the control vs post-vaccine booster cycles conclusively showed that pituitary-ovarian axis was not adversely affected by the vaccine.
Hormonal profile of the menstrual cycle in Chinese women after tubal sterilization.
Ten women after tubal sterilization were studied for the hormonal profile of the menstrual cycle. They had undergone sterilization procedures, on the average 5.3 years (range 1.5-10 years) earlier. The serum concentrations of LH, FSH, prolactin, estradiol and progesterone were measured by RIA in daily blood samples of a complete menstrual cycle. Another ten normal women were studied at the same time and were used as the control group. There were no significant differences in the hormonal patterns of the menstrual cycle between the two groups. There was a significantly lower LH level in the early luteal phase of the tubal ligation group compared to the control group. Also, a significantly lower E2 luteal peak compared to the preovulatory peak was observed in the tubal ligation group. The physiological significance of these minor changes is not clear. Only one out of ten women in the tubal ligation group, who had undergone sterilization 1.5 years prior, showed a deficiency in luteal function, but her ovulatory function and menstrual cycle appeared normal. This study indicates that normal hormonal profiles are retained after tubal sterilization.
Steroid regulation of sexual behavior.
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Cytosol and nuclear estrogen receptor in the genital tract of the rhesus monkey.
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The antiprogestins: a recent advance in fertility regulation.
RU 468 (mifepristone) is the first antiprogestin available for clinical purposes. Its pharmacological properties are presented. It possesses antiprogestin and antiglucocorticoid activities. It is now in phase II-III clinical studies as a fertility control agent. The drug appears useful per se in four circumstances: (1) for early pregnancy (amenorrhea of less than 5 weeks' duration). Complete interruption is obtained in approximately 90% of women with a single dose of 600 mg. For this stage of pregnancy, RU 486 appears to be an interesting alternative to vacuum aspiration; (2) for late occasional luteal contraception when given as a single dose on the date of the expected period in women at risk of pregnancy; (3) for dead fetus expulsion in the 2nd or 3rd trimester of pregnancy, and (4) for cervical ripening before obstetrical procedures in pregnant women, such as D and C or vacuum aspiration. The antiglucocorticoid activity of the molecule can be demonstrated in humans by a rise in plasma cortisol, ACTH and LPH after RU 486 intake, and by blockade of some peripheral effects of cortisol. Results obtained in more than 1000 women undergoing short-term treatment with RU 486 (600 or 800 mg once) clearly indicate that the antiglucocorticoid activity of the molecule has no clinical relevance at the doses used for fertility control purposes. In conclusion, RU 486 appears to be a promising new tool for fertility control, but large-scale trials are necessary to confirm its safety and to define its optimal mode of utilization for each indication.
The effect of luteectomy-induced progesterone-withdrawal on the oxytocin and prostaglandin response of the first trimester pregnant human uterus.
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Assessment of possible luteolytic effect on intra-ovarian injection of prostaglandin F-2ALPHA in the human.
A group of five patients awaiting laparoscopic tubal diathermy were followed by daily assay of luteinising hormone (LH) and progesterone. Between five and eight days after the LH peak, prostaglandin F-2ALPHA (PGF-2ALPHA) was injected into either the corpus luteum or the ovarian stroma. Doses of 100 mu-g into the corpus tuteum, 1000 mu-g into the adjacent stroma and 500 mu-g into an indeterminate ovarian structure had no effect on peripheral plasma progesterone levels or uterine bleeding. An injection of 500 mu-g or 1000 mu-g given unequivocally into the corpus luteum produced a rapid and profound fall in plasma progesterone levels, the nadir coinciding with the onset of uterine bleeding which commenced 24 hours after the injection and persisted for more than seven days. Injection of 100 mu-g in the same volume of saline had no such effect. Despite continued bleeding plasma progesterone levels returned to normal luteal levels for three days and then fell again.
Effects of RU16117, an orally active weak oestrogenic compound, in postmenopausal women.
Daily oral administration of 1, 3 or 10 mg of RU16117 (11 alpha-methoxy ethinyl oestradiol) to normal postmenopausal women led to a progressive decrease of basal serum LH levels to 60.4 +/- 17.0, 35.1 +/- 9.1 and 20.1 +/- 2.8% of control (pretreatment values, P less than 0.01), respectively, after 4 wk of drug administration. Although the pattern was similar, the inhibitory effect of RU16117 was even more pronounced on FSH than LH levels: a 50% decrease of basal LH and FSH levels was obtained at the daily 1.8 and 1.2 mg doses of RU16117, respectively. No significant change of basal serum gonadotrophin levels was observed with the daily 0.3 mg dose. Administration of 1 mg of RU16117 every second day or 10 mg once a week led to a relatively small but significant (P less than 0.05) 20--25% decrease of basal serum LH levels after 4 wk of treatment in four out of five women. While daily 0.3 and 1.0 mg doses of RU16117 had no significant effect on the LH response to 100 microgram LHRH, the 3.0 mg dose delayed the response up to 90 min. The 10 mg dose, on the other hand, led to a markedly delayed and reduced response. Treatment for the same period (4 wk) with 1 mg RU16117 every second day or 10 mg once a week led to a small (20--25%, P less than 0.05) inhibition of the LH response to LHRH. At the dose of 10 mg once a week, RU16117 had no or minimal effect on endometrial histology. Since RU16117, an orally active weak oestrogenic compound, has been shown to have anticarcinogenic activity in the rat, the present findings suggest that this new steroid could be useful for the treatment of climacteric symptoms.
A comparative endocrinological and pharmacological view of the maintenance or interruption of pregnancy.
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Human cervical mucus. II. Changes in viscoelasticity during the ovulatory menstrual cycle.
Quantitative viscoelasticity measurements were made on individual human cervical mucus samples by microrheometry. Increases in mean values for mucus spinnbarkeit, ferning, and wet weight were associated with the ovulatory phase of the menstrual cycle, while no significant differences versus time were noted for mean values for sample pH or nondialyzable dry weight. A nadir in mucus nondialyzable solids (NDS) concentration and in visoelasticity was seen at or near midcycle. Substantial, highly reproducible, variations in mucus viscoelasticity were observed when mucus from different donors was compared. When the contribution of (NDS) to viscoelasticity was minimized by data normalization or by sample reconstitution, a significant increase in viscoelasticity was associated with the ovulatory phase of the cycle, suggesting the occurrence of a relative increase in mucin concentration or a compositional change in the mucus.
Studies on the effects of pharmacologic doses of cortisone acetate and several nonsteroidal anti-inflammatory compounds on ovo-implantation, early pregnancy, and the deciduomal response in the rat.
Cortisone acetate (10 mg/day), alone or in combination with progesterone (4 mg/day); progesterone (4 mg/day); progesterone (4 mg/day) plus estrone (1 microng/day); indomethacin (0.75 mg/day); phenylbutazone (20 mg/day); flufenamic acid (10 mg/day); and Compound 83161 (tetrazolo less than 1,5-alpha greater than s-triazolo less than 3,4-c greater than quinoxoline) (8 mg/day and 12 mg/day) were each given to intact rats during early pregnancy (days 1 and/or 2 through day 8). Only cortisone acetate treatment caused a true delay in ovo-implantation. Both progesterone treatment beginning on day 1 and cortisone acetate treatment beginning on day 1 or 2 caused an increased postimplantation fetal death rate. Compound 83161, at doses causing signs of general toxicity (12 mg/day), caused a marginal inhibition of implantation. Treatment with indomethacin, phenylbutazone, or flufenamic acid caused some inhibition of the traumatic deciduomal response in spayed rats treated with progesterone, while treatment with cortisone acetate and Compound 83161 did not.
Failure to interrupt established pregnancy in humans by D-tryptophan-6-luteinizing hormone-releasing hormone.
Four women 5 to 8 weeks into pregnancy, scheduled for therapeutic abortions, were given an analog of gonadotropin-releasing hormone, D-tryptophan-6-LHRH, in an effort to interrupt pregnancy. The treatment consisted of 100-micrograms injections, given twice daily for 5 to 10 days. No decline in serum beta-hCG or progesterone was noted, and menstrual extraction was needed in all women for pregnancy interruption. These data indicate that D-Trp-6-LHRH is not effective as an abortifacient in established pregnancy.
Absence of chorionic gonadotropin in sera of women who use intrauterine devices.
A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the intrauterine contraceptive device (IUD). Starting on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, we collected daily blood samples from three groups of normally menstruating young women. The study groups were (A) IUD users (n = 30), (B) women with tubal ligation (n = 30), and (C) women trying to become pregnant (n = 15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. Two subjects who became pregnant, as judged by progressive increases in hCG and P levels in the luteal phase, belonged to the group planning pregnancy. The finding of two pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure.