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[The effect of different types of oral contraceptives upon ovarian function (author's transl)].

An investigation on the influence of different types of oral contraceptives upon serum gonadotropins, estradiol and progesterone was carried out in 10 volunteers. The effect of a change from a normophasic type preparation to a sequential preparation (Ovanon and Kombiquens) and from a combined preparation to a minipill (Neogynon and Exlutona) was studied. Two new 3-phase step-up preparations were also tested. Ovulation was inhibited in each case as the preovulatory LH-peak and the subsequent rise of serum progesterone were found to be missing. The basal LH- and FSH-secretion and serum estradiol were demonstrated to be significantly diminished in the volunteers taking combined and sequential preparations. The release of gonadotropines was not inhibited as much when the 3-phase step-up preparations (SHB 261 AB and SHB 264 AB) were used. When Exlutona was taken, the basal LH-secretion was lower than during the pre- and postovulatory phase of the normal cycle, but follicular development did not appear to be inhibited much as both FSH and estradiol were found to be in the normal range.

Adult↗

[Effects of lead administered during pregnancy to C57B1 mice].

Treatment of female mice with high doses of lead from different times of the gestation, induces abortion or retardation of growth of the embryos. When it is given from birth, it provokes important mortality in the youngs and a retardation of the postnatal growth. In most cases, lead administered from the first day of gestation delays slightly the development of the embryo and inhibits its implantation. It seems that a deficiency in the plasmatic progesterone levels is directly implied in this inhibition.

Abortion, Spontaneous↗

Pituitary and ovarian response to acute stimulation with LH-RH in normal and anovulatory women.

The LH FSH estradiol and progesterone responses to acute stimulation with LH-RH were studied in 12 normal women with ovulatory cycles (4 in the initial follicular phase, 4 in the mid-follicular phase and 4 in the late follicular phase) and in two castrated women, two under hormonal contraception, two with ovarian amenorrhea, twelve with central amenorrhea of no detectable origin (6 with normal and 6 with low basal gonadotrophins), eleven anovulatory patients with pseudomenstruation, two with anorexia nervosa, and two with pituitary amenorrhea. Each woman received a rapid i.v. injection of 100 microgram synthetic LH-RH at 9:00 a.m. Serum levels of LH, FSH, estradiol and progesterone were determined by radioimmunoassay in samples collected before and 60, 120, 240 and 480 minutes after injection. The findings were : 1) A significant rise in estradiol and progesterone levels, in addition to LH and FSH elevation, in normal women; 2) A lack of ovarian steroid response in the castrated women and in ovarian amenorrheas, which suggests that the source of steroid response to stimulation is not extragonadal; 3) Significant differences in the responses of the four hormones to LH-RH in the women with central amenorrhea in comparison with the normal group with great variability of results; the steroid response in the presence of a positive LH response might correlate with the severity and/or prognosis of the disorder, a point deserving further study; 4) In anovulatory women with pseudomenstruation, LH responses for the most part normal, and particularly, progesterone responses.

Adult↗

Ovulatory dysfunction during continuous administration of low-dose levonorgestrel by subdermal implants.

OBJECTIVE: To study the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. DESIGN: Observational, prospective, case-controlled comparative study. SETTING: The Family Planning Clinic of PROFAMILIA, in Santo Domingo, Dominican Republic. PATIENTS, PARTICIPANTS: Thirty one regularly cycling Norplant users and 12 nonhormonal contraceptors who volunteered to participate. INTERVENTIONS: Norplant contraceptive implants were inserted in 31 subjects between 13 and 77 months before this study. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for one menstrual cycle. RESULTS: Almost half of the cycles among Norplant users were anovulatory; all the rest (55%) had some form of dysfunction: diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from normal controls. CONCLUSIONS: Anovulation is clearly one of the main mechanisms of action of Norplant, but even in presumptive ovulatory cycles, the dysfunctions described possibly contribute to the high contraceptive effectiveness of Norplant.

Adult↗

The resumption of ovulation and menstruation in a well-nourished population of women breastfeeding for an extended period of time.

We have studied a large group of Australian women breastfeeding for an extended period of time to determine the duration of lactational anovulation (n = 89) and amenorrhea (n = 101). Salivary progesterone assays were used to determine ovulation. These women had a mean of 322 days of anovulation and 289 days amenorrhea. Less than 20% had ovulated and less than 25% had menstruated by 6 months postpartum. The latest ovulation was at 750 days and the latest menstruation at 698 days. There was no significant correlation between any measure of maternal nutritional status and the duration of anovulation or amenorrhea. Neither the time of first supplement introduction to the baby nor the amount of supplement given was an accurate predictor of the return of ovulation or menstruation. However, our results clearly show that lactational amenorrhea can provide good protection against pregnancy in the 1st 6 months postpartum, even in well-nourished women who are giving their babies supplemental feeds.

Adult↗

Effects of progesterone on the response to epidermal growth factor and other growth factors in cultured human meningioma cells.

The presence of receptors for progesterone in a large proportion of human meningioma tissues is well established. The occurrence of increased rates of growth of meningiomas in situ during pregnancy suggests the existence of a relationship between high progesterone levels and the growth of meningiomas. However, experiments with cultured meningioma tissue (cells or explants) have shown only minimal effects of progesterone. It has been shown recently that many meningiomas have receptors for epidermal growth factor. In this paper we have investigated the response of cultured human meningioma cells to epidermal growth factor and other growth factors and the modulation of this response by progesterone and the progesterone-receptor blocking agent mifepristone (RU 38486). The results suggest that the presence of progesterone in the culture medium increases the sensitivity of meningioma cells to mitogenic stimuli, whereas mifepristone can counteract the stimulating effects of progesterone.

Adult↗

Accelerated dissolution of luteal-endometrial integrity by the administration of antagonists of gonadotropin-releasing hormone and progesterone to late-luteal phase women.

Sequential blockade of gonadotropin-releasing hormone (GnRH) and progesterone (P) receptors by potent antagonists (Nal-Glu GnRH antagonist and RU486) was conducted in late-luteal phase women to develop a once-a-month birth control method by timed advancement of ongoing luteolysis and endometriolysis. Hormonal dynamics and timing of uterine bleeding during the antagonists' imposed luteal-follicular transition were compared with spontaneous (1st to 2nd) and recovery (2nd to 3rd) cycles in 10 normally cycling women. Serum luteinizing hormone (LH) and follicle-stimulating hormone levels declined (47 +/- 4.3% and 24 +/- 3.0%, respectively) by 24 hours after Nal-Glu injection, which accelerated the ongoing luteolytic process, as evidenced by more rapid declines of serum concentrations of estradiol, P, and ir-inhibin, as compared with the corresponding control cycle. This was accompanied by the prompt (16 +/- 3.2 hours after RU486) onset of a single episode of uterine bleeding, which was advanced by 2 days. Whereas the luteal phase length was foreshortened by 2 days, the subsequent follicular phase duration was prolonged by 2 days with a normal sequence of follicular maturation, LH surge, and luteal function during the recovery cycle. We conclude that the late-luteal sequential administration of antagonists of GnRH and P resulted in acceleration of the ongoing luteolytic and endometriolytic processes without functional alterations of the subsequent cycle.

Adult↗

[The effect of Enzaprost-F (PGF2) cervical tablets on the corpus luteum in the human body].

Authors removed dextro-ovary of a patient having 7-9th week of gestation for ovarian cyst during abortion. Preoperative cervical dilation was performed by Enzaprost-F cervical tablet containing 20 mg PGF2 agent. Before and 2, 4 and 6 hours after treatment, serum-progesterone and 17-beta-estradiol level was determined. Drug cervical dilation enabled instrumental termination of pregnancy within 4 hours. Histological finding of yellow body showed initial signs of colloid-cystic degeneration, which was followed by minimal decrease of values of serum-steroid concentrations. Authors presume that change in histological picture of yellow body was caused by effect of cervical tablet containing PGF2 agent.

Abortion, Therapeutic↗

Postnidatory effects of luteinizing hormone releasing hormone (LHRH) in hamsters.

Whereas the administration of LHRH to pregnant hamsters has no effect during the prenidatory period, the hormone is effective in terminating pregnancy when given after implantation (days 6-10). The ED50 for pregnancy termination over this period approximates a dose of 0.35-0.4 mg b.i.d. When given to pregnant females in a second study, the effects of LHRH at this dose were completely reverse by minute doses of progesterone (30 microgram and above). Finally, administration of LHRH at 1.5 mg b.i.d., from days 6-10 was followed by daily sacrifice through day 12; bloods were sampled at autopsy for progesterone evaluation. Autopsies on days 7 and 8 showed few differences between controls and LHRH-treated hamsters, although decreased weights of the uterine/conceptus units signaled the initation of resorption. Significant LHRH-induced decreases in circulating progesterone were seen by day 9. Fetal resorption continued and was essentially complete by day 11, while progesterone levels continued depressed through the end of the study.

Animals↗

A comparative evaluation of the safety and contraceptive effectiveness of 65 mg and 100 mg of 90-day norethindrone (NET) injectable microspheres: a multicenter study.

The first of a second generation of slow-release injectable contraceptives is the norethindrone (NET) microspheres with a 90-day duration of action. It was evaluated at 65-mg and 100-mg doses for safety and contraceptive effectiveness in two randomized, single-blind trials among 131 women: 94 women for 12 months and 37 women for 6 months. The 6-month trial included additional evaluations of ovarian function and serum NET values. In the 6-month trial, no indication of ovulation was detected in the 100-mg dose group, while 3 of the 19 women in the 65-mg group showed signs of ovulation (progesterone greater than 3 ng/ml). No pregnancies were reported in the 100-mg group and one pregnancy in the 65-mg group resulted in a life-table pregnancy rate for that dose of 2.6 per 100 woman-years (95% confidence interval, 0 to 7.5). Days of vaginal bleeding were analyzed for 30 days before treatment and in 90-day reference periods after treatment. The mean number of vaginal bleeding and spotting days increased initially after the first injection in both dose groups, but decreased to below baseline in both dose groups after 6 months. The two doses appear comparable in clinical safety, side effects, vaginal bleeding patterns, and laboratory measures. With the preliminary estimate of efficacy, the 65-mg dose would be the minimally effective dose for the NET 90-day injectable contraceptive.

Adult↗

Inhibition of ovulation by a new low-dose monophasic contraceptive containing gestodene.

Twenty-five healthy women volunteers were selected to evaluate ovulation inhibition by a monophasic oral contraceptive preparation containing 75 micrograms gestodene and 30 micrograms ethinyl estradiol. Each subject participated for eight consecutive cycles, consisting of a pretreatment cycle, six treatment cycles, and a posttreatment cycle. During five explored cycles, serum LH, FSH, estradiol, and progesterone levels were measured daily on cycle days 8 through 17; in addition, progesterone was measured once, around cycle day 21. Pelvic ultrasounds were performed on cycle days 6, 8, 10, 12, 14, and 16. In the 18 volunteers completing the entire study, LH and FSH levels were strongly depressed, in equivalent degree, during the first, third, and sixth treated cycles. From treated cycle days 8 to 17, a significant decline of LH and FSH levels occurred, reaching values on the lower limit of detection. Luteal activity was not detected in any of the treated cycles. Follicular activity, as reflected by estradiol levels, was more strongly depressed during the first treated cycle (first contraceptive pill taken on day 1 of menstruation) than in the third and sixth treated cycles (the first pill taken after a seven-day pill-free interval). The excellent inhibition of follicular maturation was confirmed by ultrasonic assessment of the ovaries. Restoration of ovarian function during the first posttreatment cycle was excellent, showing a midcycle hormonal profile identical to that of the pretrial cycle.

Adult↗

Response to the antiprogestagen RU 486 (mifepristone) during early pregnancy and the menstrual cycle in women.

RU 486 has wide potential utility as an abortifacient drug when used within the first 6 weeks of pregnancy and has the ability to induce an abortion in about 80% of subjects. Administration of low doses of prostaglandins together with RU 486 increases the success rate. It is possible that alterations in metabolism of RU 486 may explain non-responsiveness to the drug in some women. Mid-luteal phase administration of RU 486 produces bleeding within 72 h and in one-third of subjects there was luteolysis with decrease in serum FSH, oestradiol and progesterone concentrations. Administration of RU 486 in the late luteal phase does not disturb menstrual cycle length, bleeding patterns, ovulation, or hormonal parameters in treatment or posttreatment cycles. However, the drug alone cannot be used as a 'menses regulator' or 'once monthly pill' since some pregnancies do continue. Possibly the efficacy of RU 486 may be enhanced when it is combined with prostaglandins or other agents. Administration of RU 486 in the follicular phase blocks ovulation, delays the LH surge, and is associated with low concentrations of oestradiol. This is presumably the result of gonadotrophin inhibition.

Abortion, Induced↗

Does gender or the menstrual cycle affect colonic transit?

Controversy exists as to whether slowing of colonic transit occurs in the high progesterone luteal phase of the menstrual cycle. To clarify this issue, colonic transit studies using radiopaque markers were performed on 10 women in the follicular phase, 10 women in the luteal phase of the menstrual cycle, and five women on oral contraceptives, and the results were compared with transit times in 11 male controls. No significant differences in colonic transit were found between either phase of the menstrual cycle. Colonic transit in women was slower than in men, but this was not statistically significant. In the clinical setting, therefore, colonic transit studies can be performed throughout the menstrual cycle or when taking oral contraceptives. In addition, a single standard for normal values can be used for both men and women.

Adult↗

Pure crystalline estradiol pellet implantation for contraception.

The subcutaneous implantation of estradiol pellets was found to be a simple and effective contraceptive method with good patient acceptance and minimal untoward effects. The pellets (25 mg each) were implanted through a Kearn's trocar into the abdominal wall, 2.5 to 5 cm above and parallel to Poupart's ligament. The regimen began with four pellets, and the dose was maintained or decreased by one pellet every 6 months (four, three, two, one). A potent progestogen was utilized monthly for induction of withdrawal bleeding. Altogether, 236 patients were followed for a total of 1,060 courses in 6,360 cycles (489,02 woman-years). Two pregnancies occurred during therapy. Pearl's index was 0.37. No significant alterations occurred in body weight and blood pressure. Glucose tolerance test, standard blood profiles, and Papanicolaou smears were normal during therapy. No cases of thrombophlebitis, blurred vision, headaches, gastric symptoms, or amenorrhea-galactorrhea were observed. The suppression of ovulation was confirmed by endometrial biopsies, basal body temperature, and serum follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in a selected group of patients.

Abdominal Muscles↗

[Antigonadotropic actions of prolactin. Study of 10 cases of women with hyperprolactinemia].

In order to determine the pituitary or ovarian site of the anti-gonadotrophic action of prolactin (PRL), ten women with hyperprolactinaemia were studied in the following way: 1) Repeated estimations of PRL, gonadotrophins (LH and FSH), plasma estradiol and progesterone during six weeks of treatment with bromocriptine. 2) Verification of the effects of estradiol benzoate on LH and FSH levels before and after normalisation of prolactin. 3) Exploration of the ovarian response to the administration of human menopausal gonadotrophin. Without it being possible to exclude any direct effect of prolactin on the ovary, it may be affirmed that the hormone decreases the sensitivity of the gonadotrophic cells to the positive feedback mechanism exerted by plasma estradiol.

Adult↗

Changes in pure-tone thresholds and temporary threshold shifts as a function of menstrual cycle and oral contraceptives.

The present study examined the effects of exogenous and endogenous ovarian hormones on auditory functioning in young women. Fluctuations in pure tone thresholds and temporary threshold shifts (TTS) at 4 kHz and 6 kHz were assessed across the menstrual cycle. A group of normally cycling, ovulatory women and a group of women using Ortho Novum 7/7/7, a tri-phasic oral contraceptive, were tested during menstruation, at ovulation, and during the luteal phase of their menstrual cycle. A group of men served as controls and were tested at 3 similarly spaced intervals. Only the normally cycling women had significant cyclic fluctuations in auditory sensitivity, displaying poorer thresholds at 4 kHz during the menstrual phase than at the time of ovulation or during the luteal phase. In addition, normally cycling women were found to have significantly less TTS at 6 kHz during the menstrual phase than women using oral contraceptives.

Adult↗