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Biomedical subjects

H B Croxatto

Publications and source records attributed to H B Croxatto.

At least 19 recordsLinked to original sources
PubMed1992

Changes in serum levels of SHBG, endogenous ligands and levonorgestrel induced by ethinylestradiol in Norplant users.

This work was done in search for a model to examine target organ response to fluctuations in serum levels of sex hormone-binding globulin (SHBG) and its ligands. The time course and magnitude of fluctuations of SHBG, levonorgestrel (L-Ng), estradiol (E2), testosterone (T) and dihydrotestosterone (DHT) in serum were examined during and after treatment with 50 ug of ethinylestradiol (EE2) daily for 10 days in 10 volunteer women using NORPLANT implants. Six of these volunteers were also treated with 20 ug of EE2 daily for 7 days and two additional volunteers using a copper-T IUD were treated with 50 ug of EE2 daily for 7 days. In all cases, SHBG and L-Ng levels increased in a close parallel manner several-fold above basal levels during treatment, reaching a maximum around two days after the last EE2 pill. In contrast, the levels of E2 and T increased in one subject, decreased in 5 and remained unchanged in 4, while changes of DHT were unrelated to those of the other ligands. Since the L-Ng "secretion rate" by NORPLANT implants is constant, it follows that the effect of EE2 on its levels is due to a decreased metabolic clearance rate, most likely secondary to the increased binding of L-Ng to SHBG in serum. This interpretation is in agreement with the close parallelism in the fluctuations of L-Ng and SHBG. It is concluded that in NORPLANT users, SHBG and L-Ng, but not the endogenous ligands, behave in a predictable manner in response to EE2. Thus, this model affords the possibility of exploring the influence of SHBG on tissue response to progestins.

Dihydrotestosterone↗
PubMed1992

Tissue uptake of human sex hormone-binding globulin and its influence on ligand kinetics in the adult female rat.

The distribution of human sex hormone-binding globulin (hSHBG) and its influence upon the kinetics of its ligands were assessed in the adult female rat, which lacks a comparable protein in serum. Purified hSHBG was administered i.v. to adult female rats as a single bolus. The plasma disappearance rate of immunoreactive hSHBG had one component with a half-life of 15 h. The estradiol (E2) binding activity of serum attributable to hSHBG was elevated 2-fold; during a continuous infusion of E2, hSHBG increased E2 serum levels above those of control infused animals. Treatment with hSHBG did not modify the plasma clearance of endogenous E2, but accelerated the disappearance rate of 5 alpha-dihydrotestosterone (DHT). In animals injected with a tracer dose of radioactive steroids, pretreatment with hSHBG increased uterine and oviductal accumulation of E2- but not DHT-associated radioactivity. This effect was specific to some E2 target tissues since hSHBG did not alter the concentration of E2- or DHT-associated radioactivity in the hypophysis, liver, diaphragm, or brain. Treatment with anti-E2 antibodies, which elevated E2 binding activity in serum, decreased the accumulation of E2-associated radioactivity in uterus and oviduct. Immunofluorescent localization of hSHBG revealed intense labeling of the uterine and oviductal epithelium. We conclude that this foreign hormone-binding globulin introduced in serum at concentrations that have minimal circulating reservoir effect on E2 can reach intracellular domains and affect the concentration of this ligand in target tissues.

Analysis of Variance↗
PubMed1992

Serum osteocalcin in normal menstrual cycle.

Serum osteocalcin (OC) was serially measured along an ovulatory menstrual cycle in 4 healthy unmedicated volunteers (age 33-38 years). During the study the women maintained their normal diet and daily physical activity. Starting at days 4-5 of the cycle, blood samples were taken between 09-11 AM every 2 or 3 days for OC, FSH, LH, E2 and P determinations. Daily ultrasound assessment of ovulation was performed in all subjects between days 7-18 of the cycle. Hormone determinations and OC were performed by RIA. While blood levels of FSH, LH, E2 and P changed during the cycle, according to the expected ovulatory pattern, serum OC concentrations remained stable during the cycle in each subject. In conclusion, serum OC is independent of the gonadotropin and ovarian steroid variations during the normal menstrual cycle.

Adult↗
PubMed1992

Human preimplantation development in vivo: ultrastructural observations.

The ultrastructure of a 2-cell, 4-cell, 7-cell and 16-cell human embryos fertilised and developed in vivo were compared using transmission electron microscopy. Among the structures which exhibited more notable changes throughout these developmental stages, were the mitochondria, ribosomes, nuclear envelope and nucleolus. Mitochondria which were initially round, dense with cristae oriented parallel to the surface changed to oval with less dense mitochondrial matrix and with cristae perpendicular to the mitochondrial membrane. Ribosomes and polyribosomes decreased in amount from 2 to 7-cell stages and increased again at the 16-cell stage. The nuclear envelope exhibited intense blebbing activity at the 4-cell stage, less at 7 and none at 16. The nucleolus initially very dense was progressively infiltrated by chromatin, became reticular at the 7-cell stage and appeared fully mature at the 16-cell stage. This study discloses structural details of human preimplantation embryos which may be of interest in the assessment of comparable material obtained in vitro. Some unique features that may have bearing on the ontogenesis of cell organelles and cell differentiation are discussed.

Blastocyst↗
PubMed1992

Relative contributions of anovulation and luteal phase defect to the reduced pregnancy rate of breastfeeding women.

OBJECTIVE: To evaluate the contribution of anovulation and luteal phase defects to lactational infertility. DESIGN: Prospective longitudinal follow-up. SETTING: Outpatient clinic. SUBJECTS: Forty-nine women fully nursing and amenorrheic on day 75 postpartum and 25 cycling, interval non-nursing women. INTERVENTIONS: Plasma prolactin, luteinizing hormone, estradiol (E2), and progesterone (P) levels twice a week up to the second postpartum menses. MAIN OUTCOME MEASURES: Ovulation rate and endocrine profile of the menstrual cycles. RESULTS: Ovulation rates were 37% and 97% at 6 and 12 months postpartum; 67% of ovulations occurred in amenorrhea. The luteal phase was shorter, and E2 and P levels were lower in lactating women than in non-nursing women. These parameters were closer to normal in the second cycle than the first, in spite of active nursing. The risk of ovulation and pregnancy in amenorrhea was 27.7% and 0.9% at month 6 postpartum. After the first menses, these risks were 93% and 7%, respectively. CONCLUSION: The abnormal endocrine profile of the first luteal phase offers effective protection to women who ovulate during lactational amenorrhea within the first 6 months after delivery. Later luteal phases are improved and women are at risk of pregnancy.

Adolescent↗
PubMed1991

Effect of RU486 on development and implantation of rat embryos.

This study evaluated the effects of postcoital treatment with the antiprogestin RU486 on transport, development and implantation of rat embryos. Doses of 0.1, 0.5, 1.0, 2.0, or 3.0 mg/rat of RU486 were injected subcutaneously on days 1, 1 + 2, or 4 of pregnancy. Autopsies were carried out on days 5 or 12 of pregnancy. RU486 provoked a significant dose-related reduction in the number of recovered embryos and inhibited their development (day 5) and decreased the number and size of implanted embryos (day 12). Treatment on day 4 was the least effective. Blastocysts recovered from RU486-treated rats exhibited comparable rate of trophoblastic outgrowth in vitro as the controls. Blastocysts transferred from RU486-treated rats to synchronous untreated pseudopregnant recipients yielded implanted embryos 12 days later in all recipients, although at a significantly lower rate than the controls. Blastocysts transferred from control pregnant rats to RU486-treated pseudopregnant recipients failed to implant completely when the dose was greater than or equal to 1.0 mg. The interceptive mechanism of postcoital treatment with RU486 in the rat involves loss of embryos from the reproductive tract and altered development prior to implantation. Endometrial receptivity or the ability of the uterus to retain the embryos until the time of implantation are also impaired by RU486. The embryos that survive these effects may experience delayed implantation in their mothers.

Animals↗
PubMed1991

Clinical trial with 3-keto-desogestrel subdermal implants.

The study was done to assess the clinical performance and in vivo steroid release rate of 3-keto-desogestrel subdermal implants designed to deliver 5 different doses of the progestin. Volunteers were healthy women of proven fertility who provided blood samples at scheduled intervals during treatment. No pregnancy occurred in 514 woman-months in users of implants delivering 30 and 40 micrograms per day of 3-keto-desogestrel. Three pregnancies, one ectopic, were observed in 109 woman-months recorded with implants delivering 20 micrograms per day or less. Ovulation was inhibited, as judged by depressed progesterone levels, in 57 of 59 (97%) blood samplings in women whose 3-keto-desogestrel plasma levels were greater than 0.28 nmol/L and in 39 of 75 (52%) of cases with lower levels. Users of 4 cm implants manufactured by The Population Council, New York, showed mean levels above 0.28 nmol/L until 18 months of use. Levels achieved with 4.4 cm implants manufactured by Organon, Oss, Holland, were less consistent. No changes were observed in the plasma lipoprotein pattern or clinical chemistry during treatment. The main complaint was the occurrence of bleeding irregularities, particularly with the lower doses. Ovarian cysts found during pelvic examination in 11 (22%) subjects disappeared spontaneously within 7-90 days. 3-keto-desogestrel implants releasing around 40 ug/day and providing plasma levels around 0.28 nmol/L afford efficient contraceptive protection.

Adolescent↗
PubMed1991

Contraceptive efficacy of lactational amenorrhea in urban Chilean women.

The contraceptive efficacy of breastfeeding was assessed in 236 healthy urban women who were followed at monthly intervals during the first postpartum year. Proportional hazard models were used to evaluate the influence of time postpartum, menstrual status and breastfeeding pattern upon the risk of pregnancy. Time and menstrual status had a highly significant effect on this risk. Those women who remained in amenorrhea had cumulative probabilities of pregnancy of 0.9% and 17% at 6 and 12 months postpartum, respectively. In those who recovered menstrual cycles, the risk rose to 36% and 55% at 6 and 12 months, respectively. Milk supplementation also increased significantly the risk when considered alone but not when time and/or menstrual status were included in the analysis. However, amenorrheic women who introduced bottle feeding, had a higher risk of pregnancy after 6 months postpartum than those who remained fully nursing. The analysis was unable to detect a significant influence of the nursing frequency. The results confirm that lactational amenorrhea is an effective contraceptive during the first six months postpartum. The first postpartum bleeding marks a great increase in the risk of pregnancy. Supplementation also increases the risk, particularly in amenorrheic women.

Adult↗
PubMed1991

Importance of uterine expulsion of embryos in the interceptive mechanism of postcoital oestradiol in rats.

This study compares the interceptive effectiveness of 1 microgram oestradiol given as a single s.c. injection at 0900 or 1700 hours on Day 1, 2, 3, or 4 of pregnancy in rats. Increasing the interval from ovulation to treatment accelerated the oviducal transport of a larger number of embryos, the majority of which were lost from the genital tract. However, after treatment at 1700 hours on Day 3 the majority of accelerated embryos were retained in the uterus. The number of implanted embryos on Day 14 was equal to the number of eggs remaining in the tract 24 h after treatment. As a consequence, the highest interceptive effectiveness was obtained with treatment given at 1700 hours on Day 2 and at 0900 hours on Day 3 of pregnancy. Accelerated oviducal transport and uterine expulsion of embryos begin to dissociate after Day 2 of pregnancy in the rat. This explains why the most effective treatments to accelerate oviducal transport are not always the most effective to reduce the number of implantations. These data emphasize the importance of retentive and expulsive properties of the uterus for fertility and infertility.

Animals↗
PubMed1991

Mechanism of action of progesterone as contraceptive for lactating women.

Progesterone vaginal rings releasing 5-15 mg/day were tested as a contraceptive for lactating women. Progesterone plasma levels achieved ranged from 10 to 20 nmol/L. Pregnancy rates at the end of the year were less than 1% and 39% in treated (n = 210) and untreated (n = 236) nursing women, respectively. Around 70% of treated and 30% of untreated women were amenorrheic at 8 months post partum. The endocrine profile during the first 8 months post partum was assessed in 36 treated and 28 untreated nursing women. Pre- and postsuckling prolactin (PRL) levels were measured at 1600 hr at fortnightly intervals and E2 determinations and ovarian ultrasound were performed twice a week. Prolactin increases in response to suckling and postsuckling PRL levels were higher, E2 levels were lower, and follicular growth was arrested at earlier stages in progesterone-treated than in untreated women. The pattern observed in progesterone-treated women was similar to that in prolonged lactational amenorrhea. This suggests that progesterone increases the sensitivity of the breast-hypothalamic-pituitary system to suckling and reinforces the mechanism of lactational infertility.

Breast Feeding↗
PubMed1991

Early difference in the endocrine profile of long and short lactational amenorrhea.

The endocrine profiles associated with long and short lactational amenorrhea were assessed in a longitudinal study in which morning blood samples were drawn in 48 women from the first postpartum month until the recovery of ovulation and in a cross-sectional study in which the samples were drawn throughout 24 h at the end of the third postpartum month in 10 fully nursing and amenorrheic women. PRL, LH, FSH, estradiol (E2), progesterone, cortisol, and dehydroepiandrosterone sulfate were measured. In both studies we detected a smaller PRL increase in response to suckling (P less than 0.001) and higher E2 levels (P less than 0.001) in nursing women who ovulated within 6 months postpartum compared to those in women who did not. Such differences were observed early after delivery when all women were fully nursing and amenorrheic. These results suggest some probable sources of variability in the duration of lactational amenorrhea in our population. The greater PRL response to suckling associated with longer amenorrhea may be due to higher sensitivity of the breast-hypothalamus-pituitary system or a stronger suckling stimulus in this group. Differences in plasma E2 levels between longer and shorter periods of amenorrhea may reflect dissimilar endogenous production, intake, or clearance of estrogens.

Adult↗
PubMed1990

Clinical assessment of treatments for prolonged bleeding in users of Norplant implants.

The effectiveness of three drugs in controlling prolonged bleeding in the first year of NORPLANT implants use was tested. The drugs were levonorgestrel (L-Ng, 0.03 mg twice a day for 20 days), ethinylestradiol (EE, 0.05 mg per day for 20 days) and ibuprofen (Ib, 800 mg three times a day for 5 days) and were given orally. A control group received a placebo (PL, one pill of lactose for 20 days). Treatment should start each time a woman experienced eight consecutive days of bleeding or spotting. The 183 volunteers were not aware of the drug administered. A daily record of bleeding and spotting and of treatment intake was maintained. One-hundred-forty women completed the study period; 60 never used the prescribed treatment. Women treated with the three test drugs had significantly fewer bleeding and spotting days during the treated month and also throughout the study year than women using the placebo. The mean number of bleeding plus spotting days per actually treated subject in the first year was 77, 94, 101 and 129 days for the EE, Ib, L-Ng and PL groups, respectively. The administration of EE might help in the management of prolonged bleeding during the first year of NORPLANT implants use.

Administration, Oral↗
PubMed1990

Increased secretion of adrenal progesterone explains the lack of response of oviductal embryo transport to a short intravenous infusion of estradiol in the rat.

Administration of estradiol (E2) as a single subcutaneous injection, but not as a short intravenous infusion (less than 150 min), accelerates oviductal embryo transport in pregnant rats although the first mode determines lower E2 circulating levels. Since progesterone (P) can antagonize the effect of E2 on embryo transport we examined the circulating P levels under these two modes of E2 administration. Rats were treated on day 1 of pregnancy with 5 micrograms E2 given s.c. or i.v. (10 min infusion). Other groups were either hypophysectomized (HPX), adrenalectomized (ADX) or ovariectomized (OVX) prior to E2 treatment to prevent P rise, or were treated with E2 plus RU486 to block the action of P. Some groups were autopsied at short intervals following treatment to measure P levels and others 24 h later to assess the effect of treatments on embryo transport. P was increased several fold by i.v. infusions of E2 or vehicle alone in intact and OVX rats but not in HPX or ADX rats, whereas s.c. administration of E2 did not change P levels unless it was given concomitantly with i.v. infusion of vehicle. The short i.v. infusion of E2 accelerated embryo transport in HPX, ADX, or RU486 treated rats but not in intact rats. The s.c. injection of E2 accelerated embryo transport even when it was accompanied by an i.v. infusion of vehicle. The data does not exclude the participation of glucocorticoids in the above phenomena but agrees with the view that it is the transient increase in adrenal P secretion which blunts the oviductal response to a brief pulse of E2.

Adrenalectomy↗
PubMed1989

Cumulus cell dispersion induced by estradiol in mouse oviduct in vitro.

Dispersion of cumulus cells in nonmated mice is completed in the oviduct 15-20 h after ovulation. Oviducts, isolated 1 h after ovulation (13 h post-human chorionic gonaditropin), were cultured in vitro for 40 h. In these oviducts, denuded oocytes were first seen at 30 h of culture, indicating that cumulus dispersion proceeded at a slower rate in vitro. Oocyte denudation was accelerated in a dose-dependent manner by the addition of estradiol to the culture medium in which oviducts were incubated. The addition of progesterone or cycloheximide to the culture medium strongly inhibited oocyte denudation even in the presence of estradiol. When isolated cumuli were incubated in the absence of oviductal tissue, the rate of cell dispersion was slower than that of cumuli incubated inside the oviduct and the addition of estradiol to the culture failed to accelerate this process. On the basis of these data, we propose that cumulus cell dispersion is accelerated by an estrogen-dependent protein produced by the oviduct and that this effect of estrogen is antagonized by progesterone.

Animals↗
PubMed1989

A longitudinal study on cortisol, prolactin and thyroid hormones in users of Norplant subdermal implants or a copper T device.

A longitudinal study was undertaken to assess PRL, cortisol, TSH, T3 and T4 levels in NORPLANT implant users (n = 22) and Copper T users (n = 20). Participants were healthy women with no contraindication for hormonal contraception. Samples were drawn at 0930 to 1000 h twice pretreatment and at month 2, 4, 6, 12, 24 and 36 after insertion. At the second treatment month, a second sample was obtained at 1600 h to assess cortisol diurnal variation. Hormones were measured by RIA. Values for all hormones were similar in Norplant and Copper T users. No significant changes occurred throughout the study period. Elevated PRL levels (greater than 500 mU/1) were found in three women from each group before and during treatment but no clinical evidence of hyperprolactinemia was detected. The results of this study reassure that long-term use of NORPLANT implants do not impair plasma levels of cortisol, prolactin and thyroid hormones.

Adult↗
PubMed1989

Ultrastructure of a 4-cell human embryo developed in vivo.

The ultrastructure of a 4-cell human embryo undergoing development in vivo is described. The embryo recovered from the Fallopian tube 130 h after a single episode of intercourse and 70 h after the luteinizing hormone peak in plasma, was partially surrounded by cumulus cells. The blastomeres, of even size, were nucleated and had a similar distribution of cytoplasmic organelles. No signs of abnormality or cellular degeneration were observed. Transmission electron microscopy of serial sections revealed the presence of primitive desmosomes between cells, abundant vesicles within the blebs of the outer sheet of the nuclear membrane, blebbing of the inner sheet of the nuclear membrane and close association between the inner sheet of the nuclear membrane and the intranuclear annulate lamellae. Nucleolar precursors lacking the structural organization of mature nucleoli were also found. Similarities and differences between this and other preimplantation human embryos reported earlier are analysed.

Blastomeres↗
PubMed1989

Embryos of different ages transferred to the rat oviduct enter the uterus at different times.

Indirect evidence of embryo signalling to the oviduct was sought in rats by examining the transport of embryos of different ages. One-cell or four-cell embryos were transferred to the oviducts of recipient rats on Day 1 of pregnancy, and the number, condition, and location of native and transferred embryos was assessed on Day 4. To control for the effect of the presence of foreign embryos and excess number of eggs and the transfer procedure upon the fate of native embryos, other groups of rats were sham-operated or left undisturbed. Recipients had a mean number of ova significantly higher than controls. In controls and recipients of 1-cell embryos, the majority of eggs reached the morula stage and all of them were located in the oviducts. In those animals receiving 4-cell embryos, half of the eggs had reached the blastocyst stage and 28% were in the uteri (p less than 0.005). These results support the idea that advanced embryos can influence the timing of their entrance to the uterus in rats.

Age Factors↗