Biomedical subjects

H B Croxatto

Publications and source records attributed to H B Croxatto.

At least 91 records · Page 5Linked to original sources

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↗

PubMed1989

Variable effects of RU 486 on endometrial maintenance in the luteal phase extended by exogenous hCG.

This study was designed to assess the features and conditions for endometrial bleeding induction with the synthetic antiprogestin and antiglucocorticoid RU 486 during hCG-induced prolongation of the luteal phase. Eighteen healthy, surgically sterilized women and another five women with an intrauterine contraceptive device (IUD) participated. All subjects received hCG which was injected daily in increasing doses (500 to 15,000 IU) from day 9 to day 15 of the luteal phase. Ten subjects received hCG alone, and groups of three to 16 subjects received hCG combined with RU 486 (25, 50, 100, 200 or 400 mg/day). RU 486 administration was commenced on day 12 following the LH surge and given either for 1, 4 or 7 consecutive days. In certain cycles, tamoxifen (20 mg/day) was given for 4 consecutive days with hCG, or with hCG and RU 486. All treatment cycles were separated by one or two resting cycles. Frequent blood samples were taken to monitor the endocrine response. Treatment with hCG alone or with the various combinations of RU 486 produced similar serum levels of oestradiol and progesterone which were equivalent to those observed during early pregnancy. With hCG alone, the onset of bleeding was on day 21-24 after the LH surge, coinciding with the drop in oestradiol and progesterone. With RU 486 doses of 50 mg/day or more, an early bleeding episode almost invariably occurred on day 14-17 after the LH surge in the presence of high circulating steroid levels. In contrast, 25 mg/day RU 486 for 4 days failed to induce this early onset of bleeding in three out of six cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

Circadian variation of basal plasma prolactin, prolactin response to suckling, and length of amenorrhea in nursing women.

The circadian pattern of plasma PRL levels and the PRL response to suckling were examined at various times during the first postpartum year and related to the length of lactational amenorrhea. Ten healthy women whose infants were breast-fed exclusively and who were amenorrheic 3 months postpartum were studied 3, 6, and 9-11 months postpartum. The women and their babies were admitted to a metabolic unit for 48 h. On the second day, blood samples were drawn at 2-h intervals for 26 h starting at 0800 h and also 10 and 30 min after the initiation of six of the nursing episodes. During the three postpartum periods, there was a circadian rhythm of basal plasma PRL concentrations; the peak concentrations occurred between 2400-0600 h. Suckling induced a significant rise in plasma PRL levels at all hours except 0800 h. There was a positive correlation between the duration of the nursing episode and the suckling-induced PRL increase at 30 min. Both the basal plasma PRL levels and the PRL responses to suckling diminished with time after delivery. This trend was less evident at 0400 h and was not fully explained by changes in the nursing pattern. The five women in whom menstrual cycles resumed before day 180 postpartum had lower basal and suckling-induced plasma PRL levels than the women who had amenorrhea for a longer period. This difference was present in the third month, when all women were amenorrheic and fully nursing and when the frequency and duration of nursing episodes and infant growth rates were similar. The results indicate that comparable nursing patterns may be associated with different plasma PRL levels, which are associated with different lengths of lactational amenorrhea. An early difference in the sensitivity of the breast-hypothalamus-pituitary system to suckling may explain the differences in the duration of lactational amenorrhea, which are not dependant on the breastfeeding pattern. The magnitude of the PRL response to suckling may predict the likelihood of recovering ovarian function during lactation.

Adult↗

PubMed1989

Effect of oestradiol delivered from a perioviducal device on ovum transport in mice.

Silastic devices impregnated with oestradiol and blank devices were placed around both oviducts and around skeletal muscle bundles in the forelegs to attain local and systematic delivery, respectively. Another group of mice received an oestradiol-impregnated device around one oviduct and a blank device in the contralateral oviduct. Implantation of blank devices around the oviducts and in the forelegs did not alter ovum transport. Devices impregnated with oestradiol placed around both oviducts produced a dose-dependent delay of ovum transport, which was more pronounced than the effect of devices located in the forelegs. Oviducts receiving an oestradiol-loaded device had a larger retention of ova than did the contralateral oviducts receiving a blank device. These results demonstrate a direct action of oestradiol upon the oviduct to delay ovum transport in the mouse.

Animals↗

PubMed1989

[Long-term follow-up of women treated with contraceptive implants of levonorgestrel Norplant].

This report describe the long-term follow-up of 376 women who received Norplant implants in the period october 1974 through may 1979. One-hundred-and-ten subjects received replacement implants after variable lengths of use of the first set. The average levonorgestrel plasma levels declined steadily through eight years of use of Norplant capsules (r = -937). Values were 0.35 ng/ml, 0.29 ng/ml and 0.22 ng/ml at treatment years 1, 5 and 8, respectively. Levonorgestrel plasma levels after replacement with a second set of implants were similar to those observed after the first insertion, either when placed in the same site as the first set or in a different area. The levonorgestrel half-life after implant removal was 42 +/- 16 h (X +/- S.E.) and only trace amounts are detected after 96 h. Nineteen pregnancies occurred during 18,530 woman-months of use of the first set of implants, eleven of them during years 6 through 8 of treatment. The Pearl Index for the first years of Norplant implants use was 0.63. No pregnancy has occurred in 5.020 woman-months observed during treatment with a second set of capsules. Fifty-six women (14.9%) out of 376 acceptors of the first implant and 12 (10.9%) out of 110 acceptors of the replacement implants were terminated for other medical reasons, mainly side effects commonly associated with hormonal contraception. Removals for bleeding problems occurred in 5.6% and 3.6% of the acceptors of the first and second implant, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Estradiol plasma levels during long-term treatment with Norplant subdermal implants.

Estradiol-(E2) plasma levels were assessed in forty-seven women treated for one through seven years with the same set of Norplant implants. Each woman was subjected to one (n = 34), two (n = 11) or three (n = 2) sampling runs. At each sampling run, blood samples were drawn every third or fourth day during 5 or 6 consecutive weeks. Sampling runs were classified as ovulatory (n = 11), anovulatory (n = 49) or uncertain (n = 1) according to progesterone levels. Controls were Copper T users (n = 8), all classified as ovulatory. No significant differences were found for the mean E2 levels between Norplant users and Copper T users and between ovulatory and anovulatory cases. The mean of the peak E2 value found in each sampling run was significantly higher in anovulatory Norplant subjects than in the control group. The mean of the minimum E2 level observed was significantly lower in Norplant cases than in Copper T users. A single woman from the Norplant group and none from the Copper T group had all E2 values below 370 pmol/l. The inhibition of the reproductive function induced by Norplant implants is associated with a wider range of E2 circulating levels. None of the values observed at the extremes should cause serious concerns. High peaks are transitory and opposed by the antiestrogenic effect of levonorgestrel. Persistent low levels which could be associated with a hypoestrogenic state were observed in a single case.

Adult↗

PubMed1988

Lactational amenorrhea and the recovery of ovulation and fertility in fully nursing Chilean women.

The probability of experiencing the first postpartum bleeding, the first ovulation and the risk of pregnancy during exclusive breastfeeding was assessed in a selected group of urban Chilean women. Admission criteria included having had a normal pregnancy and a vaginal term delivery of a healthy infant and the desire to maintain breastfeeding for as long as possible. The risk of bleeding and the recovery of ovulation was assessed in 48 women selected for being amenorrheic and fully nursing at day 75 postpartum and their willingness to participate in the blood sampling protocol. The first bleeding and ovulation was experienced while fully nursing by 28% and 26% of these subjects, respectively, at day 180 postpartum. The probability of experiencing the first bleeding and the probability of pregnancy during full nursing were calculated for 236 women not contracepting who were enrolled during the first month postpartum. The cumulative probability of bleeding and of pregnancy was 52% and 9.4% at day 180 postpartum, respectively. The risk of pregnancy was less than 2% in the subset of amenorrheic cases. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with infertility was too weak to serve as an effective birth spacer, except for the period of lactational amenorrhea. When the first postpartum bleeding took place before the sixth postpartum month in fully nursing women, it had a good predictive value to indicate the onset of a higher risk period.

Actuarial Analysis↗

PubMed1988

Inhibition of sperm migration, fertilization and implantation in rats by precoital intrauterine administration of gossypol or nonoxynol-9.

The effects of precoital intrauterine administration of Gossypol, Nonoxynol-9 or p-Aminobenzamidine on reproductive function were investigated in rats. The drugs were instilled in one uterine horn in the evening of proestrus prior to caging with a fertile male. The opposite side was similarly treated with the vehicle and served as control. Animals were killed in the morning following mating to assess the number of spermatozoa at the site of fertilization or on days 2-3 of pregnancy to determine the proportion of penetrated oocytes or on day 12 to count implanted embryos. Gossypol 0.05 to 5 mg or Nonoxynol-9 0.1 - 10 microliter reduced the number of spermatozoa reaching the ampullae and the number of penetrated oocytes in a dose-dependent fashion. At the highest dose both compounds prevented pregnancy exclusively in the treated side. p-Aminobenzamidine at a dose of 10 mg failed to affect the proportion of penetrated eggs found on days 2 or 3 of pregnancy. The results indicate that the rat bioassay is suitable to screen agents that can affect sperm function or viability since it can discriminate between drugs and doses and disclose differential effects upon sperm migration and fertilizing capacity.

Animals↗

PubMed1988

Clearance of levonorgestrel from the circulation following removal of NORPLANT subdermal implants.

The disappearance of levonorgestrel from plasma after the removal of NORPLANT subdermal implants was studied in 12 women who had been treated from 5.5 to 78 months. The existence of one or two half-lives for the rate of disappearance was assessed. The influence of body weight, body fat and length of treatment upon levonorgestrel clearance was studied through stepwise regression analysis. It was found that the levonorgestrel decay rate after implant removal can be entirely accounted assuming one half-life of 42 +/- 16 h (mean +/- SD; range 13 to 62 h). Stepwise regression analysis showed that levonorgestrel half-life is positively correlated with body weight and not significantly correlated with the length of treatment or body fat. It is concluded that, after long-term administration of levonorgestrel via subdermal implants, the major part of the steroid is cleared from plasma within 96 h and that only trace amounts are detected in the following days.

Adult↗

PubMed1988

Progesterone abbreviates the nuclear retention of estrogen receptor in the rat oviduct and counteracts estrogen action on egg transport.

Progesterone has synergistic or antagonistic effects on several estrogenic actions. The effects of progesterone on estrogen-induced accelerated ovum transport and on the dynamics of estrogen receptors in the rat oviduct were examined. The involvement of the progesterone receptors in these phenomena was assessed. On Day 1 of pregnancy, rats were treated with estradiol, estradiol plus progesterone, or either one plus the progesterone receptor-blocking agent RU486. Control animals received the oil vehicle alone. The number of eggs remaining in the oviduct was assessed 24 h after treatment. Cytoplasmic and nuclear estrogen receptor levels in the oviduct, as well as plasma concentrations of estradiol and progesterone, were measured at various intervals--up to 11 h and 24 h after treatment, respectively. Accelerated oviductal egg transport induced by estrogen was blocked by the concomitant administration of progesterone. This effect of progesterone was not associated with changes in estrogen circulating levels and was preceded by a reduction in the total amount of estrogen receptors and by a shortened retention of estrogen receptors in the nucleus. The effects of progesterone on egg transport and on the levels of estrogen receptors were reversed by blocking the progesterone receptor with RU486, suggesting that both effects were receptor-mediated. These findings demonstrate that progesterone antagonizes the effect of estrogen on oviductal egg transport in the rat, and suggest that this antagonism is mediated by a reduction both in the amount of estrogen receptors and in their retention time in the nucleus.

Animals↗

PubMed1988

Estrogen and progesterone receptors in the oviduct during egg transport in cyclic and pregnant rats.

We investigated the temporal relationships between ovum transport and changes in the concentration of nuclear steroid receptors in the oviduct of cyclic and pregnant rats. A lack of parallelism between estrogen and progesterone fluctuations in plasma and their respective nuclear receptor concentrations in the oviduct predominated during egg transport. In pregnant animals, oviductal egg transport took 24 h longer than in nonpregnant animals. In both conditions, transport was initiated while the action of estrogen and progesterone on the oviduct--measured as nuclear receptor accumulation--was decreasing. Three or four days later, depending on whether the animal was pregnant, the eggs entered the uterus shortly after an increase in the nuclear receptor accumulation of both hormones. Treatment with RU486, a progesterone receptor-blocking agent known to cause premature arrival of eggs in the uterus, advanced estrogen receptor accumulation in the oviduct of pregnant rats. These data suggest that the arrival of eggs in the uterus is timed by a transitory increase in nuclear estrogen receptor in the oviduct that does not necessarily reflect a similar change of circulating estradiol. Moreover, in pregnant rats, the onset of this estrogenic action is delayed by a progesterone receptor-mediated effect that hinders nuclear estrogen receptor accumulation.

Animals↗

PubMed1988

A study on the feasibility of suppressing ovarian activity following the end of postpartum amenorrhoea by increasing the frequency of suckling.

The aim of the study was to test the effect of increasing the frequency of breastfeeding upon ovarian function following the end of postpartum amenorrhoea. Women exclusively breastfeeding (n = 14) who experienced their first postpartum menstruation between the third and fifth month after delivery were randomly allocated to an experimental (n = 7) and a control (n = 7) group and studied during the next two cycles. Women in the experimental group agreed to increase the number of breastfeeding episodes per day throughout the second cycle. Blood samples were drawn twice a week from the first to the third postpartum menstruation for prolactin, oestradiol and progesterone determinations. The number of breastfeeding episodes per day and night and the length of each episode were recorded daily. An average frequency of 11 nursing episodes per 24 h was reported during the first study cycle in both groups. The experimental group increased by 50% the breastfeeding frequency after the second menstruation while the control group kept its spontaneous feeding pattern. The increase of suckling frequency occurred mainly during day hours. The total breastfeeding time per 24 h was not increased. The length of the menstrual cycle was not altered by the increased suckling frequency. The endocrine pattern differed neither between the first and second cycle of the experimental group nor between the experimental and control group, with the exception of PRL levels which were higher in the experimental group throughout both cycles. Twenty cycles (71%) showed progesterone values compatible with ovulation (greater than 9.5 nmol/l). The highest progesterone values and the highest oestradiol values observed in the ovulatory cycles of lactating women were within the range found in non-nursing fertile women. Plasma levels of PRL were significantly elevated in all cycles but one, in comparison with PRL levels in non-nursing women. It is concluded that if cyclic ovarian function is reestablished early in fully nursing women, a mere increase in the number of breastfeeding episodes, without augmenting total suckling time and the frequency of nocturnal episodes, does not provide a sufficient stimulus to resuppress the pituitary-ovarian axis.

Adult↗

PubMed1988

Synthetic microspheres transferred to the rat oviduct on day 1 of pregnancy mimic the transport of native ova.

Microspheres of various materials and diameters were transferred microsurgically to the rat oviduct on Day 1 of pregnancy and autopsies were done at various times thereafter up to Day 10 to assess the recovery and segmental distribution of microspheres and eggs in the genital tract or the viability of embryos. The number and distribution of eggs in the treated and control sides after unilateral transfers were not different on Day 4 and 5 and the number of embryos implanted on Day 10 was not significantly affected after bilateral transfers. The segmental distribution of eggs and starch microspheres within the oviduct on Days 2, 3 or 4 showed that both are transported partly intermingled from ampulla to uterus. When microspheres of poly(DL-lactide-co-glycolide), starch, dextran or dextran blue were transferred, their distribution in the genital tract in the morning of Day 5 showed that poly(DL-lactide-co-glycolide) and dextran microspheres stayed longer in the oviduct while starch and dextran blue microspheres were transported to the uterus at the same time as the eggs. Transfer of starch microspheres of 40-60 microns to one oviduct and 180-200 microns in diameter to the opposite oviduct showed that distribution on one side was nearly identical to that of the other side from Days 2 to 5. We conclude that the behaviour of synthetic surrogate ova in rats differs from that in rabbits. The rat oviduct does not change the rate of transport of native eggs following transfer of synthetic surrogate ova.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗