Biomedical subjects
S Díaz
Publications and source records attributed to S Díaz.
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.
[Non-infectious pulmonary complications in AIDS].
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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.
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.
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.
[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)
[Breast feeding, amenorrhea and infertility].
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[Family planning during breast feeding].
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Determinants of lactational amenorrhea.
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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.
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.
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.
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.
Breastfeeding pattern and the duration of lactational amenorrhea in urban Chilean women.
The influence of the breastfeeding pattern and several clinical variables upon the duration of postpartum amenorrhea was assessed in a group of healthy women selected for having had a normal pregnancy and delivery and being highly motivated for prolonged breastfeeding on demand. 676 women who were fully nursing at the second month postpartum entered the study. Supplements were administered to 11% and 48% of the infants by the end of the 3rd and 6th month, respectively. The first bleeding was experienced before the end of the sixth month postpartum by 57% of the cases. Supplementation had a strong negative influence while nursing frequency had a significant positive influence upon the length of amenorrhea. Notwithstanding, a frequency of 8+ suckling episodes per 24 h could not maintain amenorrhea in around half of the subjects. Age and parity had a moderate negative influence upon the risk of experiencing the first postpartum bleeding. Maternal weight and ponderal index, infant sex, birth weight and growth rate showed no significant influence upon the length of amenorrhea. In this urban population selected for having the highest motivation and best breastfeeding performance, the association of breastfeeding with amenorrhea was weak in comparison with what has been described for other populations. The risk of experiencing the first bleeding was reduced while fully breastfeeding with a high number of nursing episodes per day and night, particularly in older women with higher parity. But even in such situation 25% and 50% of the women had started to cycle by the end of the fifth and eight postpartum month.
Treatment with Norplant subdermal implants inhibits sperm penetration through cervical mucus in vitro.
Attempts were made to collect several samples of cervical mucus in each of thirty-three cycles of women using NORPLANT subdermal implants, in seven cycles from NORPLANT-2 rod users, and in 33 control cycles. The attempts to collect a mucus sample were successful on 20 of 77 and 7 of 14 occasions in NORPLANT capsule and rod users, respectively, due to the scanty amount and stickiness found in the majority. All 59 attempts in control subjects were successful. The distance travelled by the fastest sperm and by the bulk of spermatozoa through the cervical mucus in vitro was assessed after 10 min of incubation with a normal semen sample. The best score for each cycle was considered for the comparison between treated and control cases. Sperm penetration was greatly impaired in mucus samples of implant users with penetration by the fastest sperm exceeding 10 mm in only two instances and exceeding 20 mm in none. In 30 of 33 control samples, the fastest sperm travelled 21 mm or more and in 28, the bulk of spermatozoa travelled further than 10 mm. Unsuccessful attempts to collect mucus and poor sperm migration were observed in NORPLANT implant users even when circulating estradiol levels were comparable to those seen in the late follicular phase of the normal menstrual cycle. These results suggest that the principal mechanism by which NORPLANT implants prevent pregnancy is by interference of sperm migration through cervical mucus.
The place of progesterone in human contraception.
Progesterone, the natural hormone produced by the corpus luteum and other steroid-secreting glands, is endowed with antiestrogenic action and has a fundamental role in the initiation and maintenance of pregnancy and in the regulation of gonadotropin secretion. Although it was discovered half a century ago, it has found little clinical use as a therapeutic agent due to its low potency and extensive degradation following oral administration in comparison with a variety of highly potent synthetic analogs that became available in the last three decades. When delivered systemically, a large proportion of the dose bypasses degradation in the gut and liver, and progesterone can achieve effective levels in target tissues for clinical use. Sustained administration via compressed pellets implanted subdermally or silicone rubber rings placed in the vagina produced circulating levels of progesterone within the lower third of those found in the luteal phase of the human menstrual cycle. Those levels were shown to delay the recovery of fertility in nursing women without adverse effects to the mother or the infant. Progesterone transferred to the babies via the breast milk did not change their rate of pregnandiol-3-alpha glucuronide excretion. It is concluded that sustained administration of the natural hormone progesterone may be an effective and safe contraceptive method for nursing women.
Long-term follow-up of women treated with Norplant implants.
This report describes 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. 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 5 years of NORPLANT implants use was 0.63. No pregnancy has occurred in 4194 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 10 (9.1%) out of 110 acceptors of the replacement implants were terminated for other medical reasons, mainly bleeding problems and side effects commonly associated with hormonal contraception. Two women died while using NORPLANT implants, one of a cardiac arrest after surgery for a gallbladder disease and one because of endocranial hypertension originating from the rupture of an aneurism of the median cerebral artery. The bleeding pattern observed in the three months after NORPLANT capsules replacement was similar to that observed in the 90 days before replacement and different from that experienced by the same women in the first 90 days of implant use. This finding can be interpreted as an indicator of adaptive changes experienced by the target organs during long-term continuous administration of levonorgestrel. The prompt recovery of fertility after removal of NORPLANT implants suggests that these changes are reversible.