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Biomedical subjects

A Brandeis

Publications and source records attributed to A Brandeis.

17 recordsLinked to original sources

Development of a radioimmunoassay for Cebus apella prolactin.

Prolactin (PRL) is a pituitary hormone that plays important roles in mammalian reproductive physiology, specially lactation. The regulation of PRL secretion shows important species differences. To study PRL regulation in a subhuman primate, the Cebus apella, we developed an heterologous radioimmunoassay using an antibody against rhesus PRL (anti-m5PRL) and a Cebus apella pituitary extract as PRL standard. The assay has a sensitivity that allows measurements of cebus PRL in small amounts of Cebus apella plasma obtained from animals in different physiological conditions. Plasma cebus PRL concentrations (+/-SEM) varied in different reproductive stages. PRL concentration in adult Cebus apella females that have regular menstrual cycles (161.6 +/- 15.0 mIU/ml) was similar to that found in adult (100.3 +/- 7.6 mIU/ml) and prepuberal males (101.2 +/- 3.9 mIU/ml). PRL concentration was higher in pregnant (677.8 +/- 11.8 mIU/ml) and in nursing (625.0 +/- 47.0 mIU/ml) Cebus apella females than in 15-d post-partum non-nursing (369.0 +/- 19.0 mIU/ml) and cycling females. PRL concentration in Cebus apella newborns (719.0 +/- 49.2 mIU/ ml) was similar to that found in pregnant and nursing females, and higher than in the other females as well as adult and prepuberal males. These differences in PRL concentration in different physiological conditions are similar to that observed in humans and other primates. A PRL response to thyrotropin releasing hormone (TRH) was demonstrated in 2 nursing Cebus apella females, similar to the response found in nursing woman and rhesus. Altogether, the data presented support the proposal that the assay developed to measure PRL in Cebus apella is an adequate tool to study the physiology of PRL in this species.

Animals↗

Clinical trial with Nestorone subdermal contraceptive implants.

The clinical performance and the in vivo release rate of a single 4-cm Nestorone subdermal implant were investigated. Implants manufactured by two different procedures were compared. Volunteers were 70 healthy women of proven fertility. Forty women provided blood samples twice a week in the pretreatment cycle and for 5-6 weeks at 6-month intervals during treatment. Additional control cycles (n = 31) were studied in 19 Copper T users. No pregnancy occurred in 1570 woman-months. Nestorone plasma levels (x +/- S.E.) declined from 112 +/- 8 to 86 +/- 3 pmol/L (Implant A) and from 145 +/- 8 to 57 +/- 5 pmol/L (Implant B) from the first to the 24th month. Progesterone levels were < 9.5 nmol/L in 166 (93%) of 178 blood samplings taken during treatment. Progesterone levels > 16 nmol/L were found in only 7 sampling periods (3.9%) in treated women and in 70 (98.6%) out of 71 control cycles. No ovulation occurred with Nestorone plasma levels above 105 pmol/L. No abnormal changes were observed in plasma lipoproteins or other clinical chemistry parameters during treatment. The implants were well tolerated. The most frequent complaint was the occurrence of irregular bleeding. Enlarged follicles found during pelvic examination in 8 subjects (11.4%) disappeared spontaneously in 10 days to 6 weeks. Implants were removed because of medical (n = 10, 14.3%) or personal reasons (n = 6, 8.6%) or at the 24th month of treatment (n = 54, 77.1%). The estimated average daily in vivo release rate of Nestorone was 45-50 micrograms/day. A single Nestorone subdermal implant affords efficient contraceptive protection during two years.

Adolescent↗

Luteinizing hormone pulsatile release and the length of lactational amenorrhoea.

The pattern of luteinizing hormone (LH) pulsatile release and the mean concentrations of follicle-stimulating hormone, oestradiol and progesterone were studied in nursing and non-nursing women. Blood samples were drawn at 5 min intervals between 10:00 and 14:00 h and between 22:00 and 02:00 h at months 3-4, 5-6, 7-8 and 9-10 postpartum in nursing women and in the follicular phase in non-nursing women. In nursing women, mean LH concentrations at months 3-4 were significantly lower than in non-nursing cycling women only in the subgroup which subsequently experienced > 6 months of lactational amenorrhoea, although all were fully nursing with a similar suckling frequency. LH pulses in plasma were found at all times in nursing women. There were no significant differences in the frequency (about four pulses every 4 h), amplitude or duration of LH pulses related to the duration of amenorrhoea, nor did these parameters vary significantly between amenorrhoeic or cycling nursing women and non-nursing women. Nursing amenorrhoeic women exhibited a normal frequency of LH pulse well in advance of the resumption of the first post-partum menses, suggesting that mechanisms other than the suppression of the gonadotrophin-releasing hormone pulse generator intervened in the inhibition of ovarian function during lactation.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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.

Adult↗

Plasma levonorgestrel and progesterone levels in women treated with silastic covered rods containing levonorgestrel.

Levonorgestrel and progesterone plasma levels were measured in women bearing levonorgestrel subdermal implants. Two groups using four or six levonorgestrel covered rods and one group of non-hormonal contraceptors were compared. Blood samples were drawn twice a week for six consecutive weeks at different intervals after treatment administration. The mean levonorgestrel levels (mean +/- S.D.) observed in the four rods group was .49 +/- .13 ng/ml in the first year and decreased to .34 +/- .06 in the fifth year of treatment. The mean values observed in the six rods group were .70 +/- .15 ng/ml in the second year and .43 +/- .11 in the sixth year. The levonorgestrel plasma levels were slightly above those found with Norplantr implants in the four rods group and well above it in the six rod group. The highest plasma progesterone value found in each sampling period was above 9 nmol/l in 7 (14%) out of 50 subjects in the four rods group, in 2 (4.3%) out of 47 subjects in the six rods group and in all the 49 control women. In 4 out of the 7 subjects from the 4 rods group and in the two subjects from the 6 rods group, the highest progesterone value was preceded and followed by values lower than 6 nmol/l. It was concluded that the progesterone levels were seldom compatible with the occurrence of ovulation in women treated with four or six levonorgestrel covered rods which release an estimated daily dose of 70 and 105 micrograms, respectively.

Adolescent↗

Fertility regulation in nursing women: VIII. Progesterone plasma levels and contraceptive efficacy of a progesterone-releasing vaginal ring.

The objectives of this trial were to test the contraceptive efficacy and measure progesterone plasma levels of women using progesterone-releasing rings during lactation. Two types of rings delivering an average of about 5 mg or 10 mg of progesterone per day were tested in 128 healthy nursing women. A control group was formed by 127 Copper T users. Rings were inserted at day 60 postpartum and replaced every 3 months with a new one. Initially progesterone plasma levels were around 10 nmol/l and 15 nmol/l for rings releasing 5 and 10 mg per day, respectively, and decreased slightly after 30 days. Levels observed in subsequent segments of use approximated those of the first segment. These levels are within the range shown to inhibit fertility in lactating women. One pregnancy was diagnosed in 739 woman-months of progesterone ring use, and none occurred in 794 woman-months of Copper T use, which contrasts with the high incidence of pregnancy in a group of untreated nursing women where 19 pregnancies resulted during 677 woman-months. No deleterious effects were detected lactation and infant growth or maternal and infant health. It is concluded that the vaginal rings releasing progesterone are a suitable contraceptive method for lactating women.

Clinical Trials as Topic↗

Plasma progesterone levels following subdermal implantation of progesterone pellets in lactating women.

The magnitude and duration of elevated plasma progesterone levels resulting from subdermal implantation of progesterone pellets were investigated in full nursing women. This condition was chosen because it is associated with a low rate of ovulation and minimal endogenous progesterone production. In addition, treatment with progesterone pellets was intended to be a substitute for oral or parenteral administration of synthetic progestogens to nursing mothers. A control group of full nursing women receiving no hormones provided blood samples so that basal plasma progesterone levels from the second to the sixth post-partum month could be assessed. Progesterone pellets were implanted subdermally on day 30-35 after delivery. Insertion of 2, 4 or 6 pellets each containing 100 mg of progesterone caused an initial elevation of plasma progesterone to 5.9, 9.9 and 13.5 nmol/l, respectively. This initial elevation was followed by a gradual decline, so that basal levels were attained at 70, 100 and 150 days after insertion of 2, 4 or 6 pellets. Implantation of 6 progesterone pellets led to a significant decrease in the ovulation rate of nursing women. These results indicate that subdermal implantation of 6 progesterone pellets can provide biologically effective levels of the hormone for up to 5 months.

Adolescent↗

Plasma progesterone levels during long-term treatment with levonorgestrel silastic implants.

Plasma progesterone levels were measured in 113 women using a subdermal implant containing 200 mg levonorgestrel (NORPLANT) in an attempt to assess the roles of anovulation and inadequate luteal function in the contraceptive action of this method. Twenty-two women using an IUD (Copper T 200) served as a control group. Blood samples were taken twice a week for 6 consecutive weeks. This was done one to four times in each subject during the first 7 years after insertion of NORPLANT. Plasma progesterone was measured by a specific RIA and criteria based upon normal values in this laboratory were used to define each set of samples as ovulatory, uncertain or anovulatory. The rate of anovulation varied between 25 and 80% throughout the 7 years. The highest rate was observed during the first year of treatment of treatment. The rate of anovulation was significantly correlated with the plasma levels of levonorgestrel. Varying degrees of inadequate corpus luteum function were detected among NORPLANT users. All sets of samples in the control group were ovulatory and compatible with normal luteal function. These results clearly show that continuous administration of levonorgestrel by means of NORPLANT interferes with ovulation and/or luteal function in a significant proportion of cycles throughout the first 7 years of use.

Adult↗