David I. Hoffman

The prevalence and significance of elevated dehydroepiandrosterone sulfate levels in anovulatory women

One hundred nineteen euprolactinemic anovulatory infertility patients who were being evaluated for induction of ovulation with clomiphene citrate were studied to determine the prevalence of increased adrenal androgen (AA) secretion in this group. Fifty percent of these patients exhibited increased AA secretion, as evidenced by an elevated serum dehydroepiandrosterone sulfate (DHEA-S) level. Seventy-seven percent of these women with elevated levels of DHEA-S were nonhirsute . Twenty-six patients with elevated serum DHEA-S levels underwent adrenocorticotropic hormone (ACTH) stimulation tests in order to determine a possible mechanism(s) for the increase in DHEA-S. Plasma ACTH, as well as total, low-density lipoprotein, and high-density lipoprotein cholesterol were also measured. These levels were normal and did not correlate with the elevated levels of DHEA-S. Seven of 16 patients (34%) had exaggerated responses of serum DHEA-S and of 17-OH pregnenolone to ACTH stimulation. In six of these seven patients, our data suggested the occurrence of a mild deficiency of 3 beta-ol dehydrogenase-isomerase. All of these six patients were considered to have polycystic ovary syndrome. While these data do not explain the increased AA secretion in the majority of patients with elevated levels of DHEA-S, we suggest that serum DHEA-S is frequently elevated in anovulatory infertile patients.

Plasma β-endorphin concentrations prior to and during pregnancy, in labor, and after delivery

β-Endorphin was measured by radioimmunoassay in peripheral plasma of nonpregnant women (58 ± 2.4 pg/ml, n =17, mean ± SE), during the first trimester (47 ± 2.4 pg/ml, n = 11), the second trimester (33 ± 1.9, n = 11), and the third trimester (49 ± 2.7 pg/ml, n =10) of pregnancy, during early (202 ± 32 pg/ml, n =12) and advanced labor (389 ± 78 pg/ml, n =10), and 30 to 60 minutes post partum (177 ± 22 pg/ml, n =12). Mean plasma levels of β-endorphin were significantly lower in each trimester of gestation than the levels in nonpregnant control subjects. During labor and the early postpartum period, maternal plasma levels of β-endorphin were significantly elevated. Furthermore, peripheral plasma levels of ,β-endorphin during labor fell from 189 ± 31 to 97.6 ± 12 pg/ml (n =13, p = 0.015) in response to epidural anesthesia, as compared to peripheral plasma concentrations of β-endorphin of 223 ± 71 and 193 ± 47 pg/ml prior to and after injection of saline solution into epidural catheters, respectively, in 10 control subjects. Mean plasma levels of p-endorphin in patients immediately prior to elective repeat cesarean section who were not in labor (151 ± 23 pg/ml, n =15) were significantly higher (p

β-Endorphin and β-lipotropin concentrations in umbilical cord blood ☆ ☆☆

Abstract Antisera suitable for human β-endorphin and β-lipotropin radioimmunoassay were developed, and radioimmunoassays were established to measure these peptides in umbilical cord plasma, with silicic acid extraction and gel chromatography used to separate the β-endorphin from the β-lipotropin fraction. These two peptides were determined in umbilical venous plasma from 64 newborn infants. Umbilical vein β-endorphin and β-lipotropin concentrations averaged 38.5 ± 3.2 and 50.4 ± 4.1 (± SE) fmoles/ml in the 54 newborn infants without and 115 ± 18 and 110 ± 25 fmoles/ml in the 10 newborn infants with apparent fetal distress. Neither the presence or absence of labor nor the route or mode of delivery was found to affect umbilical vein β-endorphin or β-lipotropin concentrations. However, cord plasma levels of both peptides were significantly elevated in conjunction with fetal distress, as evidenced by prolonged bradycardia, late and prolonged variable fetal heart rate decelerations, or fetal acidosis. In 18 of 22 pairs of simultaneously measured umbilical venous and arterial β-endorphin and β-lipotropin concentrations in newborn infants without apparent intrapartum distress, the venous β-endorphin concentrations, which averaged 40.4 ± 3.5 fmoles/ml, were significantly higher than the arterial β-endorphin levels, with a mean of 28.5 ± 4.2 fmoles/ml. No significant umiblical arteriovenous concentration difference could be observed for β-lipotropin. This suggests that at least a portion of the cord plasma β-endorphin is derived from the placenta. The ratio of umbilical arterial to venous β-endorphin concentrations rose as the absolute cord plasma β-endorphin levels increased. Furthermore, both the molar umbilical venous and arterial β-lipotropin to β-endorphin ratios decreased significantly in association with intrapartum fetal distress. These data indicate that the stress-related increase in umbilical plasma β-endorphin exceeds that of β-lipotropin and may be, at least in part, of fetal origin. Umbilical venous β-endorphin and β-lipotropin levels of neonates whose mothers did not receive meperidine or other narcotic agents did not differ from those of neonates whose mothers were given meperidine or other narcotics during labor. Our data, in conjunction with those of others, are consistent with the hypothesis that fetal hypoxia causes the release of neurotransmitters such as β-endorphin, which may modulate the regulation of fetal heart rate patterns.

Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics

The effects of epidural bupivacaine with and without 1:300,000 epinephrine on uterine activity, progress of labor, fetal heart rate, maternal blood pressure and heart rate, newborn Apgar scores, neonatal acid—base status, and Neurologic and Adaptive Capacity Scoring System (NACS) were compared in 32 parturients during labor and delivery. Patients in group I (n = 16) received 0.5% bupivacaine with 1:300,000 epinephrine and those in group II (n = 16) received 0.5% bupivacaine alone. Addition of epinephrine to bupivacaine had no significant effects on uterine activity, duration of first or second stages of labor, fetal heart rate and variability, or the incidence of abnormal fetal heart rate patterns. Maternal hypotension occurred less frequently in group I than in group II patients (P < 0.05). Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I than in group II (186.8 ± 11.6 vs 85.3 ± 6.1 (mean ± sem) min, P < 0.001). It is concluded that adding epinephrine to bupivacaine during epidural anesthesia in the normal parturient has no adverse effects on either mother, fetus, neonate, or the progress of labor; and that it significantly prolongs the duration of anesthesia and decreases the incidence of maternal hypotension.

Beta-endorphin in pregnancy

Concentrations of maternal plasma beta-endorphin (beta-EP) as measured by radioimmunoassay decline during pregnancy, reaching a nadir during the second trimester, rise during labor, remain elevated during the early postpartum period and are increased prior to elective cesarean section in the absence of labor. They decline in response to epidural anesthesia during labor and increase during induction of general but not regional anesthesia for cesarean section. Umbilical venous plasma beta-EP levels are not affected by the route or mode of delivery nor the presence or absence of labor, but rise in conjunction with fetal distress. In the presence of fetal distress, umbilical arterial plasma beta-EP levels appear to rise faster than umbilical venous beta-EP concentrations. Amniotic fluid beta-EP levels are higher during the second than third trimester. These data indicate that peripheral plasma beta-EP concentrations reflect stress in both mother and fetus. In the mother, pregnancy itself does not appear to be stressful, whereas pain associated with labor rather than uterine contractions as such increase plasma beta-EP levels. In the fetus, hypoxia and acidosis effectively raise plasma beta-EP concentrations. The origin and physiologic significance of amniotic fluid beta-EP, which appears to be unrelated to fetal maturity, remain to be established.

Serum dehydroepiandrosterone sulfate and the use of clomiphene citrate in anovulatory women

Serum dehydroepiandrosterone sulfate (DHEA-S) is frequently elevated in anovulatory women. This study was carried out to determine whether the ovulatory response with clomiphene citrate (CC) in patients with elevated levels of serum DHEA-S is influenced by the pretreatment level. Also evaluated was whether this response rate was similar to or different from that of anovulatory patients who had normal levels of DHEA-S. CC was administered to 40 anovulatory patients who had elevated levels of DHEA-S. Rankit analysis of these 40 elevated DHEA-S levels indicated that two populations existed. These patients were, therefore, divided into two groups of 29 and 11 with DHEA-S levels of less than 5 and greater than 5 micrograms/ml, respectively. Fifty-nine anovulatory patients with normal DHEA-S levels were also treated with CC. Patients with elevated and normal DHEA-S levels had similar rates of ovulation with CC (75% and 78%). Among patients with elevated levels of DHEA-S, ovulation occurred in 55% of patients with levels greater than 5 micrograms/ml and 83% with levels less than 5 micrograms/ml. The dose of CC at which ovulation occurred was unrelated to the level of DHEA-S. Pregnancies occurred in 15 of the 40 patients after at least four ovulatory cycles and were not influenced by the level of DHEA-S. It is concluded that CC is effective in inducing ovulation in patients with elevated levels of adrenal androgens. However, in patients with DHEA-S levels greater than 5 micrograms/ml, the ovulatory response rate may be decreased.

The relative bioavailability of levonorgestrel and ethinyl estradiol administered as a low-dose combination oral contraceptive

The relative bioavailability of levonorgestrel (LNG) and ethinyl estradiol (EE) administered concomitantly both as an oral tablet and as a solution was assessed in a randomized two-period crossover study in 24 healthy women. Serum concentrations were monitored for 96 h after each administration. The relative bioavailability (Fr) of LNG in the tablet with respect to the solution was 107%; thus the two formulations were bioequivalent with respect to LNG. The relative bioavailability of EE, however, was significantly lower for the tablet (Fr 83%) compared to the solution. This difference may have been due to either decreased absorption or enhanced presystemic elimination of EE from the tablet formulation.

Effects of induction of general and regional anesthesia for cesarean section on maternal plasma β-endorphin levels

Plasma beta-endorphin was measured in 40 healthy pregnant women undergoing cesarean section. Group 1 patients (N = 14) received general anesthesia by rapid-sequence induction and endotracheal intubation with curare, thiopental, and succinylcholine. Anesthesia was maintained with nitrous oxide, oxygen, and muscle relaxant until delivery. Group 2 patients (N = 26) received regional anesthesia (spinal, 14, and epidural, 12). Maternal blood samples were drawn from indwelling venous catheters prior to and after induction of either general or regional anesthesia. Plasma beta-endorphin was determined by radioimmunoassay following silicic acid extraction and gel chromatography. In the 14 patients who underwent general anesthesia, the mean (+/- SEM) plasma beta-endorphin increased significantly (p less than 0.025) from 46 +/- 7.4 to 111.6 +/- 8.9 fmol/ml. There was no significant change in plasma beta-endorphin level of the 26 patients who underwent regional anesthesia; beta-endorphin levels averaged 44.5 +/- 5.1 and 47.6 +/- 4.8 fmol/ml prior to and after induction of anesthesia, respectively. These data demonstrate that plasma beta-endorphin concentrations are elevated following induction of general anesthesia but not with induction of regional anesthesia, which suggests that less stress is associated with regional than with general anesthesia induction in patients undergoing cesarean section.

Chlamydia trachomatis is not an important cause of abnormal postcoital tests in ovulating patients

To examine the role of Chlamydia trachomatis infections of the cervix and abnormal postcoital tests (PCT) in a general infertility clinic, 63 consecutive patients undergoing a midcycle PCT during a routine infertility workup underwent endocervical curettage, and a 10-ml blood sample was obtained. The endocervical tissue was cultured for C. trachomatis; the serum sample was analyzed for chlamydial IgG and IgM antibodies using an indirect microimmunofluorescence assay. A negative titer was considered to be less than or equal to 1:8 dilution for IgG antibodies and less than or equal to 1:32 dilution for IgM antibodies. A good PCT was defined as greater than or equal to 5 motile sperm per high power field (HPF). A poor PCT was defined as less than 2 motile sperm/HPF, and a fair PCT was defined as 2 to 4 motile sperm/HPF. Of the 63 PCTs done, 27 (42.9%) were good, 14 (22.2%) were fair, and 22 (34.9%) were poor. All endocervical tissue cultures for C. trachomatis obtained during PCTs were negative. All IgM chlamydial antibody titers were negative (less than or equal to 1:32 dilution), 55 (87.3%) of the patients having a zero titer. Eleven (17.5%) of the patients had negative IgG chlamydial antibody titers (less than or equal to 1:8 dilution), none of the patients had a 1:16 dilution, and 52 (82.5%) had positive IgG chlamydial antibody titers (greater than or equal to 1:32 dilution). Thus, chlamydial infections of the endocervix are rare and not commonly associated with poor PCTs in this patient population.

Effect of intrathecal morphine during labor on maternal plasma β-endorphin levels

Plasma beta-endorphin was measured in 16 patients in labor prior to and after complete onset of analgesia with 1 mg of morphine administered intrathecally. Human beta-endorphin levels were determined by radioimmunoassay following silicic acid extraction of plasma samples and separation of the beta-endorphin fraction by gel chromatography. Plasma beta-endorphin levels decreased significantly (p less than 0.005) after intrathecal morphine from 76 +/- 9.7 to 46.3 +/- 9.1 fmol/ml (mean +/- SE), possibly because of decreased pituitary beta-endorphin secretion in response to alleviation of labor pain.