Robert M. Nakamura

Comparison of pharmacodynamic properties of various estrogen formulations.

A group of 23 healthy postmenopausal women received one or more 2-week courses of daily administration of the following estrogen preparations: piperazine estrone sulfate (Ogen), 0.3, 0.625, 1.25, 2.5, and 5.0 mg; micronized estradiol (Estrace), 1, 2, and 10 mg; conjugated estrogens (Premarin), 0.3, 0.625, 1.25, and 2.5 mg; ethinyl estradiol (Estinyl), 10 and 20 micrograms; and diethylstilbestrol, 0.1 and 0.5 mg. Each dosage of each formulation was ingested by three women. In those women who received more than one dosage, each course was separated by a drug-free interval of at least 4 weeks. Pretreatment and posttreatment levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), corticosteroid-binding globulin-binding capacity, sex hormone-binding globulin-binding capacity, angiotensinogen, estrone, and estradiol were determined. The relative potency of these five estrogen formulations was determined by parallel line analysis for each of these responses, except LH. On a weight basis, piperazine estrone sulfate and micronized estradiol were equipotent for all responses. Conjugated estrogens suppressed FSH in a fashion equipotent to that of the other nonsynthetic estrogens; however, for all three hepatic parameters, the response was exaggerated twofold to threefold. The synthetic estrogens, diethylstilbestrol and ethinyl estradiol, were relatively more potent on a weight basis for every response and produced the most marked response (fourfold to eighteenfold in excess of their FSH suppression) for the hepatic parameters.

Exercise in pregnancy

We investigated cardiovascular and metabolic responses in 23 healthy pregnant volunteers in their third trimester prior to, during, and after a 15-minute period of treadmill exercise. The energy utilization of this exercise was 2.33 MET with an oxygen consumption under 0.5 L/minute. Exercise induced a significant increase in maternal heart rate and a shortening of the R time intervals; both returned to baseline by 30 minutes of recovery. This light exercise also induced a significant increase in glucagon, norepinephrine, and epinephrine concentrations, all of which were transitory and reversed within 30 minutes of the recovery period. No change in glucose or cortisol concentration resulted from this exercise. We conclude that light exercise of brief duration elicits appropriate and transitory cardiovascular and metabolic responses in normal pregnancy.

Serum gonadotropin and steroid patterns during the normal menstrual cycle

At the University of Southern California School of Medicine, the reproductive hormones follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, and estradiol were measured in serum samples obtained daily from a group of women throughout a normal menstrual cycle. Competitive binding techniques were used for the analysis of aliquots from the 10 women, aged 20-28, whose hormonal levels were studied. The results were generally in agreement with those of previous investigators, whose separate researches were less extensive than the research described here. FSH showed an early follicular phase rise, a late follicular phase decline, and a midcycle peak occurring on the day of the LH peak or on the day before and followed by a luteal phase decline. LH showed a slight progressive rise in the follicular phase, a midcycle peak, and a slight fall in the luteal phase. Estradiol also reached a midcycle peak. After the midcycle peaks, a rise progesterone. Progesterone and estradiol fell a few days before menstruation.

Clinical experience with the amniotic fluid lecithin/sphingomyelin ratio

Abstract Amniotic fluid lecithin/sphingomyelin (L/S ratios were measured in 425 pregnancies and restrospectively correlated with neonatal pulmonary performance. L/S ratios of 2.0 and greater, a value reached at about 34 weeks of gestation, were associated with 3.7 per cent morbidity from idiopathic respiratory distress syndrome (RDS) and a 0.3 per cent mortality rate from hyaline membrane disease (HMD) among 347 newborn infants. A 63 per cent morbidity from RDS and 23 per cent mortality rate from HMD, however, were found among 48 newborn infants delivered within 72 hours of having an L/S ratio of less than 2.0. The association of an L/S ratio greater than 2.0 with a low incidence of RDS and virtual absence of HMD substantiates the value of this method as a predictor of fetal pulmonary maturity.

A comparison of clindamycin-gentamicin and penicillin-gentamicin in the treatment of post-cesarean section endomyometritis.

A random comparison of clindamycin-gentamicin (C-G) and penicillin-gentamicin was made in 200 women who developed endomyometritis following cesarean section. All pretreatment profiles indicated similar populations. The clinical response was more favorable in the women receiving clindamycin-gentamicin. The implications of these results upon clinical practice is discussed.

The relation of serum 17-hydroxyprogesterone and estradiol-17β levels during the human menstrual cycle ☆

Abstract Concentrations of 17-hydroxyprogesterone (17-OHP) were measured in serum samples obtained daily through 9 menstrual cycles. These samples had previously been assayed for estradiol, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone. The concentration of 17-OHP increased at mid-cycle and continued to be high throughout the luteal phase of the cycle. The first sustained rise in 17-OHP levels was associated with the initiation of the mid-cycle LH surge. The results of this study indicate that the mid-cycle rise of 17-OHP may well be one of the earliest indicators of luteinization of the follicle as this hormone appears to be initially secreted by luteintzed thecal cells and then by the corpus luteum. It is concluded that estradiol levels rather than 17-OHP levels provide a good index of follicular maturation, whereas rising concentrations of the latter hormone indicate luteinization of the follicle.

Serum gonadotropin and steroid patterns in early human gestation

Estradiol (E), progesterone (P), 17-hydroxyprogesterone (17-P), follicle stimulating hormone (FSH), luteinizing hormone-human chorionic gonadotropin (LH-HCG), and human placental lactogen (HPL) concentrations were measured in serum samples obtained daily from 3 women from the last menstrual period (LMP) throughout the 1st few months of gestation. Radioimmunassay of serum samples was used. FSH levels declined after implantation in 1 subject and remained unchanged in the others. HCG levels began to rise above luteal phase LH values 11-14 days after the midcycle LH peak. HPL became detectable 34-38 days after the LH peak. E levels rose steadily after the postovulatory nadir, increasing rapidly 4 weeks after the LH peak. Patterns of P and 17-P were similar initially; both rose after ovulation, remained elevated for several weeks, and then declined. About 11 weeks after the LMP, levels of P again increased whereas 17-P remained low. Single serum samples were obtained from an additional 158 gravid women 6-16 weeks after the LMP, and E, P, and 17-P were measured in each. Mean levels of E steadily increased and 17-P steadily decreased. Mean P dropped to a nadir at 9 weeks and rose therafter. Since the 17-P is mainly of luteal origin, these findings indicated that in normal pregnancy the corpus luteum has maximal activity for about 4 weeks after ovulation. Falling levels of P in the 3 weeks prior to increased trophoblastic production of this hormone may contribute to the cause of 1st trimester uterine bleeding in some women who have normal term pregnancies.

Log normal distribution of gonadotropins and ovarian steroid values in the normal menstrual cycle

In the statistical analysis of the values of luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone obtained from normal menstrual cycles, a depature from normality was noted. Chi square, W test, and linear transformation were used to check the normality of the distributions. The results of this investigation showed that the distributions were not normal (Gaussian) but log-normal. By plotting the probit of the percentages of cumulative frequency on a log scale (probit-log), linearity of the data was obtained. This resulted in direct graphical estimations of values with a useful clinical range, which included the mean and the 95 per cent confidence interval.

Estrogenic activity in women receiving an injectable progestogen for contraception

121 multiparous women (aged 15-37) who had received injections of 150 mg of depomedroxyprogesterone acetate (DMPA) every 3 months as a contraceptive for more than 1 year, were examined to assess possible clinical alterations due to low estrogen levels. Serum samples were taken to evaluate estradiol levels by radioimmunoassay. Clinical examination did not reveal any sign of estrogen deficiency, except a smaller uterine than expected. Serum estradiol concentrations (36-42 pg/ml) were in the range of the follicular phase estradiol levels of the normal ovulating woman. As this follicular level probably persists throughout treatment, total estrogenic stimulation of end organs was much lower than for cycling women, but greater than for post-menapausal women. Patients receiving DPMA have functioning ovaries which continue to secrete estradiol at follicular levels. Uterine atrophy and shift in maturation index during contraceptive treatment with this drug is due to the large dose of progestogen outweighing the low levels of estradiol. It is suggested that long-term studies are needed to determine the possible advantage of increasing the estrogen effect on end organs over the known adverse effects of estrogen administration.

Serum prolactin patterns in early human gestation.

The relation between levels of human prolactin (HPRL), other protein hromones, and estradiol in serum immediately prior to and for the first weeks after conception was determined. HPRL was measured by radioimmunoassay in serum samples obtained daily from these women during the menstrual cycle in which conception took place and for several weeks therafter. It was found that the concentration of HPRL initally increased above nonpregnant levels 32 to 36 days after the luteinizing hormone (LH) peak. The patterns of estradiol and HPRL were similar in early gestation, while there was no similarity between the patterns of HPRL and human placental lactogen. These results are in aggreement with other studies showing that high levels of estrogen influence HPRL secretion in the human subject.