Gonadotropin responses to graded GNRF injections in women with prior twin pregnancies.

Fifteen women with prior twin pregnancies and 20 women with prior singleton pregnancies were investigated in the luteal phase of their menstrual cycles. Measurements were made of their basal LH, FSH, estradiol, progesterone, testosterone and dihydrotestosterone levels as well as their LH and FSH responses to serial graded (0.5 microgram, 5.0 micrograms and 50.0 micrograms) intravenous injections of gonadotropin-releasing factor. The women with prior twin pregnancies were heavier and had a higher parity. Their basal serum progesterone and testosterone levels were not different, but they had lower basal serum estradiol levels and higher basal serum dihydrotestosterone levels. No differences were noted between either the basal or the stimulated gonadotropin (LH and FSH) levels. Thus, no identifiable pituitary trophic factors associated with or causing twinning could be identified in the population studied.

Blood glucose and plasma insulin studies during three months' use of a low-estrogen type oral contraceptive.

Blood glucose and plasma insulin levels were measured during an oral glucose tolerance test in 18 women before and after 3 months' use of a low-estrogen oral contraceptive containing 0.035 mg of ethinylestradiol and 0.5 mg of norethindrone. There was no significant change in either of these two metabolic parameters. In addition, the blood pressures and weights of the women were unchanged during that time. Although these are only preliminary data, they are encouraging, for similar studies with higher-dose preparations often showed significant alterations in carbohydrate tolerance.

Prospective carbohydrate metabolism studies in women using a low-estrogen oral contraceptive for one year.

Three-hour oral glucose tolerance tests were done before and after one year of use of a low-estrogen-type oral contraceptive (OC) in 14 women. The drug contained 0.035 mg ethinyl estradiol and 0.4 mg norethindrone. Both blood glucose and plasma insulin were measured. During the year there were no significant changes in the subjects' weights, whereas their blood pressures decreased. The results showed a significance decrease in the fasting blood glucose level after one year for women with a "normal" control test while the remainder of the values remained unchanged. For women with a "borderline" abnormal control test there was a significant decrease in the two-hour glucose level. There were no significant changes in the plasma insulin levels. These results confirm that this low-estrogen-type oral contraceptive produces minimal changes in the carbohydrate metabolism of users.

PIP: A prospective study was undertaken to determine the carbohydrate metabolic effects in women taking low-estrogen OCs (oral contraceptives) for a year. 14 volunteers received a low-dose combined OC containing .035 mg ethinyl estradiol and .4 mg norethindrone for the period of a year. Results from the study support earlier findings that low-estrogen OCs have a minimal effect on carbohydrate metabolism. 3-hour oral glucose tolerance tests were done before and after 1 year of the OC use. Both blood glucose and plasma insulin were measured. Weight did not change and blood pressure decreased over the year. There was significant decrease in the fasting blood glucose level after 1 year for women with a "normal" control test. For women with a "borderline" abnormal control test, there was a significant decrease in the 2-hour glucose level. Plasma insulin levels did not change.

Insulin receptors in circulating erythrocytes and monocytes from women on oral contraceptives or pregnant women near term.

Altered carbohydrate metabolism occurs in women during pregnancy and in those using oral contraceptives (OC). Insulin binding to circulating erythrocytes and monocytes was studied in 77 nonobese, healthy women volunteers; they were divided into 4 groups: 1) late pregnant (n = 19),2) OC users taking 50 microgram estrogen daily (OC-50; n = 19),3) OC users taking 35 microgram estrogen daily (OC-35; n = 18), and 4) a control group (n = 21). All nonpregnant volunteers were in the luteal phase (days 18-21) of the menstrual cycle. Oral glucose tolerance tests were normal in all groups. Fasting plasma insulin was higher (P < 0.001) in the pregnant group, and plasma insulin responses to the oral glucose tolerance test were higher (P < 0.05) in the pregnant, OC-35, and OC-50 groups compared to that in the control group. The percentage of specific binding of [125I]insulin to 1.2 x 10(7) monocytes/ml (and 4.4 x 10(9) erythrocytes/ml) was similar in all groups (mean +/- SE): pregnant, 6.85 +/- 0.48% (6.85 +/- 0.59%); OC-35, (6.85 +/- 0.40%); OC-50, 6.95 +/- 0.55% (6.73 +/- 0.59%); and control 6.66 +/- 0.64% (7.17 +/- 0.44%). No correlation was found between insulin binding to erythrocytes and monocytes. Average affinity profiles and binding sites per cell (70/erythrocyte and 50,000/monocyte, respesctively) were similar in all groups. Since insulin binding to monocytes in decreased during the secretory phase of the menstrual cycle, one could extrapolate from our data that pregnant women will have lower insulin binding compared to nonpregnant women in the proliferative phase of the cycle; such a report has appeared recently (Beck-Nielsen et al., J Clin Endocrinol Metab 49: 810, 1979). Differences in plasma levels of estrogen and progesterone between the secretory and proliferative phases of the cycle are much smaller than between the nonpregnant state and late pregnancy. Therefore, it remains to be seen whether these steroid hormones would cause, by the same mechanism, a decrease in insulin binding (and insulin resistance) during late pregnancy and in the secretory phase of the cycle.

PIP: This study of altered carbohydrate metabolism in pregnant women and oral contraceptive (OC) users measured insulin binding to circulating erythrocytes and monocytes in 77 nonobese healthy women volunteers. The 77 women were divided into 4 groups: 1) third trimester pregnant (n=19); 2) OC users using 50 mcg estrogen formulations (n=19; OC50); 3) OC users with 35 mcg formulations (n=18; OC35); and 4) controls (n=21). Nonpregnant participants in the study were between menstrual cycle Days 18 and 21 (luteal phase). Oral glucose tolerance tests were performed on all groups, and results were normal for all 4 groups. When fasting plasma insulin was tested, it was higher (P .001) in the pregnant group, and plasma insulin responses to oral glucose tolerance test were higher (p .05) in the pregnant, OC35, and OC 50 groups compared with controls. Specific binding of tritiated insulin to monocytes showed similar percentage in all 4 groups. There was no correlation between insulin binding to erythrocytes and monocytes. The average affinity profiles and binding sites per cell (70/erythrocyte and 50,000/monocyte) were similar in all groups as well.

Studies of pituitary gonadotropin response to graded GNRF injections in women using a low-estrogen oral contraceptive for six months.

PIP: This study measures basal and stimulatable LH (luteinizing hormone) and FSH (follicle stimulating hormone) levels before and after 6 months of low estrogen oral contraceptive (OC) use, as well as basal plasma ovarian steroids. 8 normal women at least 8 weeks postpartum and desiring oral pills had sequential intravenous injections of 0.5, 5.0 and 50 mcg og gonadotropin-releasing factor (GNRF) before and after 6 months of use of low estrogen type OC containing 35 mcg ethinyl estradiol and 0.4 mgm Norethindrone. Radioimmunoassay was used to measure the hormone levels. Each woman served as her own control. Measurements of basal gonadal steroid revealed no dfiferences in the levels of progesterone, testosterone and dihydrotestosterone but there was a significant reduction in plasma estradiol levels with OC use. A rise in LH was observed after each GNRF injection, but the rise is significant in both the 5.0 mcg and 50 mcg GNRF injections after 6 months of OC usage while during the control test, only the injection of 50.0 mcg GNRF achieved a significant LH rise. A significant rise in FSH was observed during the 6 months of OC use (after the 50 mcg injection). The findings show that this low estrogen type OC does not produce a strong suppression of pituitary gonadotropin cell function. Clinical implications of these findings in terms of pregnancy prevention, cycle control and postpill amenorrhea were briefly discussed.^ieng