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Biomedical subjects

E D Schriock

Publications and source records attributed to E D Schriock.

9 recordsLinked to original sources

Suppression of circulating delta 4-androstenedione and dehydroepiandrosterone sulfate during oral glucose tolerance test in normal females.

Extending a series of previous investigations on the regulatory interaction of insulin and androgens, this study tests the hypothesis that the physiological insulinemia after oral glucose suppresses circulating dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), and androstenedione (delta 4A) delta 4 in normal women. Accordingly, seven normal weight, ovulatory women were randomized to receive first either a 75 g glucose dose or a sham control for diurnal rhythm consisting of distilled water at 1700 h. After this insulin stimulus, DHEA-S suppressed below sham control at 90 and 120 min (P less than 0.05) whereas delta 4A suppress at 60, 90, and 120 min (P less than 0.05). Furthermore, as serum insulin increased after glucose, DHEA-S (r2 = 0.351, P less than 0.05) and delta 4A (r2 = 0.314, P less than 0.05) decreased in an inverse linear relationship with insulin. There was no significant suppression below sham at any point in time for DHEA, testosterone, or cortisol. Thus, the endogenous serum insulin response after oral glucose in normal women is associated with suppression of serum DHEA-S and delta 4A with absence of testosterone and cortisol suppression.

Administration, Oral

Practical aspects of pulsatile gonadotropin-releasing hormone administration.

Pulsatile administration of gonadotropin-releasing hormone represents a major advance in the treatment of anovulation in women who fail to ovulate with clomiphene citrate and is an alternative for many women who currently receive human menopausal gonadotropin. Four issues must be addressed before administering pulsatile gonadotropin-releasing hormone: (1) safety, (2) efficacy, (3) convenience, and (4) cost. Each of these issues will be affected by the three major decisions a physician makes with gonadotropin-releasing hormone therapy: (1) patient selection, (2) route of administration, and (3) dose of gonadotropin-releasing hormone. The ideal candidate for gonadotropin-releasing hormone therapy is a patient with an absence of endogenous pulsatile gonadotropin-releasing hormone, as seen in hypothalamic amenorrhea. Although women with polycystic ovarian disease can be treated with pulsatile gonadotropin-releasing hormone, a decreased ovulation rate should be expected. The route of administration, intravenous or subcutaneous, and the degree of monitoring can be tailored by the physician to fit each patient's needs. Pulsatile gonadotropin-releasing hormone therapy is a safe, effective, convenient, and economical alternative to human menopausal gonadotropin for ovulation induction in women resistant to clomiphene.

Adult

Failure to demonstrate significant antisperm antibodies in peritoneal fluid of patients with endometriosis.

Endometriosis, even in mild cases, decreases monthly fecundity. Immunologic disorders have been suggested as the mechanism. In light of possible increases in serum autoimmune antibodies, increased peritoneal macrophages, and increased sperm phagocytosis associated with this disease, we postulated that peritoneal fluid antisperm antibodies would be increased and might be the cause of increased sperm phagocytosis and its associated infertility. Peritoneal fluid, from 18 patients with endometriosis and 10 infertile controls, was tested with the antisperm antibody immunobead test validated for peritoneal fluid. One of 18 patients with endometriosis and none of 10 controls had antisperm antibodies present. Therefore, increased sperm phagocytosis is unlikely a result of peritoneal antisperm antibodies in endometriosis patients.

Antibodies

GnRH agonists.

The development of GnRH agonists has had a major impact on the practice of gynecology and reproductive endocrinology. The clinical usefulness of GnRH agonists will increase as modes of administration are improved and indications become better defined. GnRH agonists and, potentially, antagonists will provide a prompt, effective, and reversible method of suppressing ovarian function. GnRH agonists may soon become a treatment of choice for many of the noncontraceptive uses of oral contraceptives. Current indications for GnRH agonist administration are best divided into two groups: short-term (less than 6 months) and long-term (greater than 6 months) suppression. Short-term administration of GnRH agonist include most of the current usage of GnRH agonists. Short-term administration avoids most of the side effects of GnRH agonist and offers the most potential for development of GnRH antagonists. Short-term therapy has been shown to be particularly effective in the preoperative treatment of fibroids, suppression of ovarian function before ovulation induction, for short-term suppression of endometriosis, and for diagnostic purposes to determine whether a medical illness is related to ovarian function. Chronic administration of GnRH agonist has produced varying degrees of success. The treatment of precocious puberty is probably the perfect indication for GnRH agonist suppression. The disease is completely reversed with a remarkable absence of side effects. Long-term administration for metastatic breast or prostatic cancer has been shown to be as efficacious as other forms of gonadal suppression and the potential benefits of suppression outweigh the potential side effects of long-term suppression. The risk-benefit ratio must be carefully analyzed for the other indications for long-term suppression. Long-term suppression could be used for medical illnesses exacerbated by the menstrual cycle, painful symptoms related to endometriosis, contraception, and suppression of hyperandrogynism. Although initial studies show the agonist to be quite effective in treating all of these disorders, long-term suppression also may result in potential serious side effects related to hypoestrogenism including hot flashes and osteoporosis. Long-term administration of GnRH agonist may become feasible by lowering the dose and degree of suppression or by combining GnRH agonist with estrogen or progestin replacement, or both.

Female

Divergent correlations of circulating dehydroepiandrosterone sulfate and testosterone with insulin levels and insulin receptor binding.

We evaluated the insulin response to a standard oral glucose tolerance test (OGTT) and in vitro insulin binding to erythrocytes (RBC) in 26 women from 3 groups: Group NW, normal women (n = 11); Group DS, women (n = 9) with elevated serum DHEAS concentrations, greater than 400 micrograms/dl (greater than 10.84 mumol/L); and Group IR, women (n = 6) with elevated basal plasma insulin concentrations (IRI). There was a significant linear correlation between the area under the insulin response curve (IRI-AUC) and serum testosterone (T) (r = 0.78, p = 0.0001). Using stepwise multiple linear regression, IRI-AUC was characterized as a function of both serum T and DHEAS; positively with T and negatively with DHEAS. In vitro (n = 17), there was a positive correlation between RBC-insulin binding and serum DHEAS (r = 0.54, p = 0.029) and a negative correlation between RBC-binding and T (r = -0.57, p = 0.017). We conclude that DHEAS may enhance insulin binding and action and that DHEAS and T have divergent functional relationships with IRI. DHEAS and T may therefore exert opposing effects on insulin secretion and action.

Dehydroepiandrosterone

Effect on corpus luteum function of luteal phase administration of a potent gonadotropin-releasing hormone analog (nafarelin).

Fourteen women with ovulatory menstrual cycles were treated with a superactive agonistic analog of gonadotropin-releasing hormone (6-D-[2-naphthyl]-alanyl)-GnRH (nafarelin). Eight of the women received a single subcutaneous injection of nafarelin during the luteal phase at a dosage of 2, 5, or 100 micrograms for determination of the dose-response and pharmacokinetic characteristics of the drug. All doses stimulated the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Maximal release was obtained with the 5-micrograms dose (mean +/- standard deviation: delta LH = 297 +/- 75 mIU/ml; delta FSH = 29 +/- 7 mIU/ml), and there was no greater release of gonadotropin with the 100-micrograms dose. To investigate the contraceptive potential of nafarelin as a luteolytic agent, six of the women were treated with 100 micrograms of analog by daily injection for 10 days, beginning either 2 to 3 days or 5 to 7 days after ovulation. Gonadotroph desensitization or down-regulation developed within 24 hours, but serum concentrations of LH and FSH did not fall below normal values during treatment. There were no significant changes in mean estradiol or progesterone concentrations. There also was no change in mean length of the luteal phase (13.7 +/- 2.1 days [control] versus 13.6 +/- 1.4 days). Thus, nafarelin, like other superactive analogs of GnRH, does not appear to be clinically useful as a luteolytic agent in contraceptive development.

Corpus Luteum