Practical applications of home diagnostic products. A symposium.
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Blood Glucose↗
Biomedical subjects
R W Rebar
Publications and source records attributed to R W Rebar.
Increased adrenocortical responsiveness to exogenous ACTH in oral contraceptive users.
To evaluate the effects of changing steroid milieu on adrenocortical function, basal levels and responses of cortisol, 17-hydroxyprogesterone (17PO), androstenedione (A), dehydroepiandrosterone (DHEA), and testosterone to exogenous synthetic ACTH were investigated in six normal women during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle and in five women on an oral contraceptive (OC) agent (35 micrograms ethinyl estradiol and 1 mg ethynodiol diacetate, Demulen). Baseline serum steroid and cortisol binding globulin (CBG) levels were measured on days 3-7 and 21-23 of the menstrual cycle in the normal subjects and on days 3-7 of OC treatment cycles. ACTH stimulation (10 micrograms m-2 i.v. bolus) was performed following dexamethasone suppression (0.5 mg p.o. q 6 h X 4). Basal levels of cortisol and CBG as well as cortisol responses to ACTH were increased in OC users relative to normal women tested during both the EF and ML phases of the cycle. In addition, 17PO levels were increased during the ML phase both before and following dexamethasone suppression compared to levels present in the EF phase and in OC users, no doubt because of increased ovarian steroidogenesis.
17-alpha-Hydroxyprogesterone↗
Increased cortisol production in women runners.
Because we previously found increased basal serum cortisol levels in women runners, we examined adrenocortical function in amenorrheic running women (AR), eumenorrheic running women (R), and normal nonexercising women (NC) in further detail. Mean 24-h urinary cortisol levels were significantly elevated (P less than 0.001) in six AR [45.1 +/- 7.2 (+/- SEM) micrograms/24 h] and eight R (38.5 +/- 6.9 micrograms/24 h) compared to four NC (13.9 +/- 2.8 micrograms/24 h). After adrenal suppression with 2 mg dexamethasone, integrated responses and absolute maximal elevations in serum cortisol levels in response to 10 micrograms/m2 exogenous ACTH (1-24) administered as an iv bolus dose, were not significantly different among six AR, six R, and six NC. This dose of ACTH results in maximal steroid release. The disappearance rates of cortisol (5 mg, iv) after dexamethasone suppression were similar in four AR, five R, and four NC and corresponded to a two-compartment model with mean half-lives of 4.9 and 93.8 min, respectively. Cortisol-binding globulin levels were also similar among the groups. These data document higher cortisol secretion and suggest increased ACTH secretion in running women.
Adolescent↗
Hirsutism in young adolescent girls.
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Adolescent↗
Reproductive hormone increases in response to acute exercise in men.
The increase in serum testosterone levels generally observed with intense, short-term exercise remains unexplained since most investigators have not reported any increase in the levels of luteinizing hormone, the pituitary glycoprotein most responsible for testicular steroidogenesis. Hemoconcentration and decreased metabolic clearance have been suggested as mechanisms to explain the exercise-associated testosterone increase. Such non-specific mechanisms should apply to other steroid hormones as well as to testosterone. To investigate whether the exercise-induced changes in other steroid hormones were similar to that of testosterone, we measured serum levels of testosterone, androstenedione, dehydroepiandrosterone, and cortisol as well as gonadotropins, luteinizing hormone and follicle-stimulating hormone, and prolactin at 5-15 min intervals throughout progressive maximal intensity exercise on a cycle ergometer. Significant increases were observed with all hormones with exercise. The increase in serum testosterone began prior to exercise, peaked at 20 min after the beginning of exercise, and fell to baseline within 10 min. The serum luteinizing hormone increase was synchronous with that of testosterone, suggesting that gonadotropin stimulation was not responsible for the testosterone increment. The increments in serum cortisol, androstenedione, dehydroepiandrosterone, and prolactin levels were simultaneous but began 25-30 min after that of testosterone in all subjects. These findings, therefore, suggest that, contrary to previous evidence, the exercise-associated increase in serum testosterone results predominantly from a specific mechanism, presumably involving increased testicular production without gonadotropin stimulation.
Adult↗
Relationship of migraine headache and stroke to oral contraceptive use.
Are oral contraceptive users who also suffer from migraine headaches at higher risk of having a cerebrovascular accident? The data are inconclusive in establishing that women who used the relatively higher-dose pills prescribed in the 1960s have a higher risk of either thrombotic or hemorrhagic stroke. Furthermore, a review of the literature does not support the belief that those women who use oral contraceptives have a higher incidence of migraine headache. The available data do not indicate that migraine headache is necessarily a contraindication to prescribing oral contraceptives.
Cerebral Hemorrhage↗
Modulation of thymosin beta 4 by estrogen.
The endocrine thymus produces several hormone-like peptides (generically termed thymosins) which control development of the thymic-dependent lymphoid system and participate in the process of immune regulation. In addition, recent literature supports the hypothesis that gonadal steroids in general and estrogens in particular affect the immune system. To determine whether steroid hormones modulate secretion of thymic peptides, basal concentrations of thymosins alpha 1 and beta 4 were determined by radioimmunoassay in morning blood samples from 87 women in various clinical states. Basal concentrations of thymosin alpha 1 were similar in all women sampled. Basal levels of thymosin beta 4 were similar in normal women during the early follicular phase, women with premature ovarian failure, postmenopausal women not receiving estrogen, and individuals with gonadal dysgenesis. However, the marked variability of basal levels in premature ovarian failure and in postmenopausal women suggests that these groups are quite heterogeneous. Thymosin beta 4 concentrations were reduced in castrated women not receiving estrogen and were decreased more in both postmenopausal women and castrated women who were on chronic estrogen therapy. These data suggest that estrogens can modulate the circulating levels of thymosin beta 4 but not of thymosin alpha 1. We do not yet know whether sex steroids modulate secretion of other thymic peptides.
Adult↗
Congenital adrenal hyperplasia and luteal dysfunction.
A case of 21-hydroxylase deficiency diagnosed and first treated at the age of 3 years is presented. Although pubertal development was delayed, full reproductive function was attained, with menses occurring at 14-33-day intervals. Infertility evaluation at age 20 revealed elevated 17-hydroxyprogesterone (17Po) and androgen concentrations and reduced luteal phase progesterone levels consistent with inadequate luteal function. This was corrected with additional corticosteroid replacement. Normal pregnancy and delivery followed.
17-alpha-Hydroxyprogesterone↗
The effects of thymus-derived peptides on hypothalamic LRF and pituitary gonadotropin content in prepubertal congenitally athymic nude mice and their normal heterozygous littermates.
Congenitally athymic nude mice have recognized reproductive defects, accompanied by decreased pituitary gonadotropin and hypothalamic LRF concentrations at 3 weeks of age, compared to their normal heterozygous littermates. To determine if these hormonal changes are due to decreased secretion of thymic peptides, we measured pituitary concentrations of LH and FSH and hypothalamic LRF content at 21 days of age in 122 congenitally athymic nude (nu/nu) mice and in 190 heterozygous (nu/+) littermates administered daily injections of a crude thymic extract, semipurified thymosin fraction 5, or a synthetic thymic protein preparation. All animals receiving crude thymic protein extract, and some receiving either thymosin or synthetic thymic factor, had reduced levels of hypothalamic LRF. The changes in concentrations of gonadotropins were more variable. All mice receiving crude thymic extract (with reduced hypothalamic LRF content) appeared to have increased pituitary concentrations of LH, FSH, or both when compared to control animals, although statistical significance was not achieved in all groups. A similar but less marked trend toward increased pituitary gonadotropins was also noted in mice receiving thymic factor. These preliminary results suggest that thymus-derived peptides can affect hypothalamic-pituitary function and support our hypothesis that thymic hormones may play a role in programming the hypothalamic-pituitary axis in the prepubertal period in rodents.
Animals↗
Lack of consistency in the indirect methods of estimating percent body fat.
Several studies have emphasized the relationship between body composition and the initiation and/or maintenance of cyclic ovarian function in women. A number of methods of indirectly calculating percent body fat have been used, but there is no clear evidence that the various calculations produce consistent results. We therefore compared five different ways of estimating the "percent body fat" in a total of 18 young women, including 6 normal control subjects who did not exercise, 6 regularly menstruating runners, and 6 amenorrheic runners. There was considerable individual variation in the estimates of body fat; and significant differences among groups were found by some, but not all, methods of calculation. It is suggested that because of the inconsistency of estimates, the use of the term "percent body fat" is misleading and that opposite conclusions may result from the use of different methods of calculating body fat in the same groups of individuals.
Adipose Tissue↗
Hypothalamic function in amenorrheic runners.
We have examined temperature regulation in eight amenorrheic runners and gonadotropin response to an opioid antagonist in seven amenorrheic runners, 18 to 29 years of age, running 20 to 70 miles a week. Following equilibration, oral temperature was measured continuously, first in a cold room at 39 degrees F and then in a sauna at 172 degrees F in eight amenorrheic runners, in eight eumenorrheic runners, and in eight control subjects in the early follicular phase of the menstrual cycle. Studies were terminated if a subject's temperature fell below 94 degrees F or rose above 102 degrees F, and all studies were conducted in the afternoon. The rates of temperature change, calculated from total net temperature change divided by elapsed time in the test chamber, were not significantly different among the three groups of women. Seven other amenorrheic runners failed to have any significant changes in luteinizing hormone or follicle-stimulating hormone levels in response to the opioid receptor antagonist naloxone administered as an intravenous infusion at 1.6 mg/hour for 4 hours. If opioids inhibit gonadotropin secretion in exercise-associated amenorrhea, an increase in gonadotropins in response to naloxone would have been anticipated. Although it is possible that the dose of naloxone selected was inappropriate and that temperature responses under other conditions might differ from those of normal women, these data suggest that endogenous opiates do not play a direct role in the amenorrhea associated with exercise and that temperature regulatory centers in the hypothalamus are intact in this disorder, compared with other causes of amenorrhea such as anorexia nervosa. Further studies of hypothalamic function are warranted to test these possibilities.
Adolescent↗
Complete development of secondary sex characteristics in a case of 46,XY pure gonadal dysgenesis.
Although pubertal development is unusual in 46,XY gonadal dysgenesis, it may occur in association with gonadal tumors. The authors report a case of 46,XY gonadal dysgenesis in a 17-year-old girl remarkable for H-Y+ phenotype and bilateral gonadoblastomas accompanied by dysgerminomatous change and nearly complete female secondary sex development. Endocrinologic activity of the gonads was indicated by marked decrease in sex steroid production after gonadectomy. Occurrence of gonadal neoplasia in this case is consistent with the observation that neoplastic transformation is likely in H-Y+ cases of 46,XY gonadal dysgenesis.
Adolescent↗
Evidence for decreased endogenous dopamine and opioid inhibitory influences on LH secretion in polycystic ovary syndrome.
The inhibitory role of the dopaminergic and opioidergic mechanisms in the control of LH secretion in patients with polycystic ovary syndrome (PCO) was evaluated. The administration of an opiate receptor antagonist, naloxone, of a dopamine receptor antagonist, metoclopramide, or of human synthetic beta h-endorphin, were unable to alter LH secretory activity in patients with PCO. Since identical doses of these antagonists and the opiate agonist have elicited respectively a rise and fall of LH levels in normal cycling women, these findings suggest that an underlying hypothalamic component of defect in endogenous dopamine and opioid control may be responsible for the inappropriate gonadotrophin secretion in this syndrome.
Depression, Chemical↗
Endocrine comparison of obese menstruating and amenorrheic women.
10 examine the relationship between obesity and chronic anovulation, we compared basal serum LH, FSH, and PRL levels, determined at 20-min intervals, and basal C21 [progesterone, 17- hydroxyprogesterone , pregnenolone, 17-hydroxypregnenolone ( 17Pe ), and cortisol], C19 [testosterone (T), delta 4-androstenedione (A), and dehydroepiandrosterone] and C18 (estrone and estradiol) steroid hormone concentrations measured at 1- to 2-h intervals for a 24-h period in five normal weight cycling women (NC) and in two groups of weight-matched obese women. Five of the obese women were regularly cycling (OC), and six were amenorrheic (OA). Sex hormone-binding globulin (SHBG) and non-SHBG-bound T and estradiol concentrations were also measured in each woman. Compared to NC women, OC women had normal basal protein and steroid hormone concentrations, except for reduced 17Pe levels (P less than 0.05). Mean SHBG concentrations were reduced by approximately 30%, and non-SHBG-bound T was increased by 70%, although the differences were not significant. In addition, when six precursors of testosterone (pregnenolone, 17Pe , dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, and A) were considered together as a group and the data analyzed by the kappa 2 test, a reduction in basal levels of these precursors was found in OC women relative to those in NC women (P less than 0.005). In OA women, mean concentrations of SHBG were markedly reduced and those of total T, A, estrone, and non-SHBG-bound T were significantly increased compared to those in both NC and OC women. Mean 24-h concentrations of LH tended to be greatest and FSH lowest in this group, but were not significantly different from those in the other groups. The mean LH pulse frequency was significantly greater in OA than in OC women (P less than 0.05). Mean 24-h PRL and cortisol levels were also reduced in OA women relative to those in NC women. These data suggest the possibility of a compensatory decline in total T production in OC women in an attempt to maintain normal hormonal homeostasis; as a consequence, ovulation continues in a cyclic fashion. In OA women, such compensatory mechanisms are no longer operative. Instead, a central and/or peripheral defect, resulting in overproduction of androgen, may also exist and lead to anovulation in OA women. In conclusion, our data imply that obesity is not a primary factor causing chronic anovulation. However, obesity may aggravate an already existing subtle defect in some women and result in amenorrhea.
Adult↗
Pulsatile administration of low-dose gonadotropin-releasing hormone. Ovulation and pregnancy in women with hypothalamic amenorrhea.
We administered pulsatile low doses of gonadotropin-releasing hormone (GnRH) (1 to 5 micrograms) to patients whose anovulation was caused by relative and absolute deficiency of endogenous GnRH. Eight such patients, including one with previous pituitary stalk transection, were treated during a total of 23 cycles; pulses of GnRH were administered via a portable pump every 96 or 120 minutes. Activation of pituitary-ovarian function with orderly development of a single dominant follicle, a luteinizing hormone surge, and ovulation occurred in 20 of the 23 cycles. The other three cycles were anovulatory. All patients responded, and five (62%) of the eight conceived, for a total of seven pregnancies and four full-term deliveries of normal infants. This study demonstrates that small pulsatile doses of GnRH can activate cyclic pituitary-ovarian function in hypogonadotropin-acyclic women and induce ovulation resulting in pregnancy and live birth.
Amenorrhea↗
Human chorionic gonadotropin and testicular function: stimulation of testosterone, testosterone precursors, and sperm production despite high estradiol levels.
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Adult↗
Exercise and reproductive function in women.
Recent studies have documented that women engaged in strenuous exercise programs may develop reproductive defects, including delayed menarche, shortened luteal phase, and amenorrhea. The etiological bases for these abnormalities have not been determined, but physical, hormonal, nutritional, psychological, and environmental factors may be involved and may differ in importance in affected individuals. The consequences of the altered reproductive function associated with exertion will not be identified until prospective long-term investigations are conducted. In the absence of data to the contrary, however, we currently believe that exercise-associated defects in reproduction are not serious and may be reversed by changes in life-style.
Amenorrhea↗
Shortened luteal phase after ovulation induction with human menopausal gonadotropin and human chorionic gonadotropin.
Serum hormonal profiles were characterized in 126 treatment cycles from 24 anovulatory women who underwent ovulation induction therapy with sequential human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Of the 98 presumptively ovulatory treatment cycles, 18 had luteal phases lasting 11 days or less. Sixteen of these 18 cycles had one or more of the following features: serum hCG concentrations of less than 75 mIU/ml 24 hours after hCG administration or peak preovulatory estradiol (E2) levels either less than 200 pg/ml or greater than 2000 pg/ml. Midluteal serum progesterone levels were less than 10 ng/ml in seven of the shortened cycles. Only one of these features (E2 greater than 2000 pg/ml) was present in any cycle (n = 2) resulting in pregnancy. Our observations suggest that serum E2 and hCG levels will reflect the apparent adequacy of luteal function during hMG/hCG treatment cycles.
Adult↗