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Biomedical subjects

R W Rebar

Publications and source records attributed to R W Rebar.

At least 37 records · Page 2Linked to original sources

Depletion of luteal phase serum progesterone during constant infusion of cortisol phosphate in the cynomolgus monkey.

OBJECTIVE: To study the impact of chronic infusions of cortisol phosphate on ovarian function in the cynomolgus monkey. DESIGN: Cortisol phosphate at doses of 5 or 15 mg/d or saline were infused for periods of up to 8 weeks using subcutaneously implanted osmotic pumps. SETTING: Animals were maintained in the Center for Experimental Animal Resources, Northwestern University. MAIN OUTCOME MEASURES: Serum total and unbound cortisol concentrations, serum total and unbound progesterone (P) concentrations, urinary P metabolites. RESULTS: Mean increases in serum cortisol of 56% and 77% above control levels were achieved. Mean serum P concentrations were not decreased with low-dose cortisol phosphate infusion during the 12 days preceding menses, but mean serum P levels were decreased by 69% to 2.3 ng/mL during high-dose cortisol phosphate infusion. No corresponding decrease in excretion of conjugated immunoreactive P metabolites was found in daily urine samples during cortisol phosphate infusion, suggesting that production rates of P were unaltered by the cortisol phosphate treatment. Unbound serum cortisol increased by a mean of 162% above control levels during high-dose cortisol phosphate infusion, but no increase occurred in the percentage of unbound serum P. CONCLUSIONS: We conclude that elevation of serum cortisol in the range observed in chronically stressed individuals may severely decrease the available P to target organs by displacement of P from plasma proteins but does not inhibit ovarian steroidogenesis or ovulation.

Animals↗

Gonadotropin dynamics in women receiving immediate or delayed transdermal estradiol after oophorectomy.

A prospective study was performed in 24 premenopausal women to evaluate the gonadotropin dynamics of pharmacologic doses of transdermal estradiol-17 beta (E2) administered after bilateral oophorectomy. Patients were given 0.2-mg transdermal E2 patches for 2 weeks, followed by 0.1-mg patches for 4 weeks either immediately postoperatively (immediate estrogen replacement therapy [ERT]) or beginning 12-14 days after surgery (delayed ERT). Serum gonadotropins and E2 levels were measured serially, and postmenopausal symptoms were prospectively recorded. Administration of 0.2 mg transdermal E2 immediately after surgery suppressed the post-castration rise in gonadotropins for at least 4 days, but LH and FSH levels did increase to the menopausal range after 2 weeks despite continued therapy. Sustained circulating levels of E2 with transdermal E2 therapy were comparable to follicular phase values. Vasomotor symptoms were well controlled by 0.2 mg of transdermal E2 in the majority of patients during the clinical trial. There was no significant estrogen-related morbidity despite the large doses used. Two patients had skin irritation at the patch site causing discontinuation of therapy. These data suggest that large doses of transdermal E2 can suppress gonadotropin levels only for a brief interval. We were unable to demonstrate any long-term alteration in the hypothalamic-pituitary set point for sensitivity to exogenous E2.

Administration, Cutaneous↗

Comparison of endometrial biopsy and urinary pregnanediol glucuronide concentration in the diagnosis of luteal phase defect.

To determine if pregnanediol glucuronide (PG) excretion is useful in luteal phase assessment, we compared daily first morning urinary PG concentrations during the luteal phase in nine normal and nine deficient cycles. Total luteal pregnanediol excretion (44.1 +/- 11.3 versus 64.0 +/- 11.6 area units +/- SEM) was not different. However, significantly less pregnanediol was excreted by the abnormal group during the 1st 5 days of the luteal phase (12.7 +/- 1.2 versus 18.0 +/- 1.7 area units +/- SEM, respectively). Thus, delayed PG excretion may be characteristic of luteal phase defect and measurement of urinary PG may be useful only if daily samples during the early luteal phase are obtained.

Biopsy↗

Clinical features of young women with hypergonadotropic amenorrhea.

One hundred fifteen women under age 40 presenting with hypergonadotropic amenorrhea (follicle-stimulating hormone greater than 40 mIU/mL) were evaluated. Incomplete pubertal maturation and chromosomal abnormalities were more likely in the 18 women (15.7%) with primary amenorrhea than in those with secondary amenorrhea. The 97 women with secondary hypergonadotropic amenorrhea were significantly more apt to complain of symptoms of estrogen deficiency, have been pregnant before diagnosis, and have evidence of ovulation after diagnosis. Withdrawal bleeding occurred commonly (greater than 48%) in those women administered exogenous progestin. Immune abnormalities occurred with approximately equal frequency (17.4%), and spinal bone density was decreased in both groups.

Adult↗

Management of problems during menopause.

Many women pass through menopause with no problems and no complaints. They should be encouraged to pursue healthy life-styles. For those who do experience difficulties or for those who are at risk for developing problems, the aforementioned treatment options can be considered. At this time, the benefits of HRT appear to outweigh the risks and offer substantial improvement in the quality of life to appropriately selected women. With the realization that women can expect to live one third of their lives after menopause, it becomes clear that it is important to discuss menopausal health issues with each women in order to make the postmenopausal period as enjoyable as possible.

Cardiovascular Diseases↗

Pituitary function in isolated gonadotrophin deficiency.

Hypothalamic-pituitary function was assessed in 24 individuals with isolated gonadotrophin deficiency (IGD). Thirteen had normal olfaction (Group I) while 11 (Group II) had anosmia (Kallmann's syndrome). In response to a 10 micrograms intravenous (i.v.) bolus of GnRH, the minimal dose required to evoke a consistent gonadotrophin response in normal subjects, the patients responded with significant LH and FSH increases over baseline (P less than 0.01). In Group II patients, large doses (150 micrograms) of GnRH, which elicit maximal release of gonadotrophin in normal subjects did not increase gonadotrophin release beyond that produced by a 10 micrograms bolus. In response to two 10 micrograms GnRH doses, at times 0 and 120 min, the IGD patients responded with similar LH increases to both boluses (both P less than 0.01 compared to baseline). The maximal PRL responses to arginine infusion and to TRH in the male patients were similar to those of normal males. However, in the IGD females, the PRL response to TRH was less than in normal females. The TSH responses to TRH in IGD males and females were similar to each other and similar to normal. The IGD male GH response to arginine infusion was comparable to that in normal males. We conclude that (1) IGD patients appear to retain minimal endogenous GnRH secretion so that the IGD pituitary responds to a minimal dose of GnRH without priming; (2) IGD is a heterogeneous syndrome in which affected individuals with and without normal olfaction represent parts of the spectrum of the same disease; and (3) except for the PRL response in females, the PRL, TSH and GH responses demonstrate that the IGD pituitaries are largely intact.

Adolescent↗

Differences between serum and urinary LH in hypergonadotropic states.

In an attempt to investigate the relationship between molecular configuration, immunoreactivity, radioligand binding, and biological activity, we compared the elution profiles of immunoreactive and radioligand receptor-active LH following gel filtration over Sephadex G-100 (1.6 X 100 cm column). Samples of sera and urinary acetone-insoluble material from normal cycling women during the LH surge (n = 4) and postmenopausal (n = 2) and castrate women (n = 2) were examined. One major peak of LH immunoreactivity was present in the sera and the urinary samples from all subjects. However, this peak of immunoreactive LH in the urinary precipitate consistently occurred 8-10 fractions later than the peak activity observed in the sera. Despite the differences in the profiles of immunoreactivity between sera and urinary precipitates, the major peak of radioligand receptor activity for LH was observed in the same fractions in all samples and corresponded to the major peak of immunoreactivity observed in the sera. Thus, binding activity was sometimes observed in urinary fractions containing little immunoreactivity for LH. Bioassay of selected fractions using the rat interstitial cell-testosterone assay revealed good agreement between receptor activity and bioactivity but not between immunoreactivity and bioactivity. The ratios of total radioreceptor-active to total immunoreactive LH were consistently higher in the sera than in the urinary precipitates. These data suggest alterations in molecular form during metabolism and/or excretion of LH. Whether these alterations represent differences in peptide structure or merely carbohydrate moieties remains to be determined.

Chromatography, Gel↗

Molecular forms of LH subunits in hypergonadotropic states.

To determine whether differences in subunits of LH exist in various hypergonadotropic states, we compared the elution profiles of immunoreactive alpha LH and beta LH following gel filtration over Sephadex G-100 (1.6 X 100 cm column) of sera and urinary acetone-insoluble precipitates from normal cycling women during the LH surge and untreated agonadal women and those receiving estrogen replacement. The elution profiles for the alpha subunit were similar in all subjects in both sera and urinary precipitates. In contrast, the elution profiles of beta LH varied between sera and urinary extracts among the 3 groups of subjects. Sera and urinary precipitates from the individual agonadal women eluted identically, but the profiles were distinct from those in samples from each of the cycling women. Exogenous estrogen therapy had no effect on the elution profiles of immunoreactive urinary beta LH in agonadal women but altered the ratios of beta LH/alpha LH excreted to those observed in normal cycling women. These data document the existence of immunoreactive subunits of LH in sera and urinary acetone-insoluble precipitates and confirm the existence of multiple forms of immunoreactive beta LH. The data further suggest that gonadal steroids may modulate the metabolism and/or excretion of beta LH in various hypergonadotropic states.

Chromatography, Gel↗

The physiology and measurement of hot flushes.

Hot flushes occur in the vast majority of women at menopause or after bilateral oophorectomy. Yet only in the last decade have the physiologic changes associated with hot flushes been identified. It is now clear that hot flushes occur together with pulsatile release of luteinizing hormone. Available data implicate the anterior hypothalamus in the pathogenesis of the hot flush and suggest involvement of catecholamines and endogenous opiates. Estrogen withdrawal appears to be the stimulus to the development of hot flushes in susceptible women, and likewise estrogen is the most effective agent in reducing the frequency and intensity of the hot flush.

Catecholamines↗

Characteristics of menopausal women seeking assistance.

Using a questionnaire approach, we have determined the demographic, social, and clinical characteristics of the first 100 participants attending our menopause clinic. Of the respondents, 79% reported onset of significant physical symptoms and 63% significant emotional symptoms during the menopause. Among the participants, 65% had varying degrees of depression as determined by the Zung self-rating depression scale. This seemed to be more prevalent in patients with previous pelvic operations. Only half the women were on a regimen of estrogen replacement therapy, and most were receiving estrogen in an unopposed fashion. In our menopause clinic, more than half the women were over their ideal body weight, which is in contrast to the popular misconception that only thin women develop menopausal symptoms. Data from our patients suggest the need for multidisciplinary menopause clinics to adequately address the physical and emotional problems of menopausal women.

Adult↗

Insulin resistance and abnormal ovarian responses to human chorionic gonadotropin in chronically anovulatory women.

We studied the interrelationships between insulin resistance, obesity, and abnormal ovarian androgen secretion in chronically anovulatory women with clinical or biochemical evidence of hyperandrogenism. Four groups of six subjects each were studied: (1) normal weight (within 10% ideal body weight) anovulatory, (2) obese (greater than 120% ideal body weight) anovulatory, (3) normal weight eumenorrheic, and (4) obese eumenorrheic. After dexamethasone suppression, human chorionic gonadotropin (2000 IU/1.5m2 body surface area intramuscularly) was administered to each subject. Serum testosterone levels were subsequently determined hourly for 17 hours. On a separate occasion, an oral glucose tolerance test was administered to five subjects from each group. Serum glucose and immunoreactive insulin levels were determined before and after the ingestion of a standard 100 gm glucose load. As a group, the anovulatory women had higher (p less than 0.05) basal testosterone levels (1005 +/- 97 pg/ml) than did the ovulatory women (241 +/- 21 pg/ml) (values +/- SE). Obesity per se was not associated with increased basal testosterone levels. Testosterone levels rose in response to human chorionic gonadotropin (p less than 0.005) only in obese anovulatory women, reached maximal levels after 3 hours, and subsequently remained stable. Basal immunoreactive insulin levels were elevated (p less than 0.05) only in obese anovulatory women (52.4 +/- 20 microU/ml) compared with obese eumenorrheic (8.7 +/- 1.0 microU/ml), normal weight anovulatory (5.8 +/- 2.4 microU/ml), and normal weight eumenorrheic (4.6 +/- 0.4 microU/ml) women. Similarly, maximal increases in immunoreactive insulin levels after glucose ingestion were significantly greater (p less than 0.01) in obese anovulatory women compared with other groups. Of note is the observation that maximal changes in testosterone observed within the first 3 hours after human chorionic gonadotropin and maximal changes in insulin were correlated (r = 0.91, p less than 0.01). These data suggest that (1) both insulin resistance and an abnormal acute response to human chorionic gonadotropin are seen only in obese anovulatory women and (2) the degree to which these two abnormalities are manifested is clearly correlated. The mechanism(s) responsible for this interrelationship, as well as the underlying cause(s) of these biochemical defects, remain to be elucidated.

Adult↗

Are we exploiting the infertile couple?

We hope that this article brings into focus some problems that merit consideration and debate. These thoughts come from a group of individuals who are actively engaged in reproductive endocrine/infertility practices with special interests ranging from ovulation induction to IVF to laser surgery. As a group, we practice in all parts of the country, and the problems mentioned are not restricted to any individual or region. We urge that all of us be candid with ourselves and our colleagues about what we can and cannot do for the infertile couple. We suggest that gynecologists ask themselves this question and proceed when the answer is affirmative: "Is this procedure really in the patient's best interest?"

Advertising↗

Menstrual disorders in the adolescent age group.

Menstrual problems of adolescence are routinely encountered by physicians caring for teenagers. The spectrum of menstrual and associated reproductive problems ranges from minor disorders to serious life-threatening diseases. Many diagnostic and therapeutic modalities are available; however, a sound knowledge of the physiology of maturational events in the hypothalamic-pituitary-ovarian axis is necessary for correct diagnosis and management. The physician must always consider the patient's sensitivity and vulnerability in evaluating and treating various abnormalities of menstruation.

Adolescent↗