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Biomedical subjects

R L Barbieri

Publications and source records attributed to R L Barbieri.

At least 19 recordsLinked to original sources

Evaluation of hormonal testing in the screening for in vitro fertilization (IVF) of women with tubal factor infertility.

PURPOSE: To evaluate the frequency of abnormal prolactin and thyroid stimulating hormone (TSH) test results in ovulatory women with tubal factor infertility who were screened for in vitro fertilization (IVF). METHODS: Charts were identified from 112 ovulatory women with follicle stimulating hormone (FSH) < 20 mIU/ml who were diagnosed with tubal factor infertility and were screened for IVF with thyroid stimulating hormone (TSH) and prolactin levels. Women previously diagnosed with thyroid disease were subsequently excluded and 98 subjects remained. All subjects were determined to be ovulatory by biphasic basal body temperature (BBT) charts, luteal phase progesterone > 4 ng/ml, or endometrial biopsy revealing secretory endometrium. Results of cycle day 3 serum TSH and prolactin concentrations were recorded. The normal range for each test reflects the geometric mean +/- 2 standard deviations (i.e., 95% interval), as obtained from the reference laboratory. Under this construct, hypothesis tests were performed to determine whether or not our study population was consistent with the reference range of normal hormone levels. Under the null hypothesis (normal levels), we expected 5% of the TSH tests to be abnormal (i.e., high or low levels), and 2.5% of the prolactin tests to be abnormal (i.e., high levels). Exact bionomial confidence intervals and P-values were calculated. We also tested for age trend in the proportion of abnormal results. RESULTS: Study subjects had an age range of 25-43. In the study group, 4 (0.041) out of the 98 women screened had abnormal TSH levels. Of these four abnormal TSH results, three were elevated (i.e., TSH > 4.6 microIU/ml) and one was low (i.e., TSH < 0.6 microIU/ml). The frequency of an abnormal TSH value was not significantly different from that expected from the reference laboratory normal values (95% CI 0.011, 0.101). Of the 98 subjects, 7 (0.071) had abnormal prolactin levels, which was significantly different from that expected from the reference laboratory normal values (95% CI 0.029, 0.142; P = 0.023). When stratified by age, there was no observed trend of abnormalities for TSH or prolactin levels with increasing age. CONCLUSIONS: In ovulatory women presenting for IVF with tubal factor infertility, our results show that routine screening with a TSH test does not yield a significantly higher proportion of abnormal results than that expected from the reference laboratory normal values. However, prolactin level screening was found to yield a higher incidence of abnormal tests than expected from the reference laboratory normal values.

Adult

Progesterone: a critical role in the pathogenesis of uterine myomas.

Uterine leiomyomas are monoclonal tumors. However, the factors involved in their initiation and growth remain poorly understood. The neoplastic transformation of myometrium to leiomyoma likely involves somatic mutations of normal myometrium and the complex interactions of sex steroids and local growth factors. Traditionally, estrogen has been considered the major promoter of myoma growth. The purpose of this review is to highlight the biochemical, histologic, and clinical evidence that supports an equally important role for progesterone in the growth of uterine myomas. Biochemical studies suggest that progesterone, progestins, and the progesterone receptor modulate myoma mitotic activity. Several clinical trials demonstrate that progestins inhibit and/or reverse the ability of hypoestrogenism induced by a gonadotropin-releasing hormone agonist to shrink uterine myomas, suggesting a critical role for progesterone in growth of myomas. A new hypothesis to explain the pathogenesis of myomas is presented.

Female

Effects of previous use of oral contraceptives on early follicular phase follicle-stimulating hormone.

OBJECTIVE: To determine if previous oral contraceptive (OC) use is associated with changes in early follicular phase FSH, LH or E2. DESIGN: A cross-sectional study examining determinants of early follicular phase hormone levels. SUBJECTS: Subjects included 106 premenopausal women with a family history of ovarian cancer and 116 premenopausal women without this history who were not taking OCs currently. All subjects completed a structured interview and gave an early follicular phase blood sample. SETTING: Gynecologic Epidemiology Center and Familial Ovarian Cancer Research Center. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, LH, and E2 were measured in early follicular phase plasma samples. RESULTS: Recency or length of prior OC use did not affect early follicular phase LH or E2 levels. Length of OC use did not affect FSH levels in all subjects; but lower levels of FSH were observed in women over age 45 who had used OCs for > 5 years. Early follicular phase FSH is lower in women with OC use within the past 5 years compared with women with more remote use or who never used OCs, after adjustment for age, smoking, and family history status. CONCLUSIONS: Past use of OCs may have a residual effect on basal FSH levels in women not using them currently that depends on recency of use and to a lesser extent duration of prior use.

Adult

Effect of acute ethanol ingestion on prolactin in menopausal women using estradiol replacement.

Epidemiologic studies suggest that women who consume ethanol are at an increased risk for developing breast cancer. Two randomized, crossover studies were performed to examine the effects of ethanol on prolactin in menopausal women using transdermal estradiol. In study 1, transdermal estradiol patches (0.15 mg) were administered to menopausal women (n = 7) the day before ethanol administration. At 8.00 h, the women ingested ethanol (1 ml/kg, 95% ethanol) or an isocaloric carbohydrate drink. Prolactin levels were measured frequently for 6.3 h. Serum ethanol levels reached a broad peak from 40 to 100 min after initiation of ethanol ingestion. Serum prolactin levels were significantly higher after ethanol ingestion than after the isocaloric carbohydrate drink ingestion (p < 0.03). Study 2 was identical to study 1 except that the transdermal estradiol patches were removed after completion of ethanol or carbohydrate ingestion. In study 2, serum prolactin was greater after ethanol ingestion than after carbohydrate ingestion (p < 0.001). In menopausal women using transdermal estradiol, acute ethanol ingestion is associated with an increase in serum prolactin.

Administration, Cutaneous

Total serum calcium reference intervals in postmenopausal outpatients.

The distribution of values of serum calcium has been studied in the following four outpatient populations: premenopausal (n = 411) and postmenopausal women (n = 399), men less than 50 years old (n = 365) and men over 55 years old (n = 361). Their respective average total serum calcium values (mg/dl) were 9.42, 9.56, 9.53, and 9.45. The reference intervals derived for total serum calcium (mg/dl) were 8.4-10.3 (premenopausal women), 8.4-10.7 (postmenopausal women), 8.6-10.5 (men less than 50 years old), and 8.4-10.4 (men over 55 years old). Increased total serum calcium levels were observed in the postmenopausal women as compared with both premenopausal women (p < 0.001) and with men over 55 years old (p < 0.003). Eight percent of the values obtained in postmenopausal women were above the current reference interval, as compared to 1.7% in premenopausal women, and 3.3% in men over 55 years old. In conclusion, the age-related increase in total serum calcium in postmenopausal female outpatients warrants a higher upper limit of the reference interval for this subpopulation.

Calcium

The effects of ethanol on the clearance of estradiol in postmenopausal women.

OBJECTIVE: To determine whether acute alcohol ingestion affects the pattern of decline of circulating E2 levels after removal of transdermal E2 patches. DESIGN: A randomized, placebo-controlled, crossover study. SETTING: The study was performed in the Clinical Research Center of the Brigham and Women's Hospital. PARTICIPANTS: Twelve healthy postmenopausal women were enrolled. INTERVENTIONS: Transdermal E2 patches, 0.15 mg, were applied 13 hours before subjects ingested alcohol (1 mL/kg 95% ethanol) or carbohydrate placebo punch. The patches were removed immediately after drink ingestion. MAIN OUTCOME MEASURES: Estradiol, estrone (E1), and ethanol levels were measured. RESULTS: Serum samples were obtained for 40 minutes before drink ingestion and 5 hours after drink ingestion and E2 patch removal. At the time of patch removal, E2 levels rose acutely over 10 minutes and then decreased rapidly, suggesting a bolus effect that was more marked after ethanol ingestion. After ethanol ingestion and patch removal the half-life of E2 was calculated to be 378 minutes, and after carbohydrate punch and patch removal 245 minutes. There were no significant changes in E1 concentrations over the time course of the study between groups. CONCLUSIONS: Ethanol ingestion may decrease E2 clearance after removal of transdermal E2 patches.

Administration, Cutaneous

Dehydroepiandrosterone sulfate and the risk of myocardial infarction in US male physicians: a prospective study.

High levels of dehydroepiandrosterone sulfate (DHEAS) have been associated with decreased risks of cardiovascular disease. The authors analyzed DHEAS in plasma collected at baseline among 169 participants in the Physicians' Health Study who subsequently had a myocardial infarction and 169 matched controls. The mean prediagnostic plasma DHEAS levels between cases (p = 0.33) (mean, 3.54 mumol/liter; standard deviation, 2.30) and controls (mean, 3.61 mumol/liter; standard deviation, 2.16) did not differ significantly. The relative risk was 1.04 (95 percent confidence interval 0.42-2.60) comparing extreme quintiles after adjustment for several coronary risk factors. In conclusion, these findings do not support the hypothesis that elevated plasma DHEAS is associated with a decreased risk of coronary disease in men, but a small to moderate association cannot be excluded.

Adult

17 beta-Hydroxysteroid dehydrogenase: enzymatic activity and mRNA species in choriocarcinoma cells.

Two human choriocarcinoma cell lines, BeWo and Jar, were used as a model system to study 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity. Northern blot, Western blot and 3H-water assay were performed to investigate the mRNA species, protein and enzyme activity of 17 beta-HSD. Two sizes of 17 beta-HSD mRNA, 1.3 and 2.2 kb, were detected in BeWo and Jar cells. In BeWo cells the predominant mRNA species is 1.3 kb. Western blot analysis demonstrated high level of 17 beta-HSD immunoreactivity and the 3H-water assay demonstrated significant enzyme activity in BeWo cells. In contrast, in Jar cells, the predominant mRNA species is 2.2 kb. Jar cells contain very low 17 beta-HSD enzyme activity and Western blot failed to show detectable 17 beta-HSD immunoreactivity. It is possible that the 2.2-kb 17 beta-HSD mRNA cannot be efficiently translated into protein because of the presence of multiple AUGs and termination signals (UGAs, UAAs, and UAGs) at the 5'-untranslated and termination signals (UGAs, UAAs, and UAGs) at the 5'-untranslated region of the 2.2-kb mRNA.

17-Hydroxysteroid Dehydrogenases

Determinants of basal follicle-stimulating hormone levels in premenopausal women.

The (basal) level of FSH measured during early menses is emerging as a predictor of ovarian competence. In this study, correlates of basal FSH were examined in 222 premenopausal women who were not using oral contraceptives and selected from either the general population or a clinic for women with family histories of ovarian cancer. Using analysis of variance, the effect on FSH by age, smoking history, and reproductive variables was examined. Dietary galactose (as a potential oocyte toxin) was estimated, and red cell activity of galactose-1-phosphate uridyl transferase (GALT) was measured. Qualitative features of GALT were described by its electrophoretic or molecular genetic patterns. Possession of GALT polymorphisms previously linked with low GALT activity, including the Q188R mutation of classic galactosemia or N314D mutation of the Duarte galactosemia variant, was associated with significantly higher FSH, even in the heterozygous state. Other factors significantly influencing FSH included age, smoking history, cycle length, and cycle regularity. No effect of current galactose consumption was found, and GALT activity was only weakly correlated (inversely) with FSH. Applying multiple linear regression, variables independently predictive of high FSH were age of 40 yr or more, current smoking, and possession of a GALT polymorphism.

Adult

Hormone treatment of endometriosis: the estrogen threshold hypothesis.

In women with recurrent pelvic pain caused by endometriosis, hormonal therapy with a gonadotropin-releasing hormone agonist is an effective alternative to surgical therapy. The basis for medical treatment of endometriosis is that endometriosis lesions are dependent on estradiol for continued growth. Further, end organ tissue varies in its sensitivity to estradiol. This forms the basis of the estrogen threshold hypothesis, that is, that a concentration of estradiol that will partially prevent bone loss may not stimulate endometrial growth. Thus there is a hierarchy of organ response to estradiol such that calcium metabolism is most sensitive followed by gonadotropin secretion, vaginal epithelial growth, lipid metabolism, and liver protein production. Similarly, breast cancer is most sensitive and endometriosis is least sensitive to estrogen. These differences may allow the design of regimens with a gonadotropin-releasing hormone agonist that maintain a therapeutic response and ameliorate potential adverse effects.

Bone Density

Human ovarian 17-ketosteroid oxidoreductase: unique characteristics of the granulosa-luteal cell and stromal enzyme.

OBJECTIVES: We attempted to test the hypothesis that distinct forms of the 17-ketosteroid oxidoreductase exist in the human ovary and to compare its activity in stroma obtained from normally cycling women and from hyperandrogenic women. STUDY DESIGN: Human ovarian granulosa-luteal cell and stromal 17-ketosteroid oxidoreductase were examined in cell incubations and subcellular homogenates. RESULTS: In subcellular homogenates of granulosa-luteal cells 17-ketosteroid oxidoreductase activity was greater in the cytosol fraction than in the membrane fraction. In contrast, in homogenates of both ovarian stroma and Leydig cells its activity was greater in the membrane fraction than in the cytosol fraction. At the substrate concentrations used estrone was a better substrate than androstenedione for the granulosa-luteal cell 17-ketosteroid oxidoreductase. In contrast, androstenedione was a better substrate than estrone for that in ovarian stromal and Leydig cell membranes. In incubations of ovarian stroma from hyperandrogenic women, significantly more testosterone accumulated in the medium per milligram of tissue than in the medium of incubations of ovarian stroma from normally cycling women (142 +/- 48 vs 7.9 +/- 7.5 pg testosterone per milligram of tissue per 48 hours, mean +/- SD, p less than 0.05). The ratio of testosterone to androstenedione was significantly higher in the medium of incubations of ovarian stroma from hyperandrogenic women than in that from normally cycling women (0.61 vs 0.25, mean, p less than 0.05). The ratio of serum testosterone to androstenedione was significantly greater in hyperandrogenic women than in normally cycling control women (0.31 +/- 0.11 vs 0.20 +/- 0.03, mean +/- SD, p less than 0.05). CONCLUSION: The localization (cytosol fraction) and substrate specificity (estrone) of the granulosa-luteal cell 17-ketosteroid oxidoreductase enzyme resembles that seen in human placenta. The localization (membrane fraction) and substrate specificity (androstenedione) of the ovarian stromal 17-ketosteroid oxidoreductase enzyme resembles that seen in Leydig cells. It may be one enzyme that exists in multiple forms or it may be two (or more) enzymes. In some hyperandrogenic women the ovarian stromal 17-ketosteroid oxidoreductase may be more active than in normally cycling women, contributing to an abnormally increased testosterone production rate.

17-Hydroxysteroid Dehydrogenases

Directionality of menstrual flow: cervical os diameter as a determinant of retrograde menstruation.

OBJECTIVE: To develop a mathematical model to examine the factors that control the directionality of menstrual flow. DESIGN: The model consisted of a rigid cavity, filled with a viscous liquid, with three outflow ports: a set of paired outflow ports (fallopian tube ostia) and an additional single outflow port (cervical os). The Darcy-Weisbach equation was used to calculate flow rates through the ports. RESULTS: At cervical os diameters of less than 0.5 mm, more than 50% of flow was through the fallopian tubes over a wide range of values for cervical length and fallopian tube ostia diameter and length. The diameter of the fallopian tube ostia was also an important determinant of the directionality of flow. The lengths of the cervical os and fallopian tube ostia were of secondary importance in determining directionality of menstrual flow. CONCLUSION: If retrograde menstruation is a risk factor for the development of endometriosis, menstruating women with cervical os diameters less than 2.0 mm may be at increased risk for developing endometriosis.

Biomechanical Phenomena

Effects of age, smoking and vitamins on plasma DHEAS levels: a cross-sectional study in men.

In recent years, relationships of dehydroepiandrosterone and its sulfate ester dehydroepiandrosterone sulfate (DHEAS) with decreased risks of cardiovascular disease as well as a possible role in the aging process have been postulated. To explore the effects of cigarette smoking, a risk factor for cardiovascular disease, as well as age, on the levels of these adrenal androgens, we measured plasma levels of DHEAS in 543 healthy male subjects from the Physicians' Health Study. Blood specimens were collected between August 1982 and December 1984 and stored at -80 C. The overall mean DHEAS level was 3.47 mumol/L (+/- 2.12 SD). DHEAS levels were positively correlated with smoking habits (r = +0.16, P = 0.0002); current smokers had the highest age-adjusted DHEAS concentrations (4.27 mumol/L, P = 0.0005 compared with never smokers), followed by past smokers (3.47 mumol/L, P = 0.02) and never smokers (3.10 mumol/L). A marked linear decline of levels with age was observed, with an average decrease of 3% per year. These data suggest a moderate direct association with cigarette smoking and a powerful influence of age on decreasing levels of DHEAS. After adjusting for age and smoking habits, DHEAS concentrations were also inversely correlated with reported use of multivitamins (r = -0.16, P = 0.0002) and positively correlated with plasma retinol levels (r = 0.14, P = 0.002).

Adult

Hyperandrogenism: new insights into etiology, diagnosis, and therapy.

Mutations in the genes for the insulin receptor, 21-hydroxylase, 11 beta-hydroxylase, and 3 beta-hydroxysteroid dehydrogenase isomerase enzymes are associated with hyperandrogenism. These genetic causes of hyperandrogenism account for less than 10% of all cases. A major goal of future research will be to identify other genetic causes of hyperandrogenism. Evidence continues to accumulate that luteinizing hormone, insulin-like growth factor I, and insulin are major factors regulating ovarian androgen production. Optimal therapy for hyperandrogenism probably includes simultaneous suppression of androgen production and blockade of androgen action.

3-Hydroxysteroid Dehydrogenases

Menstrual cyclicity of CA-125 in patients with endometriosis.

OBJECTIVE: To examine the serum levels of CA-125 in the menstrual, follicular, and luteal phases of the menstrual cycle in women with endometriosis and to determine if serum CA-125 levels drawn during menses improve the clinical utility of the test in diagnosing endometriosis. DESIGN: Serum CA-125 was measured in the menstrual, follicular, and luteal phases of the cycle preceding surgery. CA-125 levels for each phase were categorized by postoperative diagnosis and endometriosis stage. SETTING: The reproductive endocrine unit of a tertiary care university-affiliated hospital. PATIENTS: A total of 65 patients were recruited from the Fertility and Endocrine Unit and the Gynecology Service of Brigham and Women's Hospital. MAIN OUTCOME MEASURE: Serum CA-125 levels were measured by an immunoradiometric assay and were stratified by menstrual cycle phase, diagnosis, and stage of endometriosis. The menstrual cycle phase was confirmed by serum estradiol and progesterone measurements. RESULTS: Serum CA-125 levels in patients with stages II to IV endometriosis were significantly elevated in the menstrual phase compared with levels drawn in the nonmenstrual follicular and luteal phases. The sensitivity and specificity of CA-125 for the diagnosis of endometriosis were not significantly better in the menstrual than in the follicular or luteal phases. CONCLUSIONS: Despite menstrual cyclicity of CA-125, measurement of serum CA-125 during menses does not improve the clinical utility of the test in the diagnosis of endometriosis.

Antigens, Tumor-Associated, Carbohydrate

Effects of growth hormone administration on dehydroepiandrosterone sulphate, androstenedione, testosterone and cortisol metabolism during nutritional repletion.

This study evaluated whether pharmacological doses of recombinant human growth hormone (hGH) influences androgen or cortisol metabolism during nutritional repletion following prolonged illness. Stable hospitalized adults (three males, seven female) receiving constant calorie and protein intake were studied. An initial control week was followed by a treatment period during which hGH (10 mg/day s.c.) was administered daily. Prior to hGH treatment, serum and 24-h urinary concentrations of dehydroepiandrosterone sulphate (DS) were below the normal range; serum androstenedione and testosterone concentrations were within the lower limit of normal. In contrast, serum cortisol (F) and 24-h urinary F excretion were normal. During hGH treatment, nitrogen balance became positive and plasma insulin-like growth factor I (IGF-I) concentrations rose five to seven-fold. However, serum DS, androstenedione, testosterone and F, and urinary F excretion did not change, while 24-h urinary DS excretion fell significantly. Growth hormone administration markedly stimulated protein anabolism but did not increase the low concentrations of circulating androgens or alter the disassociation between adrenal androgen and F release in stable hospitalized males and females. Thus, hGH does not appear to function as a cortical adrenal androgen stimulating hormone (CASH) or regulate adrenal cortisol or gonadal androgen release in this clinical setting.

Adrenal Cortex