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Biomedical subjects

R L Barbieri

Publications and source records attributed to R L Barbieri.

At least 55 records · Page 3Linked to original sources

Primary gonadotropin-releasing hormone agonist therapy for suspected endometriosis: a nonsurgical approach to the diagnosis and treatment of chronic pelvic pain.

Chronic pelvic pain is a condition that affects one in seven women of reproductive age in the United States. Direct and indirect medical costs associated with this condition are estimated to be more than $3 billion annually before factoring in the costs of diagnostic testing. At many medical centers, endometriosis is the most common single cause of chronic pelvic pain; other causes include intra-abdominal adhesions, chronic pelvic inflammatory disease, ovarian cysts, and adenomyosis. The current approach to diagnosis and treatment of chronic pelvic pain is a two-step approach, with medical history, physical examination, laboratory testing, and empiric therapy (nonsteroidal anti-inflammatory drugs, oral contraceptives, and/or antibiotics) comprising Step 1 and surgical diagnosis with laparoscopy as Step 2. At many centers, the most common diagnosis at the time of laparoscopy for chronic pelvic pain is endometriosis, typically minimal to mild disease that can be effectively treated with hormonal therapy. Therefore, a rational alternative approach is a 3-month empiric course of therapy with a gonadotropin-releasing hormone agonist before laparoscopy. The advantages of this approach are the high rate of pain relief in women, the possibility of avoiding an invasive procedure (laparoscopy), the ability to extend therapy, if pain is relieved, to the full 6-month therapeutic course of endometriosis, and a potentially lower cost relative to laparoscopy.

Chronic Disease↗

Effects of alcohol ingestion on estrogens in postmenopausal women.

OBJECTIVE: To determine if moderate alcohol drinking increases circulating estradiol levels in postmenopausal women who are taking estrogen replacement. DESIGN: Randomized, double-blind, placebo-controlled crossover study of the effects of alcohol ingestion on plasma estradiol and estrone. SETTING: Inpatient Clinical Research Center. PARTICIPANTS: Twelve healthy postmenopausal women receiving oral estrogen (estradiol, 1 mg/day) and progestin (medroxyprogesterone acetate) replacement therapy were compared with 12 postmenopausal women who were not using estrogen replacement therapy (ERT). INTERVENTION: Each group drank alcohol (0.7 g/kg) and an isoenergetic (isocaloric) placebo (randomized sequence) on consecutive days. Women who were taking ERT were studied during the estrogen-only portion of their replacement cycle, and estrogen was administered each evening at 2100 hours. MAIN OUTCOME MEASURE: The impact of alcohol ingestion on plasma estradiol and estrone levels. RESULTS: Alcohol ingestion lead to a 3-fold increase in circulating estradiol in women on ERT; however, alcohol did not change estradiol significantly in control women who were not on ERT. In women using ERT, estradiol levels increased from 297 to 973 pmol/L (81 to 265 pg/mL) within 50 minutes (P<.001) during the ascending limb of the blood alcohol curve and remained significantly above baseline for 5 hours (P<.001). No significant increase in circulating estrone was detected in either group. However, estrone levels decreased after alcohol and placebo in women on ERT (P<.05). Blood alcohol levels did not differ significantly in women who used ERT and those who did not. Peak blood alcohol levels of 21 mmol/L were attained in each of the 2 groups within 50 to 60 minutes after drinking began. Changes in estradiol were significantly correlated with changes in blood alcohol levels on both the ascending (P<.001) and descending (P<.001) limb of the blood alcohol curve. CONCLUSIONS: Acute alcohol ingestion may lead to significant and sustained elevations in circulating estradiol to levels 300% higher than those targeted in clinical use of ERT. Potential health risks and benefits of the interactions between acute alcohol ingestion and ERT should be further evaluated.

Alcohol Drinking↗

Endometriosis associated with the N314D mutation of galactose-1-phosphate uridyl transferase (GALT).

To explore a possible connection between endometriosis, Müllerian anomalies, and possession of the N314D allele of the gene for galactose-1-phosphate uridyl transferase (GALT), we studied 33 women with endometriosis attending a fertility clinic. Patients completed questionnaires and had DNA tested for the N314D mutation of GALT. A previously completed general population survey of 111 women which obtained the same information was available for comparison. Women with endometriosis were more likely to carry at least one N314D allele (30% compared with 14%) and more likely to report a medical history of scoliosis (21% compared with 2%) compared to general population controls: two features we have described in women with vaginal agenesis. Compared with endometriosis cases without the N314D allele, those cases with the allele tended to have more advanced disease and a family history of endometriosis. We speculate that endometriosis may arise due to defects of canalization of the cervix leading to cervical stenosis and retrograde menstruation. The relevance of the N314D mutation, via this model, may derive from an association between abnormalities of galactose metabolism and vaginal agenesis which represents a canalization defect of the vaginal plate of the Müllerian tubercle, the same structure which gives rise to the cervix.

Contraceptives, Postcoital, Synthetic↗

Induction of ovulation with the sole use of clomiphene citrate in late-onset 21-hydroxylase deficiency.

Late-onset 21-hydroxylase deficiency (21-OHD) is a congenital enzymatic defect in the glucocorticoid and mineralocorticoid steroidogenic pathways. The manifestations, including hirsutism and infertility, usually occur at puberty or young adulthood. In infertile, anovulatory women with late-onset 21-OHD, the usual therapy is glucocorticoids for ovulation induction. In this case, we report the sole use of clomiphene citrate to induce ovulation in a patient with late-onset 21-OHD. A hirsute and oligomenorrheic woman was diagnosed as having polycystic ovary syndrome at age 25. Her hirsutism responded to oral contraceptives. At age 31, she was given clomiphene citrate alone for ovulation induction and conceived in her fourth cycle. At age 36, because of increased hirsutism she was diagnosed with late-onset 21-OHD by an ACTH stimulation test. The induction of ovulation in late-onset 21-OHD patients has been with glucocorticoids. Given the success in inducing ovulation with clomiphene citrate alone in this patient with well-documented late-onset 21-OHD, it may be worthwhile to study the sole use of clomiphene citrate for ovulation induction in these patients.

17-Hydroxycorticosteroids↗

In vitro fertilization: a cost-effective alternative for infertile couples?

OBJECTIVE: To evaluate the cost of in vitro fertilization by calculating the cost of a live birth using this technology and determine cost variation according to the clinical characteristics of a particular population. DESIGN: Retrospective review of infertile couples who presented for their first IVF cycle in 1993. A fraction of the total population was assigned to three groups A, B, and C with high, intermediate and low probability of pregnancy respectively and their reproductive performance was evaluated until September 1994 or a maximum of three IVF cycles have been completed. SETTING: The in vitro fertilization program at the Brigham and Women's Hospital, Boston. PATIENTS: 182 couples who presented for their first IVF cycle in 1993. MAIN OUTCOME MEASURE: The cost of a successful pregnancy using IVF in the three groups and in the general population was calculated by dividing the average cost of an IVF cycle by the fraction of the cycles resulting in a successful pregnancy. RESULTS: The cost of a successful pregnancy in group A, B and C ranged from $22,857 to $42,666 after 1 cycle and from $26,800 to $74,666 after 3 IVF cycles. The average cost for the 182 patients was $29,120 after 1 cycle and $31,590 after a maximum of 3 IVF cycles. CONCLUSION: The cost of a successful pregnancy: (1) was comparable to other options available to an infertile couple such as adoption and tubal surgery, (2) was 50% to 70% cheaper in the group with a highest probability of pregnancy when compared to the group with the lowest probability of pregnancy, and (3) did not vary significantly after 1 or 3 IVF cycles in most groups.

Cost-Benefit Analysis↗

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↗

Hormone testing in women with adult-onset amenorrhea.

To assess the clinical utility of routine endocrine testing in women with adult-onset amenorrhea, charts were identified from 127 women diagnosed with adult-onset amenorrhea who had a thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and prolactin (PRL) level performed. Women who were pregnant or previously diagnosed with thyroid disease were subsequently excluded and 120 subjects remained. Of the 120 women screened, 12 (0.100) had abnormal FSH levels, 9 (0.075) had abnormal PRL levels, and 5 (0.042) had abnormal TSH levels. The incidence of an abnormal FSH level (95% CI 0.053, 0.168; p < 0.001) and PRL level (95% CI 0.035, 0.138; P = 0.007) was significantly elevated as compared to the reference laboratory normal values. However, the incidence of an abnormal TSH level in the study population was not statistically different from that of the reference laboratory normal values (95% CI 0.014, 0.095, p = 0.88). The evaluation of 120 women with adult-onset amenorrhea demonstrated abnormal concentrations of FSH, PRL and TSH in 10, 7.5 and 4.2% of patients, respectively. A rank ordering of these endocrine tests may be useful when evaluating women with adult-onset amenorrhea.

Adolescent↗

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↗

Characteristics of women with a family history of ovarian cancer. II. Follicular phase hormone levels.

BACKGROUND: Although there is a basis for linking pituitary or ovarian hormones with experimentally induced ovarian cancer, establishing their role in women is complicated because the usual case-control methods cannot be applied. In this study, hormonal levels in women with a family history of ovarian cancer (FOC) and who are at higher risk for the disease are compared with women without such a history. METHODS: The authors studied 106 unrelated women (FOC patients) with at least one primary or two second-degree relatives with ovarian cancer compared with 116 age- and residence-matched controls without a family history of ovarian cancer (FOC control subjects). All women were premenopausal, between the ages of 25 and 49 years, not currently using oral contraceptives, and had blood drawn during the early follicular phase for gonadotropins, estradiol (E2), and CA-125. RESULTS: Women with a family history of ovarian cancer and control subjects did not differ significantly in follicle stimulating hormone (FSH) levels, E2, or CA-125. Patients with a family history of ovarian cancer had significantly lower luteinizing hormone (LH) levels compared with control subjects and produced more E2 and FSH relative to their level of LH. The ratios of LH to E2 and LH to FSH were correlated with the enzymatic activity of galactose-1-phosphate uridyl transferase, which was shown previously to differ between FOC patients and control subjects. CONCLUSION: Lower LH and higher E2 are reported in women with breast, endometrial, and ovarian cancer (before surgery). The authors speculate that these observations reflect greater LH binding and estradiol production in ovaries at risk for these cancers--the ovarian cortical hyperplasia postulated in older gynecologic literature as the precursor to estrogen dependent neoplasia.

Adult↗

Phosphorylation of 17 beta-hydroxysteroid dehydrogenase in BeWo choriocarcinoma cells.

OBJECTIVE: The purpose of this study was to test whether 17 beta-hydroxysteroid dehydrogenase might exist in a phosphorylated form. STUDY DESIGN: Phosphorylation of 17 beta-hydroxysteroid dehydrogenase was evaluated in BeWo choriocarcinoma cells. The phosphorylation of 17 beta-hydroxysteroid dehydrogenase expressed in Escherichia coli as a glutathione transferase fusion protein was also studied. RESULTS: Human BeWo choriocarcinoma cells were metabolically labeled with phosphorus 32 orthophosphate. Immunoprecipitates were prepared with rabbit anti-17 beta-hydroxysteroid dehydrogenase antiserum from the labeled cells and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A phosphorylated protein with a molecular size of 35 kd was obtained from anti-17 beta-hydroxysteroid dehydrogenase immunoprecipitates, which suggested that 17 beta-hydroxysteroid dehydrogenase was phosphorylated in BeWo cells. The predominant phosphoamino acid was phosphoserine. 17 beta-Hydroxysteroid dehydrogenase expressed in E. coli as a glutathione transferase fusion protein was a substrate of protein kinase A in vitro. Protein kinase A phosphorylated the recombinant 17 beta-hydroxysteroid dehydrogenase exclusively on serine. Incubation of BeWo cell lysates with bacterial alkaline phosphatase led to a decrease in the oxidative activity of 17 beta-hydroxysteroid dehydrogenase. Incubation of the alkaline phosphatase inhibitor levamisole with BeWo cell lysates resulted in a higher estradiol-to-estrone conversion rate, compared with cell lysates without any treatment. CONCLUSION: Our data suggest that 17 beta-hydroxysteroid dehydrogenase may exist in phosphorylated forms and that phosphorylation may regulate the activity of 17 beta-hydroxysteroid dehydrogenase in vivo.

17-Hydroxysteroid Dehydrogenases↗

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↗