Raquel Ochoa

Transdermal estradiol in menopausal women depresses interleukin-6 without affecting other markers of immune response

Objective: The aim of this study was to analyze the effect of transdermal estradiol replacement therapy (HRT) on immune function in menopausal women. Study Design: A prospective comparative study was carried out in 30 women, aged 48–55 years, who were divided into two groups; 20 of them received transdermal estradiol 50 µg/day during 3 months and 10 who refused to receive HRT served as controls. Serum interleukins were quantified by specific immunoenzymatic assays; in addition, hormones of somatotropin axis and prolactin (PRL) were quantified by IRMA and RIA. Results: Baseline elevated interleukin (IL)-6 levels decreased significantly (p < 0.001) after transdermal HRT as compared with the nontreated group. Contrarily, IL-2 and IL-10 levels as well as mitogenic induced T-cell proliferation were unchanged under HRT. Insulin-like growth factor-I, growth hormone and PRL levels were unaltered by transdermal HRT. Conclusion: Decrement of IL-6 in parallel with absent effect on some indices of immune activity suggests a beneficial action of transdermal HRT. These findings contrast with those demonstrating an increment of immune response in women taking oral HRT. Thus, the route of administra tion determines the effect of HRT on immune function.

Biochemical evaluation of disease activity after pituitary surgery in acromegaly: a critical analysis of patients who spontaneously change disease status.

Background  The definition of biochemical cure in acromegaly involves both the normalization of IGF‐1 and a glucose‐suppressed GH level of < 1 ng/ml. These criteria were reached by several consensus meetings, although no evidence‐based recommendations as to the optimal time to perform biochemical evaluations were made, nor was the fact that several patients may change biochemically upon long‐term follow‐up taken into consideration.

Serum leptin and somatotropin components correlate with neonatal birth weight.

Objective: To determine whether cord sera leptin and components of the somatotropin axis – growth hormone (GH), total (t) and free (f) insulin-like growth factor (IGF), IGF-binding protein-3 (IGFBP-3), and insulin – correlate with birth weight. Design: Cross-sectional study of 22 newborns, 12 with normal birth weight (NBW) and 10 with low birth weight (LBW), in a population of healthy mothers with an apparent normal pregnancy. Methods: Paired mother–neonate blood samples were obtained at vaginal delivery in order to measure leptin and the somatotropin axis components. Results: In all cases maternal blood concentrations of leptin, t and fIGF-I, its carrier protein IGFBP-3, and insulin were higher than in the cord sera of the newborns, regardless of their birth weight. On the contrary, maternal GH levels were lower than in their neonates. LBW neonates had decreased levels of leptin, tIGF-I, and IGFBP-3 as compared with those levels in NBW offspring; however, GH concentrations were higher in LBW neonates. Birth weight showed a significant correlation with cord sera leptin, tIGF-I, IGFBP-3, and GH; nevertheless birth weight was neither interrelated with fIGF-I nor with insulin levels. Conclusion: These data demonstrate that birth weight is significantly correlated with both leptin and some components of the somatotropin axis; on the other hand, no correlation was observed between leptin concentrations and each one of the components of the somatotropin axis. It is suggested that fetal leptin and the somatotropin axis cooperate in intrauterine growth and birth weight.

Increased serum levels of growth hormone and insulin-like growth factor-I associated with simultaneous decrease of circulating insulin in postmenopausal women receiving hormone replacement therapy.

OBJECTIVE Decreases in circulating growth hormone (GH) and its main biological messenger insulin-like growth factor-I (IGF-I) have been interpreted as part of the aging process. Because estrogens participate in modulating GH synthesis and secretion, hypoestrogenism in menopausal women may lead to GH deficiency. The aim of the present study was to determine the effect of hormone replacement therapy (HRT) on both GH and IGF-I levels as well as insulin concentrations in 50 menopausal women. DESIGN Patients were assigned randomly into two treatment groups of 25 each; one group received three cycles of conjugated equine estrogen (CEE) 0.625 mg/day for 21 days, and the other, 1.25 mg/day during 21 days. Each also received chlormadinone acetate for 5 days. There was a control group consisting of regularly menstruating women. RESULTS In the menopausal women, HRT increased significantly (p < 0.001) the low levels of GH and IGF-I; on the contrary the baseline insulin levels declined (p < 0.001) with HRT. A significant linear correlation (r = 0.90) was found between GH and IGF-I as well as with estradiol levels (r = 0.74) in the group of menopausal women receiving CEE 0.625 mg/day. This group of patients had a significant correlation (r = -0.63) between insulin and estradiol levels. No correlation was observed in the group receiving CEE 1.25 mg/day. CONCLUSIONS HRT restored GH, IGF-I, and insulin levels to normal values in all women. Further research needs to be done to establish the beneficial effect of HRT regarding the prevention of the metabolic effects presumably caused by derangement in the somatotropic axis associated with aging.

Low-dose conjugated equine estrogens elevate circulating neurotransmitters and improve the psychological well-being of menopausal women

OBJECTIVE To assess the effect of low-dose conjugated equine estrogens (E) on circulating neurotransmitters and the efficacy for the treatment of psychological symptoms. DESIGN Controlled comparative clinical study. SETTING Endocrine Research Unit, Instituto Mexicano del Seguro Social, Mexico. PATIENT(S) Thirty postmenopausal women received conjugated equine E. Ten women acted as a comparison group. INTERVENTION(S) Conjugated equine E, 0.312 mg/day, for 21 days per cycle during six cycles and added chlormadinone acetate, 2 mg/day, for the last 5 days of each cycle. Green scale for climateric women and Blatt-Kupperman Menopausal Index were used for measuring psychological well-being. MAIN OUTCOME MEASURE(S) Serum levels of dopamine (DA), noradrenaline, serotonin, and beta-endorphin were quantified by specific assays at baseline and at the end of treatment. RESULT(S) Low baseline levels of DA, serotonin, and beta-endorphin increased significantly (P<.001) from 181.9 +/- 47.8 pg/mL to 202.9 +/- 32.8 pg/mL (mean +/- SD); from 206.4 +/- 94.2 ng/mL to 279.2 +/- 67.9 ng/mL; from 11.2 +/- 1.8 pmol/L to 13.8 +/- 2.4 pmol/L, respectively, after conjugated equine E. In parallel, augmented baseline noradrenaline levels diminished significantly (P<.05) from 30.2 +/- 4.7 ng/mL to 24.0 +/- 4.7 ng/mL. All neurotransmitter levels had a significant correlation with 17beta-E(2) concentrations at the end of the study. Alleviation of psychological symptoms was observed in all but eight treated women. CONCLUSION(S) Low-dose conjugated equine E associated with periodic administration of chlormadinone acetate elicited favorable changes in neurotransmitters and relieved psychological symptoms.

Elevation of activity of creatine phosphokinase (CK) and its isoenzymes in the newborn is associated with fetal asphyxia and risk at birth

OBJECTIVE To investigate the relationship of creatine phosphokinase and its isoenzymes with fetal asphyxia and risk at birth. METHODS Thirty-five pregnant women with high-risk pregnancy were studied. RESULTS In 21 patients, fetal distress was diagnosed by interpretation of the fetal heart rate tracing (FHR). The remaining 14 women, having normal fetal cardiotocography, were considered as the control group. Total CK and its isoenzymes activity was measured in cord sera and 24 h after birth in peripheral blood. Abnormal FHR patterns correlate well with elevated enzyme activities. Total CK and its isoenzymes (CK-MM, CK-MB, and CK-BB) exhibited higher values in asphyxiated infants as compared to normal neonates. Electrocardiographic ischemia occurred in seven newborns who had elevated CK-MB and CK-BB levels, both at birth and within 24 h postpartum. Chromatographic study showed in normal neonates that the predominant isoenzyme was CK-MM, whereas CK-BB activity was negligible. In the newborns with abnormal FHR, CK-MB and CK-BB were increased with predominance of CK-MB. CONCLUSIONS Antepartum fetal distress is associated with release of CK-BB, and particularly CK-MB; therefore, these biochemical markers may indicate either brain or myocardial damage.

Expression of Growth Hormone Receptor Isoform Exon-3-Excluding and Exon-3-Retaining Messenger RNAs in Peripheral Lymphocytes from Normal and Acromegalic Subjects

Aim: To determine the expression of two isoforms of the growth hormone (GH) receptor (GHR), which differ by the presence (GHR3+) or absence (GHR3–) of exon 3, and their correlation with circulating GH and insulin-like growth factor I (IGF-I) in normal subjects and in acromegalic patients. Methods: The expression of GHR isoforms was determined by reverse-transcriptase polymerase chain reaction in lymphocytes from 12 normal subjects and from 11 patients with acromegaly. The levels of GHR mRNA were normalized to those of β-actin, and ratios were calculated to assess the relative levels of expression. Results: All samples showed expression of both GHR isoforms, but the expression of GHR3+ and GHR3– was similar in acromegalic patients (6.0 ± 1.7 vs. 8.3 ± 2.0%, mean ± SE). In contrast, in healthy subjects, GHR3– was the predominant isoform (11.8 ± 3.0 vs. 5.1 ± 0.68%; p < 0.05), and the levels of expression of GHR3– correlated significantly with IGF-I. Conclusions: These data demonstrate coexpression of both GHR isoforms under normal and pathological conditions; however, GHR3– is the predominant form in normal subjects and shows a negative correlation with IGF-I levels.

Usefulness of insulin-like growth factor binding protein-3 levels to determine acromegaly activity and effectiveness of transsphenoidal pituitary surgery.

BACKGROUND Several series reported in the literature concerning the results of the treatment of acromegaly have been difficult to evaluate because the indicators are inaccurate. METHODS We investigated the usefulness of insulin-like growth factor binding protein-3 (IGFBP) levels to determine disease activity after surgical treatment of acromegaly in 13 patients with confirmed somatotroph adenoma. RESULTS Before surgery, all 13 non-treated patients had elevated serum levels of IGFBP-3 as well as total and free IGF-I. In addition, there was no overlap with the normal controls (p < 0.001). IGFBP-3 levels correlated significantly (0.91, p < 0.001) with GH suppressibility by glucose after surgery. CONCLUSIONS These data confirm that IGFBP-3 is a better indicator of acromegalic activity than either total or free IGF-I. There was a high correlation with GH suppressibility by glucose after surgery; both free and total IGF-I could be considered sensitive markers only for diagnosis of active acromegaly but not for efficacy of surgery.

Distribution of growth hormone isoforms in sera from women with normal ovarian function, galactorrhea, and normoprolactinemia *

OBJECTIVE To demonstrate if GH concentrations and molecular heterogeneity of GH correlates with the presence of galactorrhea in normoprolactinemic women with normal ovarian function. DESIGN Aliquots of sera from women with normal ovarian function and normoprolactinemic galactorrhea were subjected to gel filtration chromatography, and the fractions were assayed for GH by the use of radioimmunoassay. Molecular weight of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, molecular weight (MW), and partition coefficient. RESULTS Basal serum GH levels were moderately elevated in all six normoprolactinemic women exhibiting galactorrhea. Chromatographic study of sera from these normoprolactinemic women showed the predominance of 40 to 50 kd molecular forms of GH as well as some very low MW GH isoforms. This pattern was different from that obtained in sera from normal women without galactorrhea who presented a predominance of heavier (> 60 kd) isoforms eluted before the GH labeled standard. The monomeric forms were present in less proportion but there was no significant difference as compared with galactorrheic group. CONCLUSIONS Our investigation demonstrated elevated GH basal serum levels is normoprolactinemic women with galactorrhea, and chromatography in gel showed a low proportion of the large MW GH variants associated with a higher proportion of the dimeric forms and very low MW forms of GH. This is different from normal women without galactorrhea who had a predominance of heavier MW GH variants and lesser proportion of < 16 kd isoforms. It is concluded that an increased GH secretion may be responsible for abnormal lactation despite normal PRL levels in some women with normal ovarian function.

Gastrin levels in mothers and neonates at delivery in various perinatal conditions

Background. This study was designed to assess the variations of gastrin (Ga) serum levels in mothers and newborns at birth in some perinatal disorders.